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Sample records for allelic expression imbalances

  1. 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

    Background: One aspect in which RNA sequencing is more valuable than microarray-based methods is the ability to examine the allelic imbalance of the expression of a gene. This process is often a complex task that entails quality control, alignment, and the counting of reads over heterozygous single...... 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 of...... RNA sequencing. The visualization features can reveal notable, non-trivial allelic imbalance behavior over specific regions, such as exons. Conclusions: The software provides a complete framework to perform allelic imbalance analyses of aligned RNA sequencing data, from detection to visualization...

  2. Allelic gene expression imbalance of bovine IGF2, LEP and CCL2 genes in liver, kidney and pituitary

    OpenAIRE

    Olbromski, R.; Siadkowska, E.; Żelazowska, B.; Zwierzchowski, L.

    2012-01-01

    Allelic expression imbalance (AEI) is an important genetic factor being the cause of differences in phenotypic traits that can be heritable. Studying AEI can be useful in searching for factors that modulate gene expression and help to understand molecular mechanisms underlying phenotypic changes. Although it was commonly recognized in many species and we know many genes show allelic expression imbalance, this phenomena was not studied on a larger scale in cattle. Using the pyrosequencing meth...

  3. Allelic imbalance metre (Allim), a new tool for measuring allele-specific gene expression with RNA-seq data

    OpenAIRE

    Pandey, Ram Vinay; Franssen, Susanne U.; Futschik, Andreas; Schlötterer, Christian

    2013-01-01

    Estimating differences in gene expression among alleles is of high interest for many areas in biology and medicine. Here, we present a user-friendly software tool, Allim, to estimate allele-specific gene expression. Because mapping bias is a major problem for reliable estimates of allele-specific gene expression using RNA-seq, Allim combines two different strategies to account for the mapping biases. In order to reduce the mapping bias, Allim first generates a polymorphism-aware reference gen...

  4. Allelic expression imbalance of JAK2 V617F mutation in BCR-ABL negative myeloproliferative neoplasms.

    Directory of Open Access Journals (Sweden)

    Hye-Ran Kim

    Full Text Available The discovery of a single point mutation in the JAK2 gene in patients with BCR/ABL-negative myeloproliferative neoplasms (MPNs has not only brought new insights and pathogenesis, but also has made the diagnosis of MPNs much easier. Although, to date, several mechanisms for the contribution of single JAK2V617F point mutation to phenotypic diversity of MPNs have been suggested in multiple studies, but it is not clear how a unique mutation can cause the phenotypic diversity of MPNs. In this study, our results show that allelic expression imbalance of JAK2 V617F mutant frequently occurs and contributes to phenotypic diversity of BCR-ABL-negative MPNs. The proportion of JAK2 V617F mutant allele was significantly augmented in RNA levels as compared with genomic DNA differently by distinct MPNs subtypes. In detail, preferential expression of JAK2 mutant allele showed threefold increase from the cDNA compared with the genomic DNA from patients with essential thrombocythemia and twofold increase in polycythemia vera. In conclusion, allelic expression imbalance of JAK2 V617F mutant proposes another plausible mechanism for the contribution of single JAK2 point mutation to phenotypic diversity of MPNs.

  5. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2012-02-01

    BACKGROUND: The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC). AIM: To determine the role played by APC gene in the genesis of cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance\\/loss of heterozygosity (AI\\/LOH) was examined in twenty-two histologically confirmed cutaneous squamous cell carcinomas (SCC) using microsatellite markers, proximal to the APC gene. Immunohistochemical analysis of APC protein expression was also examined in the cutaneous SCC. RESULTS: AI\\/LOH was detected in 60% of the SCC samples using D5S346 marker (proximal to the APC gene). Ninty-five percent of the SCC samples showed positive reduced APC expression, however the localization of the APC protein was abnormal. CONCLUSION: The abnormal expression of APC suggests that APC gene may play a role in cutaneous SCC development.

  6. 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...

  7. Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells

    DEFF Research Database (Denmark)

    Djurisic, S; Teiblum, S; Tolstrup, Cæcilie Krogsgaard;

    2015-01-01

    The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy...... complications, partly explained by HLA-G polymorphisms which are associated with differences in the alternative splicing pattern and of the stability of HLA-G mRNA. Of special importance is a 14 bp insertion/deletion polymorphism located in the 3'-untranslated region of the HLA-G gene. In the current study, we......RNA transcripts, which was further associated with low levels of HLA-G surface expression on primary trophoblast cells. Full gene sequencing of HLA-G allowed us to study correlations between HLA-G extended haplotypes and single-nucleotide polymorphisms and HLA-G surface expression. We found that a 1:1 expression...

  8. Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus.

    Science.gov (United States)

    Nakaoka, Hirofumi; Gurumurthy, Aishwarya; Hayano, Takahide; Ahmadloo, Somayeh; Omer, Waleed H; Yoshihara, Kosuke; Yamamoto, Akihito; Kurose, Keisuke; Enomoto, Takayuki; Akira, Shigeo; Hosomichi, Kazuyoshi; Inoue, Ituro

    2016-04-01

    Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging "allele-specific" functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage. PMID:27055116

  9. Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus

    Science.gov (United States)

    Nakaoka, Hirofumi; Gurumurthy, Aishwarya; Hayano, Takahide; Ahmadloo, Somayeh; Omer, Waleed H; Yoshihara, Kosuke; Yamamoto, Akihito; Kurose, Keisuke; Enomoto, Takayuki; Akira, Shigeo; Hosomichi, Kazuyoshi; Inoue, Ituro

    2016-01-01

    Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging “allele-specific” functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage. PMID:27055116

  10. 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

  11. 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...... mutation. 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...

  12. Telomerase activity in high-grade cervical lesions is associated with allelic imbalance at 6Q14-22.

    NARCIS (Netherlands)

    Duin, van M.; Steenbergen, R.D.M.; Wilde, de J.; Helmerhorst, TJ; Verheijen, R.H.M.; Risse, E.K.J.; Meijer, C.J.L.M.; Snijders, P.J.F.

    2003-01-01

    Our study attempts to establish the relationship between telomerase activity and allelic imbalance (AI) on chromosomes 3p and 6 in high-risk HPV-containing cervical lesions. These chromosomes were implicated previously in telomerase regulation in HPV containing immortalized cells and cervical cancer

  13. Data analysis issues for allele-specific expression using Illumina's GoldenGate assay

    Directory of Open Access Journals (Sweden)

    Dermitzakis Emmanouil T

    2010-05-01

    Full Text Available Abstract Background High-throughput measurement of allele-specific expression (ASE is a relatively new and exciting application area for array-based technologies. In this paper, we explore several data sets which make use of Illumina's GoldenGate BeadArray technology to measure ASE. This platform exploits coding SNPs to obtain relative expression measurements for alleles at approximately 1500 positions in the genome. Results We analyze data from a mixture experiment where genomic DNA samples from pairs of individuals of known genotypes are pooled to create allelic imbalances at varying levels for the majority of SNPs on the array. We observe that GoldenGate has less sensitivity at detecting subtle allelic imbalances (around 1.3 fold compared to extreme imbalances, and note the benefit of applying local background correction to the data. Analysis of data from a dye-swap control experiment allowed us to quantify dye-bias, which can be reduced considerably by careful normalization. The need to filter the data before carrying out further downstream analysis to remove non-responding probes, which show either weak, or non-specific signal for each allele, was also demonstrated. Throughout this paper, we find that a linear model analysis of the data from each SNP is a flexible modelling strategy that allows for testing of allelic imbalances in each sample when replicate hybridizations are available. Conclusions Our analysis shows that local background correction carried out by Illumina's software, together with quantile normalization of the red and green channels within each array, provides optimal performance in terms of false positive rates. In addition, we strongly encourage intensity-based filtering to remove SNPs which only measure non-specific signal. We anticipate that a similar analysis strategy will prove useful when quantifying ASE on Illumina's higher density Infinium BeadChips.

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

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    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.

  15. CEQer: a graphical tool for copy number and allelic imbalance detection from whole-exome sequencing data.

    Directory of Open Access Journals (Sweden)

    Rocco Piazza

    Full Text Available Copy number alterations (CNA are common events occurring in leukaemias and solid tumors. Comparative Genome Hybridization (CGH is actually the gold standard technique to analyze CNAs; however, CGH analysis requires dedicated instruments and is able to perform only low resolution Loss of Heterozygosity (LOH analyses. Here we present CEQer (Comparative Exome Quantification analyzer, a new graphical, event-driven tool for CNA/allelic-imbalance (AI coupled analysis of exome sequencing data. By using case-control matched exome data, CEQer performs a comparative digital exonic quantification to generate CNA data and couples this information with exome-wide LOH and allelic imbalance detection. This data is used to build mixed statistical/heuristic models allowing the identification of CNA/AI events. To test our tool, we initially used in silico generated data, then we performed whole-exome sequencing from 20 leukemic specimens and corresponding matched controls and we analyzed the results using CEQer. Taken globally, these analyses showed that the combined use of comparative digital exon quantification and LOH/AI allows generating very accurate CNA data. Therefore, we propose CEQer as an efficient, robust and user-friendly graphical tool for the identification of CNA/AI in the context of whole-exome sequencing data.

  16. Detection of cis-acting regulatory SNPs using allelic expression data

    OpenAIRE

    Xiao, Rui; Scott, Laura J.

    2011-01-01

    Allelic expression (AE) imbalance between the two alleles of a gene can be used to detect cis-acting regulatory SNPs (rSNPs) in individuals heterozygous for a transcribed SNP (tSNP). In this paper, we propose three tests for AE analysis focusing on phase-unknown data and any degree of linkage disequilibrium (LD) between the rSNP and tSNP: a test based on the minimum p-value of a one-sided F and two-sided t tests proposed previously for phase-unknown data, a test that combines these two p-valu...

  17. Effects of sequence variation on differential allelic transcription factor occupancy and gene expression.

    Science.gov (United States)

    Reddy, Timothy E; Gertz, Jason; Pauli, Florencia; Kucera, Katerina S; Varley, Katherine E; Newberry, Kimberly M; Marinov, Georgi K; Mortazavi, Ali; Williams, Brian A; Song, Lingyun; Crawford, Gregory E; Wold, Barbara; Willard, Huntington F; Myers, Richard M

    2012-05-01

    A complex interplay between transcription factors (TFs) and the genome regulates transcription. However, connecting variation in genome sequence with variation in TF binding and gene expression is challenging due to environmental differences between individuals and cell types. To address this problem, we measured genome-wide differential allelic occupancy of 24 TFs and EP300 in a human lymphoblastoid cell line GM12878. Overall, 5% of human TF binding sites have an allelic imbalance in occupancy. At many sites, TFs clustered in TF-binding hubs on the same homolog in especially open chromatin. While genetic variation in core TF binding motifs generally resulted in large allelic differences in TF occupancy, most allelic differences in occupancy were subtle and associated with disruption of weak or noncanonical motifs. We also measured genome-wide differential allelic expression of genes with and without heterozygous exonic variants in the same cells. We found that genes with differential allelic expression were overall less expressed both in GM12878 cells and in unrelated human cell lines. Comparing TF occupancy with expression, we found strong association between allelic occupancy and expression within 100 bp of transcription start sites (TSSs), and weak association up to 100 kb from TSSs. Sites of differential allelic occupancy were significantly enriched for variants associated with disease, particularly autoimmune disease, suggesting that allelic differences in TF occupancy give functional insights into intergenic variants associated with disease. Our results have the potential to increase the power and interpretability of association studies by targeting functional intergenic variants in addition to protein coding sequences. PMID:22300769

  18. Allelic imbalance and fine mapping of the 17p13.3 subregion in sporadic breast carcinomas

    DEFF Research Database (Denmark)

    Hoff, C; Mollenhauer, J; Waldau, B;

    2001-01-01

    region is suspected to harbor another tumor suppressor gene. In order to get more information concerning the pattern of AIs in 17p13.3, we performed analysis of AI of 49 breast carcinomas at 6 polymorphic loci in 17p13.3. Eighty-six percent of the tumors present AI at least at one marker in 17p13......Chromosome arm 17p is frequently altered in a variety of human cancers, especially in breast cancer, and allelic imbalances (AIs) in the region 17p13.1 do not always coincide with mutations in the TP53 gene. A second interval that frequently shows AIs at 17p is the chromosomal band 17p13.3. This.......3. Among all loci tested, the highest percentage of Al was observed at loci D17S5 (77%) and D17S1528 (72%). According to these results, a minimal region of deletion could be determined between the markers D17S28 and D17S5. Fine mapping of this region revealed that the size of the deleted region is about...

  19. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    OpenAIRE

    Richards, Alexander L.; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V.; Levinson, Douglas F.; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M.; Craddock, Nick; Owen, Michael J.; Holmans, Peter; O’Donovan, Michael C

    2011-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs s...

  20. Allelic imbalance and cytogenetic deletion of 1p in colorectal adenomas: a target region identified between DIS199 and DIS234

    DEFF Research Database (Denmark)

    Bomme, L; Heim, S; Bardi, G;

    1998-01-01

    Both cytogenetic and molecular genetic analyses have shown that many colorectal adenomas carry an acquired deletion distally in the short arm of one chromosome 1, but the two methods have never been brought to bear on the same tumors. The major part of this study was the analysis of 53 previously...... short-term cultured and karyotyped colorectal adenomas for allelic imbalance at eight microsatellite loci in 1p. Allelic imbalances were detected in seven of the 12 adenomas that had cytogenetically visible abnormalities of chromosome 1, as well as in four adenomas that either had a normal karyotype...... (one case) or had clonal chromosome abnormalities that did not seem to involve chromosome 1 (three cases); i.e., 30% of the adenomas had abnormalities involving 1p by the combined approach. A minimal region of overlap seemed to map to between DIS199 and DIS234, suggesting that this is a relevant target...

  1. Different patterns of allelic imbalance in sporadic tumors and tumors associated with long-term exposure to gamma-radiation.

    Science.gov (United States)

    Litviakov, Nikolai V; Freidin, Maxim B; Sazonov, Aleksey E; Khalyuzova, Maria V; Buldakov, Mikhail A; Karbyshev, Mikhail S; Albakh, Еlena N; Isubakova, Daria S; Gagarin, Аleksey A; Nekrasov, Gennadiy B; Mironova, Elena B; Izosimov, Аndrey S; Takhauov, Ravil M; Karpov, Аndrei B

    2015-12-01

    The study aimed to reveal cancer related mutations in DNA repair and cell cycle genes associated with chronic occupational exposure to gamma-radiation in personnel of the Siberian Group of Chemical Enterprises (SGCE). Mutations were analyzed by comparing genotypes of malignant tumors and matched normal tissues of 255 cancer patients including 98 exposed to external gamma-radiation (mean dose 128.1±150.5mSv). Also a genetic association analysis was carried out in a sample of 149 cancer patients and 908 healthy controls occupationally exposed to gamma-radiation (153.2±204.6mSv and 150.5±211.2mSv, respectively). Eight SNPs of genes of DNA excision repair were genotyped (rs13181, rs1052133, rs1042522, rs2305427, rs4244285, rs1045642, rs1805419 and rs1801133). The mutation profiles in heterozygous loci for selected SNP were different between sporadic tumors and tumors in patients exposed to radiation. In sporadic tumors, heterozygous genotype Arg/Pro of the rs1042522 SNP mutated into Arg/0 in 15 cases (9.6%) and 0/Pro in 14 cases (8.9%). The genotype Lys/Gln of the rs13181 SNP mutated into Lys/0 and 0/Gln in 9 and 4 cases, respectively. In tumors of patients exposed to low-level radiation, the rs1042522 Arg/0 mutated genotype was found in 12 cases (12.1%), while in 2 cases (2%) 0/Pro mutation was observed. Finally, the rs13181 0/Gln mutated genotype was observed in 15 cases (16,5%) . Thus, our study showed the difference in patterns of allelic imbalance in tumors appeared under low-level radiation exposure and spontaneous tumors for selected SNPs. This suggests different mechanisms of inactivation of heterozygous genotypes in sporadic and radiation-induced tumors. PMID:26653978

  2. 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...

  3. Diagnostic Detection of Allelic Losses and Imbalances by Next-Generation Sequencing: 1p/19q Co-Deletion Analysis of Gliomas.

    Science.gov (United States)

    Dubbink, Hendrikus J; Atmodimedjo, Peggy N; van Marion, Ronald; Krol, Niels M G; Riegman, Peter H J; Kros, Johan M; van den Bent, Martin J; Dinjens, Winand N M

    2016-09-01

    Cancer cells are genomically unstable and accumulate tumor type-specific molecular aberrations, which may represent hallmarks for predicting prognosis and targets for therapy. Co-deletion of chromosomes 1p and 19q marks gliomas with an oligodendroglioma component and predicts a better prognosis and response to chemotherapy. In the current study, we present a novel method to detect chromosome 1p/19q co-deletion or loss of heterozygosity (LOH) in a diagnostic setting, based on single-nucleotide polymorphism (SNP) analysis and next-generation sequencing (NGS). We selected highly polymorphic SNPs distributed evenly over both chromosome arms. To experimentally determine the sensitivity and specificity of targeted SNP analysis, we used DNAs extracted from 49 routine formalin-fixed, paraffin-embedded glioma tissues and compared the outcome with diagnostic microsatellite-based LOH analysis and calculated estimates. We show that targeted SNP analysis by NGS allows reliable detection of 1p and/or 19q deletion in a background of 70% of normal cells according to calculated outcomes, is more sensitive than microsatellite-based LOH analysis, and requires much less DNA. This specific and sensitive SNP assay is broadly applicable for simultaneous allelic imbalance analysis of multiple genomic regions and can be incorporated easily into NGS mutation analyses. The combined mutation and chromosomal imbalance analysis in a single NGS assay is suited perfectly for routine glioma diagnostics and other diagnostic molecular pathology applications. PMID:27461031

  4. 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.

  5. The functional importance of sequence versus expression variability of MHC alleles in parasite resistance.

    Science.gov (United States)

    Axtner, Jan; Sommer, Simone

    2012-12-01

    Understanding selection processes driving the pronounced allelic polymorphism of the major histocompatibility complex (MHC) genes and its functional associations to parasite load have been the focus of many recent wildlife studies. Two main selection scenarios are currently debated which explain the susceptibility or resistance to parasite infections either by the effects of (1) specific MHC alleles which are selected frequency-dependent in space and time or (2) a heterozygote or divergent allele advantage. So far, most studies have focused only on structural variance in co-evolutionary processes although this might not be the only trait subject to natural selection. In the present study, we analysed structural variance stretching from exon1 through exon3 of MHC class II DRB genes as well as genotypic expression variance in relation to the gastrointestinal helminth prevalence and infection intensity in wild yellow-necked mice (Apodemus flavicollis). We found support for the functional importance of specific alleles both on the sequence and expression level. By resampling a previously investigated study population we identified specific MHC alleles affected by temporal shifts in parasite pressure and recorded associated changes in allele frequencies. The allele Apfl-DRB*23 was associated with resistance to infections by the oxyurid nematode Syphacia stroma and at the same time with susceptibility to cestode infection intensity. In line with our expectation, MHC mRNA transcript levels tended to be higher in cestode-infected animals carrying the allele Apfl-DRB*23. However, no support for a heterozygote or divergent allele advantage on the sequence or expression level was detected. The individual amino acid distance of genotypes did not explain individual differences in parasite loads and the genetic distance had no effect on MHC genotype expression. For ongoing studies on the functional importance of expression variance in parasite resistance, allele

  6. Aneuploidy: the impact of chromosome imbalance on nuclear organization and overall genome expression.

    Science.gov (United States)

    Hervé, B; Coussement, A; Gilbert, T; Dumont, F; Jacques, S; Cuisset, L; Chicard, M; Hizem, S; Bourdoncle, P; Letourneur, F; Dupont, C; Vialard, F; Choiset, A; Dupont, J-M

    2016-07-01

    The organization and dynamics of chromatin within the interphase nucleus as chromosome territories (CTs) and the relationship with transcriptional regulation are not fully understood. We studied a natural example of chromosomal disorganization: aneuploidy due to trisomies 13, 18 and 21. We hypothesized that the presence of an extra copy of one chromosome alters the CT distribution, which perturbs transcriptional activity. We used 3D-FISH to study the position of the chromosomes of interest (18 and 21) in cultured amniocytes and chorionic villus cells from pregnancies with a normal or aneuploid karyotype. We studied the volumes of nuclei and CTs in both conditions and performed a compared transcriptome analysis. We did not observe any differences between euploid and aneuploid cells in terms of the radial and relative CT positions, suggesting that the same rules govern nuclear organization in cases of trisomy. We observed lower volumes for CTs 18 and 21. Overall genome expression profiles highlighted changes in the expression of a subset of genes in trisomic chromosomes, while the majority of transcriptional changes concerned genes located on euploid chromosomes. Our results suggest that a dosage imbalance of the genes on trisomic chromosomes is associated with a disturbance of overall genomic expression. PMID:27283765

  7. 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

  8. 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.

  9. Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Pauline E Jullien

    2010-03-01

    Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

  10. Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3

    Directory of Open Access Journals (Sweden)

    Ratnayake Madhushika

    2012-03-01

    Full Text Available Abstract Background A genome-wide association scan with subsequent replication study that involved over 67,000 individuals of European ancestry has produced evidence of association of single nucleotide polymorphism rs2277831 to primary osteoarthritis (OA with a P-value of 2.9 × 10-5. rs2277831, an A/G transition, is located in an intron of MICAL3. This gene is located on chromosome 22q11.21 and the association signal encompasses two additional genes, BCL2L13 and BID. It is becoming increasingly apparent that many common complex traits are mediated by cis-acting regulatory polymorphisms that influence, in a tissue-specific manner, gene expression or transcript stability. Methods We used total and allelic expression analysis to assess whether the OA association to rs2277831 is mediated by an influence on MICAL3, BCL2L13 or BID expression. Using RNA extracted from joint tissues of 60 patients who had undergone elective joint replacement surgery, we assessed whether rs2277831 correlated with allelic expression of either of the three genes by: 1 measuring the expression of each gene by quantitative PCR and then stratifying the data by genotype at rs2277831 and 2 accurately discriminating and quantifying the mRNA synthesised from the alleles of OA patients using allelic-quantitative PCR. Results We found no evidence for a correlation between gene expression and genotype at rs2277831, with P-values of 0.09 for BCL2L13, 0.07 for BID and 0.33 for MICAL3. In the allelic expression analysis we observed several examples of significant (p BCL2L13 (P = 0.004, 2.09 at BID (P = 0.001 and the most extreme case being at MICAL3, with an allelic expression ratio of 5.47 (P = 0.001. However, there was no correlation observed between the pattern of allelic expression and the genotype at rs2277831. Conclusions In the tissues that we have studied, our data do not support our hypothesis that the association between rs2277831 and OA is due to the effect this SNP has on

  11. Heterologous expression of the Arabidopsis etr1-1 allele inhibits the senescence of carnation flowers

    NARCIS (Netherlands)

    Bovy, A.G.; Angenent, G.C.; Dons, H.J.M.; Altvorst, van A.

    1999-01-01

    The Arabidopsis thaliana etr1-1 allele, capable of conferring ethylene insensitivity in a heterologous host, was introduced into transgenic carnation plants. This gene was expressed under control of either its own promoter, the constitutive CaMV 35S promoter or the flower-specific petunia FBP1 promo

  12. The allelic modulation of apolipoprotein E expression by oestrogen: potential relevance for Alzheimer's disease

    OpenAIRE

    Lambert, J; Coyle, N; Lendon, C

    2004-01-01

    Background: The ε4 allele of the apolipoprotein E (APOE) gene is a major genetic risk factor for Alzheimer's disease but appears to be associated with greater risk in women than in men. Some studies suggest that the level of APOE may of its own modulate the risk for Alzheimer's disease. Sex differences and an apparent benefit of oestrogen therapy suggest a role for oestrogen. APOE expression is influenced by oestrogen and oestrogen therapy may not benefit women bearing an APOE ε4 allele. Thes...

  13. Differential allelic expression of a fibrillin gene (FBNI) in patients with Marfan syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hewett, D.; Lynch, J.; Sykes, B. [Univ. of Oxford (United Kingdom); Firth, H. [Churchill Hospital, Oxford (United Kingdom); Child, A. [St. George`s Hospital Medical School, London (United Kingdom)

    1994-09-01

    Marfan syndrome is a connective-tissue disorder affecting cardiovascular, skeletal, and ocular systems. The major Marfan locus has been identified as the FBN1 gene on chromosome 15; this codes for the extracellular-matrix protein fibrillin, a 350-kD constituent of the 8-10-nm elastin-associated microfibrils. The authors identified five MFS patients who were heterozygous for an RsaI restriction-site dimorphism in the 3{prime} UTR of the FBN1 gene. This expressed variation was used to distinguish the mRNA output from each of the two FBN1 alleles in fibroblast cultures from these five patients. Three of the patients were shown to produce <5% of the normal level of FBN1 transcripts from one of their alleles. This null-allele phenotype was not observed in 10 nonmarfanoid fibroblast cell lines. 26 refs., 4 figs.

  14. Attenuated Expression of DFFB is a Hallmark of Oligodendrogliomas with 1p-Allelic Loss

    Directory of Open Access Journals (Sweden)

    Fuller Gregory N

    2005-09-01

    Full Text Available Abstract Allelic loss of chromosome 1p is frequently observed in oligodendroglioma. We screened 177 oligodendroglial tumors for 1p deletions and found 6 tumors with localized 1p36 deletions. Several apoptosis regulation genes have been mapped to this region, including Tumor Protein 73 (p73, DNA Fragmentation Factor subunits alpha (DFFA and beta (DFFB, and Tumor Necrosis Factor Receptor Superfamily Members 9 and 25 (TNFRSF9, TNFRSF25. We compared expression levels of these 5 genes in pairs of 1p-loss and 1p-intact tumors using quantitative reverse-transcriptase PCR (QRTPCR to test if 1p deletions had an effect on expression. Only the DFFB gene demonstrated decreased expression in all tumor pairs tested. Mutational analysis did not reveal DFFB mutations in 12 tested samples. However, it is possible that DFFB haploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development.

  15. Gamma ray-induced loss of expression of HLA and glyoxalase I alleles in lymphoblastoid cells

    Energy Technology Data Exchange (ETDEWEB)

    Kavathas, P.; Bach, F.H.; DeMars, R.

    1980-07-01

    Gamma rays from a cesium source were used to generate human lymphoblastoid cell line variants that had lost expression of all major histocompatibility complex antigens coded for by a single haplotype. The cell line was heterozygous at the glyoxalase I locus and had the HLA haplotypes HLA-A1, B8, DRw3, and HLA-A2, B5, DRw1. We selected with anti-HLA-B8 antiserum in a population of cells that had been irradiated with 300R. The incidence of B8-loss variants was 4.1 X 10/sup -5/ on day 5 after irradiation. Analysis of variants showed that expressions of HLA and GLO alleles trans to B8 were retained. However, expression of additional cis-linked HLA and GLO gene products was lost in 12 of 17 variants. Variants that had lost expression of (i) HLA-B8, (ii) HLA-B8, A1, (iii) HLA-B8, A1, DRw3, or (iv) HLA-B8, A1, DRw3 and the cis-linked glyoxalase I allele were obtained. Karyotype analysis was performed on eight variants that had lost expression of two or more cis-linked alleles. Three variants had two normal appearing no. 6 chromosomes, four variants had a deletion that included the region coding for HLA genes on the short arm of one no. 6 chromosome, and one variant had an inversion or translocation involving the short arm of one no. 6.

  16. Gamma ray-induced loss of expression of HLA and glyoxalase I alleles in lymphoblastoid cells

    International Nuclear Information System (INIS)

    Gamma rays from a cesium source were used to generate human lymphoblastoid cell line variants that had lost expression of all major histocompatibility complex antigens coded for by a single haplotype. The cell line was heterozygous at the glyoxalase I locus and had the HLA haplotypes HLA-A1, B8, DRw3, and HLA-A2, B5, DRw1. We selected with anti-HLA-B8 antiserum in a population of cells that had been irradiated with 300R. The incidence of B8-loss variants was 4.1 X 10-5 on day 5 after irradiation. Analysis of variants showed that expressions of HLA and GLO alleles trans to B8 were retained. However, expression of additional cis-linked HLA and GLO gene products was lost in 12 of 17 variants. Variants that had lost expression of (i) HLA-B8, (ii) HLA-B8, A1, (iii) HLA-B8, A1, DRw3, or (iv) HLA-B8, A1, DRw3 and the cis-linked glyoxalase I allele were obtained. Karyotype analysis was performed on eight variants that had lost expression of two or more cis-linked alleles. Three variants had two normal appearing no. 6 chromosomes, four variants had a deletion that included the region coding for HLA genes on the short arm of one no. 6 chromosome, and one variant had an inversion or translocation involving the short arm of one no. 6

  17. 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

  18. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2011-05-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC).

  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. Common chromosomal imbalances and stemness-related protein expression markers in endometriotic lesions from different anatomical sites

    DEFF Research Database (Denmark)

    Silveira, Cássia G T; Abrão, Mauricio S; Dias, João A;

    2012-01-01

    genomic alterations in stromal and epithelial cells from different anatomical sites of the same patient and the expression of stemness-related markers suggested that endometriosis arises as a clonal proliferation with the putative involvement of stem cells....... clonal origin of the endometriotic cells and the putative involvement of stem cells. Positive immunostaining for CD9, CD34, c-Kit and Oct-4 markers was detected in isolated epithelial and/or stromal cells in eutopic and ectopic endometrium in the majority of cases. CONCLUSIONS: The presence of shared......, its pathogenesis is still unclear. METHODS: High-resolution comparative genomic hybridization was applied to screen for genomic imbalances in laser microdissected stromal and epithelial cells from 20 endometriotic lesions and three samples of eutopic endometrium derived from eight patients. The...

  1. No association between germline allele-specific expression of TGFBR1 and colorectal cancer risk in Caucasian and Ashkenazi populations

    OpenAIRE

    Seguí, N; Stevens, K. N.; Guinó, E.; Rozek, L S; Moreno, V R; Capellá, G; Gruber, S B; Valle, L.

    2011-01-01

    Background: Germline allele-specific expression (ASE) of the TGFBR1 gene has been reported as a strong risk factor for colorectal cancer (CRC) with an odds ratio close to 9. Considering the potential implications of the finding, we undertook the task of validating the initial results in this study. Methods: Allele-specific expression was measured using the highly quantitative and robust technique of pyrosequencing. Individuals from two different populations were studied, one Caucasian-dominat...

  2. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    OpenAIRE

    Stringer Saundra L; Fischer Jared M; Yin Moying; Larson Jon S; Stringer James R

    2006-01-01

    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 a...

  3. Nonsyntenic Genes Drive Tissue-Specific Dynamics of Differential, Nonadditive, and Allelic Expression Patterns in Maize Hybrids.

    Science.gov (United States)

    Baldauf, Jutta A; Marcon, Caroline; Paschold, Anja; Hochholdinger, Frank

    2016-06-01

    Distantly related maize (Zea mays) inbred lines display an exceptional degree of genomic diversity. F1 progeny of such inbred lines are often more vigorous than their parents, a phenomenon known as heterosis. In this study, we investigated how the genetic divergence of the maize inbred lines B73 and Mo17 and their F1 hybrid progeny is reflected in differential, nonadditive, and allelic expression patterns in primary root tissues. In pairwise comparisons of the four genotypes, the number of differentially expressed genes between the two parental inbred lines significantly exceeded those of parent versus hybrid comparisons in all four tissues under analysis. No differentially expressed genes were detected between reciprocal hybrids, which share the same nuclear genome. Moreover, hundreds of nonadditive and allelic expression ratios that were different from the expression ratios of the parents were observed in the reciprocal hybrids. The overlap of both nonadditive and allelic expression patterns in the reciprocal hybrids significantly exceeded the expected values. For all studied types of expression - differential, nonadditive, and allelic - substantial tissue-specific plasticity was observed. Significantly, nonsyntenic genes that evolved after the last whole genome duplication of a maize progenitor from genes with synteny to sorghum (Sorghum bicolor) were highly overrepresented among differential, nonadditive, and allelic expression patterns compared with the fraction of these genes among all expressed genes. This observation underscores the role of nonsyntenic genes in shaping the transcriptomic landscape of maize hybrids during the early developmental manifestation of heterosis in root tissues of maize hybrids. PMID:27208302

  4. Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression

    Directory of Open Access Journals (Sweden)

    Hanamura Ichiro

    2006-10-01

    Full Text Available Abstract Background A high proliferative capacity of tumor cells usually is associated with shortened patient survival. Disruption of the RB pathway, which is critically involved in regulating the G1 to S cell cycle transition, is a frequent target of oncogenic events that are thought to contribute to increased proliferation during tumor progression. Previously, we determined that p18INK4c, an essential gene for normal plasma cell differentiation, was bi-allelically deleted in five of sixteen multiple myeloma (MM cell lines. The present study was undertaken to investigate a possible role of p18INK4c in increased proliferation of myeloma tumors as they progress. Results Thirteen of 40 (33% human myeloma cell lines do not express normal p18INK4c, with bi-allelic deletion of p18 in twelve, and expression of a mutated p18 fragment in one. Bi-allelic deletion of p18, which appears to be a late progression event, has a prevalence of about 2% in 261 multiple myeloma (MM tumors, but the prevalence is 6 to10% in the 50 tumors with a high expression-based proliferation index. Paradoxically, 24 of 40 (60% MM cell lines, and 30 of 50 (60% MM tumors with a high proliferation index express an increased level of p18 RNA compared to normal bone marrow plasma cells, whereas this occurs in only five of the 151 (3% MM tumors with a low proliferation index. Tumor progression is often accompanied by increased p18 expression and an increased proliferation index. Retroviral-mediated expression of exogenous p18 results in marked growth inhibition in three MM cell lines that express little or no endogenous p18, but has no effect in another MM cell line that already expresses a high level of p18. Conclusion Paradoxically, although loss of p18 appears to contribute to increased proliferation of nearly 10% of MM tumors, most MM cell lines and proliferative MM tumors have increased expression of p18. Apart from a small fraction of cell lines and tumors that have inactivated

  5. Paramutation:A Heritable Change in Gene Expression by Allelic Interactions In Trans

    Institute of Scientific and Technical Information of China (English)

    Maike Stam

    2009-01-01

    Epigenetic gene regulation involves the stable propagation of gene activity states through mitotic,and sometimes even meiotic,cell divisions without changes in DNA sequence.Paramutation is an epigenetic phenomenon involving changes in gene expression that are stably transmitted through mitosis as well as meiosis.These heritable changes are mediated by in trans interactions between homologous DNA sequences on different chromosomes.During these in trans interactions,epigenetic information is transferred from one allele of a gene to another allele of the same gene,resulting in a change in gene expression.Although paramutation was initially discovered in plants,it has recently been observed in mammals as well,suggesting that the mechanisms underlying paramutation might be evolutionarily conserved.Recent findings point to a crucial role for small RNAs in the paramutation process.In mice,small RNAs appear sufficient to induce paramutation,whereas in maize,it seems not to be the only player in the process.In this review,potential mechanisms are discussed in relation to the various paramutation phenomena.

  6. Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue

    Directory of Open Access Journals (Sweden)

    Broderick Gordon

    2012-09-01

    Full Text Available Abstract Background As Chronic Fatigue Syndrome (CFS has been known to follow Epstein-Bar virus (EBV and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM. We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively. Methods Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70, 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection. Results Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls. Conclusion These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

  7. Analysis of the vomeronasal receptor repertoire, expression and allelic diversity in swine.

    Science.gov (United States)

    Dinka, Hunduma; Le, Minh Thong; Ha, Heekyun; Cho, Hyesun; Choi, Min-Kyeung; Choi, Hojun; Kim, Jin-Hoi; Soundarajan, Nagasundarapandian; Park, Jin-Ki; Park, Chankyu

    2016-05-01

    Here we report a comprehensive analysis of the vomeronasal receptor repertoire in pigs. We identified a total of 25 V1R sequences consisting of 10 functional genes, 3 pseudogenes, and 12 partial genes, while functional V2R and FPR genes were not present in the pig genome. Pig V1Rs were classified into three subfamilies, D, F, and J. Using direct high resolution sequencing-based typing of all functional V1Rs from 10 individuals of 5 different breeds, a total of 24 SNPs were identified, indicating that the allelic diversity of V1Rs is much lower than that of the olfactory receptors. A high expression level of V1Rs was detected in the vomeronasal organ (VNO) and testes, while a low expression level of V1Rs was observed in all other tissues examined. Our results showed that pigs could serve as an interesting large animal model system to study pheromone-related neurobiology because of their genetic simplicity. PMID:26482471

  8. Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase

    OpenAIRE

    Carney, Amanda E.; Rebecca D Sanders; Garza, Kerry R.; McGaha, Lee Anne; Bean, Lora J. H.; Coffee, Bradford W.; Thomas, James W; Cutler, David J.; Kurtkaya, Natalie L.; Fridovich-Keil, Judith L.

    2009-01-01

    Duarte galactosemia is a mild to asymptomatic condition that results from partial impairment of galactose-1-phosphate uridylyltransferase (GALT). Patients with Duarte galactosemia demonstrate reduced GALT activity and carry one profoundly impaired GALT allele (G) along with a second, partially impaired GALT allele (Duarte-2, D2). Molecular studies reveal at least five sequence changes on D2 alleles: a p.N314D missense substitution, three intronic base changes and a 4 bp deletion in the 5′ pro...

  9. 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.

  10. Effect of metallothionein 2A gene polymorphism on allele-specific gene expression and metal content in prostate cancer

    International Nuclear Information System (INIS)

    Metallothioneins (MTs) are highly conserved, small molecular weight, cysteine rich proteins. The major physiological functions of metallothioneins include homeostasis of essential metals Zn and Cu and protection against cytotoxicity of heavy metals. The aim of this study was to determine whether there is an association between the − 5 A/G single nucleotide polymorphism (SNP; rs28366003) in core promoter region and expression of metallothionein 2A (MT2A) gene and metal concentration in prostate cancer tissues. MT2A polymorphism was determined by the polymerase chain reaction–restriction fragment length polymorphism technique (PCR–RFLP) using 412 prostate cancer tissue samples. MT2A gene expression analysis was performed by real-time RT-PCR method. A significant association between rs28366003 genotype and MT2A expression level was found. The average mRNA level was found to be lower among minor allele carriers (the risk allele) than average expression among homozygotes for the major allele. Metal levels were analyzed by flamed atomic absorption spectrometer system. Highly statistically significant associations were detected between the SNP and Cd, Zn, Cu and Pb levels. The results of Spearman's rank correlation showed that the expressions of MT2A and Cu, Pb and Ni concentrations were negatively correlated. On the basis of the results obtained in this study, we suggest that SNP polymorphism may affect the MT2A gene expression in prostate and this is associated with some metal accumulation. - Highlights: • MT2A gene expression and metal content in prostate cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn, Cu and Pb levels • Negative correlation between MT2A gene expression and Cu, Pb and Ni levels

  11. Effect of metallothionein 2A gene polymorphism on allele-specific gene expression and metal content in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Krześlak, Anna; Forma, Ewa [Department of Cytobiochemistry, University of Łódź, Pomorska 141/143, 90-236 Łódź (Poland); Chwatko, Grażyna [Department of Environmental Chemistry, University of Łódź, Pomorska 163, 90-236 Łódź (Poland); Jóźwiak, Paweł; Szymczyk, Agnieszka [Department of Cytobiochemistry, University of Łódź, Pomorska 141/143, 90-236 Łódź (Poland); Wilkosz, Jacek; Różański, Waldemar [2nd Department of Urology, Medical University of Łódź, Pabianicka 62, 93-513 Łódź (Poland); Bryś, Magdalena, E-mail: zreg@biol.uni.lodz.pl [Department of Cytobiochemistry, University of Łódź, Pomorska 141/143, 90-236 Łódź (Poland)

    2013-05-01

    Metallothioneins (MTs) are highly conserved, small molecular weight, cysteine rich proteins. The major physiological functions of metallothioneins include homeostasis of essential metals Zn and Cu and protection against cytotoxicity of heavy metals. The aim of this study was to determine whether there is an association between the − 5 A/G single nucleotide polymorphism (SNP; rs28366003) in core promoter region and expression of metallothionein 2A (MT2A) gene and metal concentration in prostate cancer tissues. MT2A polymorphism was determined by the polymerase chain reaction–restriction fragment length polymorphism technique (PCR–RFLP) using 412 prostate cancer tissue samples. MT2A gene expression analysis was performed by real-time RT-PCR method. A significant association between rs28366003 genotype and MT2A expression level was found. The average mRNA level was found to be lower among minor allele carriers (the risk allele) than average expression among homozygotes for the major allele. Metal levels were analyzed by flamed atomic absorption spectrometer system. Highly statistically significant associations were detected between the SNP and Cd, Zn, Cu and Pb levels. The results of Spearman's rank correlation showed that the expressions of MT2A and Cu, Pb and Ni concentrations were negatively correlated. On the basis of the results obtained in this study, we suggest that SNP polymorphism may affect the MT2A gene expression in prostate and this is associated with some metal accumulation. - Highlights: • MT2A gene expression and metal content in prostate cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn, Cu and Pb levels • Negative correlation between MT2A gene expression and Cu, Pb and Ni levels.

  12. Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival.

    LENUS (Irish Health Repository)

    Bray, Isabella

    2009-01-01

    MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145) that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR) and for DNA copy number alterations (array CGH) to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96) and a validation set (n = 49) for data analysis. Thirty-seven miRNAs were significantly over- or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics.

  13. Ribosomal protein genes are highly enriched among genes with allele-specific expression in the interspecific F1 hybrid catfish.

    Science.gov (United States)

    Chen, Ailu; Wang, Ruijia; Liu, Shikai; Peatman, Eric; Sun, Luyang; Bao, Lisui; Jiang, Chen; Li, Chao; Li, Yun; Zeng, Qifan; Liu, Zhanjiang

    2016-06-01

    Interspecific hybrids provide a rich source for the analysis of allele-specific expression (ASE). In this work, we analyzed ASE in F1 hybrid catfish using RNA-Seq datasets. While the vast majority of genes were expressed with both alleles, 7-8 % SNPs exhibited significant differences in allele ratios of expression. Of the 66,251 and 177,841 SNPs identified from the datasets of the liver and gill, 5420 (8.2 %) and 13,390 (7.5 %) SNPs were identified as significant ASE-SNPs, respectively. With these SNPs, a total of 1519 and 3075 ASE-genes were identified. Gene Ontology analysis revealed that genes encoding cytoplasmic ribosomal proteins (RP) were highly enriched among ASE genes. Parent-of-origin was determined for 27 and 30 ASE RP genes in the liver and gill, respectively. The results indicated that genes from both channel catfish and blue catfish were involved in ASE. However, each RP gene appeared to be almost exclusively expressed from only one parent, indicating that ribosomes in the hybrid catfish were in the "hybrid" form. Overall representation of RP transcripts among the transcriptome appeared lower in the F1 hybrid catfish than in channel catfish or blue catfish, suggesting that the "hybrid" ribosomes may work more efficiently for translation in the F1 hybrid catfish. PMID:26747053

  14. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque

    Science.gov (United States)

    Fan, Yue-Mei; Hernesniemi, Jussi; Oksala, Niku; Levula, Mari; Raitoharju, Emma; Collings, Auni; Hutri-Kähönen, Nina; Juonala, Markus; Marniemi, Jukka; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Mennander, Ari; Tarkka, Matti; Kangas, Antti J.; Soininen, Pasi; Salenius, Juha Pekka; Klopp, Norman; Illig, Thomas; Laitinen, Tomi; Ala-Korpela, Mika; Laaksonen, Reijo; Viikari, Jorma; Kähönen, Mika; Raitakari, Olli T.; Lehtimäki, Terho

    2014-01-01

    Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT < CT < CC and rs1556259 AA < AG < GG as well as according to USF1 H3 (GCCCGG) copy number 0 < 1 < 2. Furthermore, the carriers of minor alleles of rs2516839 (C) and rs1556259 (G) of USF1 gene had decreased USF1 expression in atherosclerotic plaques (P = 0.028 and 0.08, respectively) as compared to non-carriers. The genetic variation in USF1 influence USF1 transcript expression in advanced atherosclerosis and regulates levels and metabolism of circulating apoB and apoB-containing lipoprotein particles in sex-dependent manner, but is not a major determinant of early markers of atherosclerosis. PMID:24722012

  15. Organ-specific gene expression in maize: The P-wr allele. Final report, August 15, 1993--August 14, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, T.A.

    1997-06-01

    The ultimate aim of our work is to understand how a regulatory gene produces a specific pattern of gene expression during plant development. Our model is the P-wr gene of maize, which produces a distinctive pattern of pigmentation of maize floral organs. We are investigating this system using a combination of classical genetic and molecular approaches. Mechanisms of organ-specific gene expression are a subject of intense research interest, as it is the operation of these mechanisms during eukaryotic development which determine the characteristics of each organism Allele-specific expression has been characterized in only a few other plant genes. In maize, organ-specific pigmentation regulated by the R, B, and Pl genes is achieved by differential transcription of functionally conserved protein coding sequences. Our studies point to a strikingly different mechanism of organ-specific gene expression, involving post-transcriptional regulation of the regulatory P gene. The novel pigmentation pattern of the P-wr allele is associated with differences in the encoded protein. Furthermore, the P-wr gene itself is present as a unique tandemly amplified structure, which may affect its transcriptional regulation.

  16. Swine Leukocyte Antigen (SLA) class I allele typing of Danish swine herds and the identification of commonly expressed haplotypes using sequence specific low- and high resolution primers

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Fink, Dorte Rosenbek; Jungersen, Gregers

    The genomic region (SLA) of the swine major histocompatibility complex (MHC), which bind and present endogenous peptides to circulating T cells of the immune system, is extremely polymorphic comprising high numbers of different alleles, many of which encode a distinct MHC class I molecule. Each SLA...... individual. Therefore analyses of the prevalence of SLA alleles in a population are fundamental to employ pathogen-specific subunits or peptides in novel vaccines or immune diagnostics. In this study we present the use of low- and high-resolution PCR-based typing methods to identify individual and commonly...... expressed SLA class I alleles in Danish outbred swine. A total of 108 animals from eight different production herds were tested, and with low resolution sequence specific primer (SSP)-PCR typing the top five most commonly expressed SLA class I allele groups were found to be SLA-3*04XX, SLA-1*08XX, SLA-1...

  17. ANALYSIS OF SEQUENCE POLYMORPHISM OF SCR CLASS I AND II ALLELES AND STUDY REGULATION OF THEIR EXPRESSION

    Directory of Open Access Journals (Sweden)

    Jana ŽALUDOVÁ

    2012-06-01

    Full Text Available Self-incompatibility (AI is a widespread mechanism used by flowering plants to prevent inbreeding depression and helps create and maintain genetic diversity within a species. Oilseed rape (Brassica napus L. and especially its modern varieties are characterized by high level of self-fertility. In an effort to increase the production current breeding is focused on the production of inbred lines for making the F1 hybrids and the self-incompatibility can be an interesting tool for production self- sterile lines. In Brassica napus, we found two recessive alleles of a gene SCR II. Different expression of both alleles does not correspond to phenotypic manifestation of self-incompatibility and we can assume that it is prevailed by repressor gene that does not lie on the S-locus. This is also reason, why the SCR gene cannot serve as a molecular marker of self-incompatibility in Brassica napus, although many authors believe that this gene is essential in AI reaction. Brassica napus belong to plants with complex genetic constitution, is composed by two genomes, A and C, which give the possibility of different interactions and makes it difficult to study compared with diploid B. rapa and B. oleracea. In further study it is therefore important to focus on the interactions between genes SCR, SRK and SLG, and their influence on others, such as supressor gene systems.

  18. Imbalance between expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in invasiveness and metastasis of human gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sheng Zhang; Li Li; Jian-Yin Lin; Hua Lin

    2003-01-01

    AIM: The expressive balance between matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a critical role in maintaining the degradation and synthesis of extracellular matrix. Loss of such balance is associated with invasion and metastasis of tumors. This study aimed to determine the expression of MMP-9 and TIMP-1 in gastric carcinoma, and the association of the expressive imbalance between MMP9 and TIMP-1 with the invasion and metastasis and prognosis of gastric carcinoma.METHODS: We used immunohistochemistry to determine the expressions of MMP-9, TTMP-1 and proliferating cell nuclear antigen Ki-67 in the gastric specimens taken from 256 patients with primary gastric carcinoma. The patients were followed-up for up to 96 months.RESULTS: No association between the expression of MMP9 and TIMP-1 and patients' sex and age, tumor size and location of gastric carcinoma was observed. The incidence of the positive expression of MMP-9 in cases with tumors invasion to muscularis propria and visceral peritoneum (70.13% and 69.09%, respectively) was significantly higher than that in cases with tumor invasion only to lamina propria or submucosa (42.50 %, P=0.0162). The positive correlation between MMP-9 expression and the depth of tumor invasion was observed (Pearson correlation coefficient=0.2129,P=0.016). Along with the increase of the metastatic station of lymph nodes, the incidence of the MMP-9 expression was increased by degrees; a positive correlation between them was observed (Pearson correlation coefficient=0.2910,P=0.0001). There was also a significant correlation between MMP-9 expression and the TNM stage in gastric carcinoma (Pearson correlation coefficient=0.3027, P<0.0001). The incidence of MMP-9 expression in stage Ⅱ and Ⅲ/Ⅳ (75.00%and 76.15%, respectively) was significantly higher than those in stage Ⅰ (46.15 %, P<0.0001). A negative correlation between TIMP-1 immunoreactivity and the depth of invasion

  19. Hybrid sterility and evolution in Hawaiian Drosophila: differential gene and allele-specific expression analysis of backcross males.

    Science.gov (United States)

    Brill, E; Kang, L; Michalak, K; Michalak, P; Price, D K

    2016-08-01

    The Hawaiian Drosophila are an iconic example of sequential colonization, adaptive radiation and speciation on islands. Genetic and phenotypic analysis of closely related species pairs that exhibit incomplete reproductive isolation can provide insights into the mechanisms of speciation. Drosophila silvestris from Hawai'i Island and Drosophila planitibia from Maui are two closely related allopatric Hawaiian picture-winged Drosophila that produce sterile F1 males but fertile F1 females, a pattern consistent with Haldane's rule. Backcrossing F1 hybrid females between these two species to parental species gives rise to recombinant males with three distinct sperm phenotypes despite a similar genomic background: motile sperm, no sperm (sterile), and immotile sperm. We found that these three reproductive morphologies of backcross hybrid males produce divergent gene expression profiles in testes, as measured with RNA sequencing. There were a total of 71 genes significantly differentially expressed between backcross males with no sperm compared with those backcross males with motile sperm and immotile sperm, but no significant differential gene expression between backcross males with motile sperm and backcross males with immotile sperm. All of these genes were underexpressed in males with no sperm, including a number of genes with previously known activities in adult testis. An allele-specific expression analysis showed overwhelmingly more cis-divergent than trans-divergent genes, with no significant difference in the ratio of cis- and trans-divergent genes among the sperm phenotypes. Overall, the results indicate that the regulation of gene expression involved in sperm production likely diverged relatively rapidly between these two closely related species. PMID:27220308

  20. Options on capacity imbalance

    International Nuclear Information System (INIS)

    Since the start of this year, the Dutch energy company Nuon has been using a computer system to formulate real-time responses to national capacity imbalances in the electricity supply market. The work earns Nuon a fixed fee from TenneT (Dutch Transmission System Operator) and ensures a more stable imbalance price for everyone. The key to success has been the decision to start the project from scratch

  1. Allele-specific expression of mutated in colorectal cancer (MCC) gene and alternative susceptibility to colorectal cancer in schizophrenia

    Science.gov (United States)

    Wang, Yang; Cao, Yanfei; Huang, Xiaoye; Yu, Tao; Wei, Zhiyun; McGrath, John; Xu, Fei; Bi, Yan; Li, Xingwang; Yang, Fengping; Li, Weidong; Zou, Xia; Peng, Zhihai; Xiao, Yanzeng; Zhang, Yan; He, Lin; He, Guang

    2016-01-01

    Evidence has indicated that the incidence of colorectal cancer (CRC) among schizophrenia is lower than normal. To explore this potential protective effect, we employed an innovative strategy combining association study with allele-specific expression (ASE) analysis in MCC gene. We first genotyped four polymorphisms within MCC in 312 CRC patients, 270 schizophrenia patients and 270 controls. Using the MassArray technique, we performed ASE measurements in a second sample series consisting of 50 sporadic CRC patients, 50 schizophrenia patients and 52 controls. Rs2227947 showed significant differences between schizophrenia cases and controls, and haplotype analysis reported some significant discrepancies among these three subject groups. ASE values of rs2227948 and rs2227947 presented consistently differences between CRC (or schizophrenia) patients and controls. Of the three groups, highest frequencies of ASE in MCC were concordantly found in CRC group, whereas lowest frequencies of ASE were observed in schizophrenia group. Similar trends were confirmed in both haplotype frequencies and ASE frequencies (i.e. CRC > control > schizophrenia). We provide a first indication that MCC might confer alterative genetic susceptibility to CRC in individuals with schizophrenia promising to shed more light on the relationship between schizophrenia and cancer progression. PMID:27226254

  2. Production of a Marfan cellular phenotype by expressing a mutant human fibrillin allele on a normal human or murine genetic background

    Energy Technology Data Exchange (ETDEWEB)

    Eldadah, Z.A.; Dietz, H.C. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Brenn, T. [Stanford Univ. Medical Center, CA (United States)] [and others

    1994-09-01

    The Marfan Syndrome (MFS) is a heritable disorder of connective tissue caused by defects in fibrillin (FBN1), a 350 kD glycoprotein and principal component of the extracellular microfibril. Previous correlations of mutant transcript level and disease severity suggested a dominant negative model of MFS pathogenesis. To address this hypothesis we assembled an expression construct containing the mutant allele from a patient with severe MFS. This mutation causes skipping of FBN1 exon 2 and a frame shift, leading to a premature termination codon in exon 4. The predicted peptide would thus consist of 55 wild type and 45 missense amino acids. The construct was stably transfected into cultured human and mouse fibroblasts, and several clonal cell populations were established. Human and mouse cells expressing the truncated peptide exhibited markedly diminished fibrillin deposition and disorganized microfibrillar architecture by immunofluorescence. Pulse-chase analysis of these cells demonstrated normal levels of fibrillin synthesis but substantially decreased fibrillin deposition into the extracellular matrix. These data illustrate that expression of a mutant FBN1 allele, on a background of two normal alleles, is sufficient to disrupt normal fibrillin aggregation and reproduce the MFS cellular phenotype. This provides confirmation of a dominant negative model of MFS pathogenesis and may offer mutant allele knockout as a strategy for gene therapy. In addition, these data underscore the importance of the FBN1 amino-terminus in normal multimer formation and suggest that expression of the human extreme 5{prime} FBN1 coding sequence may be sufficient, in isolation, to produce an animal model of MFS. Indeed, transgenic mice harboring this mutant allele have been produced, and phenotype analysis is currently in progress.

  3. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque

    OpenAIRE

    Fan, Yue-Mei; Hernesniemi, Jussi; Oksala, Niku; Levula, Mari; Raitoharju, Emma; Collings, Auni; Hutri-Kähönen, Nina; Juonala, Markus; Marniemi, Jukka; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Mennander, Ari; Tarkka, Matti; Kangas, Antti J.; Soininen, Pasi

    2014-01-01

    Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Ris...

  4. 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

  5. Allelic variation, alternative splicing and expression analysis of Psy1 gene in Hordeum chilense Roem. et Schult.

    Directory of Open Access Journals (Sweden)

    Cristina Rodríguez-Suárez

    Full Text Available BACKGROUND: The wild barley Hordeum chilense Roem. et Schult. is a valuable source of genes for increasing carotenoid content in wheat. Tritordeums, the amphiploids derived from durum or common wheat and H. chilense, systematically show higher values of yellow pigment colour and carotenoid content than durum wheat. Phytoene synthase 1 gene (Psy1 is considered a key step limiting the carotenoid biosynthesis, and the correlation of Psy1 transcripts accumulation and endosperm carotenoid content has been demonstrated in the main grass species. METHODOLOGY/PRINCIPAL FINDINGS: We analyze the variability of Psy1 alleles in three lines of H. chilense (H1, H7 and H16 representing the three ecotypes described in this species. Moreover, we analyze Psy1 expression in leaves and in two seed developing stages of H1 and H7, showing mRNA accumulation patterns similar to those of wheat. Finally, we identify thirty-six different transcripts forms originated by alternative splicing of the 5' UTR and/or exons 1 to 5 of Psy1 gene. Transcripts function is tested in a heterologous complementation assay, revealing that from the sixteen different predicted proteins only four types (those of 432, 370, 364 and 271 amino acids, are functional in the bacterial system. CONCLUSIONS/SIGNIFICANCE: The large number of transcripts originated by alternative splicing of Psy1, and the coexistence of functional and non functional forms, suggest a fine regulation of PSY activity in H. chilense. This work is the first analysis of H. chilense Psy1 gene and the results reported here are the bases for its potential use in carotenoid enhancement in durum wheat.

  6. Dissemination of the highly expressed Bx7 glutenin subunit (Glu-B1al allele) in wheat as revealed by novel PCR markers and RP-HPLC.

    Science.gov (United States)

    Butow, B J; Gale, K R; Ikea, J; Juhász, A; Bedö, Z; Tamás, L; Gianibelli, M C

    2004-11-01

    Increased expression of the high molecular weight glutenin subunit (HMW-GS) Bx7 is associated with improved dough strength of wheat (Triticum aestivum L.) flour. Several cultivars and landraces of widely different genetic backgrounds from around the world have now been found to contain this so-called 'over-expressing' allelic form of the Bx7 subunit encoded by Glu-B1al. Using three methods of identification, SDS-PAGE, RP-HPLC and PCR marker analysis, as well as pedigree information, we have traced the distribution and source of this allele from a Uruguayan landrace, Americano 44D, in the mid-nineteenth century. Results are supported by knowledge of the movement of wheat lines with migrants. All cultivars possessing the Glu-B1al allele can be identified by the following attributes: (1) the elution of the By sub-unit peak before the Dx sub-unit peak by RP-HPLC, (2) high expression levels of Bx7 (>39% Mol% Bx), (3) a 43 bp insertion in the matrix-attachment region (MAR) upstream of the gene promoter relative to Bx7 and an 18 bp nucleotide duplication in the coding region of the gene. Evidence is presented indicating that these 18 and 43 bp sequence insertions are not causal for the high expression levels of Bx7 as they were also found to be present in a small number of hexaploid species, including Chinese Spring, and species expressing Glu-B1ak and Glu-B1a alleles. In addition, these sequence inserts were found in different isolates of the tetraploid wheat, T. turgidum, indicating that these insertion/deletion events occurred prior to hexaploidization. PMID:15340686

  7. Insulin Like Growth Factor 2 Expression in the Rat Brain Both in Basal Condition and following Learning Predominantly Derives from the Maternal Allele

    OpenAIRE

    Xiaojing Ye; Amy Kohtz; Gabriella Pollonini; Andrea Riccio; Alberini, Cristina M

    2015-01-01

    Insulin like growth factor 2 (Igf2) is known as a maternally imprinted gene involved in growth and development. Recently, Igf2 was found to also be regulated and required in the adult rat hippocampus for long-term memory formation, raising the question of its allelic regulation in adult brain regions following experience and in cognitive processes. We show that, in adult rats, Igf2 is abundantly expressed in brain regions involved in cognitive functions, like hippocampus and prefrontal cortex...

  8. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine.

    Directory of Open Access Journals (Sweden)

    Hayley C Whitaker

    Full Text Available BACKGROUND: Microseminoprotein-beta (MSMB regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. CONCLUSIONS: These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

  9. Molecular cloning of a full-length cDNA for dentatorubral-pallidoluysian atrophy and regional expressions of the expanded alleles in the CNS

    Energy Technology Data Exchange (ETDEWEB)

    Onodera, Osamu; Oyake, Mutsuo; Takano, Hiroki [Niigata Univ. (Japan)] [and others

    1995-11-01

    Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by genetic anticipation and variable combinations of symptoms including myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia. Recently, we discovered that DRPLA is caused by unstable expansion of a CAG repeat of a gene on the short arm of chromosome 12. We determined the consensus DRPLA cDNA sequence containing the complete coding region for 1,185 amino acids. The CAG repeat, which is expanded in DRPLA, is located 1,462 bp downstream from the putative methionine initiation codon and encodes a poly-glutamine tract. Although poly-serine and proline tracts exist near the CAG repeats, these poly-serine or proline tracts did not show any polymorphisms, which is in strong contrast to the high heterogeneity in the length of the CAG repeat. Northern blot analysis revealed a 4.7-kb transcript that is widely expressed in various tissues including heart, lung, kidney, placenta, skeletal muscle, and brain. Reverse transcription-PCR analysis revealed that the expanded alleles are transcribed to levels comparable to those of normal alleles. These results indicate that there is no difference in transcriptional efficiency between expanded and normal alleles. Furthermore, mRNA from cerebellar hemispheres of DRPLA patients showed smaller sizes of CAG repeats compared with other regions of the brain, which reflects somatic mosaicism of the expanded alleles of the DRPLA gene. 49 refs., 6 figs.

  10. Europe and Global Imbalances

    OpenAIRE

    Philip R. Lane; Gian Maria Milesi-Ferretti

    2007-01-01

    Although Europe in the aggregate is a not a major contributor to global current account imbalances, its trade and financial linkages with the rest of the world mean that it will still be affected by a shift in the current configuration of external deficits and surpluses. We assess the macroeconomic impact on Europe of global current account adjustment under alternative scenarios, emphasizing both trade and financial channels. Finally, we consider heterogeneous exposure across individual Europ...

  11. Allele-specific transcription factor binding to common and rare variants associated with disease and gene expression.

    Science.gov (United States)

    Cavalli, Marco; Pan, Gang; Nord, Helena; Wallerman, Ola; Wallén Arzt, Emelie; Berggren, Olof; Elvers, Ingegerd; Eloranta, Maija-Leena; Rönnblom, Lars; Lindblad Toh, Kerstin; Wadelius, Claes

    2016-05-01

    Genome-wide association studies (GWAS) have identified a large number of disease-associated SNPs, but in few cases the functional variant and the gene it controls have been identified. To systematically identify candidate regulatory variants, we sequenced ENCODE cell lines and used public ChIP-seq data to look for transcription factors binding preferentially to one allele. We found 9962 candidate regulatory SNPs, of which 16 % were rare and showed evidence of larger functional effect than common ones. Functionally rare variants may explain divergent GWAS results between populations and are candidates for a partial explanation of the missing heritability. The majority of allele-specific variants (96 %) were specific to a cell type. Furthermore, by examining GWAS loci we found >400 allele-specific candidate SNPs, 141 of which were highly relevant in our cell types. Functionally validated SNPs support identification of an SNP in SYNGR1 which may expose to the risk of rheumatoid arthritis and primary biliary cirrhosis, as well as an SNP in the last intron of COG6 exposing to the risk of psoriasis. We propose that by repeating the ChIP-seq experiments of 20 selected transcription factors in three to ten people, the most common polymorphisms can be interrogated for allele-specific binding. Our strategy may help to remove the current bottleneck in functional annotation of the genome. PMID:26993500

  12. Short rare hTERT-VNTR2-2nd alleles are associated with prostate cancer susceptibility and influence gene expression

    International Nuclear Information System (INIS)

    The hTERT (human telomerase reverse transcriptase) gene contains five variable number tandem repeats (VNTR) and previous studies have described polymorphisms for hTERT-VNTR2-2nd. We investigated how allelic variation in hTERT-VNTR2-2nd may affect susceptibility to prostate cancer. A case-control study was performed using DNA from 421 cancer-free male controls and 329 patients with prostate cancer. In addition, to determine whether the VNTR polymorphisms have a functional consequence, we examined the transcriptional levels of a reporter gene linked to these VNTRs and driven by the hTERT promoter in cell lines. Three new rare alleles were detected from this study, two of which were identified only in cancer subjects. A statistically significant association between rare hTERT-VNTR2-2nd alleles and risk of prostate cancer was observed [OR, 5.17; 95% confidence interval (CI), 1.09-24.43; P = 0.021]. Furthermore, the results indicated that these VNTRs inserted in the enhancer region could influence the expression of hTERT in prostate cancer cell lines. This is the first study to report that rare hTERT VNTRs are associated with prostate cancer predisposition and that the VNTRs can induce enhanced levels of hTERT promoter activity in prostate cancer cell lines. Thus, the hTERT-VNTR2-2nd locus may function as a modifier of prostate cancer risk by affecting gene expression

  13. Co-Occurrence of Two Allelic Variants of CYP51 in Erysiphe necator and Their Correlation with Over-Expression for DMI Resistance.

    Science.gov (United States)

    Rallos, Lynn Esther E; Baudoin, Anton B

    2016-01-01

    Demethylation inhibitors (DMIs) have been an important tool in the management of grapevine powdery mildew caused by Erysiphe necator. Long-term, intensive use of DMIs has resulted in reduced sensitivity in field populations. To further characterize DMI resistance and understand resistance mechanisms in this pathogen, we investigated the cyp51 sequence of 24 single-spored isolates from Virginia and surrounding states and analyzed gene expression in isolates representing a wide range of sensitivity. Two cyp51 alleles were found with respect to the 136th codon of the predicted EnCYP51 sequence: the wild-type (TAT) and the mutant (TTT), which results in the known Y136F amino acid change. Some isolates possessed both alleles, demonstrating gene duplication or increased gene copy number and possibly a requirement for at least one mutant copy of CYP51 for resistance. Cyp51 was over-expressed 1.4- to 19-fold in Y136F-mutant isolates. However, the Y136F mutation was absent in one isolate with moderate to high resistance factor. Two additional synonymous mutations were detected as well, one of which, A1119C was present only in isolates with high cyp51 expression. Overall, our results indicate that at least two mechanisms, cyp51 over-expression and the known target-site mutation in CYP51, contribute to resistance in E. necator, and may be working in conjunction with each other. PMID:26839970

  14. Co-Occurrence of Two Allelic Variants of CYP51 in Erysiphe necator and Their Correlation with Over-Expression for DMI Resistance.

    Directory of Open Access Journals (Sweden)

    Lynn Esther E Rallos

    Full Text Available Demethylation inhibitors (DMIs have been an important tool in the management of grapevine powdery mildew caused by Erysiphe necator. Long-term, intensive use of DMIs has resulted in reduced sensitivity in field populations. To further characterize DMI resistance and understand resistance mechanisms in this pathogen, we investigated the cyp51 sequence of 24 single-spored isolates from Virginia and surrounding states and analyzed gene expression in isolates representing a wide range of sensitivity. Two cyp51 alleles were found with respect to the 136th codon of the predicted EnCYP51 sequence: the wild-type (TAT and the mutant (TTT, which results in the known Y136F amino acid change. Some isolates possessed both alleles, demonstrating gene duplication or increased gene copy number and possibly a requirement for at least one mutant copy of CYP51 for resistance. Cyp51 was over-expressed 1.4- to 19-fold in Y136F-mutant isolates. However, the Y136F mutation was absent in one isolate with moderate to high resistance factor. Two additional synonymous mutations were detected as well, one of which, A1119C was present only in isolates with high cyp51 expression. Overall, our results indicate that at least two mechanisms, cyp51 over-expression and the known target-site mutation in CYP51, contribute to resistance in E. necator, and may be working in conjunction with each other.

  15. Functional nsSNPs from carcinogenesis-related genes expressed in breast tissue: Potential breast cancer risk alleles and their distribution across human populations

    Directory of Open Access Journals (Sweden)

    Savas Sevtap

    2006-03-01

    Full Text Available Abstract Although highly penetrant alleles of BRCA1 and BRCA2 have been shown to predispose to breast cancer, the majority of breast cancer cases are assumed to result from the presence of low-moderate penetrant alleles and environmental carcinogens. Non-synonymous single nucleotide polymorphisms (nsSNPs are hypothesised to contribute to disease susceptibility and approximately 30 per cent of them are predicted to have a biological significance. In this study, we have applied a bioinformatics-based strategy to identify breast cancer-related nsSNPs from 981 carcinogenesis-related genes expressed in breast tissue. Our results revealed a total of 367 validated nsSNPs, 109 (29.7 per cent of which are predicted to affect the protein function (functional nsSNPs, suggesting that these nsSNPs are likely to influence the development and homeostasis of breast tissue and hence contribute to breast cancer susceptibility. Sixty-seven of the functional nsSNPs presented as commonly occurring nsSNPs (minor allele frequencies ≥ 5 per cent, representing excellent candidates for breast cancer susceptibility. Additionally, a non-uniform distribution of the common functional nsSNPs among different human populations was observed: 15 nsSNPs were reported to be present in all populations analysed, whereas another set of 15 nsSNPs was specific to particular population(s. We propose that the nsSNPs analysed in this study constitute a unique resource of potential genetic factors for breast cancer susceptibility. Furthermore, the variations in functional nsSNP allele frequencies across major population backgrounds may point to the potential variability of the molecular basis of breast cancer predisposition and treatment response among different human populations.

  16. SNP55, a new functional polymorphism of MDM2-P2 promoter, contributes to allele-specific expression of MDM2 in endometrial cancers

    OpenAIRE

    OKAMOTO, KANAKO; Tsunematsu, Ryosuke; Tahira, Tomoko; Sonoda, Kenzo; Asanoma, Kazuo; Yagi, Hiroshi; Yoneda, Tomoko; Hayashi, Kenshi; Wake, Norio; Kato, Kiyoko

    2015-01-01

    Background The functional single nucleotide polymorphism (SNP) in the MDM2 promoter region, SNP309, is known to be associated with various diseases, particularly cancer. Although many studies have been performed to demonstrate the mechanism of allele-specific expression (ASE) on SNP309, they have only utilized in vitro techniques. It is unknown whether ASE of MDM2 is ascribed solely to SNP309, in vivo. Methods We attempted to evaluate ASE of MDM2 in vivo using post-labeling followed by automa...

  17. Functional characterization of a full length pregnane X receptor, expression in vivo, and identification of PXR alleles, in Zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Bainy, Afonso C.D. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Departamento de Bioquímica, CCB, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900 (Brazil); Kubota, Akira; Goldstone, Jared V. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Lille-Langøy, Roger [Department of Biology, University of Bergen, N-5020 Bergen (Norway); Karchner, Sibel I. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Celander, Malin C. [Department of Biological and Environmental Sciences, University of Gothenburg, SE 405 30 Göteborg (Sweden); Hahn, Mark E. [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States); Goksøyr, Anders [Department of Biology, University of Bergen, N-5020 Bergen (Norway); Stegeman, John J., E-mail: jstegeman@whoi.edu [Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)

    2013-10-15

    Highlights: •Full-length pxr has been cloned from zebrafish. •Alleles of pxr were identified in zebrafish. •Full length Pxr was activated less strongly than ligand binding domain in cell-based reporter assays. •High levels of pxr expression were found in eye and brain as well as in liver. •TCPOBOP and PB did not significantly alter expression of pxr in liver. -- Abstract: The pregnane X receptor (PXR) (nuclear receptor NR1I2) is a ligand activated transcription factor, mediating responses to diverse xenobiotic and endogenous chemicals. The properties of PXR in fish are not fully understood. Here we report on cloning and characterization of full-length PXR of zebrafish, Danio rerio, and pxr expression in vivo. Initial efforts gave a cDNA encoding a 430 amino acid protein identified as zebrafish pxr by phylogenetic and synteny analysis. The sequence of the cloned Pxr DNA binding domain (DBD) was highly conserved, with 74% identity to human PXR-DBD, while the ligand-binding domain (LBD) of the cloned sequence was only 44% identical to human PXR-LBD. Sequence variation among clones in the initial effort prompted sequencing of multiple clones from a single fish. There were two prominent variants, one sequence with S183, Y218 and H383 and the other with I183, C218 and N383, which we designate as alleles pxr*1 (nr1i2*1) and pxr*2 (nr1i2*2), respectively. In COS-7 cells co-transfected with a PXR-responsive reporter gene, the full-length Pxr*1 (the more common variant) was activated by known PXR agonists clotrimazole and pregnenolone 16α-carbonitrile but to a lesser extent than the full-length human PXR. Activation of full-length Pxr*1 was only 10% of that with the Pxr*1 LBD. Quantitative real time PCR analysis showed prominent expression of pxr in liver and eye, as well as brain and intestine of adult zebrafish. The pxr was expressed in heart and kidney at levels similar to that in intestine. The expression of pxr in liver was weakly induced by ligands for

  18. Diurnal Expression Pattern, Allelic Variation, and Association Analysis Reveal Functional Features of the E1 Gene in Control of Photoperiodic Flowering in Soybean

    Science.gov (United States)

    Wu, Hongyan; Zhang, Yupeng; Zhang, Xingzheng; Yang, Jiayin; Wang, Yaying; Yang, Guang; Qiu, Hongmei; Cui, Tingting; Xia, Zhengjun

    2015-01-01

    Although four maturity genes, E1 to E4, in soybean have been successfully cloned, their functional mechanisms and the regulatory network of photoperiodic flowering remain to be elucidated. In this study, we investigated how the diurnal expression pattern of the E1 gene is related to photoperiodic length; and to what extent allelic variation in the B3-like domain of the E1 gene is associated with flowering time phenotype. The bimodal expression of the E1 gene peaked first at around 2 hours after dawn in long-day condition. The basal expression level of E1 was enhanced by the long light phase, and decreased by duration of dark. We identified a 5bp (3 SNP and 2-bp deletion) mutation, referred to an e1-b3a, which occurs in the middle of B3 domain of the E1 gene in the early flowering cultivar Yanhuang 3. Subcellular localization analysis showed that the putative truncated e1-b3a protein was predominately distributed in nuclei, indicating the distribution pattern of e1-b3a was similar to that of E1, but not to that of e1-as. Furthermore, genetic analysis demonstrated allelic variations at the E1 locus significantly underlay flowering time in three F2 populations. Taken together, we can conclude the legume specific E1 gene confers some special features in photoperiodic control of flowering in soybean. Further characterization of the E1 gene will extend our understanding of the soybean flowering pathway in soybean. PMID:26275311

  19. 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.

  20. Expression of the Drosophila retrovirus gypsy as ultrastructurally detectable particles in the ovaries of flies carrying a permissive flamenco allele.

    Science.gov (United States)

    Lécher, P; Bucheton, A; Pélisson, A

    1997-09-01

    The endogenous retrovirus gypsy is controlled by the Drosophila gene flamenco (flam). New insertions of gypsy occur in any individual Drosophila if its mother is homozygous for the flam1 permissive allele and contains functional gypsy proviruses. The ovaries of flam1 females also contain high amounts of gypsy RNAs. Unexpectedly however, gypsy derepression does not occur in the flam1 female germ-line proper but in the somatic follicular epithelium of the ovary. Since extracts from these females are able to efficiently infect the germ-line of a strain devoid of active gypsy proviruses, we assume that a similar kind of germ-line infection, which would occur inside the flam1 females themselves, could be required for gypsy insertions to occur in their progeny. This hypothesis was confirmed by electron microscopy observations showing that non-enveloped intracytoplasmic particles containing gypsy RNAs accumulate in the apical region of the flam1 follicle cells, close to specific membrane domains to which the gypsy envelope proteins are targeted, whereas both are absent in the flam+ controls. Low amounts of similar virus-like particles were also observed in flam1 oocytes, but it is not yet known whether they entered passively or as a result of membrane fusion. This is the first report of the beginning of a retrovirus cycle in invertebrates and these observations should be taken into account when explaining the maternal effect of the flamenco gene on the multiplication of gypsy proviruses. PMID:9292028

  1. Genomewide Expression Analysis in Zebrafish mind bomb Alleles with Pancreas Defects of Different Severity Identifies Putative Notch Responsive Genes

    OpenAIRE

    Hegde, Ashok; Qiu, Nick Chuanxin; Qiu, Xuehui; Ho, Steven Hao-Kee; Tay, Kenny Qi-Ye; George, Joshy; Ng, Felicia Soo Lee; Govindarajan, Kunde Ramamoorthy; Gong, Zhiyuan; Mathavan, Sinnakaruppan; Jiang, Yun-Jin

    2008-01-01

    Background Notch signaling is an evolutionarily conserved developmental pathway. Zebrafish mind bomb (mib) mutants carry mutations on mib gene, which encodes a RING E3 ligase required for Notch activation via Delta/Jagged ubiquitylation and internalization. Methodology/Principal Findings We examined the mib mutants for defects in pancreas development using in situ hybridization and GFP expression analysis of pancreas-specific GFP lines, carried out the global gene expression profile analysis ...

  2. Imbalance problem in community detection

    Science.gov (United States)

    Sun, Peng Gang

    2016-09-01

    Community detection gives us a simple way to understand complex networks' structures. However, there is an imbalance problem in community detection. This paper first introduces the imbalance problem and then proposes a new measure to alleviate the imbalance problem. In addition, we study two variants of the measure and further analyze the resolution scale of community detection. Finally, we compare our approach with some state of the art methods on random networks as well as real-world networks for community detection. Both the theoretical analysis and the experimental results show that our approach achieves better performance for community detection. We also find that our approach tends to separate densely connected subgroups preferentially.

  3. Differential expression of a BMP4 reporter allele in anterior fungiform versus posterior circumvallate taste buds of mice

    Directory of Open Access Journals (Sweden)

    Barlow Linda A

    2010-10-01

    Full Text Available Abstract Background Bone Morphogenetic Protein 4 (BMP4 is a diffusible factor which regulates embryonic taste organ development. However, the role of BMP4 in taste buds of adult mice is unknown. We utilized transgenic mice with LacZ under the control of the BMP4 promoter to reveal the expression of BMP4 in the tongues of adult mice. Further we evaluate the pattern of BMP4 expression with that of markers of specific taste bud cell types and cell proliferation to define and compare the cell populations expressing BMP4 in anterior (fungiform papillae and posterior (circumvallate papilla tongue. Results BMP4 is expressed in adult fungiform and circumvallate papillae, i.e., lingual structures composed of non-taste epithelium and taste buds. Unexpectedly, we find both differences and similarities with respect to expression of BMP4-driven ß-galactosidase. In circumvallate papillae, many fusiform cells within taste buds are BMP4-ß-gal positive. Further, a low percentage of BMP4-expressing cells within circumvallate taste buds is immunopositive for markers of each of the three differentiated taste cell types (I, II and III. BMP4-positive intragemmal cells also expressed a putative marker of immature taste cells, Sox2, and consistent with this finding, intragemmal cells expressed BMP4-ß-gal within 24 hours after their final mitosis, as determined by BrdU birthdating. By contrast, in fungiform papillae, BMP4-ß-gal positive cells are never encountered within taste buds. However, in both circumvallate and fungiform papillae, BMP4-ß-gal expressing cells are located in the perigemmal region, comprising basal and edge epithelial cells adjacent to taste buds proper. This region houses the proliferative cell population that gives rise to adult taste cells. However, perigemmal BMP4-ß-gal cells appear mitotically silent in both fungiform and circumvallate taste papillae, as we do not find evidence of their active proliferation using cell cycle immunomarkers

  4. Oxidative Imbalance and Anxiety Disorders

    OpenAIRE

    R, Krolow; D. M, Arcego; C, Noschang; S. N, Weis; C, Dalmaz

    2014-01-01

    The oxidative imbalance appears to have an important role in anxiety development. Studies in both humans and animals have shown a strong correlation between anxiety and oxidative stress. In humans, for example, the increased malondialdehyde levels and discrepancies in antioxidant enzymes in erythrocytes have been observed. In animals, several studies also show that anxiety-like behavior is related to the oxidative imbalance. Moreover, anxiety-like behavior can be caused by pharmacological-ind...

  5. Human bronchial epithelial cells exposed in vitro to diesel exhaust particles exhibit alterations in cell rheology and cytotoxicity associated with decrease in antioxidant defenses and imbalance in pro- and anti-apoptotic gene expression.

    Science.gov (United States)

    Seriani, Robson; de Souza, Claudia Emanuele Carvalho; Krempel, Paloma Gava; Frias, Daniela Perroni; Matsuda, Monique; Correia, Aristides Tadeu; Ferreira, Márcia Zotti Justo; Alencar, Adriano Mesquita; Negri, Elnara Marcia; Saldiva, Paulo Hilário Nascimento; Mauad, Thais; Macchione, Mariangela

    2016-05-01

    Diesel exhaust particles (DEPs) from diesel engines produce adverse alterations in cells of the airways by activating intracellular signaling pathways and apoptotic gene overexpression, and also by influencing metabolism and cytoskeleton changes. This study used human bronchial epithelium cells (BEAS-2B) in culture and evaluates their exposure to DEPs (15ug/mL for 1 and 2 h) in order to determine changes to cell rheology (viscoelasticity) and gene expression of the enzymes involved in oxidative stress, apoptosis, and cytotoxicity. BEAS-2B cells exposed to DEPs were found to have a significant loss in stiffness, membrane stability, and mitochondrial activity. The genes involved in apoptosis [B cell lymphoma 2 (BCL-2 and caspase-3)] presented inversely proportional expressions (p = 0.05, p = 0.01, respectively), low expression of the genes involved in antioxidant responses [SOD1 (superoxide dismutase 1); SOD2 (superoxide dismutase 2), and GPx (glutathione peroxidase) (p = 0.01)], along with an increase in cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) (p = 0.01). These results suggest that alterations in cell rheology and cytotoxicity could be associated with oxidative stress and imbalance between pro- and anti-apoptotic genes. PMID:26856867

  6. The environment exerts a greater influence than the transgene on the transcriptome of field-grown wheat expressing the Pm3b allele.

    Science.gov (United States)

    Quijano, Carolina Diaz; Brunner, Susanne; Keller, Beat; Gruissem, Wilhelm; Sautter, Christof

    2015-02-01

    Wheat provides 20 % of the calories consumed worldwide. Powdery mildew infections of wheat can result in more than 30 % yield loss but it has been demonstrated that wheat overexpressing Pm3b, an allele of the R gene Pm3, has enhanced resistance against powdery mildew under field conditions. A gene expression profile study using GeneChip Wheat Genome Array and Fluidigm 96.96 Dynamic Arrays was performed to obtain insights into the mode of action of Pm3b and to elucidate the molecular basis of pleiotropic effects observed in three out of four independent transgenic events under field conditions. A cluster analysis of the microarray data and a principal component analysis of the Fluidigm 96.96 Dynamic Arrays data showed that transgenic lines and null segregants grouped together. The microarray analysis of samples from fungicide-treated plants revealed that significantly fewer genes were differentially expressed in Pm3b#1 than in Pm3b#2, which had a pleiotropic phenotype in the field, compared to their null segregants. Together, our data provide evidence that the environment influenced gene expression in the Pm3b lines more than the transgene itself. PMID:25095900

  7. HMG CoA Lyase (HL): Mutation detection and development of a bacterial expression system for screening the activity of mutant alleles from HL-deficient patients

    Energy Technology Data Exchange (ETDEWEB)

    Robert, M.F.; Ashmarina, L.; Poitier, E. [Hospital Ste-Justine, Montreal (Canada)] [and others

    1994-09-01

    HL catalyzes the last step of ketogenesis, and autosomal recessive HL deficiency in humans can cause episodes of hypoglycemia and coma. Structurally, HL is a dimer of identical 325-residue peptides which requires a reducing environment to maintain activity. We cloned the human and mouse HL cDNAs and genes and have performed mutation analysis on cells from 30 HL-deficient probands. Using SSCP and also genomic Southern analysis we have identified putative mutations on 53/60 alleles of these patients (88%). To date, we have found 20 mutations: 3 large deletions, 4 termination mutations, 5 frameshift mutations, and 8 missense mutations which we suspect to be pathogenic based on evolutionary conservation and/or our previous studies on purified HL protein. We have also identified 3 polymorphic variants. In order to directly test the activity of the missense mutations, we established a pGEX-based system, using a glutathione S transferase (GST)-HL fusion protein. Expressed wild-type GST-HL was insoluble. We previously located a reactive Cys at the C-terminus of chicken HL which is conserved in human HL. We produced a mutant HL peptide, C323S, which replaced Cys323 with Ser. Purified C323S is soluble and has similar kinetics to wild-type HL. C323S-containing GST-HL is soluble and enzymatically active. We are cloning and expressing the 8 missense mutations.

  8. The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression.

    Science.gov (United States)

    Lavebratt, C; Olsson, S; Backlund, L; Frisén, L; Sellgren, C; Priebe, L; Nikamo, P; Träskman-Bendz, L; Cichon, S; Vawter, M P; Osby, U; Engberg, G; Landén, M; Erhardt, S; Schalling, M

    2014-03-01

    The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P=0.005, n=19) or schizophrenia (P=0.02, n=36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg(452) allele was associated with psychotic features during manic episodes (P=0.003). KMO Arg(452) was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg(452) associated with increased levels of CSF KYNA (P=0.03) and reduced lymphoblastoid and hippocampal KMO expression (P≤0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes. PMID:23459468

  9. A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5

    Science.gov (United States)

    Sigurdsson, Snaevar; Nordmark, Gunnel; Garnier, Sophie; Grundberg, Elin; Kwan, Tony; Nilsson, Olof; Eloranta, Maija-Leena; Gunnarsson, Iva; Svenungsson, Elisabet; Sturfelt, Gunnar; Bengtsson, Anders A.; Jönsen, Andreas; Truedsson, Lennart; Rantapää-Dahlqvist, Solbritt; Eriksson, Catharina; Alm, Gunnar; Göring, Harald H.H.; Pastinen, Tomi; Syvänen, Ann-Christine; Rönnblom, Lars

    2008-01-01

    Systemic lupus erythematosus (SLE) is the prototype autoimmune disease where genes regulated by type I interferon (IFN) are over-expressed and contribute to the disease pathogenesis. Because signal transducer and activator of transcription 4 (STAT4) plays a key role in the type I IFN receptor signaling, we performed a candidate gene study of a comprehensive set of single nucleotide polymorphism (SNPs) in STAT4 in Swedish patients with SLE. We found that 10 out of 53 analyzed SNPs in STAT4 were associated with SLE, with the strongest signal of association (P = 7.1 × 10−8) for two perfectly linked SNPs rs10181656 and rs7582694. The risk alleles of these 10 SNPs form a common risk haplotype for SLE (P = 1.7 × 10−5). According to conditional logistic regression analysis the SNP rs10181656 or rs7582694 accounts for all of the observed association signal. By quantitative analysis of the allelic expression of STAT4 we found that the risk allele of STAT4 was over-expressed in primary human cells of mesenchymal origin, but not in B-cells, and that the risk allele of STAT4 was over-expressed (P = 8.4 × 10−5) in cells carrying the risk haplotype for SLE compared with cells with a non-risk haplotype. The risk allele of the SNP rs7582694 in STAT4 correlated to production of anti-dsDNA (double-stranded DNA) antibodies and displayed a multiplicatively increased, 1.82-fold risk of SLE with two independent risk alleles of the IRF5 (interferon regulatory factor 5) gene. PMID:18579578

  10. Drivers of imbalance cost of wind power

    DEFF Research Database (Denmark)

    Obersteiner, C.; Siewierski, T.; Andersen, Anders

    2010-01-01

    In Europe an increasing share of wind power is sold on the power market. Therefore more and more wind power generators become balancing responsible and face imbalance cost that reduce revenues from selling wind power. A comparison of literature illustrates that the imbalance cost of wind power...... varies in a wide range. To explain differences we indentify parameters influencing imbalance cost and compare them for case studies in Austria, Denmark and Poland. Besides the wind power forecast error also the correlation between imbalance and imbalance price influences imbalance cost significantly....... Especially in systems with significant wind shares, an assessment of imbalance cost based on the amount of imbalance and average System Sell and System Buy Prices is therefore not reliable. While imbalance cost rather reflects cash flows within the clearing of imbalances, the presented concept of cost...

  11. Chronic vitamin C deficiency promotes redox imbalance in the brain but does not alter sodium-dependent vitamin C transporter 2 expression

    DEFF Research Database (Denmark)

    Paidi, Maya Devi; Schjoldager, Janne Gram; Lykkesfeldt, Jens;

    2014-01-01

    Vitamin C (VitC) has several roles in the brain acting both as a specific and non-specific antioxidant. The brain upholds a very high VitC concentration and is able to preferentially retain VitC even during deficiency. The accumulation of brain VitC levels much higher than in blood is primarily...... achieved by the sodium dependent VitC transporter (SVCT2). This study investigated the effects of chronic pre-and postnatal VitC deficiency as well as the effects of postnatal VitC repletion, on brain SVCT2 expression and markers of oxidative stress in young guinea pigs. Biochemical analyses demonstrated...... significantly decreased total VitC and an increased percentage of dehydroascorbic acid, as well as increased lipid oxidation (malondialdehyde), in the brains of VitC deficient animals (p < 0.0001) compared to controls. VitC repleted animals were not significantly different from controls. No significant changes...

  12. The FOXO3A rs2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3A mRNA Expression in Twins

    DEFF Research Database (Denmark)

    Banasik, Karina; Ribel-Madsen, Rasmus; Gjesing, Anette P;

    2011-01-01

    Objective: The minor G-allele of FOXO3A rs2802292 has been associated with longevity. We aimed to investigate whether a phenotype related to healthy metabolic aging could be identified in individuals carrying the longevity-associated FOXO3A rs2802292 G-allele. Research Design and Methods: rs2802292...... hyperinsulinemic, euglycemic clamp. Basal and insulin-stimulated FOXO3A mRNA expression was assessed in skeletal muscle biopsies from the twin population. Results: In the twin sample, carriers of the minor G-allele of rs2802292 showed reduced fasting plasma insulin [per allele effect (ß) = -13% (-24; -1) (95......% confidence interval), P = 0.03] and lower incremental area under the curve 0–120 min for insulin after an oral glucose load [ß = -14% (-23; -5), P = 0.005]. The G-allele was associated with increased peripheral insulin action [glucose disposal rate clamp, ß = 0.85 mg · kgfat-free mass-1 · min-1 (0.049; 1...

  13. Dijet imbalance in hadronic collisions

    CERN Document Server

    Boer, Daniel; Pisano, Cristian

    2009-01-01

    The imbalance of dijets produced in hadronic collisions has been used to extract the average transverse momentum of partons inside the hadrons. In this paper we discuss new contributions to the dijet imbalance that could complicate or even hamper this extraction. They are due to polarization of initial state partons inside unpolarized hadrons that can arise in the presence of nonzero parton transverse momentum. Transversely polarized quarks and linearly polarized gluons produce specific azimuthal dependences of the two jets that in principle are not suppressed. Their effects cannot be isolated just by looking at the angular deviation from the back-to-back situation, rather they enter jet broadening observables. In this way they directly affect the extraction of the average transverse momentum of unpolarized partons that is thought to be extracted. We discuss appropriately weighted cross sections to isolate the additional contributions.

  14. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D.

    Directory of Open Access Journals (Sweden)

    Sreeram V Ramagopalan

    2009-02-01

    Full Text Available Multiple sclerosis (MS is a complex trait in which allelic variation in the MHC class II region exerts the single strongest effect on genetic risk. Epidemiological data in MS provide strong evidence that environmental factors act at a population level to influence the unusual geographical distribution of this disease. Growing evidence implicates sunlight or vitamin D as a key environmental factor in aetiology. We hypothesised that this environmental candidate might interact with inherited factors and sought responsive regulatory elements in the MHC class II region. Sequence analysis localised a single MHC vitamin D response element (VDRE to the promoter region of HLA-DRB1. Sequencing of this promoter in greater than 1,000 chromosomes from HLA-DRB1 homozygotes showed absolute conservation of this putative VDRE on HLA-DRB1*15 haplotypes. In contrast, there was striking variation among non-MS-associated haplotypes. Electrophoretic mobility shift assays showed specific recruitment of vitamin D receptor to the VDRE in the HLA-DRB1*15 promoter, confirmed by chromatin immunoprecipitation experiments using lymphoblastoid cells homozygous for HLA-DRB1*15. Transient transfection using a luciferase reporter assay showed a functional role for this VDRE. B cells transiently transfected with the HLA-DRB1*15 gene promoter showed increased expression on stimulation with 1,25-dihydroxyvitamin D3 (P = 0.002 that was lost both on deletion of the VDRE or with the homologous "VDRE" sequence found in non-MS-associated HLA-DRB1 haplotypes. Flow cytometric analysis showed a specific increase in the cell surface expression of HLA-DRB1 upon addition of vitamin D only in HLA-DRB1*15 bearing lymphoblastoid cells. This study further implicates vitamin D as a strong environmental candidate in MS by demonstrating direct functional interaction with the major locus determining genetic susceptibility. These findings support a connection between the main epidemiological and

  15. Nutrient imbalance in Norway spruce

    International Nuclear Information System (INIS)

    The studies presented in my thesis indicate that growing Norway spruce in monoculture does not constitute sustainable forest management in a high N and S deposition environment, such as in southern Sweden. The combination of N-induced high growth rates and leaching due to soil acidification causes soil reserves of nutrients to decrease. This will increase the risk of nutrient imbalance within the trees when nutrient demands are not met. The development of nutrient imbalance in Scania, southern Sweden, was shown as negative trends in needle and soil nutrient status from the mid-80s to the present in Norway spruce and Scots pine stands. This imbalance appears to be connected to high levels of N and S deposition. Clear negative effects on tree vitality were found when using a new branch development method. Today, growth and vitality seems to be limited by K, rather than N, in spruce stands older than 40 years. However, younger stands appear to be able to absorb the deposited N without negative effects on growth and vitality. When investigating effects of nutrient stress on tree vitality, indicators such as branch length and shoot multiplication rate, which include effects accumulated over several years, are suitable. Countermeasures are needed in order to maintain the forest production at a high level. Positive effects on tree nutrient status after vitality fertilization (N-free fertilization) was shown in two micronutrient deficient stands in south-central Sweden. In addition, tree vitality was positively affected after the application of a site-adapted fertilizer to the canopy. Site-adaption of fertilizers will most likely improve the possibilities of a positive response on tree growth and vitality in declining stands. In a survey of Norway spruce in mixtures with beech, birch, or oak compared to monocultures it was shown that spruce nutrient status was higher in mixtures with deciduous species than in monocultures. By using mixed-species stands the need for

  16. Nutrient imbalance in Norway spruce

    Energy Technology Data Exchange (ETDEWEB)

    Thelin, Gunnar

    2000-11-01

    The studies presented in my thesis indicate that growing Norway spruce in monoculture does not constitute sustainable forest management in a high N and S deposition environment, such as in southern Sweden. The combination of N-induced high growth rates and leaching due to soil acidification causes soil reserves of nutrients to decrease. This will increase the risk of nutrient imbalance within the trees when nutrient demands are not met. The development of nutrient imbalance in Scania, southern Sweden, was shown as negative trends in needle and soil nutrient status from the mid-80s to the present in Norway spruce and Scots pine stands. This imbalance appears to be connected to high levels of N and S deposition. Clear negative effects on tree vitality were found when using a new branch development method. Today, growth and vitality seems to be limited by K, rather than N, in spruce stands older than 40 years. However, younger stands appear to be able to absorb the deposited N without negative effects on growth and vitality. When investigating effects of nutrient stress on tree vitality, indicators such as branch length and shoot multiplication rate, which include effects accumulated over several years, are suitable. Countermeasures are needed in order to maintain the forest production at a high level. Positive effects on tree nutrient status after vitality fertilization (N-free fertilization) was shown in two micronutrient deficient stands in south-central Sweden. In addition, tree vitality was positively affected after the application of a site-adapted fertilizer to the canopy. Site-adaption of fertilizers will most likely improve the possibilities of a positive response on tree growth and vitality in declining stands. In a survey of Norway spruce in mixtures with beech, birch, or oak compared to monocultures it was shown that spruce nutrient status was higher in mixtures with deciduous species than in monocultures. By using mixed-species stands the need for

  17. Earth's energy imbalance and implications

    OpenAIRE

    Hansen, J; Sato, M.; Kharecha, P.; K. von Schuckmann

    2011-01-01

    Improving observations of ocean heat content show that Earth is absorbing more energy from the Sun than it is radiating to space as heat, even during the recent solar minimum. The inferred planetary energy imbalance, 0.58 ± 0.15 W m−2 during the 6-yr period 2005–2010, confirms the dominant role of the human-made greenhouse effect in driving global climate change. Observed surface temperature change and ocean heat gain together constrain the net climate forcing and ocean...

  18. Genome-wide identification and quantification of cis- and trans-regulated genes responding to Marek's disease virus infection via analysis of allele-specific expression

    Science.gov (United States)

    Background Marek’s disease (MD) is a commercially important neoplastic disease of chickens caused by the Marek’s disease virus (MDV), a naturally-occurring oncogenic alphaherpesvirus. We attempted to identify genes conferring MD resistance, by completing a genome-wide screen for allele-specific expr...

  19. The − 5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Starska, Katarzyna, E-mail: katarzyna.starska@umed.lodz.pl [I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153 Łódź (Poland); Krześlak, Anna; Forma, Ewa [Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź (Poland); Olszewski, Jurek [II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549 Łódź (Poland); Morawiec-Sztandera, Alina [Department of Head and Neck Surgery, Medical University of Łódź, Paderewskiego 4, 93-509 Łódź (Poland); Aleksandrowicz, Paweł [Department of Otolaryngology and Laryngological Oncology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin (Poland); Lewy-Trenda, Iwona [Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213 Łódź (Poland); and others

    2014-10-15

    Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that − 5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer. - Highlights: • MT2A gene expression and metal content in laryngeal cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn and Cu levels • Negative correlation between MT2A gene expression and Cd, Zn and Cu levels.

  20. The − 5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer

    International Nuclear Information System (INIS)

    Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that − 5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer. - Highlights: • MT2A gene expression and metal content in laryngeal cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn and Cu levels • Negative correlation between MT2A gene expression and Cd, Zn and Cu levels

  1. WIND TURBINE MASS AND AERODYNAMIC IMBALANCES DETERMINATION

    OpenAIRE

    Nduwayezu Eric; Mehmet Bayrak

    2015-01-01

    This paper evaluates the use of simulations to investigate wind turbine mass and aerodynamic imbalances. Faults caused by mass and aerodynamic imbalances constitute a significant portion of all faults in wind turbine. The aerodynamic imbalances effects such as deviations between the three blades pitch angle are often underrated and misunderstood. In practice, for many wind energy converters the blade adjustment is found to be sub-optimal. The dynamics of a model wind turbine was s...

  2. Multilocus Inherited Neoplasia Alleles Syndrome

    DEFF Research Database (Denmark)

    Whitworth, James; Skytte, Anne-Bine; Sunde, Lone; Lim, Derek H; Arends, Mark J; Happerfield, Lisa; Frayling, Ian M; van Minkelen, Rick; Woodward, Emma R; Tischkowitz, Marc D; Maher, Eamonn R

    Mendelian causes of inherited cancer susceptibility are mostly rare and characterized by variable expression and incomplete penetrance. Phenotypic variability may result from a range of causes including locus heterogeneity, allelic heterogeneity, genetic and environmental modifier effects, or...... chance. Another potential cause is the presence of 2 or more inherited cancer predisposition alleles in the same individual. Although the frequency of such occurrences might be predicted to be low, such cases have probably been underascertained because standard clinical practice has been to test...... candidate inherited cancer genes sequentially until a pathogenic mutation is detected. However, recent advances in next-generation sequencing technologies now provide the opportunity to perform simultaneous parallel testing of large numbers of inherited cancer genes. Herein we provide examples of patients...

  3. Swine Leukocyte Antigen (SLA) class I allele typing of Danish swine herds and the identification of commonly expressed haplotypes using sequence specific low- and high resolution primers

    OpenAIRE

    Pedersen, Lasse Eggers; Fink, Dorte Rosenbek; Jungersen, Gregers

    2012-01-01

    The genomic region (SLA) of the swine major histocompatibility complex (MHC), which bind and present endogenous peptides to circulating T cells of the immune system, is extremely polymorphic comprising high numbers of different alleles, many of which encode a distinct MHC class I molecule. Each SLA molecule is only able to bind a restricted number of peptides with specific biochemical characteristics matching important anchor positions in the peptide binding groove. Although the diversity of ...

  4. 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...

  5. 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 ...

  6. How does Chinese medicine target cytokine imbalance in rheumatoid arthritis?

    Science.gov (United States)

    Liu, Jian; Sun, Yue

    2013-11-01

    Rheumatoid arthritis (RA) manifests as an imbalance between pro- and anti-inflammatory cytokines. Cytokine imbalance is suggested to play critical roles in the development of RA. Currently, various treatments for RA, including biological agents such as antibodies against inflammation mediators, or Chinese herbal medicines, intervene the disease by restoring the balance of cytokines. Chinese medicine (CM) can not only suppress the expression of pro-inflammatory cytokines, but also induce the expression of cytokines with anti-inflammatory and immunomodulatory effects. Thus, Chinese medicine can effectively reduce inflammatory cell infiltration into synovial tissue, pannus formation, and degradation of the extracellular matrix surrounding cartilage cells, thereby reducing subchondral bone damage. This paper reviews the changes of cytokine profiling during development of RA and discuss the mechanisms by which Chinese medicine restores the cytokine balance. PMID:24170633

  7. Earth's energy imbalance and implications

    Science.gov (United States)

    Hansen, J.; Sato, M.; Kharecha, P.; von Schuckmann, K.

    2011-09-01

    Improving observations of ocean heat content show that Earth is absorbing more energy from the sun than it is radiating to space as heat, even during the recent solar minimum. The inferred planetary energy imbalance, 0.59 ± 0.15 W m-2 during the 6-year period 2005-2010, confirms the dominant role of the human-made greenhouse effect in driving global climate change. Observed surface temperature change and ocean heat gain together constrain the net climate forcing and ocean mixing rates. We conclude that most climate models mix heat too efficiently into the deep ocean and as a result underestimate the negative forcing by human-made aerosols. Aerosol climate forcing today is inferred to be -1.6 ± 0.3 W m-2, implying substantial aerosol indirect climate forcing via cloud changes. Continued failure to quantify the specific origins of this large forcing is untenable, as knowledge of changing aerosol effects is needed to understand future climate change. We conclude that recent slowdown of ocean heat uptake was caused by a delayed rebound effect from Mount Pinatubo aerosols and a deep prolonged solar minimum. Observed sea level rise during the Argo float era is readily accounted for by ice melt and ocean thermal expansion, but the ascendency of ice melt leads us to anticipate acceleration of the rate of sea level rise this decade. Humanity is potentially vulnerable to global temperature change, as discussed in the Intergovernmental Panel on Climate Change (IPCC, 2001, 2007) reports and by innumerable authors. Although climate change is driven by many climate forcing agents and the climate system also exhibits unforced (chaotic) variability, it is now widely agreed that the strong global warming trend of recent decades is caused predominantly by human-made changes of atmospheric composition (IPCC, 2007). The basic physics underlying this global warming, the greenhouse effect, is simple. An increase of gases such as CO2 makes the atmosphere more opaque at infrared

  8. Expression of sterol regulatory element-binding transcription factor (SREBF 2 and SREBF cleavage-activating protein (SCAP in human atheroma and the association of their allelic variants with sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Kytömäki Leena

    2008-12-01

    Full Text Available Abstract Background Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2 and the SREBF cleavage-activating protein (SCAP. We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314 and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD. Methods Whole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33–69 years Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes. Results Whole genome expression profiling showed a significant (p = 0.02 down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V, but not in the aorta or femoral arteries (p = NS for both, as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046. Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07–6.71, compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the

  9. Earth's Energy Imbalance and Implications

    CERN Document Server

    Hansen, James; Kharecha, Pushker; von Schuckmann, Karina

    2011-01-01

    Improving observations of ocean temperature confirm that Earth is absorbing more energy from the sun than it is radiating to space as heat, even during the recent solar minimum. The inferred planetary energy imbalance, 0.59 \\pm 0.15 W/m2 during the 6-year period 2005-2010, provides fundamental verification of the dominant role of the human-made greenhouse effect in driving global climate change. Observed surface temperature change and ocean heat gain constrain the net climate forcing and ocean mixing rates. We conclude that most climate models mix heat too efficiently into the deep ocean and as a result underestimate the negative forcing by human-made aerosols. Aerosol climate forcing today is inferred to be -1.6 \\pm 0.3 W/m2, implying substantial aerosol indirect climate forcing via cloud changes. Continued failure to quantify the specific origins of this large forcing is untenable, as knowledge of changing aerosol effects is needed to understand future climate change. A recent decrease in ocean heat uptake ...

  10. Earth's energy imbalance and implications

    Directory of Open Access Journals (Sweden)

    J. Hansen

    2011-12-01

    Full Text Available Improving observations of ocean heat content show that Earth is absorbing more energy from the Sun than it is radiating to space as heat, even during the recent solar minimum. The inferred planetary energy imbalance, 0.58 ± 0.15 W m−2 during the 6-yr period 2005–2010, confirms the dominant role of the human-made greenhouse effect in driving global climate change. Observed surface temperature change and ocean heat gain together constrain the net climate forcing and ocean mixing rates. We conclude that most climate models mix heat too efficiently into the deep ocean and as a result underestimate the negative forcing by human-made aerosols. Aerosol climate forcing today is inferred to be −1.6 ± 0.3 W m−2, implying substantial aerosol indirect climate forcing via cloud changes. Continued failure to quantify the specific origins of this large forcing is untenable, as knowledge of changing aerosol effects is needed to understand future climate change. We conclude that recent slowdown of ocean heat uptake was caused by a delayed rebound effect from Mount Pinatubo aerosols and a deep prolonged solar minimum. Observed sea level rise during the Argo float era is readily accounted for by ice melt and ocean thermal expansion, but the ascendency of ice melt leads us to anticipate acceleration of the rate of sea level rise this decade.

  11. Earth's energy imbalance and implications

    Directory of Open Access Journals (Sweden)

    J. Hansen

    2011-09-01

    Full Text Available Improving observations of ocean heat content show that Earth is absorbing more energy from the sun than it is radiating to space as heat, even during the recent solar minimum. The inferred planetary energy imbalance, 0.59 ± 0.15 W m−2 during the 6-year period 2005–2010, confirms the dominant role of the human-made greenhouse effect in driving global climate change. Observed surface temperature change and ocean heat gain together constrain the net climate forcing and ocean mixing rates. We conclude that most climate models mix heat too efficiently into the deep ocean and as a result underestimate the negative forcing by human-made aerosols. Aerosol climate forcing today is inferred to be −1.6 ± 0.3 W m−2, implying substantial aerosol indirect climate forcing via cloud changes. Continued failure to quantify the specific origins of this large forcing is untenable, as knowledge of changing aerosol effects is needed to understand future climate change. We conclude that recent slowdown of ocean heat uptake was caused by a delayed rebound effect from Mount Pinatubo aerosols and a deep prolonged solar minimum. Observed sea level rise during the Argo float era is readily accounted for by ice melt and ocean thermal expansion, but the ascendency of ice melt leads us to anticipate acceleration of the rate of sea level rise this decade.

    Humanity is potentially vulnerable to global temperature change, as discussed in the Intergovernmental Panel on Climate Change (IPCC, 2001, 2007 reports and by innumerable authors. Although climate change is driven by many climate forcing agents and the climate system also exhibits unforced (chaotic variability, it is now widely agreed that the strong global warming trend of recent decades is caused predominantly by human-made changes of atmospheric composition (IPCC, 2007.

    The basic physics underlying this global warming, the greenhouse effect, is simple. An increase of gases

  12. N-glycosylation of asparagine 8 regulates surface expression of major histocompatibility complex class I chain-related protein A (MICA) alleles dependent on threonine 24

    DEFF Research Database (Denmark)

    Pedersen, Maiken Mellergaard; Skovbakke, Sarah Line; Schneider, Christine L.;

    2014-01-01

    NKG2D is an activating receptor expressed on several types of human lymphocytes. NKG2D ligands can be induced upon cell stress and are frequently targeted post-translationally in infected or transformed cells, in order to avoid immune recognition. Virus infection and inflammation alter protein N...... addition we show that this regulatory mechanism of MICA surface expression is likely targeted during different pathological conditions....

  13. A functional polymorphism in the Eta-1 promoter is associated with allele specific binding to the transcription factor Sp1 and elevated gene expression

    DEFF Research Database (Denmark)

    Hummelshoj, Tina; Ryder, Lars P; Madsen, Hans O; Odum, Niels; Svejgaard, Arne

    2005-01-01

    Early T lymphocyte activator 1 (Eta-1), also known as Osteopontin, is a cytokine produced by macrophages and T lymphocytes. It is involved in the regulation of IL-12 and IL-10 expression in macrophages and stimulates the polarization of T cells to the Th1 subset. Three promoter polymorphisms of the...... human Eta-1 gene, -443T/C, -156delG/G, -66T/G, were investigated for possible influence on gene expression. Electrophoretic mobility shift assays (EMSA) with nuclear extract from the human myeloid leukaemia premonocyte cell line, THP-1, revealed sequence specific binding of the transcription factor Sp1...

  14. A Common Polymorphism in the Promoter Region of the TNFSF4 Gene Is Associated with Lower Allele-Specific Expression and Risk of Myocardial Infarction

    OpenAIRE

    Massimiliano Ria; Jacob Lagercrantz; Ann Samnegård; Susanna Boquist; Anders Hamsten; Per Eriksson

    2011-01-01

    BACKGROUND: The TNFSF4/TNFRSF4 system, along with several other receptor-ligand pairs, is involved in the recruitment and activation of T-cells and is therefore tentatively implicated in atherosclerosis and acute coronary syndromes. We have previously shown that genetic variants in TNFSF4 are associated with myocardial infarction (MI) in women. This prompted functional studies of TNFSF4 expression. METHODS AND RESULTS: Based on a screening of the TNFSF4 genomic region, a promoter polymorphism...

  15. Co-Occurrence of Two Allelic Variants of CYP51 in Erysiphe necator and Their Correlation with Over-Expression for DMI Resistance

    OpenAIRE

    Lynn Esther E Rallos; Baudoin, Anton B.

    2016-01-01

    Demethylation inhibitors (DMIs) have been an important tool in the management of grapevine powdery mildew caused by Erysiphe necator. Long-term, intensive use of DMIs has resulted in reduced sensitivity in field populations. To further characterize DMI resistance and understand resistance mechanisms in this pathogen, we investigated the cyp51 sequence of 24 single-spored isolates from Virginia and surrounding states and analyzed gene expression in isolates representing a wide range of sensiti...

  16. The KMO allele encoding Arg(452) is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression

    OpenAIRE

    Lavebratt, C; Olsson, S.; Backlund, L.; Frisen, L; Sellgren, C.; Priebe, L.; Nikamo, P.; Träskman Bendz, Lil; Cichon, S; Vawter, M. P.; Osby, U; Engberg, G.; Landen, M; Erhardt, S.; Schalling, M.

    2014-01-01

    The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychot...

  17. Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families.

    OpenAIRE

    Friedman, L S; Szabo, C.I.; Ostermeyer, E A; Dowd, P; Butler, L; Park, T.; Lee, M K; Goode, E.L.; Rowell, S E; King, M C

    1995-01-01

    Thirty-seven families with four or more cases of breast cancer or breast and ovarian cancer were analyzed for mutations in BRCA1. Twelve different germ-line mutations, four novel and eight previously observed, were detected in 16 families. Five families of Ashkenazi Jewish descent carried the 185delAG mutation and shared the same haplotype at eight polymorphic markers spanning approximately 850 kb at BRCA1. Expressivity of 185delAG in these families varied, from early-onset breast cancer with...

  18. The Hegelian dialectics of global imbalances

    Directory of Open Access Journals (Sweden)

    Célestin Monga

    2012-11-01

    Full Text Available Traditional narratives of external imbalances have focused on the analysis of national accounts, trade flows, and financial flows. They have generated two opposing views of the current situation of the world economy: on one side, a prudent, if not pessimistic view considers large imbalances as evidence of problems with the international monetary and financial system, and symptoms of domestic distortions (mainly in the United States and China. On the other side, a relaxed, if not optimistic view suggests that global imbalances are not anomalies but simply the predictable outcome of a world with increasingly globalized financial flows in search of the right mix of risks and returns. This paper offers a critical analysis of these competing explanations of the United States-China imbalances and suggests a way of reconciling them. The paper uses Hegel’s parable of the development of self-consciousness to explain the dynamics between the two countries. Hegel may not have been a great philosopher of history but his study of lordship and bondage provides a good framework for analyzing the dialectics of recognition and acknowledgement that currently characterizes the macroeconomic relationships between the United States and China.

  19. On the chiral imbalance and Weibel instabilities

    Science.gov (United States)

    Kumar, Avdhesh; Bhatt, Jitesh R.; Kaw, P. K.

    2016-06-01

    We study the chiral-imbalance and the Weibel instabilities in presence of the quantum anomaly using the Berry-curvature modified kinetic equation. We argue that in many realistic situations, e.g. relativistic heavy-ion collisions, both the instabilities can occur simultaneously. The Weibel instability depends on the momentum anisotropy parameter ξ and the angle (θn) between the propagation vector and the anisotropy direction. It has maximum growth rate at θn = 0 while θn = π / 2 corresponds to a damping. On the other hand the pure chiral-imbalance instability occurs in an isotropic plasma and depends on difference between the chiral chemical potentials of right and left-handed particles. It is shown that when θn = 0, only for a very small values of the anisotropic parameter ξ ∼ξc, growth rates of the both instabilities are comparable. For the cases ξc < ξ ≪ 1 or ξ ≳ 1 at θn = 0, the Weibel modes dominate over the chiral-imbalance instability if μ5 / T ≤ 1. However, when μ5 / T ≥ 1, it is possible to have dominance of the chiral-imbalance modes at certain values of θn for an arbitrary ξ.

  20. A new analysis tool for individual-level allele frequency for genomic studies

    Directory of Open Access Journals (Sweden)

    Pan Wen-Harn

    2010-07-01

    Full Text Available Abstract Background Allele frequency is one of the most important population indices and has been broadly applied to genetic/genomic studies. Estimation of allele frequency using genotypes is convenient but may lose data information and be sensitive to genotyping errors. Results This study utilizes a unified intensity-measuring approach to estimating individual-level allele frequencies for 1,104 and 1,270 samples genotyped with the single-nucleotide-polymorphism arrays of the Affymetrix Human Mapping 100K and 500K Sets, respectively. Allele frequencies of all samples are estimated and adjusted by coefficients of preferential amplification/hybridization (CPA, and large ethnicity-specific and cross-ethnicity databases of CPA and allele frequency are established. The results show that using the CPA significantly improves the accuracy of allele frequency estimates; moreover, this paramount factor is insensitive to the time of data acquisition, effect of laboratory site, type of gene chip, and phenotypic status. Based on accurate allele frequency estimates, analytic methods based on individual-level allele frequencies are developed and successfully applied to discover genomic patterns of allele frequencies, detect chromosomal abnormalities, classify sample groups, identify outlier samples, and estimate the purity of tumor samples. The methods are packaged into a new analysis tool, ALOHA (Allele-frequency/Loss-of-heterozygosity/Allele-imbalance. Conclusions This is the first time that these important genetic/genomic applications have been simultaneously conducted by the analyses of individual-level allele frequencies estimated by a unified intensity-measuring approach. We expect that additional practical applications for allele frequency analysis will be found. The developed databases and tools provide useful resources for human genome analysis via high-throughput single-nucleotide-polymorphism arrays. The ALOHA software was written in R and R GUI and

  1. Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families

    Energy Technology Data Exchange (ETDEWEB)

    Friedman, L.S.; Szabo, C.I.; Ostermeyer, E.A. [Univ. of California, Berkeley, CA (United States)] [and others

    1995-12-01

    Thirty-seven families with four or more cases of breast cancer or breast and ovarian cancer were analyzed for mutations in BRCA1. Twelve different germ-line mutations, four novel and eight previously observed, were detected in 16 families. Five families of Ashkenazi Jewish descent carried the 185delAG mutation and shared the same haplotype at eight polymorphic markers spanning {approximately}850 kb at BRCA1. Expressivity of 185delAG in these families varied, from early-onset bilateral breast cancer and ovarian cancer to late-onset breast cancer without ovarian cancer. Mutation 4184delTCAA occurred independently in two families. In one family, penetrance was complete, with females developing early-onset breast cancer or ovarian cancer and the male carrier developing prostatic cancer, whereas, in the other family, penetrance was incomplete and only breast cancer occurred, diagnosed at ages 38-81 years. Two novel nonsense mutations led to the loss of mutant BRCA1 transcript in families with 10 and 6 cases of early-onset breast cancer and ovarian cancer. A 665-nt segment of the BRCA1 3{prime}-UTR and 1.3 kb of genomic sequence including the putative promoter region were invariant by single-strand conformation analysis in 13 families without coding-sequence mutations. Overall in our series, BRCA1 mutations have been detected in 26 families: 16 with positive BRCA1 lod scores, 7 with negative lod scores (reflecting multiple sporadic breast cancers), and 3 not tested for linkage. Three other families have positive lod scores for linkage to BRCA2, but 13 families without detected BRCA1 mutations have negative lod scores for both BRCA1 and BRCA2. 57 refs., 5 figs., 3 tabs.

  2. Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families.

    Science.gov (United States)

    Friedman, L S; Szabo, C I; Ostermeyer, E A; Dowd, P; Butler, L; Park, T; Lee, M K; Goode, E L; Rowell, S E; King, M C

    1995-12-01

    Thirty-seven families with four or more cases of breast cancer or breast and ovarian cancer were analyzed for mutations in BRCA1. Twelve different germ-line mutations, four novel and eight previously observed, were detected in 16 families. Five families of Ashkenazi Jewish descent carried the 185delAG mutation and shared the same haplotype at eight polymorphic markers spanning approximately 850 kb at BRCA1. Expressivity of 185delAG in these families varied, from early-onset breast cancer without ovarian cancer. Mutation 4184delTCAA occurred independently in two families. In one family, penetrance was complete, with females developing early-onset breast cancer or ovarian cancer and the male carrier developing prostatic cancer, whereas, in the other family, penetrance was incomplete and only breast cancer occurred, diagnosed at ages 38-81 years. Two novel nonsense mutations led to the loss of mutant BRCA1 transcript in families with 10 and 6 cases of early-onset breast cancer and ovarian cancer. A 665-nt segment of the BRCA1 3'-UTR and 1.3 kb of genomic sequence including the putative promoter region were invariant by single-strand conformation analysis in 13 families without coding-sequence mutations. Overall in our series, BRCA1 mutations have been detected in 26 families: 16 with positive BRCA1 lod scores, 7 with negative lod scores (reflecting multiple sporadic breast cancers), and 3 not tested for linkage. Three other families have positive lod scores for linkage to BRCA2, but 13 families without detected BRCA1 mutations have negative lod scores for both BRCA1 and BRCA2. PMID:8533757

  3. Education in the imbalance of Nature

    Science.gov (United States)

    Shlafman, L. M.; Kontar, V. A.

    2013-12-01

    There are two concepts understanding of the real Nature: balanced and imbalanced. The traditional balanced concept understanding of Nature was originated in prehistoric times to calm the frightened souls of prehistoric man and manage groups of people. The balanced concept presupposes that Nature is isotropic, balanced, etc. The balanced concept of understanding of Nature gradually has moved to science and technology. The balanced concept of understanding of Nature is dominating from the prehistoric time up to today. But always parallel and opposite was exists the concept imbalanced understanding of Nature, which presupposes that Nature is anisotropy, imbalanced, etc. The balanced concept is much simpler than Imbalanced. The balanced concept has given mankind a lot of rough description of Nature which helped to solve a lot of practical problems but with sufficient accuracy, i.e. approximately, but not with an absolute precision. While people were few, and a lot of resources, person could take from Nature only what Nature gave willingly. During this period, people feared and respected Nature and Nature was able easily compensate the activity of people. The high accuracy of the description of Nature was not needed when resources were plentiful and people were few. But now the situation is completely different. The population has become a very large and growing. Traditional resources are almost run out and the lack of resources escalates. People are not afraid of Nature and bravely try to take by force what Nature does not give voluntarily. People invaded into imbalance Nature, and Nature can no longer compensate activity of people. The era of global change is started, including those that man provokes. In the conditions of global changes is insufficiently of the approximate solutions of the traditional balanced concept. The balanced concept is exhausted, and increasingly misleads people. The balanced concept cannot solve the problems that arise in the global change

  4. A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci

    LENUS (Irish Health Repository)

    Prendergast, James G D

    2012-05-19

    AbstractBackgroundChromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites of allele-specific histone modification (ASHM) and their relationship to human disease. The aim of this study was to investigate the extent and characteristics of sites of ASHM in human embryonic stem cells (hESCs).ResultsUsing a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders.ConclusionThese results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.

  5. RHD alleles in the Tunisian population

    Directory of Open Access Journals (Sweden)

    Mouna Ouchari

    2013-01-01

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

  6. Allele coding in genomic evaluation

    Directory of Open Access Journals (Sweden)

    Christensen Ole F

    2011-06-01

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

  7. Feature Selection in Imbalance data sets

    Directory of Open Access Journals (Sweden)

    Ilnaz Jamali

    2012-05-01

    Full Text Available Feature selection methods have been used these days in the various fields. Like information retrieval and filtering, text classification, risk management, web categorization, medical diagnosis and the detection of credit card fraud. In this paper we focus on feature selection for imbalanced problems. One of the greatest challenges in machine learning and data mining research is the class imbalance problems. Imbalance problems can appear in two different types of data sets: binary problems, where one of the two classes comprises considerably more samples than the other, and multiclass problems, where each class only contains a tiny fraction of the samples. In this paper we want to explain a prior knowledge for an expert system which can tell us which feature selection metrics perform best based on our data characteristics and regardless of the classifier used.

  8. Global trade imbalance and economic crisis

    OpenAIRE

    Pelević Branislav; Vučković Vladimir

    2011-01-01

    Global trade imbalance is one of the factors of the ongoing economic crisis. Dependence of Western countries on capital from Asian countries created a supply of innovative financial instruments, which drawn the world into financial and economic crisis. After the crisis, international trade collapsed, with some specific features: trade declined faster than production, trade in equipment and durable consumer products plunged, international supply chains suffered. Future challenges are rel...

  9. Rescuing the concept of vertical fiscal imbalance

    OpenAIRE

    Sharma, Chanchal Kumar

    2007-01-01

    This article restores the concept of vertical fiscal imbalance (VFI) to its original meaning. The literature shows that there is neither a universally accepted definition of VFI nor a commonly accepted approach to measuring it. Estimates of VFI are derived, much like accounting or deficit measurements, by comparing the revenues and expenditures of two levels of government. VFI is, however, too nuanced an issue to be described by this kind of national accounting procedure. We argue that ease ...

  10. Global trade imbalance and economic crisis

    Directory of Open Access Journals (Sweden)

    Pelević Branislav

    2011-01-01

    Full Text Available Global trade imbalance is one of the factors of the ongoing economic crisis. Dependence of Western countries on capital from Asian countries created a supply of innovative financial instruments, which drawn the world into financial and economic crisis. After the crisis, international trade collapsed, with some specific features: trade declined faster than production, trade in equipment and durable consumer products plunged, international supply chains suffered. Future challenges are related to possible protectionism and wrong approaches for global rebalancing.

  11. On the Chiral imbalance and Weibel Instabilities

    CERN Document Server

    Kumar, Avdhesh; Kaw, Predhiman K

    2016-01-01

    We study the chiral-imbalance and the Weibel instabilities in presence of the quantum anomaly using the Berry-curvature modified kinetic equation. We argue that in many realistic situations, e.g. relativistic heavy-ion collisions, both the instabilities can occur simultaneously. The Weibel instability depends on the momentum anisotropy parameter $\\xi$ and the angle ($\\theta_n$) between the propagation vector and the anisotropy direction. It has maximum growth rate at $\\theta_n=0$ while $\\theta_n=\\pi/2$ corresponds to a damping. On the other hand the pure chiral-imbalance instability occurs in an isotropic plasma and depends on difference between the chiral chemical potentials of right and left-handed particles. It is shown that when $\\theta_n=0$, only for a very small values of the anisotropic parameter $\\xi\\sim \\xi_c$, growth rates of the both instabilities are comparable. For the cases $\\xi_c<\\xi\\ll1$, $\\xi\\approx 1$ or $\\xi \\geq 1$ at $\\theta_n=0$, the Weibel modes dominate over the chiral-imbalance ins...

  12. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

    Directory of Open Access Journals (Sweden)

    Khushbu Jain

    2015-01-01

    Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

  13. Somatic mutations, allele loss, and DNA methylation of the Cub and Sushi Multiple Domains 1 (CSMD1 gene reveals association with early age of diagnosis in colorectal cancer patients.

    Directory of Open Access Journals (Sweden)

    Austin Y Shull

    Full Text Available BACKGROUND: The Cub and Sushi Multiple Domains 1 (CSMD1 gene, located on the short arm of chromosome 8, codes for a type I transmembrane protein whose function is currently unknown. CSMD1 expression is frequently lost in many epithelial cancers. Our goal was to characterize the relationships between CSMD1 somatic mutations, allele imbalance, DNA methylation, and the clinical characteristics in colorectal cancer patients. METHODS: We sequenced the CSMD1 coding regions in 54 colorectal tumors using the 454FLX pyrosequencing platform to interrogate 72 amplicons covering the entire coding sequence. We used heterozygous SNP allele ratios at multiple CSMD1 loci to determine allelic balance and infer loss of heterozygosity. Finally, we performed methylation-specific PCR on 76 colorectal tumors to determine DNA methylation status for CSMD1 and known methylation targets ALX4, RUNX3, NEUROG1, and CDKN2A. RESULTS: Using 454FLX sequencing and confirming with Sanger sequencing, 16 CSMD1 somatic mutations were identified in 6 of the 54 colorectal tumors (11%. The nonsynonymous to synonymous mutation ratio of the 16 somatic mutations was 15:1, a ratio significantly higher than the expected 2:1 ratio (p = 0.014. This ratio indicates a presence of positive selection for mutations in the CSMD1 protein sequence. CSMD1 allelic imbalance was present in 19 of 37 informative cases (56%. Patients with allelic imbalance and CSMD1 mutations were significantly younger (average age, 41 years than those without somatic mutations (average age, 68 years. The majority of tumors were methylated at one or more CpG loci within the CSMD1 coding sequence, and CSMD1 methylation significantly correlated with two known methylation targets ALX4 and RUNX3. C:G>T:A substitutions were significantly overrepresented (47%, suggesting extensive cytosine methylation predisposing to somatic mutations. CONCLUSIONS: Deep amplicon sequencing and methylation-specific PCR reveal that CSMD1

  14. An Algorithm to Evaluate Imbalances of Quadrature Mixers

    Science.gov (United States)

    Asami, Koji; Arai, Michiaki

    It is essential, as bandwidths of wireless communications get wider, to evaluate the imbalances among quadrature mixer ports, in terms of carrier phase offset, IQ gain imbalance, and IQ skew. Because it is time consuming to separate skew, gain imbalance and carrier phase offset evaluation during test is often performed using a composite value, without separation of the imbalance factors. This paper describes an algorithm for enabling separation among quadrature mixer gain imbalance, carrier phase offset, and skew. Since the test time is reduced by the proposed method, it can be applied during high volume production testing.

  15. 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.

  16. Momentum Imbalance Observables as a Probe of Gluon TMDs

    CERN Document Server

    Pisano, Cristian

    2015-01-01

    The unpolarized and linearly polarized gluon TMDs can be directly probed in heavy quark and jet pair production in unpolarized electron-proton collisions by looking at observables, like transverse momentum distributions and azimuthal asymmetries, depending on the momentum imbalance of the pair. Analytical expressions are presented for these observables and for analogous ones in Higgs plus jet and quarkonium plus photon production in unpolarized proton-proton scattering experiments. It is shown how the proposed measurements, to be performed at a future EIC and at the LHC, could provide important information on the size and shape of gluon TMDs, as well as on other fundamental properties such as their process and energy scale dependences.

  17. A South African perspective on global imbalances

    OpenAIRE

    Marcus, G.

    2011-01-01

    Financial inflows into South African financial markets have resumed in 2009 and gained momentum in 2010, largely as a result of low interest rates and an oversupply of liquidity in advanced economies. As an emerging-market country with a current-account defi cit, South Africa is to some extent reliant on these inflows to fund its own external imbalance. However, fi nancial infl ows have exerted significant upward pressure on the exchange rate of the rand, with negative effects on the exportin...

  18. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices...

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

    International Nuclear Information System (INIS)

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

  20. Allele-specific MMP-3 transcription under in vivo conditions

    International Nuclear Information System (INIS)

    A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1β, the haplotype containing the 5A-allele was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation

  1. In vitro and ex vivo analysis of CHRNA3 and CHRNA5 haplotype expression.

    Directory of Open Access Journals (Sweden)

    Glenn A Doyle

    Full Text Available Genome-wide association studies implicate variations in CHRNA5 and CHRNA3 as being associated with nicotine addiction (NA. Multiple common haplotypes ("risk", "mixed" and "protective" exist in Europeans; however, high linkage disequilibrium between variations in CHRNA5 and CHRNA3 makes assigning causative allele(s for NA difficult through genotyping experiments alone. We investigated whether CHRNA5 or CHRNA3 promoter haplotypes, associated previously with NA, might influence allelic expression levels. For in vitro analyses, promoter haplotypes were sub-cloned into a luciferase reporter vector. When assessed in BE(2-C cells, luciferase expression was equivalent among CHRNA3 haplotypes, but the combination of deletion at rs3841324 and variation at rs503464 decreased CHRNA5 promoter-derived luciferase activity, possibly due to loss of an SP-1 and other site(s. Variation within the CHRNA5 5'UTR at rs55853698 and rs55781567 also altered luciferase expression in BE(2-C cells. Allelic expression imbalance (AEI from the "risk" or "protective" haplotypes was assessed in post-mortem brain tissue from individuals heterozygous at coding polymorphisms in CHRNA3 (rs1051730 or CHRNA5 (rs16969968. In most cases, equivalent allelic expression was observed; however, one individual showed CHRNA5 AEI that favored the "protective" allele and that was concordant with heterozygosity at polymorphisms ∼13.5 kb upstream of the CHRNA5 transcription start site. Putative enhancer activity from these distal promoter elements was assessed using heterologous promoter constructs. We observed no differences in promoter activity from the two distal promoter haplotypes examined, but found that the distal promoter region strongly repressed transcription. We conclude that CHRNA5 promoter variants may affect relative risk for NA in some heterozygous individuals.

  2. Allelic losses at genomic instability-associated loci in villous adenomas and adjacent colorectal cancers.

    Science.gov (United States)

    Brenner, Bruce M; Stoler, Daniel L; Rodriguez, Luz; Karpenko, Matthew J; Swede, Helen; Petrelli, Nicholas J; Anderson, Garth R

    2007-04-01

    Allelic imbalances in premalignant villous adenomas were compared with those in adjacent microdissected colorectal carcinoma that had arisen directly from the adenomas. Carcinoma-adenoma pairs were examined from 17 patients who underwent resections for colorectal cancer. In all, 28 microsatellite markers were examined, from regions of the genome where individual allelic losses have been associated with overall genomic instability in colorectal carcinomas. Microsatellite instability (MSI) was also evaluated for each marker in each tissue type. Loss of heterozygosity for multiple markers was found in 35% of adenomas and 65% of carcinomas; the average fractional allelic loss rate was 2.5 times higher in carcinomas than in adenomas. Of the 17 patients, 4 had MSI for >30% of markers in both adenoma and carcinoma, with no significant differences between the two tissues. Markers with particularly high imbalance rates in adenomas were seen on chromosomes 11, 14, and 15. These findings provide further evidence that genomic instability is an ongoing process during carcinogenesis, with a markedly increased frequency of allelic losses seen in carcinomas, compared with adjacent adenomas. Markers on chromosomes 11, 14, and 15 may become valuable tools in the identification of patients destined to progress to colorectal carcinomas. PMID:17350461

  3. An imperative to monitor Earth's energy imbalance

    Science.gov (United States)

    von Schuckmann, K.; Palmer, M. D.; Trenberth, K. E.; Cazenave, A.; Chambers, D.; Champollion, N.; Hansen, J.; Josey, S. A.; Loeb, N.; Mathieu, P.-P.; Meyssignac, B.; Wild, M.

    2016-02-01

    The current Earth's energy imbalance (EEI) is mostly caused by human activity, and is driving global warming. The absolute value of EEI represents the most fundamental metric defining the status of global climate change, and will be more useful than using global surface temperature. EEI can best be estimated from changes in ocean heat content, complemented by radiation measurements from space. Sustained observations from the Argo array of autonomous profiling floats and further development of the ocean observing system to sample the deep ocean, marginal seas and sea ice regions are crucial to refining future estimates of EEI. Combining multiple measurements in an optimal way holds considerable promise for estimating EEI and thus assessing the status of global climate change, improving climate syntheses and models, and testing the effectiveness of mitigation actions. Progress can be achieved with a concerted international effort.

  4. iASeq: integrative analysis of allele-specificity of protein-DNA interactions in multiple ChIP-seq datasets

    Directory of Open Access Journals (Sweden)

    Wei Yingying

    2012-11-01

    Full Text Available Abstract Background ChIP-seq provides new opportunities to study allele-specific protein-DNA binding (ASB. However, detecting allelic imbalance from a single ChIP-seq dataset often has low statistical power since only sequence reads mapped to heterozygote SNPs are informative for discriminating two alleles. Results We develop a new method iASeq to address this issue by jointly analyzing multiple ChIP-seq datasets. iASeq uses a Bayesian hierarchical mixture model to learn correlation patterns of allele-specificity among multiple proteins. Using the discovered correlation patterns, the model allows one to borrow information across datasets to improve detection of allelic imbalance. Application of iASeq to 77 ChIP-seq samples from 40 ENCODE datasets and 1 genomic DNA sample in GM12878 cells reveals that allele-specificity of multiple proteins are highly correlated, and demonstrates the ability of iASeq to improve allelic inference compared to analyzing each individual dataset separately. Conclusions iASeq illustrates the value of integrating multiple datasets in the allele-specificity inference and offers a new tool to better analyze ASB.

  5. The effect of load imbalances on the performance of Monte Carlo algorithms in LWR analysis

    International Nuclear Information System (INIS)

    A model is developed to predict the impact of particle load imbalances on the performance of domain-decomposed Monte Carlo neutron transport algorithms. Expressions for upper bound performance “penalties” are derived in terms of simple machine characteristics, material characterizations and initial particle distributions. The hope is that these relations can be used to evaluate tradeoffs among different memory decomposition strategies in next generation Monte Carlo codes, and perhaps as a metric for triggering particle redistribution in production codes

  6. An Analysis of Load Imbalance in Scale-out Data Serving

    OpenAIRE

    Novakovic, Stanko; Daglis, Alexandros; Bugnion, Edouard; Falsafi, Babak; Grot, Boris

    2016-01-01

    Despite the natural parallelism across lookups, performance of distributed key-value stores is often limited due to load imbalance induced by heavy skew in the popularity distribution of the dataset. To avoid violating service level objectives expressed in terms of tail latency, systems tend to keep server utilization low and organize the data in micro-shards, which in turn provides units of migration and replication for the purpose of load balancing. These techniques reduce the skew, but inc...

  7. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  8. Golden Jubilee Photos: A Universal Imbalance

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ View along the NA48 beamline with the detector in the distance. No one is sure why the Universe wound up the way it has: all matter and no antimatter. According to prevailing theories, the early universe had equal amounts of matter and antimatter. However, whenever such opposites meet, they annihilate and become a burst of energy. This would seem to leave the Universe with neither matter nor antimatter - and thus no stars, planets, or physicists. If nature shows a bias for matter over antimatter, this could explain why the Universe is all matter. To see what might be missing from the theories, physicists search for the rare cases in which matter and antimatter behave differently. One such imbalance, called direct CP violation, showed up in the NA 31 experiment at CERN. The results from this experiment, first presented in 1993, showed that when K mesons and their antimatter cousins decay, they show a slight preference for matter over antimatter. Later experiments with neutral K mes...

  9. 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

  10. 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...

  11. CD4+T细胞亚群表达失衡在妊娠期哮喘发病中的作用及意义%Role and significance of the CD4+T cells subsets' expressing imbalance in the pathogenesis of gestation asthma

    Institute of Scientific and Technical Information of China (English)

    马佳佳; Nick Lu; 陈必良

    2012-01-01

    目的:观察妊娠期哮喘小鼠模型中Th17及Treg细胞活性分布和表达变化,探讨Th17/Treg细胞免疫平衡在妊娠期哮喘小鼠发病中的作用机制.方法:24只6~8周龄,雌性BALB/c小鼠随机分为4组,每组6只.以OVA/Al (OH)3混悬液致敏与激发构建妊娠期哮喘组(AP组)和非妊娠期哮喘组(ANP组)小鼠模型;健康妊娠组(HP组)和健康非妊娠组(HNP组)小鼠致敏与激发均以只含Al(OH)3的生理盐水混悬液替代.光镜下观察小鼠支气管肺泡灌洗液(BALF)中细胞计数及分类;HE染色评价小鼠气道炎症程度及肺组织病理学变化;流式细胞术测定小鼠外周血Th17及Treg细胞所占CD4+T细胞比例,计算Th17/Treg细胞比值;RT-PCR检测小鼠肺组织中Th17及Treg细胞相关因子表达.结果:妊娠期哮喘小鼠BALF中炎症细胞分类及计数、肺组织病理学表现和活体肺功能气道高反应性Penh值等客观指标证实,妊娠哮喘小鼠模型构建成功.外周血中,AP组CD4+IL-17+T细胞(Th17)显著升高(P<0.01);Foxp3+T细胞( Treg)显著降低(P<0.01);与HP,HNP组相比,存在Th17/Treg比例失衡(P<0.01).AP组小鼠肺组织中IL-17、IL-23,IL-10 mRNA表达水平均显著高于HP组及HNP组(P<0.01);IFN-γ mRNA则显著低于HP组及HNP组(P<0.01);ANP组各因子mRNA水平变化与AP组一致,组间无显著差异.结论:妊娠期哮喘小鼠存在细胞免疫功能失调;Th17、Treg细胞数量及免疫平衡状态发生改变,可能是妊娠期哮喘发病过程中一个重要的决定因素.%Objective:To observe the activity distribution of Thl7 and Treg cells and expression changes in mouse model of pregnancy asthma, and to study the role of Thl7/Treg cell's immune imbalance in the pathogenesis of asthma during pregnancy. Methods: 24 female BALB/c mice,6 ~8w old,were randomly divided into 4 groups(n= 6). Ovalbumin (OVA) was used to sensitize, challenge and construct the asthma during pregnancy group ( AP group

  12. 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.

  13. 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.

  14. 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.

  15. Differentially methylated obligatory epialleles modulate context-dependent LAM gene expression in the honeybee Apis mellifera.

    Science.gov (United States)

    Wedd, Laura; Kucharski, Robert; Maleszka, Ryszard

    2016-01-01

    Differential intragenic methylation in social insects has been hailed as a prime mover of environmentally driven organismal plasticity and even as evidence for genomic imprinting. However, very little experimental work has been done to test these ideas and to prove the validity of such claims. Here we analyze in detail differentially methylated obligatory epialleles of a conserved gene encoding lysosomal α-mannosidase (AmLAM) in the honeybee. We combined genotyping of progenies derived from colonies founded by single drone inseminated queens, ultra-deep allele-specific bisulfite DNA sequencing, and gene expression to reveal how sequence variants, DNA methylation, and transcription interrelate. We show that both methylated and non-methylated states of AmLAM follow Mendelian inheritance patterns and are strongly influenced by polymorphic changes in DNA. Increased methylation of a given allele correlates with higher levels of context-dependent AmLAM expression and appears to affect the transcription of an antisense long noncoding RNA. No evidence of allelic imbalance or imprinting involved in this process has been found. Our data suggest that by generating alternate methylation states that affect gene expression, sequence variants provide organisms with a high level of epigenetic flexibility that can be used to select appropriate responses in various contexts. This study represents the first effort to integrate DNA sequence variants, gene expression, and methylation in a social insect to advance our understanding of their relationships in the context of causality. PMID:26507253

  16. An Analysis of Public Service Structural Imbalances in Rural China

    Institute of Scientific and Technical Information of China (English)

    林万龙

    2008-01-01

    Rectifying the structural imbalance between the provision of and demand for rural public services can effectively boost the efficiency of public funds utilization and the level of public service provision. Based on the findings of a field survey, this article presents a summary of the structural imbalance between the provision of and demand for rural public services. This paper holds that the structural imbalance is primarily reflected in the dislocation between provision and demand, the unsuitable mode of provision, the monolithic provision mechanism, the excessive focus on construction at the expense of governance and the overemphasis of counties and townships at the cost of villages. Such structural imbalance is principally because of the limited financial strength of government at the grass-roots level due to treasury centralization and the over-dependence of public services on special funds allocated by government at or above provincial level.

  17. On the Sign-imbalance of Permutation Tableaux

    OpenAIRE

    Chen, Joanna N.; Zhou, Robin D. P.

    2016-01-01

    Permutation tableaux were introduced by Steingr\\'{\\i}msson and Williams. Corteel and Kim defined the sign of a permutation tableau in terms of the number of unrestricted columns. The sign-imbalance of permutation tableaux of length $n$ is the sum of signs over permutation tableaux of length $n$. They have btained a formula for the sign-imbalance of permutation tableaux of length $n$ by using generating functions and asked for a combinatorial proof. Moreover, they raised the question of findin...

  18. Fitness Effects of Replichore Imbalance in Salmonella enterica▿

    OpenAIRE

    Matthews, T. David; Maloy, Stanley

    2010-01-01

    A fitness cost due to imbalanced replichores has been proposed to provoke chromosome rearrangements in Salmonella enterica serovars. To determine the impact of replichore imbalance on fitness, the relative fitness of isogenic Salmonella strains containing transposon-held duplications of various sizes and at various chromosomal locations was determined. Although duplication of certain genes influenced fitness, a replichore imbalance of up to 16° did not affect fitness.

  19. Re-balancing act : global imbalances in a changing world

    OpenAIRE

    Jane Sneddon Little

    2006-01-01

    The world has been confronting unusually large current account imbalances for so long now that international policy makers have almost stopped warning that these represent a major risk to the world economic outlook. This essay featured in the 2006 annual report summarizes presentations and discussion at the 51st economic conference of the Federal Reserve Bank of Boston, “Global Imbalances - As Giants Evolve,” which was held in June 2006.

  20. MIMO OFDM receivers for systems with IQ imbalances

    OpenAIRE

    Tarighat, Alireza; Sayed, A.H.

    2005-01-01

    Orthogonal frequency division multiplexing (OFDM) is a widely recognized modulation scheme for high data rate communications. However, the implementation of OFDM-based systems suffers from in-phase and quadrature-phase (IQ) imbalances in the front-end analog processing. Such imbalances are caused by the analog processing of the received radio frequency (RF) signal, and they cannot be efficiently or entirely eliminated in the analog domain. The resulting IQ distortion limits the achievable ope...

  1. Semi-Blind Cancellation of IQ-Imbalances

    OpenAIRE

    Hesse, Matthias; Mailand, Marko; Jentschel, Hans-Joachim; Deneire, Luc; Lebrun, Jerome

    2008-01-01

    The technical realization of modern wireless receivers yields significant interfering IQ-imbalances, which have to be compensated digitally. To cancel these IQ-imbalances, we propose an algorithm using iterative blind source separation (IBSS) as well as information about the modulation scheme used (hence the term semi-blind). The novelty of our approach lies in the fact that we match the nonlinearity involved in the IBSS algorithm to the probability density function of the source signals. Mor...

  2. Cell surface expression level variation between two common Human Leukocyte Antigen alleles, HLA-A2 and HLA-B8, is dependent on the structure of the C terminal part of the alpha 2 and the alpha 3 domains

    DEFF Research Database (Denmark)

    Dellgren, Christoffer; Nehlin, Jan O; Barington, Torben

    2015-01-01

    . Moreover, recent observations suggest that even minor differences in expression levels may influence the course of viral infections and the frequency of complications to stem cell transplantation. We have shown that some human multipotent stem cells have high expression of HLA-A while HLA-B is only weakly......Constitutive cell surface expression of Human Leukocyte Antigen (HLA) class I antigens vary extremely from tissue to tissue and individual antigens may differ widely in expression levels. Down-regulation of class I expression is a known immune evasive mechanism used by cancer cells and viruses...... expressed, and demonstrate here that this is also the case for the human embryonic kidney cell line HEK293T. Using quantitative flow cytometry and quantitative polymerase chain reaction we found expression levels of endogenous HLA-A3 (median 71,204 molecules per cell) 9.2-fold higher than the expression of...

  3. Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.

    Science.gov (United States)

    Mohamedali, Azim; Gäken, Joop; Twine, Natalie A; Ingram, Wendy; Westwood, Nigel; Lea, Nicholas C; Hayden, Janet; Donaldson, Nora; Aul, Carlo; Gattermann, Norbert; Giagounidis, Aristotle; Germing, Ulrich; List, Alan F; Mufti, Ghulam J

    2007-11-01

    Low-risk myelodysplastic syndrome (MDS) with normal cytogenetics accounts for approximately 50% of MDS patients. There are no pathognomonic markers in these cases and the diagnosis rests on cytomorphologic abnormalities in bone marrow and/or peripheral blood. Affymetrix high-resolution single-nucleotide polymorphism (SNP) genotyping microarrays allow detection of cytogenetically cryptic genomic aberrations. We have studied 119 low-risk MDS patients (refractory anemia [RA] = 22; refractory cytopenia with multilineage dysplasia [RCMD] = 51; refractory anemia with ringed sideroblasts [RARS] = 12; refractory cytopenia with multilineage dysplasia with ringed sideroblasts [RCMD-RS] = 12; 5q- syndrome = 16; refractory anemia with excess blasts [RAEB] = 6) using SNP microarrays to seek chromosomal markers undetected by conventional cytogenetics. Loss of heterozygosity (LOH) detected by 50K arrays was verified using 250K and 500K arrays. We demonstrate the presence of uniparental disomy (UPD) in 46%, deletions in 10%, and amplifications in 8% of cases. Copy number (CN) changes were acquired, whereas UPDs were also detected in constitutional DNA. UPD on 4q was identified in 25% of RARS, 12% of RCMD with normal cytogenetics, 17% of RAEB, and 6% of 5q- syndrome cases. Univariate analysis showed deletions (P = .04) and International Prognostic Scoring System (IPSS; P < .001) scores correlated with overall survival; however, on multivariate analysis only IPSS scores retained prognostic significance (P < .001). We show, for the first time, that SNP microarray analysis in low-risk MDS patients reveals hitherto unrecognized UPD and CN changes that may allow stratification of these patients for early therapeutic interventions. PMID:17634407

  4. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

    Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

  5. RHD allele distribution in Africans of Mali

    Directory of Open Access Journals (Sweden)

    Moulds Joann M

    2003-09-01

    Full Text Available Abstract Background Aberrant and non-functional RHD alleles are much more frequent in Africans than in Europeans. The DAU cluster of RHD alleles exemplifies that the alleles frequent in Africans have evaded recognition until recently. A comprehensive survey of RHD alleles in any African population was lacking. Results We surveyed the molecular structure and frequency of RHD alleles in Mali (West Africa by evaluating 116 haplotypes. Only 69% could be attributed to standard RHD (55% or the RHD deletion (14%. The aberrant RHD allele DAU-0 was predicted for 19%, RHDΨ for 7% and Ccdes for 4% of all haplotypes. DAU-3 and the new RHD allele RHD(L207F, dubbed DMA, were found in one haplotype each. A PCR-RFLP for the detection of the hybrid Rhesus box diagnostic for the RHD deletion in Europeans was false positive in 9 individuals, including all carriers of RHDΨ . Including two silent mutations and the RHD deletion, a total of 9 alleles could be differentiated. Conclusion Besides standard RHD and the RHD deletion, DAU-0, RHDΨ and Ccdes are major alleles in Mali. Our survey proved that the most frequent alleles of West Africans have been recognized allowing to devise reliable genotyping and phenotyping strategies.

  6. Imbalance in treatment assignments in stratified blocked randomization.

    Science.gov (United States)

    Hallstrom, A; Davis, K

    1988-12-01

    Blocking and stratification are used in preparing randomization assignments to ensure that there will be nearly equal numbers of patients in each treatment group and that the groups will be similar with respect to important covariates. Stratified blocked randomization will create near balance within strata, but imbalance for the total trial may still occur. The variance for the total trial imbalance D is derived and examples from clinical trials are given. Under reasonable assumptions, if the blocking factor is size B in each of K strata, then max D = KB/2 and var D = K(B + 1)/6. These results may be used in planning a trial to estimate the overall imbalance expected for various choices of B and K. A conditional variance is given that allows the probability of an observed imbalance at the completion of a trial to be evaluated. Overall imbalance is about as likely with stratified blocked randomization as with simple randomization unless the total sample size N is appreciably larger than K X B. So long as the blinding is maintained, the block sizes should be chosen to be as small as possible. PMID:3203527

  7. An identification of active power imbalance using wavelet transform

    Energy Technology Data Exchange (ETDEWEB)

    Avdakovic, S.; Music, M. [Public Enterprise Elektroprivreda of Bosnia and Herzegovina, Sarajevo (Bosnia and Herzegowina). Dept. for Development; Nuhanovic, A.; Kusljugic, M. [Tuzla Univ., Tuzla (Bosnia and Herzegowina). Faculty of Electrical Engineering, Dept. of Power Systems Analysis

    2009-07-01

    Wavelet transformations were used to identify and estimate an active power imbalance as part of a wide area monitoring protection and control (WAMPC) system. A quantitative analysis of the effect of a small load change was presented in order to demonstrate the method. The study showed that the impact of a sudden active power imbalance was shared among generators during power system responses according to various criteria before arriving at a new steady state condition. The impact was followed by oscillatory power swings. The qualitative analysis demonstrated that immediately after the onset of the power imbalance, machines shared the impact according to their electric proximity to the point of impact. After a transient period, the machines shared the same impact according to different criteria. Wavelet transform was then used to estimate the frequency of the center of inertia as well as the impact of the imbalance on the machines. A 2-area test system was simulated in order to demonstrate the method. It was concluded that wavelet transform can be used to accurately detect and estimate active power imbalances. 9 refs., 4 tabs., 7 figs.

  8. Human monoclonal antibodies as a tool for the detection of HLA class I allele-specific expression loss in head-and-neck squamous cell carcinoma and corresponding lymph node metastases

    NARCIS (Netherlands)

    Koene, Geert; Mulder, Arend; van der Ven, Kevin; Eijsink, Chantal; Franke, Marry; Slootweg, Piet; Claas, Frans; Tilanus, Marcel

    2006-01-01

    Human leukocyte antigen (HLA) expression is important for the elimination of tumor cells by the immune system and immunotherapy. Activated T cells directed against tumor-associated antigens are fully capable of recognizing and eradicating neoplastic cells. Therefore, HLA expression loss is considere

  9. Adjustment of Global Imbalances and Its Impact on China's Economy

    Institute of Scientific and Technical Information of China (English)

    Jianhuai Shi

    2006-01-01

    The present paper discusses ways of adjusting the imbalances of the global economy and its impact on China's economy. The analysis in the paper shows that the cut of US fiscal deficits and the appreciation of the currencies of East Asia, including China ' s RMB, are necessary for a smooth adjustment of the global imbalances. The adjustments will have a positive impact on China's economy and will help China realize its external balance. The increase in public spending on the service sector along with the appreciation of RMB will help China realize the internal balance too. The adjustment of the global imbalances will create opportunities and an external pushing force for China in its industrial restructuring and shift in the model of economic growth.

  10. How gender disparities drive imbalances in health care leadership

    Directory of Open Access Journals (Sweden)

    Hoss MAK

    2011-11-01

    Full Text Available Mary Ann Keogh Hoss1, Paula Bobrowski2, Kathryn J McDonagh3, Nancy M Paris41Health Services Administration, Eastern Washington University, College of Business and Public Administration, Spokane, WA, USA; 2College of Liberal Arts, Auburn University, Auburn, AL, USA; 3Executive Relations, Hospira Inc, Lake Forest, IL, USA; 4Georgia Center for Oncology Research and Education, Atlanta, GA, USAAbstract: Low female representation in US hospital chief executive officer positions has persisted for decades. This article addresses gender disparity in professional development, the rationale for gender differences, and practical strategies to address this imbalance. The health care workforce consists of 75% women, but according to two recent surveys, ie, a state survey and a survey of the top 100 US hospitals, women hold only about 12% of chief executive officer positions in US hospitals. Significant and dedicated efforts by both individuals and organizations are necessary to rectify this imbalance.Keywords: gender, imbalance, leadership, United States, hospitals

  11. A method of detecting and locating electrical current imbalances

    Science.gov (United States)

    Patterson, Richard L.

    1993-01-01

    A method of detecting and locating current imbalances such as ground faults in multiwire systems using the Faraday effect is described. As an example, for 2-wire or 3-wire (1 ground wire) electrical systems, light is transmitted along an optical path which is exposed to magnetic fields produced by currents flowing in the hot and neutral wires. The rotations produced by these two magnetic fields cancel each other, therefore light on the optical path does not read the effect of either. However, when a ground fault occurs, the optical path is exposed to a net Faraday effect rotation due to the current imbalance thereby exposing the ground fault.

  12. In-phase and quadrature imbalance modeling, estimation, and compensation

    CERN Document Server

    Li, Yabo

    2013-01-01

    This book provides a unified IQ imbalance model and systematically reviews the existing estimation and compensation schemes. It covers the different assumptions and approaches that lead to many models of IQ imbalance. In wireless communication systems, the In-phase and Quadrature (IQ) modulator and demodulator are usually used as transmitter (TX) and receiver (RX), respectively. For Digital-to-Analog Converter (DAC) and Analog-to-Digital Converter (ADC) limited systems, such as multi-giga-hertz bandwidth millimeter-wave systems, using analog modulator and demodulator is still a low power and l

  13. 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...

  14. Natural Host Genetic Resistance to Lentiviral CNS Disease: A Neuroprotective MHC Class I Allele in SIV-Infected Macaques

    OpenAIRE

    Mankowski, Joseph L.; Queen, Suzanne E.; Fernandez, Caroline S.; Tarwater, Patrick M.; Karper, Jami M.; Adams, Robert J.; Kent, Stephen J.

    2008-01-01

    Human immunodeficiency virus (HIV) infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS) have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and develop...

  15. Allele-mining and natural diversity in wheat powdery mildew resistance genes

    International Nuclear Information System (INIS)

    Using map-based cloning, we have isolated the Pm3b powdery mildew resistance gene from hexaploid bread wheat (Triticum aestivum L.). Based on haplotype studies, we have developed molecular tools to isolate all the 10 known Pm3 genes conferring resistance. We found that the Pm3 genes form a true allelic series and that they are highly conserved at the molecular level. The molecular work on Pm3 resistance genes has lead to very diagnostic tools for these genes which support the cloning of new functional alleles from this locus by allele-mining. We have used these tools to screen for new Pm3 alleles in the gene pools of (i) wild and domesticated tetraploid accessions and (ii) hexaploid wheat landraces. The Pm3 locus is conserved in tetraploid wheat, allowing a comparative evolutionary study of the same resistance locus in a domesticated species and one of its wild ancestors. We have identified 61 Pm3 allelic sequences from wild and domesticated tetraploid wheat subspecies. These alleles showed low sequence diversity, differing by few polymorphic sequence blocks that were further reshuffled between alleles by gene conversion and recombination. A new functional gene was identified in a wild wheat accession from Syria. This gene, Pm3k, conferred intermediate resistance to powdery mildew and consists of a mosaic of gene segments derived from non-functional alleles. From the hexaploid wheat gene pool, a set of 1320 landraces, mostly from Asia, was screened for powdery mildew resistance and the presence of a Pm3 haplotype. Most of these lines were found to contain a susceptible Pm3 allele which is closely related to the functional Pm3 resistance genes. We have also identified resistant lines with new types of Pm3 allelic sequences, resulting from point mutations, gene conversion and illegitimate recombination events. These new alleles are currently tested for resistance activity in a transient expression assay. (author)

  16. Flux imbalance analysis and the sensitivity of cellular growth to changes in metabolite pools.

    Directory of Open Access Journals (Sweden)

    Ed Reznik

    Full Text Available Stoichiometric models of metabolism, such as flux balance analysis (FBA, are classically applied to predicting steady state rates - or fluxes - of metabolic reactions in genome-scale metabolic networks. Here we revisit the central assumption of FBA, i.e. that intracellular metabolites are at steady state, and show that deviations from flux balance (i.e. flux imbalances are informative of some features of in vivo metabolite concentrations. Mathematically, the sensitivity of FBA to these flux imbalances is captured by a native feature of linear optimization, the dual problem, and its corresponding variables, known as shadow prices. First, using recently published data on chemostat growth of Saccharomyces cerevisae under different nutrient limitations, we show that shadow prices anticorrelate with experimentally measured degrees of growth limitation of intracellular metabolites. We next hypothesize that metabolites which are limiting for growth (and thus have very negative shadow price cannot vary dramatically in an uncontrolled way, and must respond rapidly to perturbations. Using a collection of published datasets monitoring the time-dependent metabolomic response of Escherichia coli to carbon and nitrogen perturbations, we test this hypothesis and find that metabolites with negative shadow price indeed show lower temporal variation following a perturbation than metabolites with zero shadow price. Finally, we illustrate the broader applicability of flux imbalance analysis to other constraint-based methods. In particular, we explore the biological significance of shadow prices in a constraint-based method for integrating gene expression data with a stoichiometric model. In this case, shadow prices point to metabolites that should rise or drop in concentration in order to increase consistency between flux predictions and gene expression data. In general, these results suggest that the sensitivity of metabolic optima to violations of the steady

  17. Enhancement of allele discrimination by introduction of nucleotide mismatches into siRNA in allele-specific gene silencing by RNAi.

    Directory of Open Access Journals (Sweden)

    Yusuke Ohnishi

    Full Text Available Allele-specific gene silencing by RNA interference (RNAi is therapeutically useful for specifically inhibiting the expression of disease-associated alleles without suppressing the expression of corresponding wild-type alleles. To realize such allele-specific RNAi (ASP-RNAi, the design and assessment of small interfering RNA (siRNA duplexes conferring ASP-RNAi is vital; however, it is also difficult. In a previous study, we developed an assay system to assess ASP-RNAi with mutant and wild-type reporter alleles encoding the Photinus and Renilla luciferase genes. In line with experiments using the system, we realized that it is necessary and important to enhance allele discrimination between mutant and corresponding wild-type alleles. Here, we describe the improvement of ASP-RNAi against mutant alleles carrying single nucleotide variations by introducing base substitutions into siRNA sequences, where original variations are present in the central position. Artificially mismatched siRNAs or short-hairpin RNAs (shRNAs against mutant alleles of the human Prion Protein (PRNP gene, which appear to be associated with susceptibility to prion diseases, were examined using this assessment system. The data indicates that introduction of a one-base mismatch into the siRNAs and shRNAs was able to enhance discrimination between the mutant and wild-type alleles. Interestingly, the introduced mismatches that conferred marked improvement in ASP-RNAi, appeared to be largely present in the guide siRNA elements, corresponding to the 'seed region' of microRNAs. Due to the essential role of the 'seed region' of microRNAs in their association with target RNAs, it is conceivable that disruption of the base-pairing interactions in the corresponding seed region, as well as the central position (involved in cleavage of target RNAs, of guide siRNA elements could influence allele discrimination. In addition, we also suggest that nucleotide mismatches at the 3'-ends of sense

  18. Balance Responsibility and Imbalance Settlement in Northern Europe: An Evaluation

    NARCIS (Netherlands)

    Van der Veen, R.A.C.; Hakvoort, R.A.

    2009-01-01

    In liberalized power markets, balance responsibility and imbalance settlement are two closely related elements that constitute the heart of a balancing market (which is actually an institutional arrangement establishing market-based balancing). This paper aims to compare balance responsibility and i

  19. Global Imbalance:Onus On the United States

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    During the China-U.S. Business Forum held in Beijing February 14-15, Xia Bin, Director of the Financial Research Institute of the Development Research Center under the State Council, makes a speech on the United States' responsibility for global economic imbalances. His main ideas as reported in the China Business News, follow:

  20. On cuff imbalance and tripolar ENG amplifier configurations.

    Science.gov (United States)

    Triantis, Iasonas F; Demosthenous, Andreas; Donaldson, Nick

    2005-02-01

    Electroneurogram (ENG) recording techniques benefit from the use of tripolar cuffs because they assist in reducing interference from sources outside the cuff. However, in practice the performance of ENG amplifier configurations, such as the quasi-tripole and the true-tripole, has been widely reported to be degraded due to the departure of the tripolar cuff from ideal behavior. This paper establishes the presence of cuff imbalance and investigates its relationship to cuff asymmetry, cuff end-effects and interference source proximity. The paper also presents a comparison of the aforementioned amplifier configurations with a new alternative, termed the adaptive-tripole, developed to automatically compensate for cuff imbalance. The output signal-to-interference ratio of the three amplifier configurations were compared in vivo for two interference signals (stimulus artifact and M-wave) superimposed on compound action potentials. The experiments showed (for the first time) that the two interference signals result in different cuff imbalance values. Nevertheless, even with two distinct cuff imbalances present, the adaptive-tripole performed better than the other two systems in 61.9% of the trials. PMID:15709669

  1. Obesity does not Lead to Imbalance Between Myocardial Phospholamban Phosphorylation and Dephosphorylation

    Directory of Open Access Journals (Sweden)

    Paula Paccielli Freire

    2014-07-01

    Full Text Available Background: The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP, alters the structure of protein kinase A (PKA and leads to phospholamban (PLB phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA. Objective: To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation. Methods: Male Wistar rats were randomly distributed into two groups: control (n = 14, fed with normocaloric diet; and obese (n = 13, fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP-1, PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16 were assessed by Western blot. Results: Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16. Conclusion: Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system.

  2. Obesity does not Lead to Imbalance Between Myocardial Phospholamban Phosphorylation and Dephosphorylation

    International Nuclear Information System (INIS)

    The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA. To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation. Male Wistar rats were randomly distributed into two groups: control (n = 14), fed with normocaloric diet; and obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP-1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed by Western blot. Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16. Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system

  3. Obesity does not Lead to Imbalance Between Myocardial Phospholamban Phosphorylation and Dephosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Freire, Paula Paccielli, E-mail: freirepp@hotmail.com; Alves, Carlos Augusto Barnabe; Deus, Adriana Fernandes de [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade Estadual Paulista, Botucatu, SP (Brazil); Leopoldo, Ana Paula Lima; Leopoldo, André Soares [Centro de Educação Física e Desportos - Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Silva, Danielle Cristina Tomaz da; Tomasi, Loreta Casquel de; Campos, Dijon Henrique Salomé; Cicogna, Antonio Carlos [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade Estadual Paulista, Botucatu, SP (Brazil)

    2014-07-15

    The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA. To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation. Male Wistar rats were randomly distributed into two groups: control (n = 14), fed with normocaloric diet; and obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP-1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed by Western blot. Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16. Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system.

  4. Allele frequencies and segregation of human polymorphic keratins K4 and K5.

    OpenAIRE

    Mischke, D; Wille, G; Wild, A G

    1990-01-01

    Two electrophoretic variants for each of the human keratins K4 and K5 that are expressed in squamous nonkeratinizing epithelia lining the upper digestive tract could be distinguished on SDS-PAGE. Based on a sampling size of 1,299 unrelated individuals, calculation of allele frequencies showed the alleles to be in Hardy-Weinberg equilibrium. The genetic basis of this variation was confirmed by both quantitative gene dosage dependence and the transmission of the variants as Mendelian traits in ...

  5. Water and Carbon as Creators of Imbalances in Nature

    Science.gov (United States)

    Shlafman, L. M.; Kontar, V. A.

    2012-12-01

    Our studies are showing that the carbon and water are closely intertwined. There are many reasons to study the imbalance of water and carbon together. For example, in photosynthesis six molecules of water and six molecules of carbon dioxide have created one molecule of sugar and six molecules of oxygen. 6H2O + 6CO2 go C6H12O6 + 6O2 For water and carbon dioxide, regarding the point of view of the imbalance, this process is the creator of imbalance of the decreasing type. The concentration of water and carbon dioxide in the atmosphere will decrease. For oxygen this process is the creator of imbalance of the increasing type. The concentration of oxygen in the atmosphere will increase. Water and carbon dioxide can be created independently of each other. For example, water is obtained from combining two hydrogen atoms and one oxygen atom: 2 H2 + O2 go 2 H2O Carbon dioxide also is possible to create without water: Na2CO3 go Na2O + CO2 or CaCO3 go CaO + CO2 But it is very often the water and carbon dioxide made up simultaneously in one reaction. For example combustion of methane gives carbon dioxide and water: CH4 + 2 O2 go CO2 + 2 H2O Carbon dioxide can come up more complicated way. Initially created carbon monoxide and water 2 CH4 + 3 O2 go 2 CO + 4 H2O After then the carbon monoxide rapidly oxidized to carbon dioxide. The gasification of solid fuels is the reaction: C + H20 go CO + H2 In the next step carbon monoxide is oxidized to carbon dioxide, and hydrogen is oxidized to water. C3H8 + 5 O2 go 3 CO2 + 4 H2O By the incomplete combustion of propane will be produced some very interesting components: 2 C3H8 + 7 O2 go 8 H2O + 2 CO2 + 2 CO + 2 C It will be water, carbon dioxide, carbon monoxide and pure carbon. Carbon monoxide will oxidize to carbon dioxide. But the pure carbon will have a very serious going on. By the incomplete combustion of not only propane, but other hydrocarbons, will be produced and the pure carbon also. This "pure carbon" or "black carbon" plays a

  6. The A Allele of the rs1990760 Polymorphism in the IFIH1 Gene Is Associated with Protection for Arterial Hypertension in Type 1 Diabetic Patients and with Expression of This Gene in Human Mononuclear Cells

    OpenAIRE

    Bouças, Ana P.; Brondani, Letícia A.; Souza, Bianca M.; Lemos, Natália E.; Oliveira, Fernanda S.; Canani, Luis H; Crispim, Daisy

    2013-01-01

    Background The rs1990760 polymorphism of interferon induced with helicase C domain 1 (IFIH1) has been associated with type 1 diabetes mellitus (T1DM). Here, we investigated whether this polymorphism is associated with T1DM or its clinical characteristics in a Brazilian population, and if IFIH1 gene expression in mononuclear cells from T1DM patients differs according to the genotypes of this polymorphism. A meta-analysis was also conducted to evaluate if the rs1990760 polymorphism is associate...

  7. Does Protease-Antiprotease Imbalance Explain Chronic Obstructive Pulmonary Disease?

    Science.gov (United States)

    Lomas, David A

    2016-04-01

    Chronic obstructive pulmonary disease (COPD) is defined as airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with the inhalation of noxious gases, typically cigarette smoke. The protease-antiprotease paradigm suggests that the pathogenesis of COPD and emphysema is the result of an imbalance between enzymes that degrade the extracellular matrix within the lung and proteins that oppose this proteolytic activity. This review assesses the genetic evidence in support of protease-antiprotease imbalance in the pathogenesis of COPD. It also articulates why suppression of protease activity in alpha-1 antitrypsin deficiency may be insufficient to prevent the progression of COPD. Rather, alpha-1 antitrypsin deficiency may be better treated by small-molecules so reads molecules, RNA-silencing, and other strategies that target the protein misfolding and polymerization that cause the disease. PMID:27115947

  8. Spinal pedicle subtraction osteotomy for fixed sagittal imbalance patients

    Science.gov (United States)

    Hyun, Seung-Jae; Kim, Yongjung J; Rhim, Seung-Chul

    2013-01-01

    In addressing spinal sagittal imbalance through a posterior approach, the surgeon now may choose from among a variety of osteotomy techniques. Posterior column osteotomies such as the facetectomy or Ponte or Smith-Petersen osteotomy provide the least correction, but can be used at multiple levels with minimal blood loss and a lower operative risk. Pedicle subtraction osteotomies provide nearly 3 times the per-level correction of Ponte/Smith-Petersen osteotomies; however, they carry increased technical demands, longer operative time, and greater blood loss and associated significant morbidity, including neurological injury. The literature focusing on pedicle subtraction osteotomy for fixed sagittal imbalance patients is reviewed. The long-term overall outcomes, surgical tips to reduce the complications and suggestions for their proper application are also provided. PMID:24340276

  9. Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele.

    Science.gov (United States)

    Takeuchi, Hikaru; Tomita, Hiroaki; Taki, Yasuyuki; Kikuchi, Yoshie; Ono, Chiaki; Yu, Zhiqian; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

    2015-04-15

    The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence. In this study, we investigated the effect of this allele on microstructural properties of the brain and on its functional activity during externally directed attention-demanding tasks and creative performance in the 765 Asian subjects. For this purpose, we employed diffusion tensor imaging, N-back functional magnetic resonance imaging paradigms, and a test to measure creativity by divergent thinking. The 5-repeat allele was significantly associated with increased originality in the creative performance, increased mean diffusivity (the measure of how the tissue includes water molecules instead of neural and vessel components) in the widespread gray and white matter areas of extensive areas, particularly those where DRD4 is expressed, and reduced task-induced deactivation in the areas that are deactivated during the tasks in the course of both the attention-demanding working memory task and simple sensorimotor task. The observed neural characteristics of 5-repeat allele carriers may lead to an increased risk of ADHD and behavioral deficits. Furthermore, the increased originality of creative thinking observed in the 5-repeat allele carriers may support the notion of the side of adaptivity of the widespread risk allele of psychiatric diseases. PMID:25659462

  10. Global Imbalances and the Asian Economies: Implications for Regional Cooperation

    OpenAIRE

    Eichengreen, Barry

    2006-01-01

    This paper asks how Asia should prepare for the disorderly correction of global imbalances. It recommends tightening monetary policy and allowing Asian currencies to appreciate as a way of achieving a better balance between internal and external demand. Leaving the overall level of demand unchanged requires that this monetary tightening be complemented by some relaxation of fiscal policy. But because the scope for fiscal support of domestic demand differs across countries, so too does the opt...

  11. Spinal pedicle subtraction osteotomy for fixed sagittal imbalance patients

    OpenAIRE

    Hyun, Seung-Jae; Kim, Yongjung J.; Rhim, Seung-Chul

    2013-01-01

    In addressing spinal sagittal imbalance through a posterior approach, the surgeon now may choose from among a variety of osteotomy techniques. Posterior column osteotomies such as the facetectomy or Ponte or Smith-Petersen osteotomy provide the least correction, but can be used at multiple levels with minimal blood loss and a lower operative risk. Pedicle subtraction osteotomies provide nearly 3 times the per-level correction of Ponte/Smith-Petersen osteotomies; however, they carry increased ...

  12. Prediction of Defective Software Modules Using Class Imbalance Learning

    OpenAIRE

    Divya Tomar; Sonali Agarwal

    2016-01-01

    Software defect predictors are useful to maintain the high quality of software products effectively. The early prediction of defective software modules can help the software developers to allocate the available resources to deliver high quality software products. The objective of software defect prediction system is to find as many defective software modules as possible without affecting the overall performance. The learning process of a software defect predictor is difficult due to the imbal...

  13. Money and age in schools: Bullying and power imbalances.

    Science.gov (United States)

    Chaux, Enrique; Castellanos, Melisa

    2014-09-12

    School bullying continues to be a serious problem around the world. Thus, it seems crucial to clearly identify the risk factors associated with being a victim or a bully. The current study focused in particular on the role that age and socio-economic differences between classmates could play on bullying. Logistic and multilevel analyses were conducted using data from 53,316 5th and 9th grade students from a representative sample of public and private Colombian schools. Higher age and better family socio-economic conditions than classmates were risk factors associated with being a bully, while younger age and poorer socio-economic conditions than classmates were associated with being a victim of bullying. Coming from authoritarian families or violent neighborhoods, and supporting beliefs legitimizing aggression, were also associated with bullying and victimization. Empathy was negatively associated with being a bully, and in some cases positively associated with being a victim. The results highlight the need to take into account possible sources of power imbalances, such as age and socio-economic differences among classmates, when seeking to prevent bullying. In particular, interventions focused on peer group dynamics might contribute to avoid power imbalances or to prevent power imbalances from becoming power abuse. Aggr. Behav. 9999:XX-XX, 2014. © 2014 Wiley Periodicals, Inc. PMID:25219327

  14. Systemic Redox Imbalance in Chronic Kidney Disease: A Systematic Review.

    Science.gov (United States)

    Poulianiti, Konstantina P; Kaltsatou, Antonia; Mitrou, Georgia I; Jamurtas, Athanasios Z; Koutedakis, Yiannis; Maridaki, Maria; Stefanidis, Ioannis; Sakkas, Giorgos K; Karatzaferi, Christina

    2016-01-01

    Patients with chronic kidney disease (CKD) experience imbalance between oxygen reactive species (ROS) production and antioxidant defenses leading to cell and tissue damage. However, it remains unclear at which stage of renal insufficiency the redox imbalance becomes more profound. The aim of this systematic review was to provide an update on recent advances in our understanding of how the redox status changes in the progression of renal disease from predialysis stages 1 to 4 to end stage 5 and whether the various treatments and dialysis modalities influence the redox balance. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. In total, thirty-nine studies met the inclusion criteria and were reviewed. Even from an early stage, imbalance in redox status is evident and as the kidney function worsens it becomes more profound. Hemodialysis therapy per se seems to negatively influence the redox status by the elevation of lipid peroxidation markers, protein carbonylation, and impairing erythrocyte antioxidant defense. However, other dialysis modalities do not so far appear to confer advantages. Supplementation with antioxidants might assist and should be considered as an early intervention to halt premature atherogenesis development at an early stage of CKD. PMID:27563376

  15. How Many Non-coding RNAs Does It Take to Compensate Male/Female Genetic Imbalance?

    Science.gov (United States)

    Ouimette, Jean-François; Rougeulle, Claire

    2016-01-01

    Genetic sex determination in mammals relies on dimorphic sex chromosomes that confer phenotypic/physiologic differences between males and females. In this heterogametic system, X and Y chromosomes diverged from an ancestral pair of autosomes, creating a genetic disequilibrium between XX females and XY males. Dosage compensation mechanisms alleviate intrinsic gene dosage imbalance, leading to equal expression levels of most X-linked genes in the two sexes. In therian mammals, this is achieved through inactivation of one of the two X chromosomes in females. Failure to undergo X-chromosome inactivation (XCI) results in developmental arrest and death. Although fundamental for survival, a surprising loose conservation in the mechanisms to achieve XCI during development in therian lineage has been, and continues, to be uncovered. XCI involves the concerted action of non-coding RNAs (ncRNAs), including the well-known Xist RNA, and has thus become a classical paradigm to study the mode of action of this particular class of transcripts. In this chapter, we will describe the processes coping with sex chromosome genetic imbalance and how ncRNAs underlie dosage compensation mechanisms and influence male-female differences in mammals. Moreover, we will discuss how ncRNAs have been tinkered with during therian evolution to adapt XCI mechanistic to species-specific constraints. PMID:26659486

  16. Gene dosage imbalance during DNA replication controls bacterial cell-fate decision

    Science.gov (United States)

    Igoshin, Oleg

    Genes encoding proteins in a common regulatory network are frequently located close to one another on the chromosome to facilitate co-regulation or couple gene expression to growth rate. Contrasting with these observations, here we demonstrate a functional role for the arrangement of Bacillus subtilis sporulation network genes on opposite sides of the chromosome. We show that the arrangement of two sporulation network genes, one located close to the origin, the other close to the terminus leads to a transient gene dosage imbalance during chromosome replication. This imbalance is detected by the sporulation network to produce cell-cycle coordinated pulses of the sporulation master regulator Spo0A~P. This pulsed response allows cells to decide between sporulation and continued vegetative growth during each cell-cycle spent in starvation. Furthermore, changes in DNA replication and cell-cycle parameters with decreased growth rate in starvation conditions enable cells to indirectly detect starvation without the need for evaluating specific metabolites. The simplicity of the uncovered coordination mechanism and starvation sensing suggests that it may be widely applicable in a variety of gene regulatory and stress-response settings. This work is supported by National Science Foundation Grants MCB-1244135, EAGER-1450867, MCB-1244423, NIH NIGMS Grant R01 GM088428 and HHMI International Student Fellowship.

  17. Polymorphic allele of human IRGM1 is associated with susceptibility to tuberculosis in African Americans.

    Directory of Open Access Journals (Sweden)

    Katherine Y King

    Full Text Available An ancestral polymorphic allele of the human autophagy-related gene IRGM1 is associated with altered gene expression and a genetic risk for Crohn's Disease (CD. We used the single nucleotide polymorphism rs10065172C/T as a marker of this polymorphic allele and genotyped 370 African American and 177 Caucasian tuberculosis (TB cases and 180 African American and 110 Caucasian controls. Among African Americans, the TB cases were more likely to carry the CD-related T allele of rs10065172 (odds ratio of 1.54; 95% confidence interval, 1.17-2.02; P<0.01 compared to controls. Our finding suggests that this CD-related IRGM1 polymorphic allele is also associated with human susceptibility to TB disease among African Americans.

  18. ICA-based compensation for IQ imbalance in OFDM optical fiber communication

    Science.gov (United States)

    Jiang, Shan; Hu, Guijun; Li, Zhaoxi; Mu, Liping; Zhang, Jingdong

    2014-01-01

    A method based on the independent component analysis (ICA) is proposed to compensate the in-phase and quadrature-phase the (IQ) imbalance in orthogonal frequency division multiplexing (OFDM) optical fiber communication systems. The mathematical model of IQ imbalance system has been analyzed. Then, ICA algorithm is applied in the system to combat the mirror interference introduced by IQ imbalance. This algorithm can realize the joint compensation of both transmitter and receiver IQ imbalance with the optical channel that contains noise, attenuation and chromatic dispersion. The simulation shows that the performance degradation caused by IQ imbalance can be compensated by ICA algorithm effectively.

  19. 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.

  20. What is the Imbalance of Water in Nature?

    Science.gov (United States)

    Kontar, V. A.

    2011-12-01

    Look at any lake. Water comes into the lake from the atmosphere, from surface and groundwater sources. Water leaves the lake to the atmosphere, surface and underground drains, as well as for consumption by human society, wild plants and animals if they are within the boundaries of the lake's system. If quantity of water coming into the lake is equally of the quantity of water which flow from the lake, so the lake level has not changed and we have a state of equilibration or balance. The bookkeeper's book also has name "balance". But this is just a play on words. If the water is coming into the lake more than the water is coming away from lake, therefore the lake level will increase and we have a state of the imbalance of the increase type. If the water is coming into the lake less than the water is coming away from lake, therefore the lake level will decrease and we have a state of the imbalance of the decrease type. Everyone knows that the lake level rises or falls, for example during the year. Sometimes it is happened some balance. But the state of balance is rare and in of the short duration. The lake is of most the time in the conditions of the imbalance increases or the imbalance decreases type. The balance as a state of equilibrium, in the language of mathematics, is the point of the extremum between the periods of rise and fall. The balance is a special condition, which is existing very rare and a very short period of time. The people sometimes to do the great efforts for maintain the constant level of the lakes. But these facts don't change the situation. On the contrary, the human's struggle for maintain the lake in constant level just shows how difficult and expensive to go against the natural laws of Nature. When water was plentiful, these facts could be ignored. But now when the global water shortage is quickly growing, many previously ignored details are becoming crucial. There are very important to do the correct definitions of the borders and

  1. The Imbalance of Water in Nature as System

    Science.gov (United States)

    Kontar, V. A.; Imbalance of Water in Nature

    2011-12-01

    Consider some of the water-containing area. Choose some the factors which we consider important to the system. The system contains a system factors, and the external environment these factors doesn't contain. Between the system and the external environment must be some flows into the system, out of the system and along the border. If the flows into and out of the system are not equal, that means within the system exactly something is happening. But the equality of the flows into and out of the system does not mean that within the system nothing happens. It is extremely important to determine the time factor. Everything has a beginning and an end. Each factor has its own life from 0 to 1, as well as their watches. Thus that within the system and the environment at the same time are going a lot of the watches and each watch is going by their own pace. System-wide time is needed to describe the system as a whole and to be able to re-measure the individual time of each factor. It is also very important to identify each factor of the system, environment and border. Definition of each particular factor depends on the level of our knowledge. There are many examples where one factor was divided into several, and vice versa, several factors have combined in one or even disappear as a non-existent. Each factor is determined by specific people for reasons of convenience, the specific of tasks, the possible accuracy of measurement, available resources, etc. The development of the science and applications are going to the direction of the clearer separation of factors and the precision of their measurements. Now is extremely important to more clearly define the boundaries of systems, factors and the allowed accuracy of their measurements. With such a revision, many previously balanced situations become to the imbalance. There are many specific details for each case, but they do not change the basic approach described above. If not clearly resolved the questions listed above so

  2. Allele-Independent Turnover of Human Leukocyte Antigen (HLA) Class Ia Molecules.

    Science.gov (United States)

    Prevosto, Claudia; Usmani, M Farooq; McDonald, Sarah; Gumienny, Aleksandra M; Key, Tim; Goodman, Reyna S; Gaston, J S Hill; Deery, Michael J; Busch, Robert

    2016-01-01

    Major histocompatibility complex class I (MHCI) glycoproteins present cytosolic peptides to CD8+ T cells and regulate NK cell activity. Their heavy chains (HC) are expressed from up to three MHC gene loci (human leukocyte antigen [HLA]-A, -B, and -C in humans), whose extensive polymorphism maps predominantly to the antigen-binding groove, diversifying the bound peptide repertoire. Codominant expression of MHCI alleles is thus functionally critical, but how it is regulated is not fully understood. Here, we have examined the effect of polymorphism on the turnover rates of MHCI molecules in cell lines with functional MHCI peptide loading pathways and in monocyte-derived dendritic cells (MoDCs). Proteins were labeled biosynthetically with heavy water (2H2O), folded MHCI molecules immunoprecipitated, and tryptic digests analysed by mass spectrometry. MHCI-derived peptides were assigned to specific alleles and isotypes, and turnover rates quantified by 2H incorporation, after correcting for cell growth. MHCI turnover half-lives ranged from undetectable to a few hours, depending on cell type, activation state, donor, and MHCI isotype. However, in all settings, the turnover half-lives of alleles of the same isotype were similar. Thus, MHCI protein turnover rates appear to be allele-independent in normal human cells. We propose that this is an important feature enabling the normal function and codominant expression of MHCI alleles. PMID:27529174

  3. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    Directory of Open Access Journals (Sweden)

    Sulaiman S Ibrahim

    2015-10-01

    Full Text Available Scale up of Long Lasting Insecticide Nets (LLINs has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies.

  4. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    Science.gov (United States)

    Ibrahim, Sulaiman S; Riveron, Jacob M; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J I; Wondji, Charles S

    2015-10-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser) from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies. PMID:26517127

  5. Beyond the redox imbalance: Oxidative stress contributes to an impaired GLUT3 modulation in Huntington's disease.

    Science.gov (United States)

    Covarrubias-Pinto, Adriana; Moll, Pablo; Solís-Maldonado, Macarena; Acuña, Aníbal I; Riveros, Andrea; Miró, María Paz; Papic, Eduardo; Beltrán, Felipe A; Cepeda, Carlos; Concha, Ilona I; Brauchi, Sebastián; Castro, Maite A

    2015-12-01

    Failure in energy metabolism and oxidative damage are associated with Huntington's disease (HD). Ascorbic acid released during synaptic activity inhibits use of neuronal glucose, favouring lactate uptake to sustain brain activity. Here, we observe a decreased expression of GLUT3 in STHdhQ111 cells (HD cells) and R6/2 mice (HD mice). Localisation of GLUT3 is decreased at the plasma membrane in HD cells affecting the modulation of glucose uptake by ascorbic acid. An ascorbic acid analogue without antioxidant activity is able to inhibit glucose uptake in HD cells. The impaired modulation of glucose uptake by ascorbic acid is directly related to ROS levels indicating that oxidative stress sequesters the ability of ascorbic acid to modulate glucose utilisation. Therefore, in HD, a decrease in GLUT3 localisation at the plasma membrane would contribute to an altered neuronal glucose uptake during resting periods while redox imbalance should contribute to metabolic failure during synaptic activity. PMID:26456058

  6. Impact of Imbalance Usage of Social Networking Sites on Families

    OpenAIRE

    Anwar, Anika; Ahmed, Ishrat; Hashem, Tanzima; Mahmud, Jalal

    2015-01-01

    With the proliferation of social networking sites (SNSs) such as Facebook and Google+, investigating the impact of SNSs on our lives has become an important research area in recent years. Though SNS usage plays a key role in connecting people with friends and families from distant places, SNSs also bring concern for families. We focus on imbalance SNS usage, i.e., an individual remains busy in using SNSs when her family member is expecting to spend time with her. More specifically, we investi...

  7. rDNA genetic imbalance and nucleolar chromatin restructuring is induced by distant hybridization between Raphanus sativus and Brassica alboglabra.

    Science.gov (United States)

    Long, Hong; Chen, Chunli; Wang, Bing; Feng, Yanni

    2015-01-01

    The expression of rDNA in hybrids inherited from only one progenitor refers to nucleolar dominance. The molecular basis for choosing which genes to silence remains unclear. We report genetic imbalance induced by distant hybridization correlates with formation of rDNA genes (NORs) in the hybrids between Raphanus sativus L. and Brassica alboglabra Bailey. Moreover, increased CCGG methylation of rDNA in F1 hybrids is concomitant with Raphanus-derived rDNA gene silencing and rDNA transcriptional inactivity revealed by nucleolar configuration restriction. Newly formed rDNA gene locus occurred through chromosomal in F1 hybrids via chromosomal imbalance. NORs are gained de novo, lost, and/or transposed in the new genome. Inhibition of methyltransferases leads to changes in nucleolar architecture, implicating a key role of methylation in control of nucleolar dominance and vital nucleolar configuration transition. Our findings suggest that gene imbalance and methylation-related chromatin restructuring is important for rDNA gene silencing that may be crucial for synthesis of specific proteins. PMID:25723542

  8. Expression

    Directory of Open Access Journals (Sweden)

    Wang-Xia Wang

    2014-02-01

    Full Text Available The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs, sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively. In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS. In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs. Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

  9. Effects of imbalance and geometric error on precision grinding machines

    Energy Technology Data Exchange (ETDEWEB)

    Bibler, J.E.

    1997-06-01

    To study balancing in grinding, a simple mechanical system was examined. It was essential to study such a well-defined system, as opposed to a large, complex system such as a machining center. The use of a compact, well-defined system enabled easy quantification of the imbalance force input, its phase angle to any geometric decentering, and good understanding of the machine mode shapes. It is important to understand a simple system such as the one I examined given that imbalance is so intimately coupled to machine dynamics. It is possible to extend the results presented here to industrial machines, although that is not part of this work. In addition to the empirical testing, a simple mechanical system to look at how mode shapes, balance, and geometric error interplay to yield spindle error motion was modelled. The results of this model will be presented along with the results from a more global grinding model. The global model, presented at ASPE in November 1996, allows one to examine the effects of changing global machine parameters like stiffness and damping. This geometrically abstract, one-dimensional model will be presented to demonstrate the usefulness of an abstract approach for first-order understanding but it will not be the main focus of this thesis. 19 refs., 36 figs., 10 tables.

  10. TEMPOL increases NAD+ and improves redox imbalance in obese mice

    Directory of Open Access Journals (Sweden)

    Mayumi Yamato

    2016-08-01

    Full Text Available Continuous energy conversion is controlled by reduction–oxidation (redox processes. NAD+ and NADH represent an important redox couple in energy metabolism. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL is a redox-cycling nitroxide that promotes the scavenging of several reactive oxygen species (ROS and is reduced to hydroxylamine by NADH. TEMPOL is also involved in NAD+ production in the ascorbic acid–glutathione redox cycle. We utilized the chemical properties of TEMPOL to investigate the effects of antioxidants and NAD+/NADH modulators on the metabolic imbalance in obese mice. Increases in the NAD+/NADH ratio by TEMPOL ameliorated the metabolic imbalance when combined with a dietary intervention, changing from a high-fat diet to a normal diet. Plasma levels of the superoxide marker dihydroethidium were higher in mice receiving the dietary intervention compared with a control diet, but were normalized with TEMPOL consumption. These findings provide novel insights into redox regulation in obesity.

  11. TEMPOL increases NAD(+) and improves redox imbalance in obese mice.

    Science.gov (United States)

    Yamato, Mayumi; Kawano, Kimika; Yamanaka, Yuki; Saiga, Misako; Yamada, Ken-Ichi

    2016-08-01

    Continuous energy conversion is controlled by reduction-oxidation (redox) processes. NAD(+) and NADH represent an important redox couple in energy metabolism. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) is a redox-cycling nitroxide that promotes the scavenging of several reactive oxygen species (ROS) and is reduced to hydroxylamine by NADH. TEMPOL is also involved in NAD(+) production in the ascorbic acid-glutathione redox cycle. We utilized the chemical properties of TEMPOL to investigate the effects of antioxidants and NAD(+)/NADH modulators on the metabolic imbalance in obese mice. Increases in the NAD(+)/NADH ratio by TEMPOL ameliorated the metabolic imbalance when combined with a dietary intervention, changing from a high-fat diet to a normal diet. Plasma levels of the superoxide marker dihydroethidium were higher in mice receiving the dietary intervention compared with a control diet, but were normalized with TEMPOL consumption. These findings provide novel insights into redox regulation in obesity. PMID:26942863

  12. Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.

    Science.gov (United States)

    Yang, Wei; Ng, Fu Liang; Chan, Kenneth; Pu, Xiangyuan; Poston, Robin N; Ren, Meixia; An, Weiwei; Zhang, Ruoxin; Wu, Jingchun; Yan, Shunying; Situ, Haiteng; He, Xinjie; Chen, Yequn; Tan, Xuerui; Xiao, Qingzhong; Tucker, Arthur T; Caulfield, Mark J; Ye, Shu

    2016-07-01

    Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD

  13. New Adaptive Method for IQ Imbalance Compensation of Quadrature Modulators in Predistortion Systems

    Directory of Open Access Journals (Sweden)

    Hassan Zareian

    2009-01-01

    Full Text Available Imperfections in quadrature modulators (QMs, such as inphase and quadrature (IQ imbalance, can severely impact the performance of power amplifier (PA linearization systems, in particular in adaptive digital predistorters (PDs. In this paper, we first analyze the effect of IQ imbalance on the performance of a memory orthogonal polynomials predistorter (MOP PD, and then we propose a new adaptive algorithm to estimate and compensate the unknown IQ imbalance in QM. Unlike previous compensation techniques, the proposed method was capable of online IQ imbalance compensation with faster convergence, and no special calibration or training signals were needed. The effectiveness of the proposed IQ imbalance compensator was validated by simulations. The results clearly show the performance of the MOP PD to be enhanced significantly by adding the proposed IQ imbalance compensator.

  14. New Adaptive Method for IQ Imbalance Compensation of Quadrature Modulators in Predistortion Systems

    Science.gov (United States)

    Zareian, Hassan; Vakili, Vahid Tabataba

    2009-12-01

    Imperfections in quadrature modulators (QMs), such as inphase and quadrature (IQ) imbalance, can severely impact the performance of power amplifier (PA) linearization systems, in particular in adaptive digital predistorters (PDs). In this paper, we first analyze the effect of IQ imbalance on the performance of a memory orthogonal polynomials predistorter (MOP PD), and then we propose a new adaptive algorithm to estimate and compensate the unknown IQ imbalance in QM. Unlike previous compensation techniques, the proposed method was capable of online IQ imbalance compensation with faster convergence, and no special calibration or training signals were needed. The effectiveness of the proposed IQ imbalance compensator was validated by simulations. The results clearly show the performance of the MOP PD to be enhanced significantly by adding the proposed IQ imbalance compensator.

  15. Linkage disequilibrium between an allele at the dopamine D4 receptor locus and Tourette syndrome, by the transmission-disequilibrium test.

    OpenAIRE

    Grice, D. E.; Leckman, J. F.; Pauls, D L; Kurlan, R.; Kidd, K K; Pakstis, A.J.; Chang, F. M.; Buxbaum, J. D.; Cohen, D. J.; Gelernter, J.

    1996-01-01

    Dopaminergic abnormalities are implicated in the pathogenesis of Tourette syndrome (TS) and chronic multiple tics. We used the transmission-disequilibrium test (TDT) method to test for linkage disequilibrium between a specific allele (the seven-repeat allele (DRD4*7R) of the exon 3 VNTR polymorphic site) at the D4 dopamine receptor locus (DRD4) and expression of chronic multiple tics and TS. This particular allele had been shown in functional studies to have different binding properties compa...

  16. Phenotypic instability of Arabidopsis alleles affecting a disease Resistance gene cluster

    Directory of Open Access Journals (Sweden)

    Richards Eric J

    2008-04-01

    Full Text Available Abstract Background Three mutations in Arabidopsis thaliana strain Columbia – cpr1, snc1, and bal – map to the RPP5 locus, which contains a cluster of disease Resistance genes. The similar phenotypes, gene expression patterns, and genetic interactions observed in these mutants are related to constitutive activation of pathogen defense signaling. However, these mutant alleles respond differently to various conditions. Exposure to mutagens, such as ethyl methanesulfonate (EMS and γ-irradiation, induce high frequency phenotypic instability of the bal allele. In addition, a fraction of the bal and cpr1 alleles segregated from bal × cpr1 F1 hybrids also show signs of phenotypic instability. To gain more insight into the mechanism of phenotypic instability of the bal and cpr1 mutations, we systematically compared the behavior of these unusual alleles with that of the missense gain-of-function snc1 allele in response to DNA damage or passage through F1 hybrids. Results We found that the cpr1 allele is similar to the bal allele in its unstable behavior after EMS mutagenesis. For both the bal and cpr1 mutants, destabilization of phenotypes was observed in more than 10% of EMS-treated plants in the M1 generation. In addition, exceptions to simple Mendelian inheritance were identified in the M2 generation. Like cpr1 × bal F1 hybrids, cpr1 × snc1 F1 hybrids and bal × snc1 F1 hybrids exhibited dwarf morphology. While only dwarf F2 plants were produced from bal × snc1 F1 hybrids, about 10% wild-type F2 progeny were produced from cpr1 × snc1 F1 hybrids, as well as from cpr1 × bal hybrids. Segregation analysis suggested that the cpr1 allele in cpr1 × snc1 crosses was destabilized during the late F1 generation to early F2 generation. Conclusion With exposure to EMS or different F1 hybrid contexts, phenotypic instability is induced for the bal and cpr1 alleles, but not for the snc1 allele. Our results suggest that the RPP5 locus can adopt different

  17. Growth imbalance and government responsibility: From the perspective of social spending

    OpenAIRE

    Zhang, Xiaojing; WANG Hongju; Chang, Xin

    2007-01-01

    There exists a kind of growth imbalance in China's current development process, which is essentially characterized by the imbalance between the nation's wealth and the people's welfare. This paper points out that growth imbalance results mostly from insufficient government social spending on people's welfare. Consequently, the government should shoulder the basic responsibility for the provision of education, health and social security, quicken the transformation of government expenditure str...

  18. Efficient Compensation of Transmitter and Receiver IQ Imbalance in OFDM Systems

    OpenAIRE

    Tandur Deepaknath; Moonen Marc

    2010-01-01

    Radio frequency impairments such as in-phase/quadrature-phase (IQ) imbalances can result in a severe performance degradation in direct-conversion architecture-based communication systems. In this paper, we consider the case of transmitter and receiver IQ imbalance together with frequency selective channel distortion. The proposed training-based schemes can decouple the compensation of transmitter and receiver IQ imbalance from the compensation of channel distortion in an orthogonal frequency...

  19. Effects of chiral imbalance and magnetic field on pion superfluidity and color superconductivity

    OpenAIRE

    Cao, Gaoqing; Zhuang, Pengfei

    2015-01-01

    The effects of chiral imbalance and external magnetic field on pion superfluidity and color superconductivity are investigated in extended Nambu--Jona-Lasinio models. We take Schwinger approach to treat the interaction between charged pion condensate and magnetic field at finite isospin density and include simultaneously the chiral imbalance and magnetic field at finite baryon density. For the superfluidity, the chiral imbalance and magnetic field lead to catalysis and inverse catalysis effec...

  20. rDNA Genetic Imbalance and Nucleolar Chromatin Restructuring Is Induced by Distant Hybridization between Raphanus sativus and Brassica alboglabra

    OpenAIRE

    Long, Hong; Chen, Chunli; Bing WANG; Feng, Yanni

    2015-01-01

    The expression of rDNA in hybrids inherited from only one progenitor refers to nucleolar dominance. The molecular basis for choosing which genes to silence remains unclear. We report genetic imbalance induced by distant hybridization correlates with formation of rDNA genes (NORs) in the hybrids between Raphanus sativus L. and Brassica alboglabra Bailey. Moreover, increased CCGG methylation of rDNA in F1 hybrids is concomitant with Raphanus-derived rDNA gene silencing and rDNA transcriptional ...

  1. Study on Relation between Dynamic Imbalance Degree and Product of Inertia

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin-ming; WANG Li-ming; LIU Jian-he; ZHOU Hua-wen

    2008-01-01

    Based on the study of the relation between the dynamic imbalance degree and the product of inertia, a new static test method of the dynamic imbalance degree is presented. It is theoretically proved that the essence of the imbalance degree test for projectile body is the test of its product of inertia. A more precise calculation formula of dynamic imbalance degree is also given. The experiment results show that this method can not only reduce the cost of equipment, simplify the test procedures, save human resource, but also has more reliable test precision.

  2. Obtained Diversity Gain in OFDM Systems under the Influence of IQ Imbalance

    Science.gov (United States)

    Jin, Younghwan; Kwon, Jihyeon; Lee, Yuro; Lee, Dongchan; Ahn, Jaemin

    In this paper, we analyze the effects of IQ (In-phase/Quadrature-phase) imbalance at both transmitter and receiver of OFDM (Orthogonal Frequency Division Multiplexing) system and show that more diversity gain can be achieved even though there are unwanted IQ imbalance. When mixed sub-carriers within an OFDM symbol due to the IQ imbalance undergo frequency selective channels, additional diversity effects are expected during the demodulation process. Simulation results on the symbol error rate (SER) performance with ML (Maximum Likelihood) and OSIC (Ordered Successive Interference Cancellation) receiver show that significant performance gain can be achieved with the diversity gain caused by the IQ imbalance combined with the frequency selective channels.

  3. Efficient Compensation of Transmitter and Receiver IQ Imbalance in OFDM Systems

    Directory of Open Access Journals (Sweden)

    Tandur Deepaknath

    2010-01-01

    Full Text Available Radio frequency impairments such as in-phase/quadrature-phase (IQ imbalances can result in a severe performance degradation in direct-conversion architecture-based communication systems. In this paper, we consider the case of transmitter and receiver IQ imbalance together with frequency selective channel distortion. The proposed training-based schemes can decouple the compensation of transmitter and receiver IQ imbalance from the compensation of channel distortion in an orthogonal frequency division multiplexing (OFDM systems. The presence of frequency selective channel fading is a requirement for the estimation of IQ imbalance parameters when both transmitter/receiver IQ imbalance are present. However, the proposed schemes are equally applicable over a frequency flat/frequency selective channel when either transmitter or only receiver IQ imbalance is present. Once the transmitter and receiver IQ imbalance parameters are estimated, a standard channel equalizer can be applied to estimate/compensate for the channel distortion. The proposed schemes result in an overall lower training overhead and a lower computational requirement, compared to the joint compensation of transmitter/receiver IQ imbalance and channel distortion. Simulation results demonstrate that the proposed schemes provide a very efficient compensation with performance close to the ideal case without any IQ imbalance.

  4. Impact of wind power on the power system imbalances in Finland

    Energy Technology Data Exchange (ETDEWEB)

    Helander, Aleksi; Paatero, Jukka [TKK Helsinki Univ. of Technology (Finland); Holttinen, Hannele [VTT Technical Research Centre of Finland (Finland)

    2008-07-01

    This paper presents a study about the costs of balancing for wind power producers on the one hand and the cost incurred for the power system on the other hand. The general ideas about bidding in the electricity markets and paying balance settlement costs are illustrated with Nordic electricity market Nordpool and case data for one year in Finland. Both the producer side and the system side will be examined with case data on prediction errors, system net imbalances and the balancing costs. The up-scaled wind imbalances resulting from forecast errors have been combined with the system net imbalance. Comparisons and discussion about the balancing costs of wind power depending on the wind penetration is made. The results for case Finland show that two-price system for imbalances makes the imbalance costs clearly higher than one-price system. Both systems reflect the increase in costs as wind penetration increases. Increasing penetration level increases wind power prediction errors and they start to affect net system imbalances more. This can be seen also as the percentage of imbalances that are to the same side as system net imbalance. According to comparison, the increase in system costs due to wind power is lower than imbalance payments for wind power producers when using the average prices for up- and down-regulation, at least for up to 10 % penetration level in Finland. (orig.)

  5. 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

  6. Evaluating imbalances of adverse events during biosimilar development.

    Science.gov (United States)

    Vana, Alicia M; Freyman, Amy W; Reich, Steven D; Yin, Donghua; Li, Ruifeng; Anderson, Scott; Jacobs, Ira A; Zacharchuk, Charles M; Ewesuedo, Reginald

    2016-07-01

    Biosimilars are designed to be highly similar to approved or licensed (reference) biologics and are evaluated based on the totality of evidence from extensive analytical, nonclinical and clinical studies. As part of the stepwise approach recommended by regulatory agencies, the first step in the clinical evaluation of biosimilarity is to conduct a pharmacokinetics similarity study in which the potential biosimilar is compared with the reference product. In the context of biosimilar development, a pharmacokinetics similarity study is not necessarily designed for a comparative assessment of safety. Development of PF-05280014, a potential biosimilar to trastuzumab, illustrates how a numerical imbalance in an adverse event in a small pharmacokinetics study can raise questions on safety that may require additional clinical trials. PMID:27050730

  7. Electronic compressibility and charge imbalance relaxation in cuprate superconductors

    International Nuclear Information System (INIS)

    In the material SmLa1-xSrxCuO4-δ with alternating intrinsic Josephson junctions we explain theoretically the relative amplitude of the two plasma peaks in transmission by taking into account the spatial dispersion of the Josephson Plasma Resonance in c-direction due to charge coupling. From this and the magnetic field dependence of the plasma peaks in the vortex solid and liquid states it is shown that the electronic compressibility of the CuO2 layers is consistent with a free electron value. Also the London penetration depth λab∼1100 Angst near Tc can be determined. The voltage response in the IV-curve of a Bi2Sr2CaCu2O8 mesa due to microwave irradiation or current injection in a second mesa is related to the nonequilibrium charge imbalance of quasiparticles and Cooper pairs and from our experimental data the relaxation time ∼100 ps is obtained

  8. Optimal weight based on energy imbalance and utility maximization

    Science.gov (United States)

    Sun, Ruoyan

    2016-01-01

    This paper investigates the optimal weight for both male and female using energy imbalance and utility maximization. Based on the difference of energy intake and expenditure, we develop a state equation that reveals the weight gain from this energy gap. We ​construct an objective function considering food consumption, eating habits and survival rate to measure utility. Through applying mathematical tools from optimal control methods and qualitative theory of differential equations, we obtain some results. For both male and female, the optimal weight is larger than the physiologically optimal weight calculated by the Body Mass Index (BMI). We also study the corresponding trajectories to steady state weight respectively. Depending on the value of a few parameters, the steady state can either be a saddle point with a monotonic trajectory or a focus with dampened oscillations.

  9. Redox Imbalance and Viral Infections in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Dolores Limongi

    2016-01-01

    Full Text Available Reactive oxygen species (ROS are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson’s disease (PD, Alzheimer’s disease (AD, and amyotrophic lateral sclerosis (ALS.

  10. Propensity to obesity impacts the neuronal response to energy imbalance

    Directory of Open Access Journals (Sweden)

    Marc-Andre eCornier

    2015-02-01

    Full Text Available The mechanisms responsible for the propensity to gain weight or remain normal weight are poorly understood. The objective of this study was to study the neuronal response to visual food cues during short-term energy imbalance in healthy adults recruited as obesity-resistant (OR or obesity-prone (OP based on self-identification, BMI, and personal/family weight history. 25 OR and 28 OP subjects were studied in underfed (UF and overfed (OF as compared to eucaloric (EU conditions in a randomized crossover design. Each study phase included a 3 day run-in diet, 1 day of controlled feeding (basal energy needs for EU, 40% above/below basal energy needs for OF/UF, and a test day. On the test day fMRI was performed in the acute fed stated (30 minutes after a test meal while subjects viewed images of foods of high hedonic value and neutral non-food objects. Measures of appetite and hormones were also performed before and every 30 minutes after the test meal. UF was associated with significantly increased activation of insula, somatosensory cortex, inferior and medial prefrontal cortex, parahippocampus, precuneus, cingulate and visual cortex in OR. However, UF had no impact in OP. As a result, UF was associated with significantly greater activation, specifically in the insula, inferior prefrontal cortex, and somatosensory cortex in OR as compared to OP. While OF was overall associated with reduced activation of inferior visual cortex, no group interaction was observed with OF. In summary, these findings suggest that individuals resistant to weight gain and obesity are more sensitive to short-term energy imbalance, particularly with UF, than those prone to weight gain. The inability to sense or adapt to changes in energy balance may represent an important mechanism contributing to excess energy intake and risk for obesity.

  11. 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 ...

  12. The zeste-white interaction: induction and genetic analysis of a novel class of zeste alleles

    OpenAIRE

    Lifschytz, Eliezer; Green, Melvin M.

    1984-01-01

    The recovery and analysis of a novel class of zeste mutations is described. zop6 and zop11 do not require two w+ genes for their expression unless the z+ gene is present. Analysis of genetic interactions among zeste alleles proved that zop mutations are strong antagonists of the z+ gene product. zop6 is readily reverted by X-rays or by ethylmethane sulphonate to a range of intermediate zeste alleles and thus it is considered to be an insertional mutation. We suggest that z1 and op mutations a...

  13. Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans-species mode of evolution.

    OpenAIRE

    Mayer, W.E.; Jonker, M; Klein, D; Ivanyi, P; van Seventer, G; Klein, J.

    1988-01-01

    To obtain an insight into the evolutionary origin of the major histocompatibility complex (MHC) class I polymorphism, a cDNA library was prepared from a heterozygous chimpanzee cell line expressing MHC class I molecules crossreacting with allele-specific HLA-A11 antibodies. The library was screened with human class I locus-specific DNA probes, and clones encoding both alleles at the A and B loci have been identified and sequenced. In addition, the sequences of two HLA-A11 subtypes differing b...

  14. THE MAIZE UNSTABLE FACTOR FOR ORANGE1 IS A DOMINANT EPIGENETIC MODIFIER OF A TISSUE SPECIFICALLY SILENT ALLELE OF PERICARP COLOR1

    Science.gov (United States)

    We have characterized Ufo1 (unstable factor for orange1), a dominant, allele-specific modifier of expression of the maize pericarp color1 (p1) gene. The p1 gene encodes a Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments. The P1-wr allele speci...

  15. Protective Effects of the Alcohol Dehydrogenase-ADH1B*3 Allele on Attention and Behavior Problems in Adolescents Exposed to Alcohol during Pregnancy

    OpenAIRE

    Dodge, Neil C.; Jacobson, Joseph L; Jacobson, Sandra W.

    2013-01-01

    Alcohol dehydrogenase is a critical enzyme in the metabolism of alcohol. Expression of three alleles at the ADH1B locus results in enzymes that differ in turnover rate and affinity for alcohol. The ADH1B*3 allele, which appears to be unique to individuals of African descent, is associated with more rapid alcohol metabolism than the more prevalent ADH1B*1 allele. It has been previously demonstrated that the presence of at least one maternal ADH1B*3 allele confers a protective effect against al...

  16. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  17. Two domain-disrupted hda6 alleles have opposite epigenetic effects on transgenes and some endogenous targets

    KAUST Repository

    Zhang, ShouDong

    2015-12-15

    HDA6 is a RPD3-like histone deacetylase. In Arabidopsis, it mediates transgene and some endogenous target transcriptional gene silencing (TGS) via histone deacetylation and DNA methylation. Here, we characterized two hda6 mutant alleles that were recovered as second-site suppressors of the DNA demethylation mutant ros1–1. Although both alleles derepressed 35S::NPTII and RD29A::LUC in the ros1–1 background, they had distinct effects on the expression of these two transgenes. In accordance to expression profiles of two transgenes, the alleles have distinct opposite methylation profiles on two reporter gene promoters. Furthermore, both alleles could interact in vitro and in vivo with the DNA methyltransferase1 with differential interactive strength and patterns. Although these alleles accumulated different levels of repressive/active histone marks, DNA methylation but not histone modifications in the two transgene promoters was found to correlate with the level of derepression of the reporter genes between the two had6 alleles. Our study reveals that mutations in different domains of HDA6 convey different epigenetic status that in turn controls the expression of the transgenes as well as some endogenous loci.

  18. Theoretical predictions of transverse kinematic imbalance in neutrino-nucleus interactions

    CERN Document Server

    Pickering, Luke

    2016-01-01

    Distributions of transverse kinematic imbalance in neutrino-nucleus interactions in the few GeV regime are sensitive to nuclear effects. We present a study comparing the latest predictions of transverse kinematic imbalance from the interaction simulations, NuWro and GENIE. We dis- cuss the differences between the model predictions.

  19. The state line of solution of imbalances problem the wholesale electricity market of Ukraine

    Directory of Open Access Journals (Sweden)

    А.S. Kolesnichenko

    2011-10-01

    Full Text Available This article deals with the problem of formation and dynamics of imbalances of the wholesale electricity market (WEM of Ukraine. The features and prospects of imbalance control in the context of reforming the wholesale electricity market are analyzed.

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

    Directory of Open Access Journals (Sweden)

    Theißen Günter

    2011-02-01

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

  1. Imbalance of Interleukin 18 and Interleukin 18 Binding Protein in Patients with Lupus Nephritis

    Institute of Scientific and Technical Information of China (English)

    Dong Liang; Wenfeng Ma; Cuiwei Yao; Huafeng Liu; Xiaowen Chen

    2006-01-01

    To evaluate the balance status of interleukin 18 (IL-18) and interleukin 18 binding protein (IL-18BP) in circulation in patients with lupus nephritis (LN) and primary nephrotic syndrome (PNS), plasma levels as well as mRNA expression in peripheral blood mononuclear cells (PBMCs) of IL-18 and IL-18BP were measured by ELISA and RT-PCR respectively. The ratio of IL-18/IL-18BP was also calculated. Both plasma IL-18 and IL-18BP increased significantly in LN patients while only IL-18BP increased in PNS, which resulted in an elevated ratio of IL-18/IL-18BP in LN but not in PNS patients when compared with normal controls. In contrast, increased level of IL-18 mRNA was only detected in LN but not in PNS group, although IL-18BP mRNA expressions in PBMCs in both groups were higher than that in control. The imbalance of IL-18 and IL-18BP might be involved in the pathogenesis of LN, based on which a therapeutic approach is valuable to be developed for LN. Cellular & Molecular Immunology. 2006;3(4):303-306.

  2. 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

  3. Wind power predictions analysis. Part 1. TenneT imbalance price system. Development of a model for TenneT imbalance price

    International Nuclear Information System (INIS)

    To preserve the system balance in the Dutch power system 'energy-programme responsibility' was set up. The program responsibility is basically a system in which all market parties involved in the use of the network send on a daily basis their planned production, transport and use of electricity to TenneT in the form of so-called E-programmes. Using that information as a starting point TenneT, the Dutch grid system operator, can correct any imbalances or internal transmission constrains generated in the system. When a producer doesn't produce according to the predictions he has registered in the E-programme, he has to pay compensations for imbalance (difference between expected and actual output power) to TenneT. In wind energy, previsions made in the E-programme are hardly ever equal to the actual output. For this reason it is assumed that wind energy producers have to deal with large imbalance costs. Therefore it is important to have a good understanding of the imbalance pricing system that is ruling their imbalance. In this study, we have first made a global statistical description of imbalance prices for shortage and surplus in the period from February 2001 to January 2002. This first approach has highlighted the fast fluctuations of imbalance prices as well as the wide range containing these prices. Then, to have a better understanding of the behaviour we have made a spectral analysis of these prices. The main harmonics appeared for every multiple of 24 hour: a daily pattern is thus the first step to describe these prices. We can distinguish different daily patterns for the weekend and the rest of the week, as well as for every month of the year. These daily patterns seem to be linked with consumption in so far that imbalance prices remain low during the night but increase from 7 to 20 o'clock. On the basis of this description, a prediction model was developed. This model provides for the imbalance price two daily patterns for one month: one for the weekend and

  4. EXPRESS

    International Nuclear Information System (INIS)

    This paper presents EXPRESS, an expert system developed for the automation of reliability studies. The first part consists in the description of the method for static thermohydraulic systems. In this step, the authors define the knowledge representation based on the two inference engines - ALOUETTE and LCR developed by EDF. They explain all the process to construct a fault tree from a topological and functional description of the system. Numerous examples are exhibited in illustration of the method. This is followed by the lessons derived from the studies performed on some safety systems of the PALUEL nuclear plant. The development of the same approach for electric power systems is described, insisting on the difference resulting from the sequential nature of these systems. Finally, they show the main advantages identified during the studies

  5. Chromosomal imbalances revealed in primary rhabdomyosarcomas by comparative genomic hybridization

    Institute of Scientific and Technical Information of China (English)

    LI Qiao-xin; LIU Chun-xia; CHUN Cai-pu; QI Yan; CHANG Bin; LI Xin-xia; CHEN Yun-zhao; NONG Wei-xia; LI Hong-an; LI Feng

    2009-01-01

    Background Previous cytogenetic studies revealed aberrations varied among the throe subtypes of rhabdomyosarcoma. We profiled chromosomal imbalances in the different subtypes and investigated the relationships between clinical parameters and genomic aberrations.Methods Comparative genomic hybridization was used to investigate genomic imbalances in 25 cases of primary rhabdomyosarcomas and two rhabdomyosarcoma cell lines. Specimens were reviewed to determine histological type, pathological grading and clinical staging.Results Changes involving one or more regions of the genome were seen in all rhabdomyosarcomal patients. For rhabdomyosarcoma, DNA sequence gains were most frequently (>30%) seen in chromosomes 2p, 12q, 6p, 9q, 10q, 1p,2q, 6q, 8q, 15q and 18q; losses from 3p, 11p and 6p. In aggressive alveolar rhabdomyosarcoma, frequent gains were seen on chromosomes 12q, 2p, 6p, 2q, 4q, 10q and 15q; losses from 3p, 6p, 1q and 5q. For embryonic rhabdomyosarcoma, frequent gains were on 7p, 9q, 2p, 18q, 1p and 8q; losses only from 11p. Frequently gained chromosome arms of translocation associated with rhabdomyosarcoma were 12q, 2, 6, 10q, 4q and 15q; losses from 3p,6p and 5q. The frequently gained chromosome arms of nontranslocation associated with rhabdomyosarcoma were 2p,9q and 18q, while 11p and 14q were the frequently lost chromosome arms. Gains on chromosome 12q were significantly correlated with translocation type. Gains on chromosome 9q were significantly correlated with clinical staging. Conclusions Gains on chromosomes 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q and 18q and losses on chromosomes 3p, 11p and 6p may be related to rhabdomyosarcomal carcinogenesis. Furthermore, gains on chromosome 12q may be correlated with translocation and gains on chromosome 9q with the early stages of rhabdomyosarcoma.

  6. 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

  7. The man-made creators of the imbalance of water in Nature

    Science.gov (United States)

    Shlafman, L. M.; Kontar, V. A.

    2013-12-01

    At 2011 we have described the imbalance of water in Nature as the system [1]. At 2012 we have described water and carbon and the glaciers [2], [3] as creators of the imbalance of Nature. Now we are describing some man-made creators of the imbalance of Nature. The photosynthesis is a powerful creator of the imbalance of Nature. The photosynthesis significantly increases the complexity of the structures and reduces the entropy. Earth's hydrosphere contains water less than it was flowed via photosynthesis. This is an example of the imbalance of involving when the return of water has delayed because water is involved into the processes of life and other processes. People widely use photosynthesis and create not only an additional man-made imbalance of water in Nature, but also the man-made changing the albedo, and a lot of other important parameters of the planet of Earth. All of these processes are significantly imbalanced. The fossil hydrocarbons have accumulated during millions of years, but now are burned. This is an example of the imbalance delay by time. The man-made burning of the hydrocarbons is creating the imbalances of impact or explosive type, because of the burning processes is in millions of times faster than the accumulation processes. Please pay attention to the imbalance of redeployment by places. For example, oil and gas are extracted in one places, and burned in others. During combustion is standing out not only water, but energy, and other components. The temperature in the centers of big cities is always higher and there is dominating the rising air. It pollutes the environment, changes circulations, create greenhouse effect, etc. Other examples of the imbalance of relocation are shown in the production and consumption of food. The irrigation systems transfer water from one place to another. This transfer of water creates a lot of imbalances in change climate, ecosystems, etc in places where water was took and where the water was brought. Usually

  8. Does observation of postural imbalance induce a postural reaction?

    Directory of Open Access Journals (Sweden)

    Banty Tia

    Full Text Available BACKGROUND: Several studies bring evidence that action observation elicits contagious responses during social interactions. However automatic imitative tendencies are generally inhibited and it remains unclear in which conditions mere action observation triggers motor behaviours. In this study, we addressed the question of contagious postural responses when observing human imbalance. METHODOLOGY/PRINCIPAL FINDINGS: We recorded participants' body sway while they observed a fixation cross (control condition, an upright point-light display of a gymnast balancing on a rope, and the same point-light display presented upside down. Our results showed that, when the upright stimulus was displayed prior to the inverted one, centre of pressure area and antero-posterior path length were significantly greater in the upright condition compared to the control and upside down conditions. CONCLUSIONS/SIGNIFICANCE: These results demonstrate a contagious postural reaction suggesting a partial inefficiency of inhibitory processes. Further, kinematic information was sufficient to trigger this reaction. The difference recorded between the upright and upside down conditions indicates that the contagion effect was dependent on the integration of gravity constraints by body kinematics. Interestingly, the postural response was sensitive to habituation, and seemed to disappear when the observer was previously shown an inverted display. The motor contagion recorded here is consistent with previous work showing vegetative output during observation of an effortful movement and could indicate that lower level control facilitates contagion effects.

  9. Thyroid Function Test Imbalance in Epileptic Children Under Anticonvulsive Therapy

    Directory of Open Access Journals (Sweden)

    Mohammad TORKAMAN

    2012-03-01

    Full Text Available How to Cite this Article: Ravi Torkaman M, Amirsalari S, Saburi A. Thyroid Function Test Imbalance in Epileptic ChildrenUnder Anticonvulsive Therapy. Iranian Journal of Child Neurology 2012;6(1:43-44. Dear Editor,There have been many studies regarding the impact of antiepileptic drugs(AEDs on thyroid function. There are some challenging scopes which must beconsidered for conducting the study adressing the focused question. “Which oneof the thyroid hormones is related to the AEDs consumption?”. Some studiesdemonstrated that there may be alterations in all thyroid function tests (T3, T4 andTSH after antiepileptic therapy in children (1. Some studies concluded that longtermprescription of anticonvulsive medications resulted in a decline in serum T4levels, although it had no effect on serum TSH levels. However, changes in serumT3 level was challenging and it must be investigated further (2.There were some confounding factors which may interfere with the conclusion.One of them is the type of the study. There are various study plans for this purposesuch as cross-sectional, case-control, experimental, self-controlled cohort anddouble-blind randomized clinical trial studies. It seems that the proper protocol ofstudy for this propose is a double-blind randomized clinical trial study. By usingother designs, the authors cannot interpret the effect of AEDs on thyroid function;however, they can discuss the prevalence of thyroid hormone imbalance and thecoordination among T3, T4 and TSH.Moreover, one of the confounding factors is the thyroid binding globulin (TBGeffect. It has appeared that some of the AEDs may change the amount of TBGand in this way may affect the amount of thyroid hormones (3. Clonazepamand valproic acid do not have any enzyme inducing effects, but phenobarbital,carbamazepine, phenytoin and primidone may induce the hepatic enzyme (4-6. Therefore, it seems necessary to analyze each group of patients based on thetype of drug which is

  10. Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis.

    Science.gov (United States)

    Clemente-Ruiz, Marta; Murillo-Maldonado, Juan M; Benhra, Najate; Barrio, Lara; Pérez, Lidia; Quiroga, Gonzalo; Nebreda, Angel R; Milán, Marco

    2016-02-01

    Chromosomal instability (CIN) is thought to be a source of mutability in cancer. However, CIN often results in aneuploidy, which compromises cell fitness. Here, we used the dosage compensation mechanism (DCM) of Drosophila to demonstrate that chromosome-wide gene dosage imbalance contributes to the deleterious effects of CIN-induced aneuploidy and its pro-tumorigenic action. We present evidence that resetting of the DCM counterbalances the damaging effects caused by CIN-induced changes in X chromosome number. Importantly, interfering with the DCM suffices to mimic the cellular effects of aneuploidy in terms of reactive oxygen species (ROS) production, JNK-dependent cell death, and tumorigenesis upon apoptosis inhibition. We unveil a role of ROS in JNK activation and a variety of cellular and tissue-wide mechanisms that buffer the deleterious effects of CIN, including DNA-damage repair, activation of the p38 pathway, and cytokine induction to promote compensatory proliferation. Our data reveal the existence of robust compensatory mechanisms that counteract CIN-induced cell death and tumorigenesis. PMID:26859353

  11. Does Observation of Postural Imbalance Induce a Postural Reaction?

    Science.gov (United States)

    Tia, Banty; Saimpont, Arnaud; Paizis, Christos; Mourey, France; Fadiga, Luciano; Pozzo, Thierry

    2011-01-01

    Background Several studies bring evidence that action observation elicits contagious responses during social interactions. However automatic imitative tendencies are generally inhibited and it remains unclear in which conditions mere action observation triggers motor behaviours. In this study, we addressed the question of contagious postural responses when observing human imbalance. Methodology/Principal Findings We recorded participants' body sway while they observed a fixation cross (control condition), an upright point-light display of a gymnast balancing on a rope, and the same point-light display presented upside down. Our results showed that, when the upright stimulus was displayed prior to the inverted one, centre of pressure area and antero-posterior path length were significantly greater in the upright condition compared to the control and upside down conditions. Conclusions/Significance These results demonstrate a contagious postural reaction suggesting a partial inefficiency of inhibitory processes. Further, kinematic information was sufficient to trigger this reaction. The difference recorded between the upright and upside down conditions indicates that the contagion effect was dependent on the integration of gravity constraints by body kinematics. Interestingly, the postural response was sensitive to habituation, and seemed to disappear when the observer was previously shown an inverted display. The motor contagion recorded here is consistent with previous work showing vegetative output during observation of an effortful movement and could indicate that lower level control facilitates contagion effects. PMID:21423622

  12. Association of Xmn I Polymorphism and Hemoglobin E Haplotypes on Postnatal Gamma Globin Gene Expression in Homozygous Hemoglobin E

    Science.gov (United States)

    Ekwattanakit, Supachai; Monteerarat, Yuwarat; Riolueang, Suchada; Tachavanich, Kalaya; Viprakasit, Vip

    2012-01-01

    Background and Objectives. To explore the role of cis-regulatory sequences within the β globin gene cluster at chromosome 11 on human γ globin gene expression related to Hb E allele, we analyze baseline hematological data and Hb F values together with β globin haplotypes in homozygous Hb E. Patients and Methods. 80 individuals with molecularly confirmed homozygous Hb E were analyzed for the β globin haplotypes and Xmn I polymorphism using PCR-RFLPs. 74 individuals with complete laboratory data were further studied for association analyses. Results. Eight different β globin haplotypes were found linked to Hb E alleles; three major haplotypes were (a) (III), (b) (V), and (c) (IV) accounting for 94% of Hb E chromosomes. A new haplotype (Th-1) was identified and most likely converted from the major ones. The majority of individuals had Hb F < 5%; only 10.8% of homozygous Hb E had high Hb F (average 10.5%, range 5.8–14.3%). No association was found on a specific haplotype or Xmn I in these individuals with high Hb F, measured by alkaline denaturation. Conclusion. The cis-regulation of γ globin gene expression might not be apparent under a milder condition with lesser globin imbalance such as homozygous Hb E. PMID:23049556

  13. Association of Xmn I Polymorphism and Hemoglobin E Haplotypes on Postnatal Gamma Globin Gene Expression in Homozygous Hemoglobin E

    Directory of Open Access Journals (Sweden)

    Supachai Ekwattanakit

    2012-01-01

    Full Text Available Background and Objectives. To explore the role of cis-regulatory sequences within the β globin gene cluster at chromosome 11 on human γ globin gene expression related to Hb E allele, we analyze baseline hematological data and Hb F values together with β globin haplotypes in homozygous Hb E. Patients and Methods. 80 individuals with molecularly confirmed homozygous Hb E were analyzed for the β globin haplotypes and Xmn I polymorphism using PCR-RFLPs. 74 individuals with complete laboratory data were further studied for association analyses. Results. Eight different β globin haplotypes were found linked to Hb E alleles; three major haplotypes were (a (III, (b (V, and (c (IV accounting for 94% of Hb E chromosomes. A new haplotype (Th-1 was identified and most likely converted from the major ones. The majority of individuals had Hb F < 5%; only 10.8% of homozygous Hb E had high Hb F (average 10.5%, range 5.8–14.3%. No association was found on a specific haplotype or Xmn I in these individuals with high Hb F, measured by alkaline denaturation. Conclusion. The cis-regulation of γ globin gene expression might not be apparent under a milder condition with lesser globin imbalance such as homozygous Hb E.

  14. Functional loss of E-cadherin and cadherin-11 alleles on chromosome 16q22 in colonic cancer.

    Science.gov (United States)

    Braungart, E; Schumacher, C; Hartmann, E; Nekarda, H; Becker, K F; Höfler, H; Atkinson, M J

    1999-04-01

    Proteins of the cadherin family regulate cellular adhesion and motility and are believed to act as tumour suppressors. Previous studies have identified frequent mutation and allelic inactivation of the E-cadherin (cadherin-1) locus in diffuse gastric cancer. At least two other cadherin genes, P-cadherin (cadherin-3) and OB-cadherin (cadherin-11), have been mapped close to the E-cadherin gene on chromosome 16q22. As this region of the genome is frequently deleted in malignancy, multiple cadherin loci may be affected by losses of chromosome 16q22. The expression of mRNA transcripts from polymorphic alleles of the E-cadherin and cadherin-11 genes was examined in 30 cases of colonic, gastric, and renal carcinoma. In gastric cancer, loss of expression of one allele was restricted to the E-cadherin locus, whilst in renal carcinoma neither locus was affected. In colonic cancers, loss of expression of one E-cadherin allele was detected in 5 of 22 cases, whilst loss of a cadherin-11 allele was seen in 5 of 23 cases. This functional loss of cadherin gene expression may be due to gene deletion, inactivation or recombination. As no evidence of cadherin gene mutation was observed in the remaining transcripts, we can conclude that these two genes are only indirectly involved in the pathogenesis of colorectal cancer. PMID:10398117

  15. MASTR: A Technique for Mosaic Mutant Analysis with Spatial and Temporal Control of Recombination Using Conditional Floxed Alleles in Mice

    Directory of Open Access Journals (Sweden)

    Zhimin Lao

    2012-08-01

    Full Text Available Mosaic mutant analysis, the study of cellular defects in scattered mutant cells in a wild-type environment, is a powerful approach for identifying critical functions of genes and has been applied extensively to invertebrate model organisms. A highly versatile technique has been developed in mouse: MASTR (mosaic mutant analysis with spatial and temporal control of recombination, which utilizes the increasing number of floxed alleles and simultaneously combines conditional gene mutagenesis and cell marking for fate analysis. A targeted allele (R26MASTR was engineered; the allele expresses a GFPcre fusion protein following FLP-mediated recombination, which serves the dual function of deleting floxed alleles and marking mutant cells with GFP. Within 24 hr of tamoxifen administration to R26MASTR mice carrying an inducible FlpoER transgene and a floxed allele, nearly all GFP-expressing cells have a mutant allele. The fate of single cells lacking FGF8 or SHH signaling in the developing hindbrain was analyzed using MASTR, and it was revealed that there is only a short time window when neural progenitors require FGFR1 for viability and that granule cell precursors differentiate rapidly when SMO is lost. MASTR is a powerful tool that provides cell-type-specific (spatial and temporal marking of mosaic mutant cells and is broadly applicable to developmental, cancer, and adult stem cell studies.

  16. 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

  17. The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

    International Nuclear Information System (INIS)

    Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may have a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM) by profiling purified malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCLs) and 4 normal controls. Overall, a global sno/scaRNAs downregulation was found in MMs and, even more, in sPCLs compared with normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the translocation/cyclin D4 (TC4) MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by an imprinting center at 15q11, which, however, resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information to the bio-molecular complexity of plasma cell dyscrasias

  18. The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

    Science.gov (United States)

    Ronchetti, D; Todoerti, K; Tuana, G; Agnelli, L; Mosca, L; Lionetti, M; Fabris, S; Colapietro, P; Miozzo, M; Ferrarini, M; Tassone, P; Neri, A

    2012-01-01

    Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may have a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM) by profiling purified malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCLs) and 4 normal controls. Overall, a global sno/scaRNAs downregulation was found in MMs and, even more, in sPCLs compared with normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the translocation/cyclin D4 (TC4) MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by an imprinting center at 15q11, which, however, resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information to the bio-molecular complexity of plasma cell dyscrasias. PMID:23178508

  19. Tunnel injection and tunnel stimulation of superconductivity: the role of branch imbalance

    Energy Technology Data Exchange (ETDEWEB)

    Gal' perin, Y.M.; Kozub, V.I.; Spivak, B.A.

    1983-02-01

    The tunnel injection and the tunnel extraction of quasiparticles in a superconductor are considered, taking into account the branch population imbalance. The stability of nonequilibrium states with branch imbalance is discussed. It is shown that if this imbalance is large enough, the nonequilibrim state becomes unstable with respect to spatially homogeneous fluctuations of the order parameter, the characteristic increment being of the order of that for the Cooper instability of the normal state at T>T/sub c/. As a result, states with oscillating order parameter can exist in a superconductor under injection or extraction. The relation of the results obtained to experimental results is discussed.

  20. Structure and expression of the Plasmodium falciparum SERA gene.

    Science.gov (United States)

    Li, W B; Bzik, D J; Horii, T; Inselburg, J

    1989-02-01

    Plasmodium falciparum, strain FCR3, genomic DNA that encodes the SERA gene of P. falciparum was isolated and sequenced. The SERA gene coding region was interrupted by 3 introns, the largest number observed, so far, in any Plasmodium gene. Two SERA gene alleles, allele I and allele II, were identified in the FCR3 strain, while only allele I was found in the Honduras-1 strain. Allele I mRNA was abundant in vivo during the late trophozoite and schizont stages. Allele II mRNA was either not expressed, or it was labile. PMID:2651911

  1. Association of sympathovagal imbalance with cardiovascular risks in overt hypothyroidism

    Directory of Open Access Journals (Sweden)

    Avupati Naga Syamsunder

    2013-01-01

    Full Text Available Background: Cardiovascular morbidities have been reported in hypothyroidism. Aims: The objective of this study is to investigate the link of sympathovagal imbalance (SVI to cardiovascular risks (CVRs and the plausible mechanisms of CVR in hypothyroidism. Materials and Methods: Age-matched 104 females (50 controls, 54 hypothyroids were recruited and their body mass index (BMI, cardiovascular parameters, autonomic function tests by spectral analysis of heart rate variability (HRV, heart rate response to standing, deep breathing and blood pressure response to isometric handgrip were studied. Thyroid profile, lipid profile, immunological and inflammatory markers were estimated and their association with low-frequency to the high-frequency ratio (LF-HF of HRV, the marker of SVI was assessed by multivariate regression. Results: Increased diastolic pressure, decreased HRV, increased LF-HF, dyslipidemia and increased high-sensitive C-reactive protein (hsCRP were observed in hypothyroid patients and all these parameters had significant correlation with LF-HF. BMI had no significant association with LF-HF. Atherogenic index (β 1.144, P = 0.001 and hsCRP (b 0.578, P = 0.009 had independent contribution to LF-HF. LF-HF could significantly predict hypertension status (odds ratio 2.05, confidence interval 1.110-5.352, P = 0.008 in hypothyroid subjects. Conclusions: SVI due to sympathetic activation and vagal withdrawal occurs in hypothyroidism. Dyslipidemia and low-grade inflammation, but not obesity contribute to SVI and SVI contributes to cardiovascular risks.

  2. Power Imbalances, Food Insecurity, and Children's Rights in Canada.

    Science.gov (United States)

    Blay-Palmer, Alison

    2016-01-01

    Increasingly, food is provided through an industrial food system that separates people from the source of their food and results in high rates of food insecurity, particularly for the most vulnerable in society. A lack of food is a symptom of a lack of power in a system that privileges free market principles over social justice and the protection of human rights. In Canada, the high rates of food insecurity among Canadian children is a reflection of their lack of power and the disregard of their human rights, despite the adoption of the United Nations (UN) Convention on the Rights of the Child in 1991 and ratification of the International Covenant on Social, Economic and Cultural Rights in 1976, which established the right to food for all Canadians. Dueling tensions between human rights and market forces underpin this unacceptable state of affairs in Canada. Gaventa's "power cube" that describes different facets of power - including spaces, levels, and forms - is used to help understand the power imbalances that underlie this injustice. The analysis considers the impact of neoliberal free market principles on the realization of human rights, and the negative impacts this can have on health and well-being for the most vulnerable in society. Canadian case studies from both community organizations provide examples of how power can be shifted to achieve more inclusive, rights-based policy and action. Given increased global pressures toward more open trade markets and national austerity measures that hollow out social supports, Canada provides a cautionary tale for countries in the EU and the US, and for overall approaches to protect the most vulnerable in society. PMID:27563642

  3. Similar nature of ionic imbalances in cardiovascular and renal disorders

    International Nuclear Information System (INIS)

    Background: Several studies have reported improper ionic environment in cardiovascular and renal patients but how the diseases are associated on ionic basis is still not clear. Objective: The present study was aimed to investigate sodium and potassium concentrations and their transport abnormalities in cardiovascular and renal patients. Patients and Methods: Thirty patients of various cardiovascular and thirty patients of various renal disorders (53.33% males, 46.67% females) were selected. Erythrocytes were isolated from freshly drawn blood samples, washed and used for the estimation of sodium and potassium levels using flame photometer (Corning 410). Serum sodium and potassium were measured by flame photometer. RBC membranes were prepared for the estimation of Na/sup +/-K/sup +/-ATPase activity in terms of inorganic phosphate released/mg protein/hour. Results: Intra-erythrocyte and serum sodium and potassium concentrations and Na/sup +/-K/sup +/-ATPase activity were different in cardiovascular and renal patients from controls. Intra-erythrocyte sodium level was increased significantly (P<0.01) in cardiovascular patients and non-significantly in renal patients as compared to controls. Na/sup +/-K/sup +/-ATPase activity and serum sodium level were decreased significantly (P<0.01) in both the groups as compared to controls. Serum potassium was found to be decreased significantly (P<0.01) in cardiovascular patients whereas it was raised significantly (P<0.01) in renal patients as compared to control subjects. Conclusion: The results indicated similar nature of ionic and electrolyte imbalances in cardiovascular and renal disorders resulting from impaired Na/sup +/-K/sup +/-ATPase system. Further investigations in the same area, may be of help to establish an understanding of the progression of diseases, associated complications and the preventive steps that should-be taken to arrest the progression of these disorders. (author)

  4. Glycolipid and Ganglioside Metabolism Imbalances In Huntington’s Disease

    OpenAIRE

    Desplats, Paula A.; Denny, Christine. A.; Kass, Kristi E.; Gilmartin, Tim; Head, Steven R.; Sutcliffe, J. Gregor; Seyfried, Thomas N; Thomas, Elizabeth A.

    2007-01-01

    We have explored genome-wide expression of genes related to glycobiology in exon 1 transgenic Huntington’s disease (HD) mice using a custom designed GLYCOv2 chip and Affymetrix microarray analyses. We validated, using quantitative real-time PCR, abnormal expression levels of genes encoding glycosyltransferases in the striatum of R6/1 transgenic mice, as well as in postmortem caudate from human HD patients. Many of these genes show differential regional expression within the CNS, as indicated ...

  5. Improving classification of mature microRNA by solving class imbalance problem

    Science.gov (United States)

    Wang, Ying; Li, Xiaoye; Tao, Bairui

    2016-05-01

    MicroRNAs (miRNAs) are ~20–25 nucleotides non-coding RNAs, which regulated gene expression in the post-transcriptional level. The accurate rate of identifying the start sit of mature miRNA from a given pre-miRNA remains lower. It is noting that the mature miRNA prediction is a class-imbalanced problem which also leads to the unsatisfactory performance of these methods. We improved the prediction accuracy of classifier using balanced datasets and presented MatFind which is used for identifying 5‧ mature miRNAs candidates from their pre-miRNA based on ensemble SVM classifiers with idea of adaboost. Firstly, the balanced-dataset was extract based on K-nearest neighbor algorithm. Secondly, the multiple SVM classifiers were trained in orderly using the balance datasets base on represented features. At last, all SVM classifiers were combined together to form the ensemble classifier. Our results on independent testing dataset show that the proposed method is more efficient than one without treating class imbalance problem. Moreover, MatFind achieves much higher classification accuracy than other three approaches. The ensemble SVM classifiers and balanced-datasets can solve the class-imbalanced problem, as well as improve performance of classifier for mature miRNA identification. MatFind is an accurate and fast method for 5‧ mature miRNA identification.

  6. Improving classification of mature microRNA by solving class imbalance problem.

    Science.gov (United States)

    Wang, Ying; Li, Xiaoye; Tao, Bairui

    2016-01-01

    MicroRNAs (miRNAs) are ~20-25 nucleotides non-coding RNAs, which regulated gene expression in the post-transcriptional level. The accurate rate of identifying the start sit of mature miRNA from a given pre-miRNA remains lower. It is noting that the mature miRNA prediction is a class-imbalanced problem which also leads to the unsatisfactory performance of these methods. We improved the prediction accuracy of classifier using balanced datasets and presented MatFind which is used for identifying 5' mature miRNAs candidates from their pre-miRNA based on ensemble SVM classifiers with idea of adaboost. Firstly, the balanced-dataset was extract based on K-nearest neighbor algorithm. Secondly, the multiple SVM classifiers were trained in orderly using the balance datasets base on represented features. At last, all SVM classifiers were combined together to form the ensemble classifier. Our results on independent testing dataset show that the proposed method is more efficient than one without treating class imbalance problem. Moreover, MatFind achieves much higher classification accuracy than other three approaches. The ensemble SVM classifiers and balanced-datasets can solve the class-imbalanced problem, as well as improve performance of classifier for mature miRNA identification. MatFind is an accurate and fast method for 5' mature miRNA identification. PMID:27181057

  7. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging Xpd mice.

    Directory of Open Access Journals (Sweden)

    Jung Yoon Park

    Full Text Available Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. Xpd(TTD mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W, display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing Xpd(TTD mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the Xpd(TTD mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the Xpd(TTD mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis.

  8. Gene numerical imbalances in cytological specimens based on fluorescence/chromogenic in situ hybridization analysis.

    Science.gov (United States)

    Tsiambas, E; Karameris, A; Lygeros, M; Athanasiou, A E; Salemis, N S; Gourgiotis, S; Ragkos, V; Metaxas, G E; Vilaras, G; Patsouris, E

    2012-01-01

    Design and development of novel targeted therapeutic strategies is an innovation in handling patients with solid malignancies including breast, colon, lung, head & neck or even pancreatic and hepatocellular carcinoma. For a long time, immunohistocytochemistry (IHC/ICC) has been performed as a routine method in almost all labs for evaluating protein expression. Modern molecular approaches show that identification of specific structural and numerical imbalances regarding genes involved in signal transduction pathways provide important data to the oncologists. Alterations in molecules such as epidermal growth factor receptor (EGFR), HER2/neu, PTEN or Topoisomerase IIa affect the response rates to specific chemotherapeutic agents modifying also patients' prognostic rates. In situ hybridization (ISH) techniques based on fluorescence and chromogenic variants (FISH/CISH) or silver in situ hybridization (SISH) are applicable in both tissue and cell substrates. Concerning cytological specimens, FISH/CISH analysis appears to be a fast and very accurate method in estimating gene/chromosome ratios. In this paper, we sought to evaluate the usefulness of FISH/ CISH analysis in cytological specimens, describing also the advantages and disadvantages of these methods from the technical point of view. PMID:23033306

  9. Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

    Directory of Open Access Journals (Sweden)

    Lorand-Metze Irene

    2010-05-01

    Full Text Available Abstract Background Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang - are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results Patients that evolved with septic shock (n = 10 presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31. These levels correlated with sepsis severity scores. Conclusions Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia.

  10. Cross-Platform Assessment of Genomic Imbalance Confirms the Clinical Relevance of Genomic Complexity and Reveals Loci with Potential Pathogenic Roles in Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    Dias, Lizalynn M.; Thodima, Venkata; Friedman, Julia; Ma, Charles; Guttapalli, Asha; Mendiratta, Geetu; Siddiqi, Imran N.; Syrbu, Sergei; Chaganti, R. S. K.; Houldsworth, Jane

    2016-01-01

    Genomic copy number alterations (CNAs) in diffuse large B-cell lymphoma (DLBCL) have roles in disease pathogenesis but overall clinical relevance remains unclear. Herein, an unbiased algorithm was uniformly applied across three genome profiling datasets comprising 392 newly-diagnosed DLBCL specimens that defined 32 overlapping CNAs, involving 36 minimal common regions (MCRs). Scoring criteria were established for 50 aberrations within the MCRs while considering peak gains/losses. Application of these criteria to independent datasets revealed novel candidate genes with coordinated expression, such as CNOT2, potentially with pathogenic roles. No one single aberration significantly associated with patient outcome across datasets, but genomic complexity, defined by imbalance in more than one MCR, significantly portended adverse outcome in two of three independent datasets. Thus, the standardized scoring of CNAs currently developed can be uniformly applied across platforms, affording robust validation of genomic imbalance and complexity in DLBCL and overall clinical utility as biomarkers of patient outcome. PMID:26294112

  11. An allelic series of Trp63 mutations defines TAp63 as a modifier of EEC syndrome.

    Science.gov (United States)

    Vernersson Lindahl, Emma; Garcia, Elvin L; Mills, Alea A

    2013-08-01

    Human Ectrodactyly, Ectodermal dysplasia, Clefting (EEC) syndrome is an autosomal dominant developmental disorder defined by limb deformities, skin defects, and craniofacial clefting. Although associated with heterozygous missense mutations in TP63, the genetic basis underlying the variable expressivity and incomplete penetrance of EEC is unknown. Here, we show that mice heterozygous for an allele encoding the Trp63 p.Arg318His mutation, which corresponds to the human TP63 p.Arg279His mutation found in patients with EEC, have features of human EEC. Using an allelic series, we discovered that whereas clefting and skin defects are caused by loss of Trp63 function, limb anomalies are due to gain- and/or dominant-negative effects of Trp63. Furthermore, we identify TAp63 as a strong modifier of EEC-associated phenotypes with regard to both penetrance and expressivity. PMID:23775923

  12. The role of intracellular redox imbalance in nanomaterial induced cellular damage and genotoxicity

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Chauché, Caroline; Brown, David M;

    2015-01-01

    (ROS) production, neutralizing ROS (scavengers), enzymatic nucleotide pool sanitation, and DNA repair. This review discusses the importance of the maintenance of the redox balance in this context before examining studies that have investigated engineered NM induced redox imbalance and genotoxicity...

  13. An Analysis of Economic Growth, Competitiveness and Macroeconomic Imbalances in the European Union

    Directory of Open Access Journals (Sweden)

    Gheorghe Hurduzeu

    2015-09-01

    Full Text Available Taking into consideration the determinants of the economic crisis and of the sovereign debt crisis, we aim to analyze the dynamics of the European economies and discuss changes related to macroeconomic imbalances, as highlighted by the recent crises as an important factor of the unfavorable dynamics registered during the last years. In this respect we considered both internal and external imbalances, as specified in the macroeconomic imbalance procedure that was implemented for the European Union member states since 2012, as a response to the crises that affected all open economies of the world. The purpose of this article is to provide a comprehensive analysis of economic imbalances in the European Union and to determine their influence on economic growth.

  14. A novel control scheme for simultaneous elimination of imbalance, disturbance and voltage harmonic in power systems

    Institute of Scientific and Technical Information of China (English)

    Javad Olamaei; Farnoosh NarjabadiFam; Amid Nazeri

    2014-01-01

    In recent years, the increasing application of nonlinear and unbalanced electronic equipment and large single phase loads have made voltage imbalance a serious problem in power distribution systems. A novel approach has been proposed to eliminate voltage imbalance and disturbances. The main strategy of this scheme is based on series active filter. By improving control circuit toward existing schemes and proposing a new strategy to control the voltage amplitude, simultaneous elimination of voltage imbalance, faults, voltage harmonics and also compensation of voltage drop in transmission lines become possible. Eventually, the voltage on the load side is a perfectly balanced three phase voltage with specific proper amplitude. The proposed scheme has been simulated in a test network and the results show high capability of this scheme for the complete elimination of imbalance without phase shift.

  15. Analysis and compensation of I/Q imbalance in amplify-and-forward cooperative systems

    KAUST Repository

    Qi, Jian

    2012-04-01

    In this paper, dual-hop amplify-and-forward (AF) cooperative systems in the presence of in-phase and quadrature-phase (I/Q) imbalance, which refers to the mismatch between components in I and Q branches, are investigated. First, we analyze the performance of the considered AF cooperative protocol without compensation for I/Q imbalance as the benchmark. Furthermore, a compensation algorithm for I/Q imbalance is proposed, which makes use of the received signals at the destination, from the source and relay nodes, together with their conjugations to detect the transmitted signal. The performance of the AF cooperative system under study is evaluated in terms of average symbol error probability (SEP), which is derived considering transmission over Rayleigh fading channels. Numerical results are provided and show that the proposed compensation algorithm can efficiently mitigate the effect of I/Q imbalance. © 2012 IEEE.

  16. A single-to-differential low-noise amplifier with low differential output imbalance

    Institute of Scientific and Technical Information of China (English)

    Duan Lian; Huang Wei; Ma Chengyan; He Xiaofeng; Jin Yuhua; Ye Tianchun

    2012-01-01

    This paper presents a single-ended input differential output low-noise amplifier intended for GPS applications.We propose a method to reduce the gain/amplitude and phase imbalance of a differential output exploiting the inductive coupling of a transformer or center-tapped differential inductor.A detailed analysis of the theory of imbalance reduction,as well as a discussion on the principle of choosing the dimensions of a transformer,are given.An LNA has been implemented using TSMC 0.18μm technology with ESD-protected.Measurement on board shows a voltage gain of 24.6 dB at 1.575 GHz and a noise figure of 3.2 dB.The gain imbalance is below 0.2 dB and phase imbalance is less than 2 degrees.The LNA consumes 5.2 mA from a 1.8 V supply.

  17. Allelic imbalance at the beta-catenin gene (CTNNB1 at 3p22-21.3) in various human tumor types

    NARCIS (Netherlands)

    Nollet, F; van den Berg, Anke; Kersemaekers, AM; CletonJansen, AM; Berx, G; VanderVeen, AY; Eichperger, C; Wieland, [No Value; DeGreve, J; Liefers, GJ; Xiao, WH; Buys, CHCM; Cornelisse, C; VanRoy, F

    1997-01-01

    beta-catenin is a multifunctional protein: it plays a central role in the cell-cell adhesive junctions, and participates in transduction of the morphogenic Wingless/Wnt-signal. Upon detailed analysis of the human beta-catenin gene, an intragenic polymorphic microsatellite marker could be identified.

  18. 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

  19. A comparative study of imbalance reduction strategies for virtual power plant operation

    International Nuclear Information System (INIS)

    The penetration of a large amount of distributed generation (DG) technologies with intermittent output, such as photovoltaic installations and wind turbines, yields an important challenge to the electric grid. It is believed that aggregating them with controllable technologies such as cogeneration devices (CHP) can help to balance fluctuations of renewable energy. This work evaluates the ability of a virtual power plant (VPP) to reduce the imbalance error of renewable generators. The study is undertaken in a VPP that consists of several cogeneration devices and photovoltaic (PV) installations. The virtual power plant operator bids electricity into the day-ahead market using the forecast for solar irradiation and for the thermal demand. During the actual day, the imbalance due to deviations between the forecasted electricity delivered and the real output has to be settled in the balancing market. Thus, in order to compensate these errors and possible economic drawbacks, the operation of the CHP is adjusted periodically in a so called reschedule. Two different rescheduling strategies are compared against a ‘reference scenario’ in which the imbalance error is settled in the market. The first one (‘forced strategy’) aims at reducing the imbalance error every time step regardless of the imbalance prices. The second (‘economic strategy’) considers the imbalance prices and takes only action if it is economically appropriate and thus intends to reduce the total operational cost. The results show that the rescheduling technique is able to reduce the imbalance error (up to 90% depending on the season and the strategy). Additionally, the total operational cost is estimated. However, the nowadays imbalance prices only lead to a minor financial advantage that is unlikely to motivate real life operators to perform a rescheduling strategy. - Highlights: • The VPP is dispatched by a day-ahead optimization followed by a rescheduling. • A forced rescheduling strategy

  20. An Allelic Series of Trp63 Mutations Defines TAp63 as a Modifier of EEC Syndrome

    OpenAIRE

    Lindahl, Emma Vernersson; Garcia, Elvin L.; Mills, Alea A.

    2013-01-01

    Human Ectrodactyly, Ectodermal dysplasia, Clefting (EEC) syndrome is an autosomal dominant developmental disorder defined by limb deformities, skin defects, and craniofacial clefting. Although associated with heterozygous missense mutations in TP63, the genetic basis underlying the variable expressivity and incomplete penetrance of EEC is unknown. Here we show that mice heterozygous for an allele encoding the Trp63 p.Arg318His mutation, which corresponds to the human TP63 p.Arg279His mutation...

  1. Specific Silencing of L392V PSEN1 Mutant Allele by RNA Interference

    OpenAIRE

    Malgorzata Sierant; Alina Paduszynska; Julia Kazmierczak-Baranska; Benedetta Nacmias; Sandro Sorbi; Silvia Bagnoli; Elzbieta Sochacka; Barbara Nawrot

    2011-01-01

    RNA interference (RNAi) technology provides a powerful molecular tool to reduce an expression of selected genes in eukaryotic cells. Short interfering RNAs (siRNAs) are the effector molecules that trigger RNAi. Here, we describe siRNAs that discriminate between the wild type and mutant (1174 C→G) alleles of human Presenilin1 gene (PSEN1). This mutation, resulting in L392V PSEN1 variant, contributes to early onset familial Alzheimer's disease. Using the dual fluorescence assay, flow cytometry ...

  2. Allele-specific silencing of mutant Huntington’s disease gene

    OpenAIRE

    Zhang, Yu; Engelman, Joshua; Friedlander, Robert M.

    2009-01-01

    Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a poly-glutamine expansion in huntingtin, the protein encoded by the HD gene. PolyQ-expanded huntingtin is toxic to neurons, especially the medium spiny neurons (MSNs) of the striatum. At the same time, wild-type huntingtin has important -- indeed essential -- protective functions. Any effective molecular therapy must preserve the expression of wild-type huntingtin, while silencing the mutant allele. We hy...

  3. Multiple Alleles of Treponema pallidum Repeat Gene D in Treponema pallidum Isolates

    OpenAIRE

    Centurion-Lara, Arturo; Sun, Eileen S.; Barrett, Lynn K.; Castro, Christa; Lukehart, Sheila A.; Van Voorhis, Wesley C.

    2000-01-01

    Two new tprD alleles have been identified in Treponema pallidum: tprD2 is found in 7 of 12 T. pallidum subsp. pallidum isolates and 7 of 8 non-pallidum isolates, and tprD3 is found in one T. pallidum subsp. pertenue isolate. Antibodies against TprD2 are found in persons with syphilis, demonstrating that tprD2 is expressed during infection.

  4. Efficient allele-specific targeting of LRRK2 R1441 mutations mediated by RNAi.

    Directory of Open Access Journals (Sweden)

    Laura de Yñigo-Mojado

    Full Text Available Since RNA interference (RNAi has the potential to discriminate between single nucleotide changes, there is growing interest in the use of RNAi as a promising therapeutical approach to target dominant disease-associated alleles. Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene have been linked to dominantly inherited Parkinson's disease (PD. We focused on three LRRK2 mutations (R1441G/C and the more prevalent G2109S hoping to identify shRNAs that would both recognize and efficiently silence the mutated alleles preferentially over the wild-type alleles. Using a luciferase-based reporter system, we identified shRNAs that were able to specifically target the R1441G and R1441C alleles with 80% silencing efficiency. The same shRNAs were able to silence specifically mRNAs encoding either partial or full-length mutant LRRK2 fusion proteins, while having a minimal effect on endogenous wild-type LRRK2 expression when transfected in 293FT cells. Shifting of the mutant recognition site (MRS from position 11 to other sites (4 and 16, within the 19-mer window of our shRNA design reduced specificity and overall silencing efficiency. Developing an allele-specific RNAi of G2019S was problematic. Placement of the MRS at position 10 resulted in efficient silencing of reporters (75-80%, but failed to discriminate between mutant and wild-type alleles. Shifting of the MRS to positions 4, 5, 15, 16 increased the specificity of the shRNAs, but reduced the overall silencing efficiency. Consistent with previous reports, these data confirm that MRS placement influences both allele-specificity and silencing strength of shRNAs, while further modification to hairpin design or MRS position may lead to the development of effective G2019S shRNAs. In summary, the effective shRNA against LRRK2 R1441 alleles described herein suggests that RNAi-based therapy of inherited Parkinson's disease is a viable approach towards developing effective therapeutic interventions for

  5. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    International Nuclear Information System (INIS)

    heterozygosity for the nonsense mutation causes NMD degradation of the mutant transcripts blocking expression of the truncated mutant protein and an additional trans effect on lamin A protein levels expressed from the wild type allele. We discuss the possibility that skewing of the lamin A to lamin C ratio may contribute to ensuing processes that destabilize cardiomyocytes and trigger cardiomyopathy - Highlights: • We study disease mechanisms in DCM patients carrying PTC mutations in the LMNA gene. • The mutant transcript is degraded by the nonsense mediated mRNA decay system. • Skewed lamin A to lamin C protein ratio expressed from the wild type allele. • We suggest a combined pathomechanism: haploinsuffiency plus lamin A/C imbalance

  6. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    Energy Technology Data Exchange (ETDEWEB)

    Al-Saaidi, Rasha [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Rasmussen, Torsten B. [Department of Cardiology, Aarhus University Hospital, Aarhus (Denmark); Palmfeldt, Johan [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Nissen, Peter H. [Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus (Denmark); Beqqali, Abdelaziz [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Hansen, Jakob [Department of Forensic Medicine, Bioanalytical Unit, University of Aarhus (Denmark); Pinto, Yigal M. [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Boesen, Thomas [Department of Molecular Biology and Genetics, University of Aarhus (Denmark); Mogensen, Jens [Department of Cardiology, Odense University Hospital, Odense (Denmark); Bross, Peter, E-mail: peter.bross@ki.au.dk [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark)

    2013-11-15

    heterozygosity for the nonsense mutation causes NMD degradation of the mutant transcripts blocking expression of the truncated mutant protein and an additional trans effect on lamin A protein levels expressed from the wild type allele. We discuss the possibility that skewing of the lamin A to lamin C ratio may contribute to ensuing processes that destabilize cardiomyocytes and trigger cardiomyopathy - Highlights: • We study disease mechanisms in DCM patients carrying PTC mutations in the LMNA gene. • The mutant transcript is degraded by the nonsense mediated mRNA decay system. • Skewed lamin A to lamin C protein ratio expressed from the wild type allele. • We suggest a combined pathomechanism: haploinsuffiency plus lamin A/C imbalance.

  7. Examination of Potential Benefits of an Energy Imbalance Market in the Western Interconnection

    Energy Technology Data Exchange (ETDEWEB)

    Milligan, M.; Clark, K.; King, J.; Kirby, B.; Guo, T.; Liu, G.

    2013-03-01

    In the Western Interconnection, there is significant interest in improving approaches to wide-area coordinated operations of the bulk electric power system, in part because of the increasing penetration of variable generation. One proposed solution is an energy imbalance market. This study focused on that approach alone, with the goal of identifying the potential benefits of an energy imbalance market in the year 2020.

  8. Exercise training attenuates placental ischemia induced hypertension and angiogenic imbalance in the rat

    OpenAIRE

    Gilbert, Jeffrey S; Banek, Christopher T; Bauer, Ashley J.; Gingery, Anne; Needham, Karen

    2012-01-01

    An imbalance between pro-angiogenic (vascular endothelial growth factor, VEGF) and anti-angiogenic (soluble fms-like tyrosine kinase-1, sFlt-1) factors plays an important role in hypertension associated with reduced utero-placental perfusion (RUPP). Exercise has been shown to stimulate pro-angiogenic factors such as VEGF in both the pregnant and non-pregnant state, thus we hypothesized exercise training would attenuate both angiogenic imbalance and hypertension due to RUPP. Four groups of ani...

  9. The impact of labour market imbalances on regional disparities in the post-crisis context

    OpenAIRE

    Gina Cristina DIMIAN

    2012-01-01

    The paper aims to examine how existing imbalances in the labour market influence regions’ future development and to formulate a series of recommendations that will allow that catching up process to be done in an sustainable manner. Basically, the objective refers to the integration of the development and restructuring strategy of the labour market policy to strengthen regional competitive advantage. Our intentions is to stress the fact that between labour market imbalances and regional dispar...

  10. Global imbalances: the perspective of the Banco de México.

    OpenAIRE

    A. Carstens

    2011-01-01

    Global imbalances (GIs) have been with us for quite some time. To a large extent, for many years they were disregarded by the world economic powers. Such imbalances provided fertile ground for a major financial crisis to erupt. Regretfully, many of the policy measures implemented as a response to the crisis have exacerbated the damaging potential of GIs. The most recent manifestation of this is the rapid expansion of beggar-thy-neighbour policies that an uncoordinated policy response to GIs i...

  11. Can an energy balance model provide additional constraints on how to close the energy imbalance?

    OpenAIRE

    Wohlfahrt, Georg; Widmoser, Peter

    2013-01-01

    Elucidating the causes for the energy imbalance, i.e. the phenomenon that eddy covariance latent and sensible heat fluxes fall short of available energy, is an outstanding problem in micrometeorology. This paper tests the hypothesis that the full energy balance, through incorporation of additional independent measurements which determine the driving forces of and resistances to energy transfer, provides further insights into the causes of the energy imbalance and additional constraints on ene...

  12. Comprehensive Investigation on Current Imbalance among Parallel Chips inside MW-Scale IGBT Power Modules

    DEFF Research Database (Denmark)

    Wu, Rui; Smirnova, Liudmila; Wang, Huai;

    2015-01-01

    With the demands for increasing the power rating and improving reliability level of the high power IGBT modules, there are further needs of understanding how to achieve stable paralleling and identical current sharing between the chips. This paper investigates the stray parameters imbalance among...... parallel chips inside the 1.7 kV/1 kA high power IGBT modules at different frequencies by Ansys Q3D parastics extractor. The resulted current imbalance is further confirmed by experimental measurement....

  13. Comprehensive Investigation on Current Imbalance among Parallel Chips inside MW-Scale IGBT Power Modules

    OpenAIRE

    Wu, Rui; Smirnova, Liudmila; Wang, Huai; Iannuzzo, Francesco; Blaabjerg, Frede

    2015-01-01

    With the demands for increasing the power rating and improving reliability level of the high power IGBT modules, there are further needs of understanding how to achieve stable paralleling and identical current sharing between the chips. This paper investigates the stray parameters imbalance among parallel chips inside the 1.7 kV/1 kA high power IGBT modules at different frequencies by Ansys Q3D parastics extractor. The resulted current imbalance is further confirmed by experimental measurement.

  14. 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.

  15. Cenozoic carbon cycle imbalances and a variable weathering feedback

    Science.gov (United States)

    Caves, Jeremy K.; Jost, Adam B.; Lau, Kimberly V.; Maher, Kate

    2016-09-01

    The long-term stability of Earth's climate and the recovery of the ocean-atmosphere system after carbon cycle perturbations are often attributed to a stabilizing negative feedback between silicate weathering and climate. However, evidence for the operation of this feedback over million-year timescales and in response to tectonic and long-term climatic change remains scarce. For example, the past 50 million years of the Cenozoic Era are characterized by long-term cooling and declining atmospheric CO2 (pCO2). During this interval, constant or decreasing carbon fluxes from the solid Earth to the atmosphere suggest that stable or decreasing weathering fluxes are needed to balance the carbon cycle. In contrast, marine isotopic proxies of weathering (i.e., 87Sr/86Sr, δ7 Li , and 187Os/188Os) are interpreted to reflect increasing weathering fluxes. Here, we evaluate the existence of a negative feedback by reconstructing the imbalance in the carbon cycle during the Cenozoic using the surface inventories of carbon and alkalinity. Only a sustained 0.25-0.5% increase in silicate weathering is necessary to explain the long-term decline in pCO2 over the Cenozoic. We propose that the long-term decrease in pCO2 is due to an increase in the strength of the silicate weathering feedback (i.e., the constant of proportionality between the silicate weathering flux and climate), rather than an increase in the weathering flux. This increase in the feedback strength, which mirrors the marine isotope proxies, occurs as transient, 1 million year timescales remains invariant to match the long-term inputs of carbon. Over the Cenozoic, this results in stable long-term weathering fluxes even as pCO2 decreases. We attribute increasing feedback strength to a change in the type and reactivity of rock in the weathering zone, which collectively has increased the reactivity of the surface of the Earth. Increasing feedback strength through the Cenozoic reconciles mass balance in the carbon cycle with

  16. Analysis of the imbalance price scheme in the Spanish electricity market: A wind power test case

    International Nuclear Information System (INIS)

    This work investigates the interaction between wind power and electricity markets. The paper is focused on balancing markets pricing policies. The proposal of a new imbalance price scheme is included and conveniently evaluated. This proposed scheme tries to minimise the use of ancillary services to compensate for deviations in searching for a more efficient market design. The effectiveness of imbalance prices as market signals is also examined, and policy recommendations regarding imbalance services are discussed. Two test cases are included that analyse the participation of a wind power producer in the Spanish electricity market using a stochastic optimisation strategy. For this purpose, the uncertainty of the variables is considered, i.e., wind power production and prediction, intraday and imbalance prices. Test cases were run with real data for 10 months, and realistic results are presented along with a hypothetical test case. The regulation of the imbalance prices may not be adequate for the Spanish electricity market because an error drop is not sufficiently encouraged. Therefore, we suggest the application of a new imbalance price scheme, which includes an additional constraint. The conclusions of this paper can be assumed to be general policy recommendations

  17. Study of IQ imbalance effect in direct-detection optical OFDM systems

    Science.gov (United States)

    Li, Xinying; Shao, Yufeng; Zou, Shumin; Hou, Chunning; Zheng, Xi; Liu, Xiao; Zhang, Junwen; Fang, Wuliang; Chi, Nan

    2009-11-01

    In-phase/quadrature-phase (IQ) imbalance can result in severe performance degradation in optical direct-detection orthogonal-frequency-division-multiplexing (DD-OFDM) systems. We build two optical back-to-back DD-OFDM systems, which implement double-sideband (DSB) and single-sideband (SSB) modulation, respectively. The tolerance to IQ imbalance of these two systems is analyzed and compared using error vector magnitude (EVM) and symbol error rate (SER). We find that, in the back-to-back case, the DSB system has stronger robustness to IQ imbalance than the SSB System. We further build two optical DD-OFDM systems each with 40-km transmission, which respectively implement DSB and SSB transmission. Similarly, we analyze and compare the tolerance to IQ imbalance of these two systems in terms of EVM and SER. We find that, however, in the case of 40-km transmission, the SSB system has stronger robustness to IQ imbalance than the DSB system. As a result, we conclude that, in the case of transmission, SSB modulation can enhance the tolerance to IQ imbalance of DD-OFDM systems.

  18. Generation of mice harbouring a conditional loss-of-function allele of Gata6

    Directory of Open Access Journals (Sweden)

    Duncan Stephen A

    2006-04-01

    Full Text Available Abstract The zinc finger transcription factor GATA6 is believed to have important roles in the development of several organs including the liver, gastrointestinal tract and heart. However, analyses of the contribution of GATA6 toward organogenesis have been hampered because Gata6-/- mice fail to develop beyond gastrulation due to defects in extraembryonic endoderm function. We have therefore generated a mouse line harbouring a conditional loss-of-function allele of Gata6 using Cre/loxP technology. LoxP elements were introduced into introns flanking exon 2 of the Gata6 gene by homologous recombination in ES cells. Mice containing this altered allele were bred to homozygosity and were found to be viable and fertile. To assess the functional integrity of the loxP sites and to confirm that we had generated a Gata6 loss-of-function allele, we bred Gata6 'floxed' mice to EIIa-Cre mice in which Cre is ubiquitously expressed, and to Villin-Cre mice that express Cre in the epithelial cells of the intestine. We conclude that we have generated a line of mice in which GATA6 activity can be ablated in a cell type specific manner by expression of Cre recombinase. This line of mice can be used to establish the role of GATA6 in regulating embryonic development and various aspects of mammalian physiology.

  19. 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

  20. 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

  1. 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.

  2. Comparison between subjects with long- and short-allele carriers in the BOLD signal within amygdala during emotional tasks

    Science.gov (United States)

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

    2012-03-01

    Emotional tasks may result in a strong blood oxygen level-dependent (BOLD) signal in the amygdala in 5- HTTLRP short-allele. Reduced anterior cingulate cortex (ACC)-amygdala connectivity in short-allele provides a potential mechanistic account for the observed increase in amygdala activity. In our study, fearful and threatening facial expressions were presented to two groups of 12 subjects with long- and short-allele carriers. The BOLD signals of the left amygdala of each group were averaged to increase the signal-to-noise ratio. A Bayesian approach was used to estimate the model parameters to elucidate the underlying hemodynamic mechanism. Our results showed a positive BOLD signal in the left amygdala for short-allele individuals, and a negative BOLD signal in the same region for long-allele individuals. This is due to the fact that short-allele is associated with lower availability of serotonin transporter (5-HTT) and this leads to an increase of serotonin (5-HT) concentration in the cACC-amygdala synapse.

  3. Chromosomal imbalances in successive moments of human bladder urothelial carcinoma

    DEFF Research Database (Denmark)

    Nascimento e Pontes, Merielen Garcia; da Silveira, Sara Martorelli; Trindade Filho, José Carlos de Souza;

    2013-01-01

    OBJECTIVE: To understand developmental characteristics of urinary bladder carcinomas (UBC) by evaluating genomic alterations and p53 protein expression in primary tumors, their recurrences, and in the morphologically normal urothelium of UBC patients. METHODS: Tumors and their respective recurren...

  4. Drop-out probabilities of IrisPlex SNP alleles

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  5. 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.

  6. Pistil-function breakdown in a new S-allele of European pear, S21*, confers self-compatibility.

    Science.gov (United States)

    Sanzol, Javier

    2009-03-01

    European pear exhibits RNase-based gametophytic self-incompatibility controlled by the polymorphic S-locus. S-allele diversity of cultivars has been extensively investigated; however, no mutant alleles conferring self-compatibility have been reported. In this study, two European pear cultivars, 'Abugo' and 'Ceremeño', were classified as self-compatible after fruit/seed setting and pollen tube growth examination. S-genotyping through S-PCR and sequencing identified a new S-RNase allele in the two cultivars, with identical deduced amino acid sequence as S(21), but differing at the nucleotide level. Test-pollinations and analysis of descendants suggested that the new allele is a self-compatible pistil-mutated variant of S(21), so it was named S(21)*. S-genotypes assigned to 'Abugo' and 'Ceremeño' were S(10)S(21)* and S(21)*S(25) respectively, of which S(25) is a new functional S-allele of European pear. Reciprocal crosses between cultivars bearing S(21) and S(21)* indicated that both alleles exhibit the same pollen function; however, cultivars bearing S(21)* had impaired pistil-S function as they failed to reject either S(21) or S (21)* pollen. RT-PCR analysis showed absence of S(21)* -RNase gene expression in styles of 'Abugo' and 'Ceremeño', suggesting a possible origin for S(21)* pistil dysfunction. Two polymorphisms found within the S-RNase genomic region (a retrotransposon insertion within the intron of S(21)* and indels at the 3'UTR) might explain the different pattern of expression between S(21) and S(21)*. Evaluation of cultivars with unknown S-genotype identified another cultivar 'Azucar Verde' bearing S(21)*, and pollen tube growth examination confirmed self-compatibility for this cultivar as well. This is the first report of a mutated S-allele conferring self-compatibility in European pear. PMID:19096853

  7. 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

  8. 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.

  9. The experience of the applications of the equation of the water-energy imbalance in the study of water resources of China

    Science.gov (United States)

    Yang, H.; Yang, D.; Xu, X.

    2011-12-01

    The water-energy balance equation reveals a relationship of actual evaporation (E) with potential evaporation (Ep) and precipitation (P) over a long-term time scale, i.e. a stabilized relationship between E/P and Ep/P. However, this relationship becomes an imbalance at smaller time scales. A new equation, Hanbo Yang Equation, for the imbalance introduced water storage (S), which described a stabilized relationship between E/(P+S) and Ep/(P+S), called the equation of the water-energy imbalance. Hanbo Yang Equation was used to estimate actual evaporation at the Weishan experiment station in China and the Yakutsk experiment station in Russia, as well as in Luan River in northern China. The results show the equation has a good performance. Additionally, the parameter, showing a seasonal variation, can be related to vegetation status. In regions receiving additional water transported from other regions, the available water can be expressed as (P + I + S), with I representing water intake. Therefore, it leads to a new stabilized relationship between E/(P+I+S) and Ep/(P+I+S). Based on the relationship, monthly water consumption of the Yerqiang Oases, locating in Xinjiang province of China, was assessed. The results show a good agreement with that estimated by the runoff-evaporation hydrological model. It indicates that the equation is a novel tool to estimate water consumption, and a novel tool to assess water demand.

  10. Factors Influencing Oxidative Imbalance in Pulmonary Fibrosis: An Immunohistochemical Study

    Directory of Open Access Journals (Sweden)

    Simona Inghilleri

    2011-01-01

    Full Text Available Background. Idiopathic Pulmonary Fibrosis (IPF is a fatal lung disease of unknown etiology characterized by interstitial fibrosis determining irreversible distortion of pulmonary architecture. Reactive oxygen species (ROS and markers of oxidative stress play a pivotal role in human IPF pathology, possibly through induction of epithelial-mesenchymal transition (EMT. Methods. We investigated by immunohistochemistry, in UIP and COP tissue samples, the expression of most relevant markers of the molecular interplay involving RAGE, oxidant/antioxidant balance regulation, tissue nitrosylation, and mediators of EMT. Results. In both UIP and COP, the degree of RAGE expression was similarly high, while SODs and i-NOS, diffusely present in COP endoalveolar plugs, were almost absent in UIP fibroblast foci. A lower degree of tissue nitrosilation was observed in UIP than in COP. Conclusions. Fibroblast lesions of UIP and of COP share a similar degree of activation of RAGE, while antioxidant enzyme expression markedly reduced in UIP.

  11. 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

  12. Salmonella Typhi shdA: pseudogene or allelic variant?

    Science.gov (United States)

    Urrutia, I M; Fuentes, J A; Valenzuela, L M; Ortega, A P; Hidalgo, A A; Mora, G C

    2014-08-01

    ShdA from Salmonella Typhimurium (ShdASTm) is a large outer membrane protein that specifically recognizes and binds to fibronectin. ShdASTm is involved in the colonization of the cecum and the Peyer's patches of terminal ileum in mice. On the other hand, shdA gene from Salmonella Typhi (shdASTy) has been considered a pseudogene (i.e. a nonfunctional sequence of genomic DNA) due to the presence of deletions and mutations that gave rise to premature stop codons. In this work we show that, despite the deletions and mutations, shdASTy is fully functional. S. Typhi ΔshdA mutants presented an impaired adherence and invasion of HEp-2 pre-treated with TGF-β1, an inducer of fibronectin production. Moreover, shdA from S. Typhi and S. Typhimurium seem to be equivalent since shdASTm restored the adherence and invasion of S. Typhi ΔshdA mutant to wild type levels. In addition, anti-FLAG mAbs interfered with the adherence and invasion of the S. Typhi shdA-3xFLAG strain. Finally, shdASTy encodes a detectable protein when heterologously expressed in Escherichia coli DH5α. The data presented here show that shdASTy is not a pseudogene, but a different functional allele compared with shdASTm. PMID:24859062

  13. Impact of interactions between risk alleles on clinical endpoints in hypertension

    Science.gov (United States)

    Kohli, Samantha; Kumar, Rahul; Gupta, Mohit; Tyagi, Sanjay; Pasha, M A Qadar

    2016-01-01

    Objective Impairment of the renin-angiotensinogen-aldosterone system (RAAS), one of the characteristics of essential hypertension (EH), imbalances vascular homeostasis. Despite inconsistent reports on individual single nucleotide polymorphisms (SNPs) as a major predictor of EH, interactions among RAAS genetic variants are rarely investigated. Methods Using SNP markers, we studied potential interactions between angiotensin 1 converting enzyme (ACE), angiotensinogen (AGT), angiotensin II-type 1 receptor (AGTR1), and α adducin (ADD1) variants and their correlation with clinical endpoints in 545 individuals with hypertension and 400 age- and ethnicity-matched unrelated controls. Generalised multifactor dimensionality reduction (GMDR) analysis identified the models for genotype interaction. Results Although the results on single genes were significant, gene-gene interactions were more reliable and promising as markers in predisposing hypertension. The best models to represent association of multi-locus interactions with augmented hypertension susceptibility were: (a) within gene 4-locus model comprised of AGT SNPs −217G/A, −20A/C, −6G/A and 235M/T (p=0.022, OR 6.1); and (b) between genes 5-locus model comprised of AGT −217G/A, −20A/C, −6G/A, 235M/T and ACE I/D (p=0.05, OR 4.6). Stratification of 4- and 5-locus GMDR models on the basis of risk alleles from ≤1 to ≥7 increased the ORs from 2.8 to 36.1 and from 0.9 to 16.1, respectively. Moreover, compared to ≤1 risk alleles the ≥7 interacting risk alleles in both 4- and 5-locus models showed an increment of 14.2% and 11.1% in systolic blood pressure, 7.7% and 1.1% in diastolic blood pressure, and 10.5% and 5.1% in mean arterial pressure, respectively, in patients. Conclusions Interactions among the genetic loci of RAAS components may be used as a predictor for susceptibility to hypertension.

  14. A Risk Allele for Nicotine Dependence in CHRNA5 Is a Protective Allele for Cocaine Dependence

    Science.gov (United States)

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

    2008-01-01

    Background A non-synonymous coding polymorphism, rs16969968, of the CHRNA5 gene which encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence (20). The goal of the present study is to examine the association of this variant with cocaine dependence. Methods Genetic association analysis in two, independent samples of unrelated cases and controls; 1.) 504 European-American participating in the Family Study on Cocaine Dependence (FSCD); 2.) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholsim (COGA). Results In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (OR = 0.67 per allele, p = 0.0045, assuming an additive genetic model), but in the reverse direction compared to that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. Conclusion The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways. PMID:18519132

  15. Are ???Endurance??? Alleles ???Survival??? Alleles? Insights from the ACTN3 R577X Polymorphism

    OpenAIRE

    Fiuza-Luces, Carmen; Ruiz, Jonatan R.; Rodr??guez-Romo, Gabriel; Santiago, Catalina; G??mez-Gallego, F??lix; Yvert, Thomas; Cano-Nieto, Amalia; Garatechea, Nuria; Mor??n, Mar??a; Luc??a, Alejandro

    2011-01-01

    Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ???100years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein ??-actinin-3. We compared the ACTN3 R577X genotype/allele freque...

  16. Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.

    Directory of Open Access Journals (Sweden)

    Roshan Mascarenhas

    Full Text Available mRNA translation into proteins is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs, and genetic variants remains poorly understood. mRNA levels on polysomes have been shown to correlate well with expressed protein levels, pointing to polysomal loading as a critical factor. To study regulation and genetic factors of protein translation we measured levels and allelic ratios of mRNAs and ncRNAs (including microRNAs in lymphoblast cell lines (LCL and in polysomal fractions. We first used targeted assays to measure polysomal loading of mRNA alleles, confirming reported genetic effects on translation of OPRM1 and NAT1, and detecting no effect of rs1045642 (3435C>T in ABCB1 (MDR1 on polysomal loading while supporting previous results showing increased mRNA turnover of the 3435T allele. Use of high-throughput sequencing of complete transcript profiles (RNA-Seq in three LCLs revealed significant differences in polysomal loading of individual RNA classes and isoforms. Correlated polysomal distribution between protein-coding and non-coding RNAs suggests interactions between them. Allele-selective polysome recruitment revealed strong genetic influence for multiple RNAs, attributable either to differential expression of RNA isoforms or to differential loading onto polysomes, the latter defining a direct genetic effect on translation. Genes identified by different allelic RNA ratios between cytosol and polysomes were enriched with published expression quantitative trait loci (eQTLs affecting RNA functions, and associations with clinical phenotypes. Polysomal RNA-Seq combined with allelic ratio analysis provides a powerful approach to study polysomal RNA recruitment and regulatory variants affecting protein translation.

  17. Biosemiotic Entropy of the Genome: Mutations and Epigenetic Imbalances Resulting in Cancer

    Directory of Open Access Journals (Sweden)

    Samuel S. Shepard

    2013-01-01

    Full Text Available Biosemiotic entropy involves the deterioration of biological sign systems. The genome is a coded sign system that is connected to phenotypic outputs through the interpretive functions of the tRNA/ribosome machinery. This symbolic sign system (semiosis at the core of all biology has been termed “biosemiosis”. Layers of biosemiosis and cellular information management are analogous in varying degrees to the semiotics of computer programming, spoken, and written human languages. Biosemiotic entropy — an error or deviation from a healthy state — results from errors in copying functional information (mutations and errors in the appropriate context or quantity of gene expression (epigenetic imbalance. The concept of biosemiotic entropy is a deeply imbedded assumption in the study of cancer biology. Cells have a homeostatic, preprogrammed, ideal or healthy state that is rooted in genomics, strictly orchestrated by epigenetic regulation, and maintained by DNA repair mechanisms. Cancer is an eminent illustration of biosemiotic entropy, in which the corrosion of genetic information via substitutions, deletions, insertions, fusions, and aberrant regulation results in malignant phenotypes. However, little attention has been given to explicitly outlining the paradigm of biosemiotic entropy in the context of cancer. Herein we distill semiotic theory (from the familiar and well understood spheres of human language and computer code to draw analogies useful for understanding the operation of biological semiosis at the genetic level. We propose that the myriad checkpoints, error correcting mechanisms, and immunities are all systems whose primary role is to defend against the constant pressure of biosemiotic entropy, which malignancy must shut down in order to achieve advanced stages. In lieu of the narrower tumor suppressor/oncogene model, characterization of oncogenesis into the biosemiotic framework of sign, index, or object entropy may allow for more

  18. 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

  19. 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

  20. Generation of New Hairless Alleles by Genomic Engineering at the Hairless Locus in Drosophila melanogaster

    Science.gov (United States)

    Praxenthaler, Heiko; Smylla, Thomas K.; Nagel, Anja C.; Preiss, Anette; Maier, Dieter

    2015-01-01

    Hairless (H) is the major antagonist within the Notch signalling pathway of Drosophila melanogaster. By binding to Suppressor of Hairless [Su(H)] and two co-repressors, H induces silencing of Notch target genes in the absence of Notch signals. We have applied genomic engineering to create several new H alleles. To this end the endogenous H locus was replaced with an attP site by homologous recombination, serving as a landing platform for subsequent site directed integration of different H constructs. This way we generated a complete H knock out allele HattP, reintroduced a wild type H genomic and a cDNA-construct (Hgwt, Hcwt) as well as two constructs encoding H proteins defective of Su(H) binding (HLD, HiD). Phenotypes regarding viability, bristle and wing development were recorded, and the expression of Notch target genes wingless and cut was analysed in mutant wing discs or in mutant cell clones. Moreover, genetic interactions with Notch (N5419) and Delta (DlB2) mutants were addressed. Overall, phenotypes were largely as expected: both HLD and HiD were similar to the HattP null allele, indicating that most of H activity requires the binding of Su(H). Both rescue constructs Hgwt and Hcwt were homozygous viable without phenotype. Unexpectedly, the hemizygous condition uncovered that they were not identical to the wild type allele: notably Hcwt showed a markedly reduced activity, suggesting the presence of as yet unidentified regulatory or stabilizing elements in untranslated regions of the H gene. Interestingly, Hgwt homozygous cells expressed higher levels of H protein, perhaps unravelling gene-by-environment interactions. PMID:26448463

  1. 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.

  2. Detection of chromosome imbalances in retinoblastoma by parallel karyotype and CGH analyses.

    Science.gov (United States)

    Mairal, A; Pinglier, E; Gilbert, E; Peter, M; Validire, P; Desjardins, L; Doz, F; Aurias, A; Couturier, J

    2000-08-01

    We have studied a series of 20 primary retinoblastomas by karyotypic analysis and comparative genomic hybridization (CGH), to perform an exhaustive evaluation of chromosome imbalances in this tumor. In addition, 4 tumors were studied by CGH only. On the whole, CGH results were largely in agreement with those of karyotypic analysis and with known cytogenetic data. The most frequent imbalances were +6p (13/24 cases), +1q (12/24), -16/-16q (11/24), and +2p (9/24). Recurrent high-level amplifications were observed in 2p23-25 and 1q21. Amplification of 2p23-25, present in 4 cases among which 3 showed double-minute chromosomes, was related to MYCN amplification, as demonstrated by FISH and PCR. No evident correlation was found in this small series between any of the imbalances identified and either the differentiation or the histoprognostic risk. PMID:10862045

  3. Codigestion of manure and industrial organic waste at centralized biogas plants: process imbalances and limitations

    DEFF Research Database (Denmark)

    Bangsø Nielsen, Henrik; Angelidaki, Irini

    2008-01-01

    The present study focuses on process imbalances in Danish centralized biogas plants treating manure in combination with industrial waste. Collection of process data from various full-scale plants along with a number of interviews showed that imbalances occur frequently. High concentrations of...... conditions) and high fractions of industrial waste in the feedstock was also observed. The process imbalances and suboptimal conditions are mainly allowed to occur due to 1) inadequate knowledge about the waste composition, 2) inadequate knowledge about the waste degradation characteristics, 3) inadequate...... process surveillance, especially with regard to volatile fatty acids, and 4) insufficient pre-storage capacity causing inexpedient mixing and hindering exact dosing of the different waste products....

  4. CONTROL PARAMETERS FOR UNDERSTANDING AND PREVENTING PROCESS IMBALANCES IN BIOGAS PLANTS. EMPHAS IS ON VFA DYNAMICS

    DEFF Research Database (Denmark)

    Bangsø Nielsen, Henrik

    control and understanding are necessary. The work of present study was directed towards this challenge. Initially, the response of the anaerobic digestion process to various types of process imbalances was investigated with special focus on volatile fatty acid dynamics (VFA), methane production and p...... indication of process imbalances in biogas plants. At Danish full-scale biogas plants the biogas production is normally the only continuously measured parameter. In order to examine the usability of propionate as control parameter a reactor experiment was constructed in which the reactor operation either was...... carried out on the basis of the methane production or on the basis of fluctuations in the concentration of propionate. The experiment confirmed that propionate is a useful parameter for (1) indication of process imbalances and (2) for regulation and optimization of the anaerobic digestion process in CSTRs...

  5. Identification and Evolution of Functional Alleles of the Previously Described Pollen Specific Myrosinase Pseudogene AtTGG6 in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Lili Fu

    2016-02-01

    Full Text Available Myrosinases are β-thioglucoside glucohydrolases and serve as defense mechanisms against insect pests and pathogens by producing toxic compounds. AtTGG6 in Arabidopsis thaliana was previously reported to be a myrosinase pseudogene but specifically expressed in pollen. However, we found that AlTGG6, an ortholog to AtTGG6 in A. lyrata (an outcrossing relative of A. thaliana was functional, suggesting that functional AtTGG6 alleles may still exist in A. thaliana. AtTGG6 alleles in 29 A. thaliana ecotypes were cloned and sequenced. Results indicate that ten alleles were functional and encoded Myr II type myrosinase of 512 amino acids, and myrosinase activity was confirmed by overexpressing AtTGG6 in Pichia pastoris. However, the 19 other ecotypes had disabled alleles with highly polymorphic frame-shift mutations and diversified sequences. Thirteen frame-shift mutation types were identified, which occurred independently many times in the evolutionary history within a few thousand years. The functional allele was expressed specifically in pollen similar to the disabled alleles but at a higher expression level, suggesting its role in defense of pollen against insect pests such as pollen beetles. However, the defense function may have become less critical after A. thaliana evolved to self-fertilization, and thus resulted in loss of function in most ecotypes.

  6. Multi-hop amplify-and-forward relaying cooperation in the presence of I/Q imbalance

    KAUST Repository

    Qi, Jian

    2013-06-01

    In this paper, multi-hop cooperative networks implementing channel state information (CSI)-assisted amplify-and-forward (AF) relaying in the presence of in-phase and quadrature-phase (I/Q) imbalance are investigated. We propose a compensation algorithm for the I/Q imbalance. The performance of the multi-hop CSI-assisted AF cooperative networks with and without compensation for I/Q imbalance in Nakagami-m fading environment is evaluated in terms of average symbol error probability. Numerical results are provided and show that the proposed compensation method can effectively mitigate the impact of I/Q imbalance. © 2013 IEEE.

  7. Generation and characterization of a novel neural crest marker allele, Inka1-LacZ, reveals a role for Inka1 in mouse neural tube closure

    OpenAIRE

    Reid, Bethany S.; Sargent, Thomas D.; Williams, Trevor

    2010-01-01

    Previous studies identified Inka1 as a gene regulated by AP-2α in the neural crest required for craniofacial morphogenesis in fish and frog. Here, we extend the analysis of Inka1 function and regulation to the mouse by generating a LacZ knock-in allele. Inka1-LacZ allele expression occurs in the cephalic mesenchyme, heart, and paraxial mesoderm prior to E8.5. Subsequently, expression is observed in the migratory neural crest cells and their derivatives. Consistent with expression of Inka1 in ...

  8. The imbalance between TIMP3 and matrix-degrading enzymes plays an important role in intervertebral disc degeneration.

    Science.gov (United States)

    Li, Yan; Li, Kang; Han, Xiuguo; Mao, Chuanyuan; Zhang, Kai; Zhao, Tengfei; Zhao, Jie

    2016-01-15

    It is well-known that one of the most important features of intervertebral disc degeneration (IDD) is the extracellular matrix (ECM) degradation. Collagen and aggrecan are major components of ECM; the degradation of ECM in intervertebral discs (IVDs) is closely related to the activities of collagenase and aggrecanase. TIMP-3 is the most efficient inhibitor of aggrecanase in IVD. However, only few studies focus on the potential relationship between TIMP-3 and IDD. In our study, we found TIMP-3 gene expression was decreased after stimulating with LPS in rat nucleus pulposus (NP) cells. Then we used a lentivirus vector to reconstruct rat NP cells which high expressed TIMP-3 gene (LV-TIMP3). The upregulation of MMPs and ADAMTSs induced by LPS was significantly inhibited in LV-TIMP3 cells. After overexpression of TIMP-3, the aggrecan breakdown caused by LPS was also reduced in both monolayer culture and three-dimension culture model. To further study the relation between TIMP-3 and IDD, we collected human NP tissue samples of different degenerative degrees. Real-time PCR and immunohistochemical staining showed that the expression of TIMP-3 was negatively correlated with the degree of intervertebral disc degeneration, while MMP-1 and ADAMTS-4 were markedly increased in degenerative IVD. Taken together, our results suggest that the imbalance between aggrecanase and TIMP-3 may play an important role in the pathogenesis of IDD and therefore be a potential therapeutic target for treating IDD. PMID:26686417

  9. HPV16 oncoproteins induce MMPs/RECK-TIMP-2 imbalance in primary keratinocytes: possible implications in cervical carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Laura Beatriz da Silva Cardeal

    Full Text Available Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome.

  10. Effort reward imbalance is associated with vagal withdrawal in Danish public sector employees

    DEFF Research Database (Denmark)

    Eller, Nanna Hurwitz; Blønd, Morten; Nielsen, Martin;

    2011-01-01

    The current study analyzed the relationship between psychosocial work environment assessed by the Effort Reward Imbalance Model (ERI-model) and heart rate variability (HRV) measured at baseline and again, two years later, as this relationship is scarcely covered by the literature.......The current study analyzed the relationship between psychosocial work environment assessed by the Effort Reward Imbalance Model (ERI-model) and heart rate variability (HRV) measured at baseline and again, two years later, as this relationship is scarcely covered by the literature....

  11. Automatic IQ Imbalance Compensation Technique for Quadrature Modulator by Single-Tone Testing

    Science.gov (United States)

    Kim, Minseok; Konishi, Yohei; Takada, Jun-Ichi; Gao, Boxin

    This letter proposes an automatic IQ imbalance compensation technique for quadrature modulators by means of spectrum measurement of RF signal using a spectrum analyzer. The analyzer feeds back only magnitude information of the frequency spectrum of the signal. To realize IQ imbalance compensation, the conventional method of steepest descent is modified; the descent direction is empirically determined and a variable step-size is introduced for accelerating convergence. The experimental results for a four-channel transmitter operating at 11GHz are presented for verification.

  12. Photonic microwave quadrature filter with low phase imbalance and high signal-to-noise ratio performance.

    Science.gov (United States)

    Cao, Yuan; Chan, Erwin H W; Wang, Xudong; Feng, Xinhuan; Guan, Bai-ou

    2015-10-15

    A photonic microwave quadrature filter is presented. It has a very simple structure, very low phase imbalance, and high signal-to-noise ratio performance. Experimental results are presented that demonstrate a photonic microwave quadrature filter with a 3 dB operating frequency range of 10.5-26.5 GHz, an amplitude and phase imbalance of less than ±0.3  dB and ±0.15°, and a signal-to-noise ratio of more than 121 dB in a 1 Hz noise bandwidth. PMID:26469589

  13. Probing nuclear effects using single-transverse kinematic imbalance with MINERvA

    CERN Document Server

    Lu, X -G

    2016-01-01

    Kinematic imbalance of the final-state particles in the plane transverse to the neutrino direction provides a sensitive probe of nuclear effects. In this contribution, we report the MINERvA measurement of the single-transverse kinematic imbalance in neutrino charged-current quasielastic-like events on CH targets. To improve the momentum measurements of the final-state particles, we develop a method to select elastically scattering contained (ESC) protons and a general procedure to correct the transverse momentum scales.

  14. Aberrant allele-specific replication, independent of parental origin, in blood cells of cancer patients

    International Nuclear Information System (INIS)

    Allelic counterparts of biallelically expressed genes display an epigenetic symmetry normally manifested by synchronous replication, different from genes subjected to monoallelic expression, which normally are characterized by an asynchronous mode of replication (well exemplified by the SNRPN imprinted locus). Malignancy was documented to be associated with gross modifications in the inherent replication-timing coordination between allelic counterparts of imprinted genes as well as of biallelically expressed loci. The cancer-related allelic replication timing aberrations are non-disease specific and appear in peripheral blood cells of cancer patients, including those with solid tumors. As such they offer potential blood markers for non-invasive cancer test. The present study was aimed to gain some insight into the mechanism leading to the replication timing alterations of genes in blood lymphocytes of cancer patients. Peripheral blood samples derived from patients with prostate cancer were chosen to represent the cancerous status, and samples taken from patients with no cancer but with benign prostate hyperplasia were used to portray the normal status. Fluorescence In Situ Hybridization (FISH) replication assay, applied to phytohemagglutinin (PHA)-stimulated blood lymphocytes, was used to evaluate the temporal order (either synchronous or asynchronous) of genes in the patients' cells. We demonstrated that: (i) the aberrant epigenetic profile, as delineated by the cancer status, is a reversible modification, evidenced by our ability to restore the normal patterns of replication in three unrelated loci (CEN15, SNRPN and RB1) by introducing an archetypical demethylating agent, 5-azacytidine; (ii) following the rehabilitating effect of demethylation, an imprinted gene (SNRPN) retains its original parental imprint; and (iii) the choice of an allele between early or late replication in the aberrant asynchronous replication, delineated by the cancer status, is not

  15. A New Electrophoresis Technique to Seperate Microsatellite Alleles

    Science.gov (United States)

    Traditional agarose and polyacrylamide gel electrophoresis have been used commonly for microsatellite (simple sequence repeats, SSRs) analysis, but they are labor- intensive and not always able to provide accurate sizes for different alleles. Capillary sequencers provide automated analysis and accur...

  16. Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.

    Directory of Open Access Journals (Sweden)

    Carmen Fiuza-Luces

    Full Text Available Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100 years of age. Owing to its effects on muscle structure/function, a potential candidate is the Arg(R577Ter(X polymorphism (rs1815739 in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish individuals: centenarians (cases, n = 64; 57 female; age range: 100-108 years, young healthy controls (n = 283, 67 females, 216 males; 21±2 years, and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists and muscle power (63 male jumpers/sprinters. Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%, and controls (RR:31.8%; RX:49.8%; XX:18.4% or endurance athletes (RR:28.0%; RX:46%; XX:26.0%, we observed a significantly higher frequency of the X allele (P = 0.019 and XX genotype (P = 0.011 in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%. Notably, the frequency of the null XX (α-actinin-3 deficient genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain 'survival' advantage brought about by α-actinin-3 deficiency and the 'endurance'/oxidative muscle phenotype that is commonly associated with this condition.

  17. Paternal-specific S-allele transmission in sweet cherry (Prunus avium L.): the potential for sexual selection.

    Science.gov (United States)

    Hedhly, A; Wünsch, A; Kartal, Ö; Herrero, M; Hormaza, J I

    2016-03-01

    Homomorphic self-incompatibility is a well-studied example of a physiological process that is thought to increase population diversity and reduce the expression of inbreeding depression. Whereas theoretical models predict the presence of a large number of S-haplotypes with equal frequencies at equilibrium, unequal allele frequencies have been repeatedly reported and attributed to sampling effects, population structure, demographic perturbation, sheltered deleterious mutations or selection pressure on linked genes. However, it is unclear to what extent unequal segregations are the results of gametophytic or sexual selection. Although these two forces are difficult to disentangle, testing S-alleles in the offspring of controlled crosses provides an opportunity to separate these two phenomena. In this work, segregation and transmission of S-alleles have been characterized in progenies of mixed donors and fully compatible pollinations under field conditions in Prunus avium. Seed set patterns and pollen performance have also been characterized. The results reveal paternal-specific distorted transmission of S-alleles in most of the crosses. Interestingly, S-allele segregation within any given paternal or maternal S-locus was random. Observations on pollen germination, pollen tube growth rate, pollen tube cohort size, seed set dynamics and transmission patterns strongly suggest post-pollination, prezygotic sexual selection, with male-male competition as the most likely mechanism. According to these results, post-pollination sexual selection takes precedence over frequency-dependent selection in explaining unequal S-haplotype frequencies. PMID:26559165

  18. Random survey for RH allele polymorphism among 50 native Tibetans

    OpenAIRE

    Wei, Qing

    2006-01-01

    Rhesus D (RHD) allele distribution varied significantly among different population. However, no data are available for people, like Tibetans, living at extreme altitudes, where the oxygen density is decreased. A comprehensive study has been performed to define the Rhesus (RH) allele polymorphism and RH haplotype distribution in 50 native Tibetans. Nucleotide sequencing from genomic deoxyribonucleic acid (DNA) for 10 Rhesus D gene (RHD) exons in all of 50 samples plus 10 Rhesus CE gene (RHCE) ...

  19. 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.

  20. MHC-DAB allele polymorphism in Japanese flounders Paralichthys olivaceus

    OpenAIRE

    XU Tian-Jun; Chen, Song-Lin; Tian, Yong-Sheng

    2008-01-01

    Polymorphism of the major histocompatibility complex DAB gene in Japanese flounder (Paralichthys olivaceus) was investigated using sequences analysis. In this study, 24 individuals were selected to amplify partial exon1 and intron2, complete intron1 and exon2 of DAB gene. 131 sequences were subsequently used to analyze genetic variation and revealed 31 different sequences, which presented 31 novel alleles belonging to 19 allele major types according to accepted nomenclature rules. Frequency o...

  1. 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...

  2. Lichen planopilaris is associated with HLA DRB1*11 and DQB1*03 alleles.

    Science.gov (United States)

    Pavlovsky, Lev; Israeli, Moshe; Sagy, Eti; Berg, Amy L; David, Michael; Shemer, Avner; Klein, Tirza; Hodak, Emmilia

    2015-02-01

    There are no studies of the possible association of the human leukocyte antigen (HLA) system with lichen planopilaris (LPP). To determine whether the HLA system is associated with LPP, 40 consecutive Jewish Israeli patients with LPP (study group) and 252 volunteers (controls) were typed for DRB1*and DQB1* loci by molecular methods. Compared with controls, the study group had a significantly higher frequency of the DRB1*11 allele (62% vs. 21%, corrected p-value (pc) = 0.001) owing to increased frequencies of DRB1*11: 01 and DRB1*11: 04. The DQB1*03 allele was also expressed at a significantly higher frequency in the study group (70% vs. 33%, pc = 0.0005); specifically, the frequency of DQB1*03: 01 was increased. The majority (82.5%) of the patients were of non-Ashkenazi origin. We conclude that LPP appears to be over-represented in non-Ashkenazi Jewish patients and is associated with an increased frequency of HLA DRB1*11 and DQB1*03 alleles. These findings suggest that immunogenetic factors play a role in LPP. PMID:24806356

  3. Imbalance between Cysteine Proteases and Inhibitors in a Baboon Model of Bronchopulmonary Dysplasia

    OpenAIRE

    Altiok, Ozden; Yasumatsu, Ryuji; Bingol-Karakoc, Gulbin; Riese, Richard J.; Stahlman, Mildred T.; Dwyer, William; Pierce, Richard A.; Bromme, Dieter; Weber, Ekkehard; Cataltepe, Sule

    2005-01-01

    Rationale: Bronchopulmonary dysplasia (BPD) continues to be a major morbidity in preterm infants. The lung pathology in BPD is characterized by impaired alveolar and capillary development. An imbalance between proteases and protease inhibitors in association with changes in lung elastic fibers has been implicated in the pathogenesis of BPD.

  4. Short-term strategies for Dutch wind power producers to reduce imbalance costs

    International Nuclear Information System (INIS)

    The paper assesses bidding strategies for a wind power producer in the Netherlands. To this end, a three-stage stochastic optimization framework is used, maximizing wind power producer's profit using the day-ahead and cross-border intraday market, taking into account available interconnection capacity. Results show that the wind power producer can increase its profits by trading on the intraday market and – under certain imbalance prices – by intentionally creating imbalances. It has been considered uncertainties about prices, power forecast and interconnection capacity at the day-ahead and intraday timeframes. - Highlights: ► A cross-border bidding strategy model for wind power producers has been developed. ► The model was applied to a real case study of a Dutch offshore wind power producer. ► Under certain imbalance prices, it is not profitable to deliver all possible power. ► Intraday markets give the possibility to reduce imbalance costs. ► Integration of intraday markets will increase liquidity.

  5. SCOREBOARD AND THE POSSIBILITY OF EARLY STAGE IDENTIFICATION OF IMBALANCES IN THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    Marius, Gust

    2013-01-01

    Full Text Available In late 2011, the European Union (EU Council and European Parliament adopted a series of new rules on economic governance, perfecting the process begun in 2010 to strengthen the monitoring and prevention of macroeconomic imbalances, fiscal and competitiveness disparities among EU countries. In the same direction, of strengthening fiscal surveillance under the Stability and Growth Pact, also goes the Treaty on Stability, Coordination and Governance in the Economic and Monetary Union, through the fiscal Compact. Thus, the macroeconomic imbalances procedure provided in the new legislation requires as a first step the realization of a scoreboard consisting of 10 indicators, which, according to promoters, allow an early identification of imbalances, of both short-term, as well as structural, of longer-term. European Commission reports and statistics for EU Member States in 2010 and 2011, indicate that in the post-crisis period there has been a pronounced adjustment of external imbalances, but a number of countries continue to record higher values than indicative levels in the dashboard .

  6. Evaluation of electrolyte imbalance among tuberculosis patients receiving treatments in Southwestern Nigeria

    Directory of Open Access Journals (Sweden)

    Adebimpe Wasiu Olalekan

    2015-09-01

    Conclusion: Hyponatraemia, hyperkalaemia, and hypochloremia characterized some of the electrolyte imbalance among TB patients receiving treatments. The raised level of bicarbonate may be attributed to overcorrection of respiratory acidosis often found in patients with tuberculosis. Monitoring electrolytes is therefore an important component of TB management.

  7. Studies of generalized elemental imbalances in neurological disease patients using INAA [instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Evidence has been presented in the literature to implicate trace elements in the etiology of several age-related neurological diseases. Most of these studies are based on brain analyses. Using instrumental neutron activation analysis (INAA), we have observed trace element imbalances in brains of patients with Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Picks's disease. The most prevalent elemental imbalances found in the brain were for bromine, mercury, and the alkali metals. In this study the authors report INAA studies of trace elements in nonneural tissues from Alzheimer's disease and ALS patients. Samples from household relatives were collected for use as controls wherever possible. Hair samples were washed according to the International Atomic Energy Agency recommended procedure. Fingernail samples were scraped with a quartz knife prior to washing by the same procedure. For ALS patients, blood samples were also collected. These data indicate that elemental imbalances in Alzheimer's disease and ALS are not restricted to the brain. Many elements perturbed in the brain are also altered in the several nonneural tissues examined to date. The imbalances in different tissues, however, are not always in the same direction. The changes observed may represent causes, effects, or simply epiphenomena. Longitudinal studies of nonneural tissues and blood, as well as tissue microprobe analyses at the cellular and subcellular level, will be required in order to better assess the role of trace elements in the etiology of these diseases

  8. Coping, social support, job satisfaction, and work/life imbalance / Mianda Smith

    OpenAIRE

    Smith, Mianda

    2006-01-01

    This mini dissertation focuses on the effects of coping on job satisfaction when job insecurity is being experienced by a group of managers in a South African mining company. The second part of the dissertation deals with role conflict, goal clarity, and how social support affects work/life imbalance.

  9. Burnout among psychosocial oncologists : an application and extension of the effort-reward imbalance model

    NARCIS (Netherlands)

    Rasmussen, Victoria; Turnell, Adrienne; Butow, Phyllis; Juraskova, Ilona; Kirsten, Laura; Wiener, Lori; Patenaude, Andrea; Hoekstra-Weebers, Josette; Grassi, Luigi

    2016-01-01

    ObjectivesBurnout is a significant problem among healthcare professionals working within the oncology setting. This study aimed to investigate predictors of emotional exhaustion (EE) and depersonalisation (DP) in psychosocial oncologists, through the application of the effort-reward imbalance (ERI)

  10. Economic concepts to address future water supply-demand imbalances in Iran, Morocco and Saudi Arabia

    Science.gov (United States)

    Hellegers, Petra; Immerzeel, Walter; Droogers, Peter

    2013-10-01

    In Middle East and North Africa (MENA) countries, renewable groundwater and surface water supply are limited while demand for water is growing rapidly. Climate change is expected to increase water demand even further. The main aim of this paper is to evaluate the water supply-demand imbalances in Iran, Morocco and Saudi Arabia in 2040-2050 under dry, average and wet climate change projections and to show on the basis of the marginal cost and marginal value of water the optimum mix of supply-side and demand-side adjustments to address the imbalance. A hydrological model has been used to estimate the water supply-demand imbalance. Water supply and demand curves have been used to explore for which (marginal value of) water usage the marginal cost of supply-enhancement becomes too expensive. The results indicate that in the future in all cases, except in Iran under the wet climate projection, the quantity of water demanded has to be reduced considerably to address the imbalance, which is indeed what is currently happening already.

  11. Economic concepts to address future water supply-demand imbalances in Iran, Morocco and Saudi Arabia

    NARCIS (Netherlands)

    Hellegers, P.; Immerzeel, W.W.; Droogers, P.

    2013-01-01

    In Middle East and North Africa (MENA) countries, renewable groundwater and surface water supply are limited while demand for water is growing rapidly. Climate change is expected to increase water demand even further. The main aim of this paper is to evaluate the water supply–demand imbalances in Ir

  12. Ocean heat content and Earth's radiation imbalance. II. Relation to climate shifts

    International Nuclear Information System (INIS)

    In an earlier study of ocean heat content (OHC) we showed that Earth's empirically implied radiation imbalance has undergone abrupt changes. Other studies have identified additional such climate shifts since 1950. The shifts can be correlated with features in recently updated OHC data. The implied radiation imbalance may possibly alternate in sign at dates close to the climate shifts. The most recent shifts occurred during 2001–2002 and 2008–2009. The implied radiation imbalance between these dates, in the direction of ocean heat loss, was −0.03±0.06 W/m2, with a possible systematic error of [−0.00,+0.09] W/m2. -- Highlights: ► Ocean heat content (OHC) slope discontinuities match similar Earth climate features. ► OHC slopes between climate shifts give most of the implied radiation balance (IRI). ► IRI often alternates in sign at dates close to the climate shifts. ► IRI between climate shifts of 2001–2002 and 2008–2009 was −0.03±0.06 W/m2. ► Geothermal flux is relevant to analyses of radiation imbalance.

  13. ICI mitigation in concurrent multi-band receiver due to the phase noise and IQ imbalance

    Science.gov (United States)

    Lee, Hui-Kyu; Ryu, Heung-Gyoon

    2012-06-01

    For the next generation long-term evolution (LTE) advanced mobile communication system, 100 MHz bandwidth and 1 Gbit/s data speed are needed. However, there is not enough and wide vacant frequency band. Therefore, spectrum aggregation method has been studied to extend available frequency bands. Frequency synthesiser and power amplifier of transceiver should cover this wide bandwidth. The phase noise and In-phase and quadrature (IQ) imbalance would increase, which would be a serious problem in this transceiver. Also, signal-to-noise ratio becomes degraded because of nonlinearity and the quantisation noises of the Analog-to-digital conversion (ADC) in the receiver. Uplink of LTE-advanced uses Aggregated DFT-spread (NxDFT-S) orthogonal frequency division multiplexing (OFDM) signals. Since the effect of the phase noise and IQ imbalance are more serious in the multi-band Discrete Fourier transform (DFT)-spreading OFDM system, we like to analyse the effect of inter-carrier interference in frequency domain of receiver and the degradation of bit error rate (BER) performance. Also, by the channel response in frequency domain of the uplink system, we separate phase noise and IQ imbalance effect. Finally, we like to propose a compensation method that estimates the channel exactly and removes IQ imbalance and phase noise. Simulation result shows that the proposed method achieves the 2 dB performance gain of BER = 10-4.

  14. Cognitive vulnerability and implicit emotional processing : imbalance in frontolimbic brain areas?

    NARCIS (Netherlands)

    Groenewold, Nynke A.; Roest, Annelieke M.; Renken, Remco J.; Opmeer, Esther M.; Veltman, Dick J.; van der Wee, Nic J. A.; de Jonge, Peter; Aleman, Andre; Harmer, Catherine J.

    2015-01-01

    It has been proposed that the neural basis for cognitive vulnerability to depression involves an imbalance in frontolimbic activity during the processing of cues with a negative affective value. Although the question is central to cognitive theory, whether this association is amplified by diagnosis

  15. The effects of artificial gender imbalance: Science & Society Series on Sex and Science

    OpenAIRE

    Hesketh, Therese; Min, Jiang Min

    2012-01-01

    The use of reproductive technology to service a preference for male offspring has created an artificial gender imbalance, notably in Asian countries. The social effects of this large surplus of young men are not yet clear, but concerted action might be necessary to address the problem

  16. An accurate autonomous islanding microgrid reactive power, imbalance power and harmonic power sharing scheme

    DEFF Research Database (Denmark)

    He, Jinwei; Li, Yun Wei; Blaabjerg, Frede

    To address inaccurate power sharing problems in autonomous islanding microgrids, an enhanced droop control method through adaptive virtual impedance adjustment is proposed. First, a term associated with DG reactive power, imbalance power or harmonic power is added to the conventional real power-f...

  17. Joint Compensation of OFDM Frequency-Selective Transmitter and Receiver IQ Imbalance

    Directory of Open Access Journals (Sweden)

    Tandur Deepaknath

    2007-01-01

    Full Text Available Direct-conversion architectures are recently receiving a lot of interest in OFDM-based wireless transmission systems. However, due to component imperfections in the front-end analog processing, such systems are very sensitive to in-phase/quadrature-phase (IQ imbalances. The IQ imbalance results in intercarrier interference (ICI from the mirror carrier of the OFDM symbol. The resulting distortion can limit the achievable data rate and hence the performance of the system. In this paper, the joint effect of frequency-selective IQ imbalance at both the transmitter and receiver ends is studied. We consider OFDM transmission over a time-invariant frequency-selective channel. When the cyclic prefix is long enough to accommodate the channel impulse response combined with the transmitter and receiver filters, we propose a low-complexity two-tap equalizer with LMS-based adaptation to compensate for IQ imbalances along with channel distortions. When the cyclic prefix is not sufficiently long, then in addition to ICI there also exists interblock interference (IBI between the adjacent OFDM symbols. In this case, we propose a frequency domain per-tone equalizer (PTEQ obtained by transferring a time-domain equalizer (TEQ to the frequency domain. The PTEQ is initialized by a training-based RLS scheme. Both algorithms provide a very efficient post-FFT adaptive equalization and their performance is shown to be close to the ideal case.

  18. Joint Compensation of OFDM Frequency-Selective Transmitter and Receiver IQ Imbalance

    Directory of Open Access Journals (Sweden)

    Deepaknath Tandur

    2007-06-01

    Full Text Available Direct-conversion architectures are recently receiving a lot of interest in OFDM-based wireless transmission systems. However, due to component imperfections in the front-end analog processing, such systems are very sensitive to in-phase/quadrature-phase (IQ imbalances. The IQ imbalance results in intercarrier interference (ICI from the mirror carrier of the OFDM symbol. The resulting distortion can limit the achievable data rate and hence the performance of the system. In this paper, the joint effect of frequency-selective IQ imbalance at both the transmitter and receiver ends is studied. We consider OFDM transmission over a time-invariant frequency-selective channel. When the cyclic prefix is long enough to accommodate the channel impulse response combined with the transmitter and receiver filters, we propose a low-complexity two-tap equalizer with LMS-based adaptation to compensate for IQ imbalances along with channel distortions. When the cyclic prefix is not sufficiently long, then in addition to ICI there also exists interblock interference (IBI between the adjacent OFDM symbols. In this case, we propose a frequency domain per-tone equalizer (PTEQ obtained by transferring a time-domain equalizer (TEQ to the frequency domain. The PTEQ is initialized by a training-based RLS scheme. Both algorithms provide a very efficient post-FFT adaptive equalization and their performance is shown to be close to the ideal case.

  19. Relaxation of the chiral imbalance in dense matter of a neutron star

    CERN Document Server

    Dvornikov, Maxim

    2016-01-01

    Using the quantum field theory methods, we calculate the helicity flip of an electron scattering off protons in dense matter of a neutron star. The influence of the electroweak interaction between electrons and background nucleons on the helicity flip is examined. We also derive the kinetic equation for the chiral imbalance. The derived kinetic equation is compared with the results obtained by other authors.

  20. The impact of effort-reward imbalance and learning motivation on teachers' sickness absence.

    Science.gov (United States)

    Derycke, Hanne; Vlerick, Peter; Van de Ven, Bart; Rots, Isabel; Clays, Els

    2013-02-01

    The aim of this study was to analyse the impact of the effort-reward imbalance and learning motivation on sickness absence duration and sickness absence frequency among beginning teachers in Flanders (Belgium). A total of 603 teachers, who recently graduated, participated in this study. Effort-reward imbalance and learning motivation were assessed by means of self-administered questionnaires. Prospective data of registered sickness absence during 12 months follow-up were collected. Multivariate logistic regression analyses were performed. An imbalance between high efforts and low rewards (extrinsic hypothesis) was associated with longer sickness absence duration and more frequent absences. A low level of learning motivation (intrinsic hypothesis) was not associated with longer sickness absence duration but was significantly positively associated with sickness absence frequency. No significant results were obtained for the interaction hypothesis between imbalance and learning motivation. Further research is needed to deepen our understanding of the impact of psychosocial work conditions and personal resources on both sickness absence duration and frequency. Specifically, attention could be given to optimizing or reducing efforts spent at work, increasing rewards and stimulating learning motivation to influence sickness absence. PMID:22337584

  1. Studies of trace element imbalances in Alzheimer's disease using sequential NAA

    International Nuclear Information System (INIS)

    Evidence has accumulated in the literature that trace elements may be implicated in the etiology of Alzheimer's disease (AD) and other age-related neurological diseases. Even if elemental imbalances do not prove to be causative factors, observed perturbations may be markers that could aid in diagnosis, or help elucidate pathological processes. In this paper the authors present new data for trace element levels in three areas of the human brain most severely affected by AD (hippocampus, amygdala, and nucleus basalis) and in AD hair and nail samples. In some cases the specific imbalances seen previously in the bulk brain analyses are amplified in these regions. Elevated bromine levels seen in AD brain are also observed in AD hair and nail. Significant alkali metal and mercury imbalances with respect to controls occur in AD nail samples. The role of these trace element alterations in the etiology of AD has still not been determined. However, some possible physiological effects include: membrane dysfunction (alkali metals), enzyme inhibition (mercury and bromine), and interference with neurotransmitter functions (mercury, bromine, and alkali metals). The simultaneous multielement capability of this sequential NAA procedure also permits interelement correlation studies. Elemental associations may help identify potential environmental factors that could contribute to the observed trace element imbalances

  2. Sexual selection by female immunity against paternal antigens can fix loss of function alleles.

    Science.gov (United States)

    Ghaderi, Darius; Springer, Stevan A; Ma, Fang; Cohen, Miriam; Secrest, Patrick; Taylor, Rachel E; Varki, Ajit; Gagneux, Pascal

    2011-10-25

    Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to a CMAH gene inactivation, which occurred approximately three million years ago. Modern humans produce antibodies specific for Neu5Gc. We hypothesized that anti-Neu5Gc antibodies could enter the female reproductive tract and target Neu5Gc-positive sperm or fetal tissues, reducing reproductive compatibility. Indeed, female mice with a human-like Cmah(-/-) mutation and immunized to express anti-Neu5Gc antibodies show lower fertility with Neu5Gc-positive males, due to prezygotic incompatibilities. Human anti-Neu5Gc antibodies are also capable of targeting paternally derived antigens and mediate cytotoxicity against Neu5Gc-bearing chimpanzee sperm in vitro. Models of populations polymorphic for such antigens show that reproductive incompatibility by female immunity can drive loss-of-function alleles to fixation from moderate initial frequencies. Initially, the loss of a cell-surface antigen can occur due to drift in isolated populations or when natural selection favors the loss of a receptor exploited by pathogens, subsequently the same loss-of-function allele can come under sexual selection because it avoids being targeted by the female immune system. Thus, we provide evidence of a link between sexual selection and immune function: Antigenicity in females can select against foreign paternal antigens on sperm and rapidly fix loss-of-function alleles. Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines. PMID:21987817

  3. Sexual selection by female immunity against paternal antigens can fix loss of function alleles

    Science.gov (United States)

    Ghaderi, Darius; Springer, Stevan A.; Ma, Fang; Cohen, Miriam; Secrest, Patrick; Taylor, Rachel E.; Varki, Ajit; Gagneux, Pascal

    2011-01-01

    Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to a CMAH gene inactivation, which occurred approximately three million years ago. Modern humans produce antibodies specific for Neu5Gc. We hypothesized that anti-Neu5Gc antibodies could enter the female reproductive tract and target Neu5Gc-positive sperm or fetal tissues, reducing reproductive compatibility. Indeed, female mice with a human-like Cmah(−/−) mutation and immunized to express anti-Neu5Gc antibodies show lower fertility with Neu5Gc-positive males, due to prezygotic incompatibilities. Human anti-Neu5Gc antibodies are also capable of targeting paternally derived antigens and mediate cytotoxicity against Neu5Gc-bearing chimpanzee sperm in vitro. Models of populations polymorphic for such antigens show that reproductive incompatibility by female immunity can drive loss-of-function alleles to fixation from moderate initial frequencies. Initially, the loss of a cell-surface antigen can occur due to drift in isolated populations or when natural selection favors the loss of a receptor exploited by pathogens, subsequently the same loss-of-function allele can come under sexual selection because it avoids being targeted by the female immune system. Thus, we provide evidence of a link between sexual selection and immune function: Antigenicity in females can select against foreign paternal antigens on sperm and rapidly fix loss-of-function alleles. Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines. PMID:21987817

  4. Molecular characterization of both alleles in an unusual Tay-Sachs disease BI variant

    Energy Technology Data Exchange (ETDEWEB)

    Coulter-Mackie, M.B. (Univ. of Western Ontario, London (Canada) Child Health Research Institute, Children' s Hospital of Western Ontario, London (Canada) Child Parent Resource Institute, London, Ontario (Canada))

    1994-06-01

    In a recent report, the authors described an exon 6 mutation in a Tay-Sachs B1 variant patient, first reported by Gordon et al. (1988), who displayed a typical B1 variant biochemical phenotype - i.e., (a) significant levels of hexosaminidase A (Hex A) activity in an assay with a neutral synthetic substrate, 4-methylumbelliferyl-[beta]-N-acetylglucosamide, and (b) <2% of control Hex A in a test on the sulfated substrate, 4-methylumbelliferyl-[beta]-N-acetylglucosamide-6-sulfate. The patient was found to carry a double mutation (G[sub 574][yields]C [val[sub 192][yields]leu] and G[sub 598][yields]A [val[sub 200][yields]met]) inherited from her mother. Only the 574 mutation produced a deleterious effect on Hex A activity in transfected COS0-1 cells, producing a B1 variant biochemical phenotype. The paternal allele apparently caused decreased abundance of mRNA, since no candidate paternal mutations were found in cloned reverse transcription-PCR (RT-PCR) products in the reported study. The biochemical phenotype of the original patient and the properties of the cDNA carrying the G[sub 574] [yields] C mutation in transient expression studies were compatible with a B1 variant mutation. The possibility remained that there might be some contribution from the paternal allele to the patient's phenotype. However, the paternal allele produces relatively low yields of a largely mis-spliced mRNA whose product would not be functional. Therefore, the G[sub 574] [yields] C (val[yields]leu) mutation in the maternal allele is clearly confirmed as a B1 variant mutation with all the ramifications for the substrate binding site and/or catalytic center that this implies.

  5. 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

  6. Impaired Uptake and/or Utilization of Leucine by Saccharomyces cerevisiae Is Suppressed by the SPT15-300 Allele of the TATA-Binding Protein Gene

    DEFF Research Database (Denmark)

    Baerends, RJ; Qiu, Jin-Long; Rasmussen, Simon;

    2009-01-01

    mutant allele of the SPT15 gene (SPT15-300) corresponding to the three amino acid changes F177S, Y195H, and K218R has been reported (H. Alper, J. Moxley, E. Nevoigt, G. R. Fink, and G. Stephanopoulos, Science 314:1565-1568, 2006). The SPT15 gene codes for the TATA-binding protein. This finding prompted...... us to examine the effect of expression of the SPT15-300 allele in various yeast species of industrial importance. Expression of SPT15-300 in leucine-prototrophic strains of S. cerevisiae, Saccharomyces bayanus, or Saccharomyces pastorianus (lager brewing yeast), however, did not improve tolerance to...... ethanol on complex rich medium (yeast extract-peptone-dextrose). The enhanced growth of the laboratory yeast strain BY4741 expressing the SPT15-300 mutant allele was seen only on defined media with low concentrations of leucine, indicating that the apparent improved growth in the presence of ethanol was...

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Analyzing surface EMG signals to determine relationship between jaw imbalance and arm strength loss

    Directory of Open Access Journals (Sweden)

    Truong Quang Dang Khoa

    2012-08-01

    Full Text Available Abstract Background This study investigated the relationship between dental occlusion and arm strength; in particular, the imbalance in the jaw can cause loss in arm strength phenomenon. One of the goals of this study was to record the maximum forces that the subjects can resist against the pull-down force on their hands while biting a spacer of adjustable height on the right or left side of the jaw. Then EMG measurement was used to determine the EMG-Force relationship of the jaw, neck and arms muscles. This gave us useful insights on the arms strength loss due to the biomechanical effects of the imbalance in the jaw mechanism. Methods In this study to determine the effects of the imbalance in the jaw to the strength of the arms, we conducted experiments with a pool of 20 healthy subjects of both genders. The subjects were asked to resist a pull down force applied on the contralateral arm while biting on a firm spacer using one side of the jaw. Four different muscles – masseter muscles, deltoid muscles, bicep muscles and trapezoid muscles – were involved. Integrated EMG (iEMG and Higuchi fractal dimension (HFD were used to analyze the EMG signals. Results The results showed that (1 Imbalance in the jaw causes loss of arm strength contra-laterally; (2 The loss is approximately a linear function of the height of the spacers. Moreover, the iEMG showed the intensity of muscle activities decreased when the degrees of jaw imbalance increased (spacer thickness increased. In addition, the tendency of Higuchi fractal dimension decreased for all muscles. Conclusions This finding indicates that muscle fatigue and the decrease in muscle contraction level leads to the loss of arm strength.

  9. Transient vibrations of a bent rotor having residual imbalance during its rundown

    Science.gov (United States)

    Kostyuk, A. G.; Volokhovskaya, O. A.

    2015-09-01

    The model of a single-span rotor having an initial nonremovable sag and residual imbalance is used for estimating the amplitudes of its resonance vibrations at check points (on the supports and in the middle of the span) in the vicinity of critical speeds lying below the operating angular speed passed by the rotor as it rotates with an angular deceleration in the period from the turbine disconnection moment to its full stop (during the rundown). Two cases of installing the rotor on yielding anisotropic supports (sleeve-type bearings with an elliptic bore) are considered: during rig tests when there are two yielding supports, and when the rotor interacts with the remaining part of the assembled turbine set shaft system, which was modeled by using a yielding support at the left-hand end and a fixed hinge at the right-hand end. The analysis procedure is illustrated by calculations carried out for a K-300-23.5 turbine's high-pressure rotor having an initial sag and residual imbalance. The values of both excitation initiating factors were taken equal to their maximum permissible levels established by the limitations imposed from turbine sets operating experience on the hot-test values for the initial sag of a thermally unstable rotor and for its residual imbalance. The list of considered cases included lumped imbalance of the rotor resulted from separation of a blade or disk section and distributed residual imbalance remaining after preliminary balancing of the rotor on a rig. An analysis of the obtained results is presented.

  10. Identification of a new mutant allele, Grm6nob7, for complete congenital stationary night blindness

    OpenAIRE

    Qian, Haohua; Ji, Rui; Gregg, Ronald G; PEACHEY, NEAL S.

    2015-01-01

    Electroretinogram (ERG) studies identified a new mouse line with a normal a-wave but lacking the b-wave component. The ERG phenotype of this new allele, nob7, matched closely that of mouse mutants for Grm6, Lrit3, Trpm1, and Nyx, which encode for proteins expressed in depolarizing bipolar cells (DBCs). To identify the underlying mutation, we first crossed nob7 mice with Grm6nob3 mutants and measured the ERGs in offspring. All the offspring lacked the b-wave, indicating that nob7 is a new alle...

  11. Study on occurrence of the IVS8-5T allele of the CFTR gene in Ukrainian males with spermatogenesis failure

    Directory of Open Access Journals (Sweden)

    Zinchenko V. M.

    2010-07-01

    Full Text Available Aim. To study the IVS8-5T allele of the CFTR gene and it is involvement in spermatogenesis failure in men with azoospermia and oligozoospermia. Methods. The IVS8-nT polymorphism was analyzed by PCR followed by «A.L.F.-express» fragment analysis in the infertile men group, consisting of 113 azoospermic and 217 oligozoospermic patients, and the control group of 150 fertile men with proven paternity. Results. The frequency of the IVS8-5T allele among infertile males was higher than in controls. A statistically significant difference (P < 0.05 was observed in the frequencies of the IVS8-5T allele in azoospermia patients (5.3 % when compared with the control group (2.0 %. Conclusions. The IVS8-5T allele of the CFTR gene contributes to spermatogenesis failure and/or sperm maturation.

  12. IQ Imbalance Estimation Scheme in the Presence of DC Offset and Frequency Offset in the Frequency Domain

    Science.gov (United States)

    Inamori, Mamiko; Takayama, Shuzo; Sanada, Yukitoshi

    Direct conversion receivers in orthogonal frequency division multiplexing (OFDM) systems suffer from direct current (DC) offset, frequency offset, and IQ imbalance. We have proposed an IQ imbalance estimation scheme in the presence of DC offset and frequency offset, which uses preamble signals in the time domain. In this scheme, the DC offset is eliminated by a differential filter. However, the accuracy of IQ imbalance estimation is deteriorated when the frequency offset is small. To overcome this problem, a new IQ imbalance estimation scheme in the frequency domain with the differential filter has been proposed in this paper. The IQ imbalance is estimated with pilot subcarriers. Numerical results obtained through computer simulation show that estimation accuracy and bit error rate (BER) performance can be improved even if the frequency offset is small.

  13. Chloroplast genetics of chlamydomonas. I. Allelic segregation ratios

    International Nuclear Information System (INIS)

    This paper presents allelic segregation data from a series of 16 crosses segregated for nuclear and chloroplast genes. By means of pedigree analysis, segregants of chloroplast genes. By means of pedigree analysis, segregants of chloroplast markers occurring in the zygote have been distinguished from those occurring in zoospore clones. The genes ac1, ac2, and tm1 showed little if any deviation from 1:1 either in zygotic segregation or in zoospore clones. The genes sm2, ery, and spc showed a significant excess of the allele from the mt+ parent in zygotes. However, in zoospores, mt+ excess was seen only when the allele was the mutant (resistant) form but not when it was wild type (sensitive). These results show that the extent of preferential segregation differs in zygotes and in zoospores, and that preferential segregation is influenced by map location and by allele specificity. A comparison of progeny from zygotes mated after 0, 15'', 30'', and 50'' uv irradiation of the mt+ gametes demonstrated the lack of an effect of uv upon allelic segregation ratios. In total, these results exclude the multi-copy model of chloroplast genome segregation suggested by Gillham. Boynton and Lee (1974) and support the diploid model we have previously proposed

  14. Chloroplast genetics of chlamydomonas. I. Allelic segregation ratios. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Sager, R.; Ramanis, Z.

    1976-06-01

    This paper presents allelic segregation data from a series of 16 crosses segregated for nuclear and chloroplast genes. By means of pedigree analysis, segregants of chloroplast genes. By means of pedigree analysis, segregants of chloroplast markers occurring in the zygote have been distinguished from those occurring in zoospore clones. The genes ac1, ac2, and tm1 showed little if any deviation from 1:1 either in zygotic segregation or in zoospore clones. The genes sm2, ery, and spc showed a significant excess of the allele from the mt+ parent in zygotes. However, in zoospores, mt+ excess was seen only when the allele was the mutant (resistant) form but not when it was wild type (sensitive). These results show that the extent of preferential segregation differs in zygotes and in zoospores, and that preferential segregation is influenced by map location and by allele specificity. A comparison of progeny from zygotes mated after 0, 15'', 30'', and 50'' uv irradiation of the mt+ gametes demonstrated the lack of an effect of uv upon allelic segregation ratios. In total, these results exclude the multi-copy model of chloroplast genome segregation suggested by Gillham. Boynton and Lee (1974) and support the diploid model we have previously proposed.

  15. 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

  16. The maize unstable factor for orange1 is a dominant epigenetic modifier of a tissue specifically silent allele of pericarp color1.

    OpenAIRE

    Chopra, Surinder; Cocciolone, Suzy M; Bushman, Shaun; Sangar, Vineet; Michael D McMullen; Peterson, Thomas

    2003-01-01

    We have characterized Unstable factor for orange1 (Ufo1), a dominant, allele-specific modifier of expression of the maize pericarp color1 (p1) gene. The p1 gene encodes an Myb-homologous transcriptional activator of genes required for biosynthesis of red phlobaphene pigments. The P1-wr allele specifies colorless kernel pericarp and red cobs, whereas Ufo1 modifies P1-wr expression to confer pigmentation in kernel pericarp, as well as vegetative tissues, which normally do not accumulate signifi...

  17. Implication of HLA-DMA Alleles in Corsican IDDM

    Directory of Open Access Journals (Sweden)

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Defining a personal, allele-specific, and single-molecule long-read transcriptome.

    Science.gov (United States)

    Tilgner, Hagen; Grubert, Fabian; Sharon, Donald; Snyder, Michael P

    2014-07-01

    Personal transcriptomes in which all of an individual's genetic variants (e.g., single nucleotide variants) and transcript isoforms (transcription start sites, splice sites, and polyA sites) are defined and quantified for full-length transcripts are expected to be important for understanding individual biology and disease, but have not been described previously. To obtain such transcriptomes, we sequenced the lymphoblastoid transcriptomes of three family members (GM12878 and the parents GM12891 and GM12892) by using a Pacific Biosciences long-read approach complemented with Illumina 101-bp sequencing and made the following observations. First, we found that reads representing all splice sites of a transcript are evident for most sufficiently expressed genes ≤3 kb and often for genes longer than that. Second, we added and quantified previously unidentified splicing isoforms to an existing annotation, thus creating the first personalized annotation to our knowledge. Third, we determined SNVs in a de novo manner and connected them to RNA haplotypes, including HLA haplotypes, thereby assigning single full-length RNA molecules to their transcribed allele, and demonstrated Mendelian inheritance of RNA molecules. Fourth, we show how RNA molecules can be linked to personal variants on a one-by-one basis, which allows us to assess differential allelic expression (DAE) and differential allelic isoforms (DAI) from the phased full-length isoform reads. The DAI method is largely independent of the distance between exon and SNV--in contrast to fragmentation-based methods. Overall, in addition to improving eukaryotic transcriptome annotation, these results describe, to our knowledge, the first large-scale and full-length personal transcriptome. PMID:24961374

  4. Allele-specific silencing of mutant Ataxin-7 in SCA7 patient-derived fibroblasts.

    Science.gov (United States)

    Scholefield, Janine; Watson, Lauren; Smith, Danielle; Greenberg, Jacquie; Wood, Matthew J A

    2014-12-01

    Polyglutamine (polyQ) disorders are inherited neurodegenerative conditions defined by a common pathogenic CAG repeat expansion leading to a toxic gain-of-function of the mutant protein. Consequences of this toxicity include activation of heat-shock proteins (HSPs), impairment of the ubiquitin-proteasome pathway and transcriptional dysregulation. Several studies in animal models have shown that reducing levels of toxic protein using small RNAs would be an ideal therapeutic approach for such disorders, including spinocerebellar ataxia-7 (SCA7). However, testing such RNA interference (RNAi) effectors in genetically appropriate patient cell lines with a disease-relevant phenotype has yet to be explored. Here, we have used primary adult dermal fibroblasts from SCA7 patients and controls to assess the endogenous allele-specific silencing of ataxin-7 by two distinct siRNAs. We further identified altered expression of two disease-relevant transcripts in SCA7 patient cells: a twofold increase in levels of the HSP DNAJA1 and a twofold decrease in levels of the de-ubiquitinating enzyme, UCHL1. After siRNA treatment, the expression of both genes was restored towards normal levels. To our knowledge, this is the first time that allele-specific silencing of mutant ataxin-7, targeting a common SNP, has been demonstrated in patient cells. These findings highlight the advantage of an allele-specific RNAi-based therapeutic approach, and indicate the value of primary patient-derived cells as useful models for mechanistic studies and for measuring efficacy of RNAi effectors on a patient-to-patient basis in the polyQ diseases. PMID:24667781

  5. Leiomyosarcomas and most malignant fibrous histiocytomas share very similar comparative genomic hybridization imbalances: an analysis of a series of 27 leiomyosarcomas.

    Science.gov (United States)

    Derré, J; Lagacé, R; Nicolas, A; Mairal, A; Chibon, F; Coindre, J M; Terrier, P; Sastre, X; Aurias, A

    2001-02-01

    Twenty-seven tumor samples with a diagnosis of leiomyosarcomas (LMS) were characterized by comparative genomic hybridization. The results were compared with immunohistochemical analysis of the smooth muscle profile of the tumors and expression of the RB1 gene protein. The comparative genomic hybridization profiles suggested that 7 of the 27 tumors might have been misclassified. High levels of DNA amplification were detected in 20 different small regions and recurrently involved bands 1p34, q21, 12q13-15, 17p, and 22q. Most recurrent simple gains were noted at sites such as 1p3, 1q21, 15q12-15, 16p, 17p and 17q, 19, 20q, 22q, and Xp. Significant losses of chromosome 13 were detected in 19 of the 27 tumors with a putative common region of loss in bands 13q14-21. Losses of chromosomes 1q, 2p and 2q, 4q, 9p, 10p and 10q, 11p and 11q23, and 16q were also highly recurrent. A comparative analysis between the most frequent genomic imbalances observed in this study of LMS and the genomic imbalances observed in a large proportion of malignant fibrous histiocytomas (MFH) from a previous study demonstrated that both types of tumors had similar recurrent imbalances. Although MFH were once thought to be a separate member of the soft tissue sarcoma family, our observations support the hypothesis that MFH are a morphologic modulation in the tumoral progression of other sarcomas, particularly LMS. PMID:11232643

  6. Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

    Directory of Open Access Journals (Sweden)

    Quiroga-Garza Gabriela

    2012-02-01

    Full Text Available Abstract Seven percent of renal cell carcinoma (RCC cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC and a tubulocystic renal carcinoma (TCRC in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR and distal tubule cell (CK19 markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2 of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3 showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1790525735655283

  7. Platelet antigen allele frequencies in Australian aboriginal and Caucasian populations.

    Science.gov (United States)

    Chen, Z; Lester, S; Boettcher, B; McCluskey, J

    1997-11-01

    We have applied genotyping methods of PCR-SSOP and PCR-RFLP to three, bi-allelic platelet specific antigen systems HPA-1 (Pla), HPA-3 (Bak) and HPA-5 (Br). This combination of techniques offers flexibility for high volume or rapid typing. The phenotype and genotype frequencies of alleles from the three systems differ significantly between the Yuendumu Australian Aboriginals (Wailbri) and Australian Caucasians. The major differences are the very low frequencies of HPA-1b and HPA-3b in Yuendumu Aboriginals which are potentially relevant to platelet transfusion in patients of Australian Aboriginal descent. PMID:9423221

  8. 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.

  9. Floral volatile alleles can contribute to pollinator-mediated reproductive isolation in monkeyflowers (Mimulus).

    Science.gov (United States)

    Byers, Kelsey J R P; Vela, James P; Peng, Foen; Riffell, Jeffrey A; Bradshaw, Harvey D

    2014-12-01

    Pollinator-mediated reproductive isolation is a major factor in driving the diversification of flowering plants. Studies of floral traits involved in reproductive isolation have focused nearly exclusively on visual signals, such as flower color. The role of less obvious signals, such as floral scent, has been studied only recently. In particular, the genetics of floral volatiles involved in mediating differential pollinator visitation remains unknown. The bumblebee-pollinated Mimulus lewisii and hummingbird-pollinated Mimulus cardinalis are a model system for studying reproductive isolation via pollinator preference. We have shown that these two species differ in three floral terpenoid volatiles - d-limonene, β-myrcene, and E-β-ocimene - that are attractive to bumblebee pollinators. By genetic mapping and in vitro analysis of enzyme activity we demonstrate that these interspecific differences are consistent with allelic variation at two loci, LIMONENE-MYRCENE SYNTHASE (LMS) and OCIMENE SYNTHASE (OS). Mimulus lewisii LMS (MlLMS) and OS (MlOS) are expressed most strongly in floral tissue in the last stages of floral development. Mimulus cardinalis LMS (McLMS) is weakly expressed and has a nonsense mutation in exon 3. Mimulus cardinalis OS (McOS) is expressed similarly to MlOS, but the encoded McOS enzyme produces no E-β-ocimene. Recapitulating the M. cardinalis phenotype by reducing the expression of MlLMS by RNA interference in transgenic M. lewisii produces no behavioral difference in pollinating bumblebees; however, reducing MlOS expression produces a 6% decrease in visitation. Allelic variation at the OCIMENE SYNTHASE locus is likely to contribute to differential pollinator visitation, and thus promote reproductive isolation between M. lewisii and M. cardinalis. OCIMENE SYNTHASE joins a growing list of 'speciation genes' ('barrier genes') in flowering plants. PMID:25319242

  10. Positive selection of natural poly-reactive B cells in the periphery occurs independent of heavy chain allelic inclusion.

    Directory of Open Access Journals (Sweden)

    Ying Xing

    Full Text Available Natural autoreactive B cells are important mediators of autoimmune diseases. Receptor editing is known to play an important role in both central and peripheral B cell tolerance. However, the role of allelic inclusion in the development of natural autoreactive B cells is not clear. Previously, we generated μ chain (TgV(H3B4I and μ/κ chains (TgV(H/L3B4 transgenic mice using transgene derived from the 3B4 hybridoma, which produce poly-reactive natural autoantibodies. In this study, we demonstrate that a considerable population of B cells edited their B cells receptors (BCRs via light chain or heavy chain allelic inclusion during their development in TgV(H3B4I mice. Additionally, allelic inclusion occurred more frequently in the periphery and promoted the differentiation of B cells into marginal zone or B-1a cells in TgV(H3B4I mice. B cells from TgV(H/L3B4 mice expressing the intact transgenic 3B4 BCR without receptor editing secreted poly-reactive 3B4 antibody. Interestingly, however, B cell that underwent allelic inclusion in TgV(H3B4I mice also produced poly-reactive autoantibodies in vivo and in vitro. Our findings suggest that receptor editing plays a minor role in the positive selection of B cells expressing natural poly-reactive BCRs, which can be positively selected through heavy chain allelic inclusion to retain their poly-reactivity in the periphery.

  11. Positive selection of natural poly-reactive B cells in the periphery occurs independent of heavy chain allelic inclusion.

    Science.gov (United States)

    Xing, Ying; Ji, Qiuhe; Lin, Ying; Fu, Meng; Gao, Jixin; Zhang, Ping; Hu, Xingbin; Feng, Lei; Liu, Yufeng; Han, Hua; Li, Wei

    2015-01-01

    Natural autoreactive B cells are important mediators of autoimmune diseases. Receptor editing is known to play an important role in both central and peripheral B cell tolerance. However, the role of allelic inclusion in the development of natural autoreactive B cells is not clear. Previously, we generated μ chain (TgV(H)3B4I) and μ/κ chains (TgV(H/L)3B4) transgenic mice using transgene derived from the 3B4 hybridoma, which produce poly-reactive natural autoantibodies. In this study, we demonstrate that a considerable population of B cells edited their B cells receptors (BCRs) via light chain or heavy chain allelic inclusion during their development in TgV(H)3B4I mice. Additionally, allelic inclusion occurred more frequently in the periphery and promoted the differentiation of B cells into marginal zone or B-1a cells in TgV(H)3B4I mice. B cells from TgV(H/L)3B4 mice expressing the intact transgenic 3B4 BCR without receptor editing secreted poly-reactive 3B4 antibody. Interestingly, however, B cell that underwent allelic inclusion in TgV(H)3B4I mice also produced poly-reactive autoantibodies in vivo and in vitro. Our findings suggest that receptor editing plays a minor role in the positive selection of B cells expressing natural poly-reactive BCRs, which can be positively selected through heavy chain allelic inclusion to retain their poly-reactivity in the periphery. PMID:25993514

  12. 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...

  13. Comparative anatomy of chromosomal domains with imprinted and non-imprinted allele-specific DNA methylation.

    Directory of Open Access Journals (Sweden)

    Anupam Paliwal

    2013-08-01

    Full Text Available Allele-specific DNA methylation (ASM is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons, one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs, each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS peaks near CTCF binding sites with ASM.

  14. Comparative anatomy of chromosomal domains with imprinted and non-imprinted allele-specific DNA methylation.

    Science.gov (United States)

    Paliwal, Anupam; Temkin, Alexis M; Kerkel, Kristi; Yale, Alexander; Yotova, Iveta; Drost, Natalia; Lax, Simon; Nhan-Chang, Chia-Ling; Powell, Charles; Borczuk, Alain; Aviv, Abraham; Wapner, Ronald; Chen, Xiaowei; Nagy, Peter L; Schork, Nicholas; Do, Catherine; Torkamani, Ali; Tycko, Benjamin

    2013-08-01

    Allele-specific DNA methylation (ASM) is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons), one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated) while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq) in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs), each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS) peaks near CTCF binding sites with ASM. PMID:24009515

  15. Characterization of two dominant alleles of the major rhodopsin-encoding gene ninaE in Drosophila

    OpenAIRE

    Mitra, Amitavo; Chinchore, Yashodhan; Kinser, Ronald; Dolph, Patrick J.

    2011-01-01

    Purpose In this study we investigated the biochemical and cell biologic characteristics of flies expressing two novel dominant alleles of the major rhodopsin encoding gene neither inactivation nor afterpotential E (ninaE) in a heterozygous background. Methods Presence of the deep pseudopupil in flies was assayed 5 days post eclosion. For structural analysis, 1-μm-retinal cross sections were obtained from fixed and resin-embedded Drosophila heads. Confocal microscopy was performed on dissected...

  16. A new allele conferring resistance to Lysinibacillus sphaericus is detected in low frequency in Culex quinquefasciatus field populations

    OpenAIRE

    Menezes, Heverly Suzany Gouveia; Chalegre, Karlos Diogo de Melo; Romão, Tatiany Patrícia; de Oliveira, Cláudia Maria Fontes; de-Melo-Neto, Osvaldo Pompílio; Silva-Filha, Maria Helena Neves Lobo

    2016-01-01

    Background The Cqm1 α-glucosidase of Culex quinquefasciatus larvae acts as the midgut receptor for the binary toxin of the biolarvicide Lysinibacillus sphaericus. Mutations within the cqm1 gene can code for aberrant polypeptides that can no longer be properly expressed or bind to the toxin, leading to insect resistance. The cqm1 REC and cqm1 REC-2 alleles were identified in a laboratory selected colony and both displayed mutations that lead to equivalent phenotypes of refractoriness to L. sph...

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

    OpenAIRE

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

    2012-01-01

    Imisun and CLPlus are two imidazolinone tolerance traits in sunflower (Helianthus annuus L.) determined by the expression of two alleles at the locus Ahasl1. Both traits differed in their tolerance level to imazapyr —a type of imidazolinone herbicide— when aboveground biomass is considered, but the concomitant herbicide effect over the root system has not been reported. The objective of this work was to quantify the root biomass response to increased doses of imazapyr in susceptible (ahasl1/a...

  18. The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study

    International Nuclear Information System (INIS)

    TGF-β receptor type I is a mediator of growth inhibitory signals. TGFBR1*6A (rs11466445) is a common polymorphic variant of the TGF-β receptor I gene and has been associated with tumour susceptibility. Nevertheless, the role of this polymorphism as a risk factor for colorectal cancer is controversial. The aim of this study was to assess the association between TGFBR1*6A and colorectal cancer, age, sex, tumour location and tumour stage in a Spanish population. The case-control study involved 800 Spanish subjects: 400 sporadic colorectal cancer patients and 400 age-, sex-, and ethnic-matched controls. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated using unconditional logistic regression adjusted for age and sex. Analysis of somatic mutations at the GCG repeat of TGFBR1 exon 1 and germline allele-specific expression were also conducted to obtain further information on the contribution of the TGFBR1*6A allele to CRC susceptibility. There was no statistically significant association between the TGFBR1*6A allele and CRC (p > 0.05). The OR was 1.147 (95% CI: 0.799–1.647) for carriers of the TGFBR1*6A allele and 0.878 (95% CI: 0.306–2.520) for homozygous TGFBR1*6A individuals compared with the reference. The frequency of the polymorphism was not affected by age, sex or tumour stage. The TGFBR1*6A allele was more prevalent among colon tumour patients than among rectal tumour patients. Tumour somatic mutations were found in only two of 69 cases (2.9%). Both cases involved a GCG deletion that changed genotype 9A/9A in normal DNA to genotype 9A/8A. Interestingly, these two tumours were positive for microsatellite instability, suggesting that these mutations originated because of a deficient DNA mismatch repair system. Allele-specific expression of the 9A allele was detected in seven of the 14 heterozygous 9A/6A tumour cases. This could have been caused by linkage disequilibrium of the TGFBR1*6A allele with

  19. Relay Assisted Cooperative OSTBC Communication with SNR Imbalance and Channel Estimation Errors

    CERN Document Server

    Niu, Bo; Lin, Zinan; Chitrapu, Prabhakar

    2010-01-01

    In this paper, a two-hop relay assisted cooperative Orthogonal Space-Time Block Codes (OSTBC) transmission scheme is considered for the downlink communication of a cellular system, where the base station (BS) and the relay station (RS) cooperate and transmit data to the user equipment (UE) in a distributed fashion. We analyze the impact of the SNR imbalance between the BS-UE and RS-UE links, as well as the imperfect channel estimation at the UE receiver. The performance is analyzed in the presence of Rayleigh flat fading and our results show that the SNR imbalance does not impact the spatial diversity order. On the other hand, channel estimation errors have a larger impact on the system performance. Simulation results are then provided to confirm the analysis.

  20. A Novel Algorithm for Imbalance Data Classification Based on Neighborhood Hypergraph

    Directory of Open Access Journals (Sweden)

    Feng Hu

    2014-01-01

    Full Text Available The classification problem for imbalance data is paid more attention to. So far, many significant methods are proposed and applied to many fields. But more efficient methods are needed still. Hypergraph may not be powerful enough to deal with the data in boundary region, although it is an efficient tool to knowledge discovery. In this paper, the neighborhood hypergraph is presented, combining rough set theory and hypergraph. After that, a novel classification algorithm for imbalance data based on neighborhood hypergraph is developed, which is composed of three steps: initialization of hyperedge, classification of training data set, and substitution of hyperedge. After conducting an experiment of 10-fold cross validation on 18 data sets, the proposed algorithm has higher average accuracy than others.

  1. Analysis and measurement of the electrolyte imbalance in a vanadium redox flow battery

    Science.gov (United States)

    Ngamsai, Kittima; Arpornwichanop, Amornchai

    2015-05-01

    Electrolyte imbalance in vanadium redox flow batteries is an important problem for its long-term operation as it leads to loss of energy. To address this problem, a modified open circuit voltage (OCV) cell is developed by adding a middle half cell between the negative and positive half cells of a conventional OCV cell and used to predict the oxidation state of vanadium in the electrolyte solution from the measured voltage in each side of the electrolyte (positive and negative). The correlation between the oxidation state of vanadium and cell voltage is explained by a basic electrochemical principle and the Nernst equation. The experimental results show that at different oxidation states of vanadium, the predicted OCV agrees reasonably with the experimental data. In addition, the effect of the state of charge (SOC) and electrolyte imbalance on the energy capacity of a cell is discussed.

  2. Compensation for HPA nonlinearity and I/Q imbalance in MIMO beamforming systems

    KAUST Repository

    Qi, Jian

    2010-10-01

    In this paper, we investigate the effects of high-power amplifier (HPA) nonlinearity and in-phase and quadrature-phase (I/Q) imbalance on the performance of multiple-input multiple-output (MIMO) transmit beamforming (TB) systems. Specifically, we propose a compensation method for HPA nonlinearity and I/Q imbalance together in MIMO TB systems. The performance of the MIMO TB system under study is evaluated in terms of the average symbol error probability (SEP) and system capacity, considering transmission over uncorrelated frequency-flat Rayleigh fading channels. Numerical results are provided and show the effects of several system parameters, such as the HPA parameters, image-leakage ratio, numbers of transmit and receive antennas, length of pilot symbols, and modulation order of phase-shift keying (PSK), on performance. © 2010 IEEE.

  3. The impact of labour market imbalances on regional disparities in the post-crisis context

    Directory of Open Access Journals (Sweden)

    Gina Cristina DIMIAN

    2012-09-01

    Full Text Available The paper aims to examine how existing imbalances in the labour market influence regions’ future development and to formulate a series of recommendations that will allow that catching up process to be done in an sustainable manner.Basically, the objective refers to the integration of the development and restructuring strategy of the labour market policy to strengthen regional competitive advantage.Our intentions is to stress the fact that between labour market imbalances and regional disparities exists a bi-univocal relationship, both manifested in a complex external environment, dominated by variable factors and uncertainty.To achieve paper’ objectives scientific methods like: descriptive statistics, correlation analysis and aggregate indexes are applied.The main results are focused on formulating a set of scientifically based recommendations that can be used to conceive strategies whose overall objective is the reduction of economic disparities existing in certain regions through training and proper human resources development.

  4. Trade integration and trade imbalances in the European Union: a network perspective

    CERN Document Server

    Krings, Gautier M; Delvenne, Jean-Charles

    2013-01-01

    We study the ever more integrated and ever more unbalanced trade relationships between European countries. To better capture the complexity of economic networks, we propose two global measures that assess the trade integration and the trade imbalances of the European countries. These measures are the network (or indirect) counterparts to traditional (or direct) measures such as the trade-to-GDP (Gross Domestic Product) and trade deficit-to-GDP ratios. Our indirect tools account for the European inter-country trade structure and follow (i) a decomposition of the global trade flow into elementary flows that highlight the long-range dependencies between exporting and importing economies and (ii) the commute-time distance for trade integration,which measures the impact of a perturbation in the economy of a country on another country, possibly through intermediate partners by domino effect. Our application addresses the impact of the launch of the Euro. We find that the indirect imbalance measures better identify ...

  5. Targeting Imbalance between IL-1β and IL-1 Receptor Antagonist Ameliorates Delayed Epithelium Wound Healing in Diabetic Mouse Corneas.

    Science.gov (United States)

    Yan, Chenxi; Gao, Nan; Sun, Haijing; Yin, Jia; Lee, Patrick; Zhou, Li; Fan, Xianqun; Yu, Fu-Shin

    2016-06-01

    Patients with diabetes mellitus often develop corneal complications and delayed wound healing. How diabetes might alter acute inflammatory responses to tissue injury, leading to delayed wound healing, remains mostly elusive. Using a streptozotocin-induced type I diabetes mellitus mice and corneal epithelium-debridement wound model, we discovered that although wounding induced marked expression of IL-1β and the secreted form of IL-1 receptor antagonist (sIL-1Ra), diabetes suppressed the expressions of sIL-1Ra but not IL-1β in healing epithelia and both in whole cornea. In normoglycemic mice, IL-1β or sIL-1Ra blockade delayed wound healing and influenced each other's expression. In diabetic mice, in addition to delayed reepithelization, diabetes weakened phosphatidylinositol 3-kinase-Akt signaling, caused cell apoptosis, diminished cell proliferation, suppressed neutrophil and natural killer cell infiltrations, and impaired sensory nerve reinnervation in healing mouse corneas. Local administration of recombinant IL-1Ra partially, but significantly, reversed these pathological changes in the diabetic corneas. CXCL10 was a downstream chemokine of IL-1β-IL-1Ra, and exogenous CXCL10 alleviated delayed wound healing in the diabetic, but attenuated it in the normal corneas. In conclusion, the suppressed early innate/inflammatory responses instigated by the imbalance between IL-1β and IL-1Ra is an underlying cause for delayed wound healing in the diabetic corneas. Local application of IL-1Ra accelerates reepithelialization and may be used to treat chronic corneal and potential skin wounds of diabetic patients. PMID:27109611

  6. Specific chromosomal imbalances in human papillomavirus-transfected cells during progression toward immortality

    OpenAIRE

    Solinas-Toldo, Sabina; Dürst, Matthias; Lichter, Peter

    1997-01-01

    High risk human papillomaviruses (HPVs) known to be closely associated with cervical cancer, such as HPV16 and HPV18, have the potential to immortalize human epithelial cells in culture. Four lines of HPV-transfected keratinocytes were analyzed by comparative genomic hybridization at different time points after transfection. A number of chromosomal imbalances was found to be highly characteristic for the cultures progressing toward immortality. Whereas several of these were new and previously...

  7. Imbalance in the Hydrologic Cycle-Open Systems, Ebbs and Flows, and Multi-Stable States

    Science.gov (United States)

    Stonestrom, D. A.

    2011-12-01

    The hydrosphere is characterized by extraordinarily large-scale chemostasis and hydrostasis. The interconnected oceans hold >95% of the planetary water in circulation and have not greatly changed in volume since the Proterozoic, despite tectonic motions of super-continental proportions. Similarly, the chemistry of the ocean has remained relatively constant since the proliferation of widespread multicellular life and abundant oxygen some 0.6 billion years ago. Ancient humans recognized that "All rivers runneth to the sea, yet the sea doth not filleth up." The solution to this paradox is the 17th-century paradigm of the hydrologic cycle; however, the commonly made corollary assumption of hydrologic balance disappears upon analysis across the entire range of observations available through ground-based networks, satellite imaging, and proxy data on paleo-hydrologic states (chemical, isotopic, tree-rings, speleothems, etc.). Water imbalance as the normative state is supported by theoretical consideration of hydrologic responses to superimposed steady-, periodic-, and irregular forcings such as geothermal gradients, diurnal and annual cycles, and orbital irregularities. Hydrologic systems are open across all scales with respect to thermal-energy throughput and are often far from equilibrium. Temporal-spatial variations of thermal inputs and stores coupled with feedbacks from interacting biologic and geologic processes lead to chaotically punctuated water imbalances with profound consequences for ecosystem succession, water resources, long-term agricultural sustainability, and acute risk from floods and droughts. Imbalance in hydrologic systems through time is evident from studies of soils and sediments and from data on deep unsaturated zones in tropical to arid regions; these studies reveal repeated cycles of salinity accumulation and pluvial flushing and shifting frequencies of floods and droughts. Anthropogenic intensification of the hydrologic cycle-with attendant

  8. Carbon/Nitrogen Imbalance Associated with Drought-Induced Leaf Senescence in Sorghum bicolor

    OpenAIRE

    Daoqian Chen; Shiwen Wang; Binglin Xiong; Beibei Cao; Xiping Deng

    2015-01-01

    Drought stress triggers mature leaf senescence, which supports plant survival and remobilization of nutrients; yet leaf senescence also critically decreases post-drought crop yield. Drought generally results in carbon/nitrogen imbalance, which is reflected in the increased carbon:nitrogen (C:N) ratio in mature leaves, and which has been shown to be involved in inducing leaf senescence under normal growth conditions. Yet the involvement of the carbon/nitrogen balance in regulation of drought-i...

  9. Effort-reward imbalance, overcommitment and sleep in a working population

    OpenAIRE

    Kudielka, B.M.; von Knel,R.; Gander, M.-L.; Fischer, J E

    2004-01-01

    The relationship between workplace characteristics and nocturnal sleep in a working population was investigated. Data from 709 employees (mean age=39 years; 87% men) from two German companies were analysed at the entry of the longitudinal cohort study (overall accrual 73%). We investigated the association between the effort-reward imbalance model at work (Siegrist, 1996) and self-reported sleep quality and sleep disturbances, as assessed by the Jenkins Sleep Quality Index. Effort and overcomm...

  10. The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders

    OpenAIRE

    Dobryakova, Ekaterina; Genova, Helen M.; DeLuca, John; Wylie, Glenn R.

    2015-01-01

    Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis....

  11. The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders.

    OpenAIRE

    Ekaterina eDobryakova; Genova, Helen M.; John eDeLuca; Wylie, Glenn R.

    2015-01-01

    Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. ...

  12. Current Account Imbalances in the Monetary Union and the Great Recession: Causes and Policies

    OpenAIRE

    Uxó Jorge; Paúl Jesús; Febrero Eladio

    2011-01-01

    Current account imbalances within the eurozone are at the roots of its economic crisis. We argue that, though relevant, emphasis should shift from competitiveness to differential rates of growth of domestic demand as its chief explanatory factor. Euro core countries have experienced a shortage of domestic demand, with wage restraint playing a key role. This has led them to experience a current account surplus, which could not be understood independently of a buoyant domestic demand in t...

  13. Quasiparticle lifetime in ultracold fermionic mixtures with density and mass imbalance

    OpenAIRE

    Lan, Zhihao; Bruun, Georg M.; Lobo, Carlos

    2013-01-01

    We show that atomic Fermi mixtures with density and mass imbalance exhibit a rich diversity of scaling laws for the quasiparticle decay rate beyond the quadratic energy and temperature dependence of conventional Fermi liquids. For certain densities and mass ratios, the decay rate is linear whereas in other cases it exhibits a plateau. Remarkably, this plateau extends from the deeply degenerate to the high temperature classical regime of the light species. Many of these scaling laws are analog...

  14. The Building Up of New Imbalances in China: The Dilemma with ‘Rebalancing’

    OpenAIRE

    Wagner, Prof. Dr. Helmut

    2016-01-01

    This paper offers a theoretical basis for the concept of rebalancing and applies it to China, where it is currently a topical issue. Rebalancing here means the correction of economic and social imbalances built up during industrialization. This correction is accompanied by a structural transformation towards a more inward- and consumption-driven growth path, associated with growth slowdown. Attempts to mitigate this growth slowdown by either retarding this structural reform process or by usin...

  15. CLINICAL SIGNIFICANCE OF IMMUNE IMBALANCE AND AUTOIMMUNITY IN NERVOUS SYSTEM DISORDERS (NSDs)

    OpenAIRE

    SINGH Vijendra K.

    2015-01-01

    In recent years, the role of immune imbalance and autoimmunity has been experimentally demonstrated in nervous system disorders (NSDs) that include Alzheimer’s disease, autism, obsessive-compulsive disorder (OCD), tics and Tourette’s syndrome, schizophrenia, and some other NSDs. And yet, these NSDs are never counted as autoimmune diseases. Deriving from the rapidly expanding knowledge of neuro-immunology and auto-immune diseases, for example multiple scle-rosis (MS), the author of this mini-r...

  16. Photospheric Magnetic Field: Relationship Between North-South Asymmetry and Flux Imbalance

    OpenAIRE

    Vernova, E. S.; Tyasto, M. I.; Baranov, D. G.

    2012-01-01

    Photospheric magnetic fields were studied using the Kitt Peak synoptic maps for 1976-2003. Only strong magnetic fields (B>100 G) of the equatorial region were taken into account. The north-south asymmetry of the magnetic fluxes was considered as well as the imbalance between positive and negative fluxes. The north-south asymmetry displays a regular alternation of the dominant hemisphere during the solar cycle: the northern hemisphere dominated in the ascending phase, the southern one in the d...

  17. Different Probe Combinations for Assessment of Postzygotic Chromosomal Imbalances in Human Embryos

    OpenAIRE

    Bielanska, Magdalena; Tan, Seang Lin; Ao, Asangla

    2002-01-01

    Purpose: We compared three different probe combinations for detection of postzygotic mosaic imbalances in human preimplantation embryos. Methods: Two hundred and two spare cleavage stage embryos were hybridized with fluorescently labelled DNA probe mixtures specific to chromosomes X, Y, 18 (N = 67), chromosomes 2, 7, 18 (N = 71), or chromosomes 13, 16, 18, 21, 22 (N = 64). Results: An overall higher incidence of abnormalities was detected using probe mixture for five (69%) or three (72%) auto...

  18. Effort-reward imbalance and self-rated health among Gambian healthcare professionals

    OpenAIRE

    Darboe, Amadou; Lin, I-Feng; Kuo, Hsien-Wen

    2016-01-01

    Background The effort-reward imbalance (ERI) model of work stress has been widely applied in investigating association between psychosocial factors at work and health. This study examined associations between perceived psychosocial work stress as measured by the ERI model and self-rated health (SRH) among nurses and environmental health officers (EHOs) working in secondary public healthcare facilities in the Gambia. Method A cross-sectional study on a random sample of 287 health care professi...

  19. Reducing response time in fork-join systems under heavy traffic via imbalance control

    OpenAIRE

    Leite, Saul C.; Fragoso, Marcelo D.

    2013-01-01

    We consider the problem of reducing the response time of fork-join systems by maintaining the workload balanced among the processing stations. The general problem of modeling and finding an optimal policy that reduces imbalance is quite difficult. In order to circumvent this difficulty, the heavy traffic approach is taken, and the system dynamics are approximated by a reflected diffusion process. This way, the problem of finding an optimal balancing policy that reduces workl...

  20. Effort-reward imbalance and overcommitment in employees in a Norwegian municipality: a cross sectional study

    OpenAIRE

    Lau Bjørn

    2008-01-01

    Abstract Background The aim of this study was to validate a Norwegian version of the Effort-Reward Imbalance Questionnaire (ERI-Q). Methods One thousand eight-hundred and three employees in a medium-sized Norwegian municipality replied to the ERI-Q, and health-related variables such as self-reported general health, psychological distress, musculoskeletal complaints, and work-related burnout were examined. Results Sound psychometric properties were found for this Norwegian version of the ERI-Q...

  1. Myocardial Ischemia: Lack of Coronary Blood Flow or Myocardial Oxygen Supply/Demand Imbalance?

    Science.gov (United States)

    Heusch, Gerd

    2016-07-01

    Regional myocardial blood flow and contractile function in ischemic myocardium are well matched, and there is no evidence for an oxygen supply/demand imbalance. Thus, myocardial ischemia is lack of coronary blood flow with electric, functional, metabolic, and structural consequences for the myocardium. All therapeutic interventions must aim to improve blood flow to ischemic myocardium as much and as quickly as possible. PMID:27390331

  2. Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease

    OpenAIRE

    Garcia-Alloza, M; Gil-Bea, F.J. (Francisco J.); Diez-Ariza, M. (Mónica); Chen, C. P.; Francis, P.T.; Lasheras, B.; Ramirez, M.J.

    2005-01-01

    Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in...

  3. Effort/reward imbalance and sedentary lifestyle: an observational study in a large occupational cohort

    OpenAIRE

    Kouvonen, Anne; Kivimäki, Mika; Elovainio, Marko; Pentti, Jaana; Linna, Anne; Virtanen, Marianna; Vahtera, Jussi

    2006-01-01

    OBJECTIVES: To investigate the association between effort/reward imbalance (ERI) at work and sedentary lifestyle. METHODS: Cross sectional data from the ongoing Finnish Public Sector Study related to 30,433 women and 7718 men aged 17-64 were used (n = 35,918 after exclusion of participants with missing values in covariates). From the responses to a questionnaire, an aggregated mean score for ERI in a work unit was assigned to each participant. The outcome was sedentary lifestyle defined as

  4. Compensating active power imbalances in power system with large-scale wind power penetration

    OpenAIRE

    Basit, Abdul; Anca Daniela HANSEN; Altin, Müfit; Sørensen, Poul Ejnar; Gamst, Mette

    2016-01-01

    Large-scale wind power penetration can affectthe supply continuity in the power system. This is a matterof high priority to investigate, as more regulating reservesand specified control strategies for generation control arerequired in the future power system with even more highwind power penetration. This paper evaluates the impact oflarge-scale wind power integration on future power systems.An active power balance control methodology is usedfor compensating the power imbalances between thede...

  5. Microarray-based comparative genomic hybridization analysis in neonates with congenital anomalies: detection of chromosomal imbalances

    Directory of Open Access Journals (Sweden)

    Luiza Emy Dorfman

    2015-02-01

    Full Text Available OBJECTIVE: To identify chromosomal imbalances by whole-genome microarray-based comparative genomic hybridization (array-CGH in DNA samples of neonates with congenital anomalies of unknown cause from a birth defects monitoring program at a public maternity hospital. METHODS: A blind genomic analysis was performed retrospectively in 35 stored DNA samples of neonates born between July of 2011 and December of 2012. All potential DNA copy number variations detected (CNVs were matched with those reported in public genomic databases, and their clinical significance was evaluated. RESULTS: Out of a total of 35 samples tested, 13 genomic imbalances were detected in 12/35 cases (34.3%. In 4/35 cases (11.4%, chromosomal imbalances could be defined as pathogenic; in 5/35 (14.3% cases, DNA CNVs of uncertain clinical significance were identified; and in 4/35 cases (11.4%, normal variants were detected. Among the four cases with results considered causally related to the clinical findings, two of the four (50% showed causative alterations already associated with well-defined microdeletion syndromes. In two of the four samples (50%, the chromosomal imbalances found, although predicted as pathogenic, had not been previously associated with recognized clinical entities. CONCLUSIONS: Array-CGH analysis allowed for a higher rate of detection of chromosomal anomalies, and this determination is especially valuable in neonates with congenital anomalies of unknown etiology, or in cases in which karyotype results cannot be obtained. Moreover, although the interpretation of the results must be refined, this method is a robust and precise tool that can be used in the first-line investigation of congenital anomalies, and should be considered for prospective/retrospective analyses of DNA samples by birth defect monitoring programs.

  6. Naturopathy and yoga in ameliorating multiple hormonal imbalance: a single case report

    OpenAIRE

    Pradeep M.K. Nair

    2016-01-01

    Hormonal imbalances are common among the women who are in the halfway of their reproductive age. There are lot of factors like stress, diet, lifestyle etc. which contributes to this hormonal dysfunctions. However these factors are merely addressed by the existing management strategies. A 37 year old female presented with hypothyroidism and associated hyperprolactinemia had undergone Naturopathy and yoga interventions for a period of 18 months. Her baseline TSH and prolactin levels were 9.2 U/...

  7. Cardiac autonomic imbalance by social stress in rodents: understanding putative biomarkers

    OpenAIRE

    Susan K Wood, Phd

    2014-01-01

    Exposure to stress or traumatic events can lead to the development of depression and anxiety disorders. In addition to the debilitating consequences on mental health, patients with psychiatric disorders also suffer from autonomic imbalance, making them susceptible to a variety of medical disorders. Emerging evidence utilizing spectral analysis of heart rate variability (HRV), a reliable non-invasive measure of cardiovascular autonomic regulation, indicates that patients with depression and va...

  8. Would Protectionism Defuse Global Imbalances and Spur Economic Activity? A Scenario Analysis

    OpenAIRE

    Faruqee, Hamid; Laxton, Douglas; Muir, Dirk; Pesenti, Paolo

    2006-01-01

    In the evolving analysis of global imbalances, the possibility that countries will resort to increased protectionism is often mentioned but rarely analyzed. This paper attempts to fill that gap, examining the macroeconomic implications of a shift to protectionist policies through the lens of a dynamic general equilibrium model of the world economy that encompasses four regional blocs. Simulation exercises are carried out to assess the consequences of imposing uniform and discriminatory tariff...

  9. Cylinder Imbalance Detection of Six Cylinder DI Diesel Engine Using Pressure Variation

    OpenAIRE

    S. H. Gawande; L. G. Navale; M. R. Nandgaonkar; D. S. Butala; S. Kunamalla

    2010-01-01

    In this research paper a simplified methodology is presented to detect cylinder imbalance in operating sixcylinder DI diesel engine. The detailed torsional vibration analysis helps to find vibratory frequencies, mode shapes, and vibratory stresses to provide constraints on critical speed in operating engine. The crank shaft is considered to be a rigid body so that the variation of the angular speed could be directly correlated to the cylinder pressure. Actuallythe variation of crank shaft spe...

  10. Effect of complex amino acid imbalance on growth of tumor in tumor-bearing rats

    Institute of Scientific and Technical Information of China (English)

    Yin-Cheng He; Yuan-Hong Wang; Jun Cao; Ji-Wei Chen; Ding-Yu Pan; Ya-Kui Zhou

    2003-01-01

    AIM: To investigate the effect of complex amino acid imbalance on the growth of tumor in tumor-bearing (TB) rats.METHODS: Sprague-Dawlley (SD) rats underwent jejunostomy for nutritional support. A suspension of Walker256 carcinosarcoma cells was subcutaneously inoculated.TB rats were randomly divided into groups A, B, C and D according to the formula of amino acids in enteral nutritional solutions, respectively. TB rats received jejunal feedings supplemented with balanced amino acids (group A),methionine-depleted amino acids (group B), valine-depleted amino acids (group C) and methionine- and valine-depleted complex amino acid imbalance (group D) for 10 days. Tumor volume, inhibitory rates of tumor, cell cycle and life span of TB rats were investigated.RESULTS: The G0/G1 ratio of tumor cells in group D (80.5±9.0) % was higher than that in groups A, B and C which was 67.0±5.1 %, 78.9±8.5 %, 69.2±6.2 %, respectively (P<0.05). The ratio of S/G2M and PI in group D were lower than those in groups A, B and C. The inhibitory rate of tumor in groups B, C and D was 37.2 %, 33.3 % and 43.9 %,respectively (P<0.05). The life span of TB rats in group D was significantly longer than that in groups B, C, and A.CONCLUSION: Methionine/valine-depleted amino acid imbalance can inhibit tumor growth. Complex amino acids of methionine and valine depleted imbalance have stronger inhibitory effects on tumor growth.

  11. The Elephant Hiding in the Room: Currency Intervention and Trade Imbalances

    OpenAIRE

    Gagnon, Joseph E.

    2013-01-01

    Official purchases of foreign assets--a broad definition of currency intervention--are strongly correlated with current account (trade) imbalances. Causality runs in both directions, but statistical analysis using instrumental variables reveals that the effect of official asset purchases on current accounts is very large. A country’s current account balance increases between 60 and 100 cents for each dollar spent on intervention. This is a much larger effect than is widely assumed. These resu...

  12. Separately contacted edge states at high imbalance in the integer and fractional quantum Hall effect regime

    OpenAIRE

    Deviatov, E. V.; Lorke, A

    2008-01-01

    This review presents experimental results on the inter-edge-state transport in the quantum Hall effect, mostly obtained in the regime of high imbalance. The application of a special geometry makes it possible to perform I-V spectroscopy between individual edge channels in both the integer and the fractional regime. This makes it possible to study in detail a number of physical effects such as the creation of topological defects in the integer quantum Hall effect and neutral collective modes e...

  13. Bhlhb5::flpo allele uncovers a requirement for Bhlhb5 for the development of the dorsal cochlear nucleus.

    Science.gov (United States)

    Cai, Xiaoyun; Kardon, Adam P; Snyder, Lindsey M; Kuzirian, Marissa S; Minestro, Sam; de Souza, Luiza; Rubio, Maria E; Maricich, Stephen M; Ross, Sarah E

    2016-06-15

    Auditory information is initially processed in the cochlear nuclei before being relayed to the brain. The cochlear nuclei are subdivided into dorsal, anterior ventral, and posterior ventral domains, each containing several subtypes of neurons that are thought to play discrete roles in the processing of sound. However, the ontogeny of these neurons is poorly understood, and this gap in knowledge hampers efforts to understand the basic neural circuitry of this nucleus. Here, we reveal that Bhlhb5 is expressed in both excitatory (unipolar brush cells) and inhibitory neurons (cartwheel cells) of the DCN during development. To gain genetic access to Bhlhb5-expressing neurons in the DCN, we generated a Bhlhb5::flpo knockin allele. Using an intersectional genetic strategy, we labeled cartwheel cells, thereby providing proof of concept that subpopulations of Bhlhb5-expressing neurons can be genetically targeted. Moreover, fate-mapping experiments using this allele revealed that Bhlhb5 is required for the proper development of the DCN, since mice lacking Bhlhb5 showed a dramatically diminished number of neurons, including unipolar brush and cartwheel cells. Intriguingly, the Bhlhb5::flpo allele also genetically labels numerous other regions of the nervous system that process sensory input, including the dorsal horn, the retina, and the nucleus of the lateral olfactory tract, hinting at a more general role for Bhlhb5 in the development of neurons that mediate sensory integration. PMID:27151208

  14. Pulmonary ventilation and perfusion abnormalities and ventilation perfusion imbalance in children with pulmonary atresia or extreme tetralogy of Fallot

    International Nuclear Information System (INIS)

    Xenon-133 lung ventilation and perfusion scans were done preoperatively after cardiac catheterization and cineangiocardiography in 19 children; 6 had pulmonary atresia with an intact ventricular septum and hypoplastic right ventricle, 4 pulmonary atresia with associated complex univentricular heart, and 9 extreme Tetralogy of Fallot. The four patients with discrepancies in the sizes of the left and right pulmonary arteries on angiography had marked asymmetry of pulmonary perfusion and ventilation-perfusion imbalance on scintigraphy. Similar degrees of asymmetry and imbalance were present in 6 of the 15 children with equal-size pulmonary vessels. Asymmetry of pulmonary perfusion and ventilation-perfusion imbalance were associated with a poor prognosis

  15. Imbalances in the Development of Chinese Culture------about the traditional Chinese culture influenced by the west

    Institute of Scientific and Technical Information of China (English)

    李嘉晨

    2014-01-01

    During the development of Chinese culture, it absorbs a lot of exotic new things from the west. This situation directly induced two imbalances in the structure of our culture nowadays. One of these imbalances is between the Chinese traditional culture and the western culture, and the other one is the humanity culture and the science culture. Both these imbalances are rooted in the relationship between the eastern and western cultures, which are combining, interweaving and conflicting during the developing process. The differences between these two cultures and the influences from the western one determine the current imbalanced pattern of Chinese culture.

  16. Pulmonary ventilation and perfusion abnormalities and ventilation perfusion imbalance in children with pulmonary atresia or extreme tetralogy of Fallot

    Energy Technology Data Exchange (ETDEWEB)

    Dowdle, S.C.; Human, D.G.; Mann, M.D. (Univ. of Cape Town (South Africa))

    1990-08-01

    Xenon-133 lung ventilation and perfusion scans were done preoperatively after cardiac catheterization and cineangiocardiography in 19 children; 6 had pulmonary atresia with an intact ventricular septum and hypoplastic right ventricle, 4 pulmonary atresia with associated complex univentricular heart, and 9 extreme Tetralogy of Fallot. The four patients with discrepancies in the sizes of the left and right pulmonary arteries on angiography had marked asymmetry of pulmonary perfusion and ventilation-perfusion imbalance on scintigraphy. Similar degrees of asymmetry and imbalance were present in 6 of the 15 children with equal-size pulmonary vessels. Asymmetry of pulmonary perfusion and ventilation-perfusion imbalance were associated with a poor prognosis.

  17. Can an energy balance model provide additional constraints on how to close the energy imbalance?

    Science.gov (United States)

    Wohlfahrt, Georg; Widmoser, Peter

    2013-02-15

    Elucidating the causes for the energy imbalance, i.e. the phenomenon that eddy covariance latent and sensible heat fluxes fall short of available energy, is an outstanding problem in micrometeorology. This paper tests the hypothesis that the full energy balance, through incorporation of additional independent measurements which determine the driving forces of and resistances to energy transfer, provides further insights into the causes of the energy imbalance and additional constraints on energy balance closure options. Eddy covariance and auxiliary data from three different biomes were used to test five contrasting closure scenarios. The main result of our study is that except for nighttime, when fluxes were low and noisy, the full energy balance generally did not contain enough information to allow further insights into the causes of the imbalance and to constrain energy balance closure options. Up to four out of the five tested closure scenarios performed similarly and in up to 53% of all cases all of the tested closure scenarios resulted in plausible energy balance values. Our approach may though provide a sensible consistency check for eddy covariance energy flux measurements. PMID:24465072

  18. Bias-resolved measurements of charge imbalance in superconductors at ultra-low temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Huebler, Florian [Karlsruher Institut fuer Technologie, Institut fuer Nanotechnologie (Germany); Karlsruher Institut fuer Technologie, Institut fuer Festkoerperphysik (Germany); Camirand Lemyre, Julien; Beckmann, Detlef [Karlsruher Institut fuer Technologie, Institut fuer Nanotechnologie (Germany); Loehneysen, Hilbert von [Karlsruher Institut fuer Technologie, Institut fuer Festkoerperphysik (Germany); Karlsruher Institut fuer Technologie, Physikalisches Institut, Karlsruhe (Germany)

    2010-07-01

    In this study we explore charge imbalance in mesoscopic normal-metal/superconductor multiterminal hybrid structures at ultra-low temperatures (T <imbalance with magnetic field, which can be directly linked to the pair breaking parameter. In contrast practically no temperature dependence of the charge imbalance signal was observed below 0.5 K. These results are relevant for the investigation of other non-local effects such as crossed Andreev reflexion and spin diffusion.

  19. The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders.

    Directory of Open Access Journals (Sweden)

    Ekaterina eDobryakova

    2015-03-01

    Full Text Available Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS, and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research.

  20. The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders.

    Science.gov (United States)

    Dobryakova, Ekaterina; Genova, Helen M; DeLuca, John; Wylie, Glenn R

    2015-01-01

    Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome, and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research. PMID:25814977

  1. Imbalance of predator and prey armament: geographic clines in phenotypic interface and natural selection.

    Science.gov (United States)

    Toju, Hirokazu; Sota, Teiji

    2006-01-01

    The escalation of defensive/offensive arms is ubiquitous in prey-predator evolutionary interactions. However, there may be a geographically varying imbalance in the armaments of participating species that affects the outcome of local interactions. In a system involving the Japanese camellia (Camellia japonica) and its obligate seed predator, the camellia weevil (Curculio camelliae), we investigated the geographic variation in physical defensive/offensive traits and that in natural selection on the plant's defense among 17 populations over a 700-km-wide area in Japan. The sizes of the plant defensive apparatus (pericarp thickness) and the weevil offensive apparatus (rostrum length) clearly correlated with each other across populations. Nevertheless, the balance in armaments between the two species was geographically structured. In the populations for which the balance was relatively advantageous for the plant's defense, natural selection on the trait was stronger because in the other populations, most plant individuals were too vulnerable to resist the attacks of the weevil, and their seeds were infested independent of pericarp thickness. We also found that the imbalance between the defensive/offensive armaments and the intensity of natural selection showed clear latitudinal clines. Overall, our results suggest that the imbalance of armament between sympatric prey and predator could determine the strength of local selection and that climatic conditions could affect the local and overall trajectory of coevolutionary arms races. PMID:16475103

  2. Socio-economic and environmental aspects of the industry imbalances in the regional economy

    Directory of Open Access Journals (Sweden)

    Dmitriy Valer'evich Eidenzon

    2013-12-01

    Full Text Available The paper presents an analysis of current socio-economic and environmental aspects of the industry imbalances in the regional economy by the example of Ural Federal District and Siberian Federal District. The main aim of it is to identify the actual socio-economic problems in the development of the regional economies. The authors analyze the economic, ecological and social aspects in the development of regional economies by the examples. They investigate the specifics of the correlation between industrial development, ecological problems and health problems of the local population. Particular emphasis is placed on the analysis of correlations between the mortality of the population and industrial pollution of air and water. The analysis has resulted in making proposals for optimization of the regional policy in the field of investments, manufacturing and ecology. The special attention is given to environment-oriented projects. The most practicable way in solving the problem of these regional industry imbalances would be the development of regional diversification programs of the Siberia and the Ural economies. It has to support manufacturing and the largest public-private investment projects for the foundation of enterprises in agriculture, food and other industries. The most prosperous among them is the direction of bioenergy and forest-engineering-oriented businesses. The results of the research can be useful in solving the problem of the industry imbalances in the regional economic policy of the Russian Federation.

  3. Genomic imbalances in 5918 malignant epithelial tumors: an explorative meta-analysis of chromosomal CGH data

    International Nuclear Information System (INIS)

    Chromosomal abnormalities have been associated with most human malignancies, with gains and losses on some genomic regions associated with particular entities. Of the 15429 cases collected for the Progenetix molecular-cytogenetic database, 5918 malignant epithelial neoplasias analyzed by chromosomal Comparative Genomic Hybridization (CGH) were selected for further evaluation. For the 22 clinico-pathological entities with more than 50 cases, summary profiles for genomic imbalances were generated from case specific data and analyzed. With large variation in overall genomic instability, recurring genomic gains and losses were prominent. Most entities showed frequent gains involving 8q2, while gains on 20q, 1q, 3q, 5p, 7q and 17q were frequent in different entities. Loss 'hot spots' included 3p, 4q, 13q, 17p and 18q among others. Related average imbalance patterns were found for clinically distinct entities, e.g. hepatocellular carcinomas (ca.) and ductal breast ca., as well as for histologically related entities (squamous cell ca. of different sites). Although considerable case-by-case variation of genomic profiles can be found by CGH in epithelial malignancies, a limited set of variously combined chromosomal imbalances may be typical for carcinogenesis. Focus on the respective regions should aid in target gene detection and pathway deduction

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

    Science.gov (United States)

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

    1991-01-01

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

  5. Tissue-specific patterns of allelically-skewed DNA methylation

    Science.gov (United States)

    Marzi, Sarah J.; Meaburn, Emma L.; Dempster, Emma L.; Lunnon, Katie; Paya-Cano, Jose L.; Smith, Rebecca G.; Volta, Manuela; Troakes, Claire; Schalkwyk, Leonard C.; Mill, Jonathan

    2016-01-01

    ABSTRACT While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood. PMID:26786711

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Decreased Regulatory T Cells in Vulnerable Atherosclerotic Lesions: Imbalance between Pro- and Anti-Inflammatory Cells in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ilonka Rohm

    2015-01-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease of the arterial wall in which presentation of autoantigens by dendritic cells (DCs leads to the activation of T cells. Anti-inflammatory cells like Tregs counterbalance inflammation in atherogenesis. In our study, human carotid plaque specimens were classified as stable (14 and unstable (15 according to established morphological criteria. Vessel specimens (n=12 without any signs of atherosclerosis were used as controls. Immunohistochemical staining was performed to detect different types of DCs (S100, fascin, CD83, CD209, CD304, and CD123, proinflammatory T cells (CD3, CD4, CD8, and CD161, and anti-inflammatory Tregs (FoxP3. The following results were observed: in unstable lesions, significantly higher numbers of proinflammatory cells like DCs, T helper cells, cytotoxic T cells, and natural killer cells were detected compared to stable plaques. Additionally, there was a significantly higher expression of HLA-DR and more T cell activation (CD25, CD69 in unstable lesions. On the contrary, unstable lesions contained significantly lower numbers of Tregs. Furthermore, a significant inverse correlation between myeloid DCs and Tregs was shown. These data suggest an increased inflammatory state in vulnerable plaques resulting from an imbalance of the frequency of local pro- and anti-inflammatory immune cells.

  11. Sources of Potential Water Imbalance in Low-gradient Coastal Watersheds

    Science.gov (United States)

    Amatya, D. M.; Trettin, C.; Williams, T. M.

    2011-12-01

    In recent years there has been an increasing concern of water yield/balance from watersheds because of population growth, land use change, and climate change, including variability of its extremes. These concerns are equally valid for the humid Southeastern Coastal Plain as well as arid/semi-arid regions. The Coastal Plain is generally characterized by flat, low-gradient systems where the average annual rainfall generally equals or exceeds the potential evapotranspiration (ET) often resulting in excess soil-water. More than 60% of the region is covered by forest ecosystems, including wetlands, where the regional long-term water balance includes 70-80% of average annual precipitation lost to ET. Maintaining this balance is important to both economic development as well as land and water management practices in this landscape. However, both anthropogenic and natural disturbances can easily create "imbalance" of rainfall, ET, and eventually, in water yield and supply. In this presentation we summarize various reasons that can and are tending to cause the imbalance of water in this region. Clearing of forest ecosystems near the coastal waters for rapid and expanded urbanization with increased imperviousness results in decreased transpiration, dramatic increase in surface runoff and flooding as well as decrease in sustained base flows. Understanding of such imbalances from pre-developed forested conditions is critical for developing best management practices (BMPs) to create a new sustained "balance" in the developed system. An " imbalance" caused by a dramatic temporal shift in water balance as may occur in the forest ecosystem due to continuous climate change or changes in magnitude and frequency of extreme climatic events. This may be caused by shift in vegetation species and growth patterns, including invasive species and forest die-off, all of which affect rainfall-ET balance and, thereby, water yield. Similarly, the extreme climatic events characteristic to the

  12. Imbalance in Groundwater-Surface Water Interactions and its Relationship to the Coastal Zone Hazards

    Science.gov (United States)

    Kontar, Y. A.; Ozorovich, Y. R.; Salokhiddinov, A. T.

    2011-12-01

    We report here some efforts and results in studying the imbalance in groundwater-surface water interactions and processes of groundwater-surface water interactions and groundwater flooding creating hazards in the coastal zones. Hazards, hydrological and geophysical risk analysis related to imbalance in groundwater-surface water interactions and groundwater flooding have been to a large extent under-emphasized for coastal zone applications either due to economical limitations or underestimation of significance of imbalance in groundwater-surface water interactions. This is particularly true for tsunamis creating salt water intrusion to coastal aquifers, even though most tsunami hazard assessments have in the past relied on scenario or deterministic type models, and to increasing mineralization of potable water because of intensive water diversions and also the abundance of highly toxic pollutants (mainly pesticides) in water, air and food, which contribute to the deterioration of the coastal population's health. In the wake of pressing environmental and economic issues, it is of prime importance for the scientific community to shed light onto the great efforts by hydrologists and geophysicists to quantify conceptual uncertainties and to provide quality assurances of potential coastal zone hazard evaluation and prediction under conditions of imbalance in groundwater-surface water interactions. This paper proposes consideration of two case studies which are important and significant for future understanding of a concept of imbalance in groundwater-surface water interactions and development and essential for feasibility studies of hazards in the coastal zone. The territory of the Aral Sea Region in Central Asia is known as an ecological disaster coastal zone. It is now obvious that, in order to provide reasonable living conditions to the coastal zone population, it is first of all necessary to drastically improve the quality of the water dedicated to human needs. Due

  13. 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...

  14. 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.

  15. 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....

  16. Impact of I/Q imbalance on the performance of two-way CSI-assisted AF relaying

    KAUST Repository

    Qi, Jian

    2013-04-01

    In this paper, we investigate half-duplex two-way dual-hop channel state information (CSI)-assisted amplify-and-forward (AF) relaying in the presence of in-phase and quadrature-phase (I/Q) imbalance. A compensation approach for the I/Q imbalance is proposed, which employs the received signals together with their conjugations to detect the desired signal. We also derive the average symbol error probability of the considered half-duplex two-way dual-hop CSI-assisted AF relaying networks with and without compensation for I/Q imbalance in Rayleigh fading channels. Numerical results are provided and show that the proposed compensation method mitigates the impact of I/Q imbalance to a certain extent. © 2013 IEEE.

  17. The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization

    International Nuclear Information System (INIS)

    Cancer-related genes show racial differences. Therefore, identification and characterization of DNA copy number alteration regions in different racial groups helps to dissect the mechanism of tumorigenesis. Array-comparative genomic hybridization (array-CGH) was analyzed for DNA copy number profile in 40 Asian and 20 Caucasian lung cancer patients. Three methods including MetaCore analysis for disease and pathway correlations, concordance analysis between array-CGH database and the expression array database, and literature search for copy number variation genes were performed to select novel lung cancer candidate genes. Four candidate oncogenes were validated for DNA copy number and mRNA and protein expression by quantitative polymerase chain reaction (qPCR), chromogenic in situ hybridization (CISH), reverse transcriptase-qPCR (RT-qPCR), and immunohistochemistry (IHC) in more patients. We identified 20 chromosomal imbalance regions harboring 459 genes for Caucasian and 17 regions containing 476 genes for Asian lung cancer patients. Seven common chromosomal imbalance regions harboring 117 genes, included gain on 3p13-14, 6p22.1, 9q21.13, 13q14.1, and 17p13.3; and loss on 3p22.2-22.3 and 13q13.3 were found both in Asian and Caucasian patients. Gene validation for four genes including ARHGAP19 (10q24.1) functioning in Rho activity control, FRAT2 (10q24.1) involved in Wnt signaling, PAFAH1B1 (17p13.3) functioning in motility control, and ZNF322A (6p22.1) involved in MAPK signaling was performed using qPCR and RT-qPCR. Mean gene dosage and mRNA expression level of the four candidate genes in tumor tissues were significantly higher than the corresponding normal tissues (P<0.001~P=0.06). In addition, CISH analysis of patients indicated that copy number amplification indeed occurred for ARHGAP19 and ZNF322A genes in lung cancer patients. IHC analysis of paraffin blocks from Asian Caucasian patients demonstrated that the frequency of PAFAH1B1 protein overexpression was 68

  18. The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Lo Fang-Yi

    2012-06-01

    Full Text Available Abstract Background Cancer-related genes show racial differences. Therefore, identification and characterization of DNA copy number alteration regions in different racial groups helps to dissect the mechanism of tumorigenesis. Methods Array-comparative genomic hybridization (array-CGH was analyzed for DNA copy number profile in 40 Asian and 20 Caucasian lung cancer patients. Three methods including MetaCore analysis for disease and pathway correlations, concordance analysis between array-CGH database and the expression array database, and literature search for copy number variation genes were performed to select novel lung cancer candidate genes. Four candidate oncogenes were validated for DNA copy number and mRNA and protein expression by quantitative polymerase chain reaction (qPCR, chromogenic in situ hybridization (CISH, reverse transcriptase-qPCR (RT-qPCR, and immunohistochemistry (IHC in more patients. Results We identified 20 chromosomal imbalance regions harboring 459 genes for Caucasian and 17 regions containing 476 genes for Asian lung cancer patients. Seven common chromosomal imbalance regions harboring 117 genes, included gain on 3p13-14, 6p22.1, 9q21.13, 13q14.1, and 17p13.3; and loss on 3p22.2-22.3 and 13q13.3 were found both in Asian and Caucasian patients. Gene validation for four genes including ARHGAP19 (10q24.1 functioning in Rho activity control, FRAT2 (10q24.1 involved in Wnt signaling, PAFAH1B1 (17p13.3 functioning in motility control, and ZNF322A (6p22.1 involved in MAPK signaling was performed using qPCR and RT-qPCR. Mean gene dosage and mRNA expression level of the four candidate genes in tumor tissues were significantly higher than the corresponding normal tissues (PP=0.06. In addition, CISH analysis of patients indicated that copy number amplification indeed occurred for ARHGAP19 and ZNF322A genes in lung cancer patients. IHC analysis of paraffin blocks from Asian Caucasian patients demonstrated that the frequency of

  19. Applying microsatellite multiplex PCR analysis (MMPA for determining allele copy-number status and percentage of normal cells within tumors.

    Directory of Open Access Journals (Sweden)

    Carles Garcia-Linares

    Full Text Available The study of somatic genetic alterations in tumors contributes to the understanding and management of cancer. Genetic alterations, such us copy number or copy neutral changes, generate allelic imbalances (AIs that can be determined using polymorphic markers. Here we report the development of a simple set of calculations for analyzing microsatellite multiplex PCR data from control-tumor pairs that allows us to obtain accurate information not only regarding the AI status of tumors, but also the percentage of tumor-infiltrating normal cells, the locus copy-number status and the mechanism involved in AI. We validated this new approach by re-analyzing a set of Neurofibromatosis type 1-associated dermal neurofibromas and comparing newly generated data with results obtained for the same tumors in a previous study using MLPA, Paralog Ratio Analysis and SNP-array techniques.Microsatellite multiplex PCR analysis (MMPA should be particularly useful for analyzing specific regions of the genome containing tumor suppressor genes and also for determining the percentage of infiltrating normal cells within tumors allowing them to be sorted before they are analyzed by more expensive techniques.

  20. Analysis and Compensation of Transmitter and Receiver I/Q Imbalances in Space-Time Coded Multiantenna OFDM Systems

    Directory of Open Access Journals (Sweden)

    Yaning Zou

    2007-12-01

    Full Text Available The combination of orthogonal frequency division multiplexing (OFDM and multiple-input multiple-output (MIMO techniques has been widely considered as the most promising approach for building future wireless transmission systems. The use of multiple antennas poses then big restrictions on the size and cost of individual radio transmitters and receivers, to keep the overall transceiver implementation feasible. This results in various imperfections in the analog radio front ends. One good example is the so-called I/Q imbalance problem related to the amplitude and phase matching of the transceiver I and Q chains. This paper studies the performance of space-time coded (STC multiantenna OFDM systems under I/Q imbalance, covering both the transmitter and the receiver sides of the link. The challenging case of frequency-selective I/Q imbalances is assumed, being an essential ingredient in future wideband wireless systems. As a practical example, the Alamouti space-time coded OFDM system with two transmit and M receive antennas is examined in detail and a closed-form solution for the resulting signal-to-interference ratio (SIR at the detector input due to I/Q imbalance is derived. This offers a valuable analytical tool for assessing the I/Q imbalance effects in any STC-OFDM system, without lengthy data or system simulations. In addition, the impact of I/Q imbalances on the channel estimation in the STC-OFDM context is also analyzed analytically. Furthermore, based on the derived signal models, a practical pilot-based I/Q imbalance compensation scheme is also proposed, being able to jointly mitigate the effects of frequency-selective I/Q imbalances as well as channel estimation errors. The performance of the compensator is analyzed using extensive computer simulations, and it is shown to virtually reach the perfectly matched reference system performance with low pilot overhead.

  1. On the Effect of I/Q Imbalance on Energy Detection and a Novel Four-Level Hypothesis Spectrum Sensing

    OpenAIRE

    Semiari, Omid; Maham, Behrouz; Yuen, Chau

    2015-01-01

    Direct-conversion transceivers are in demand, due to low implementation cost of analog front-ends. However, these transmitters or receivers introduce imperfections such as in-phase and quadrature-phase (I/Q) imbalances. In this paper, we first investigate the effect of I/Q imbalance on the performance of primary system, and show that these impairments can severely degrade the performance of cognitive radio system that are based on orthogonal frequency division multiplexing (OFDM) multiple acc...

  2. Analysis and Compensation of Transmitter and Receiver I/Q Imbalances in Space-Time Coded Multiantenna OFDM Systems

    Directory of Open Access Journals (Sweden)

    Zou Yaning

    2008-01-01

    Full Text Available Abstract The combination of orthogonal frequency division multiplexing (OFDM and multiple-input multiple-output (MIMO techniques has been widely considered as the most promising approach for building future wireless transmission systems. The use of multiple antennas poses then big restrictions on the size and cost of individual radio transmitters and receivers, to keep the overall transceiver implementation feasible. This results in various imperfections in the analog radio front ends. One good example is the so-called I/Q imbalance problem related to the amplitude and phase matching of the transceiver I and Q chains. This paper studies the performance of space-time coded (STC multiantenna OFDM systems under I/Q imbalance, covering both the transmitter and the receiver sides of the link. The challenging case of frequency-selective I/Q imbalances is assumed, being an essential ingredient in future wideband wireless systems. As a practical example, the Alamouti space-time coded OFDM system with two transmit and M receive antennas is examined in detail and a closed-form solution for the resulting signal-to-interference ratio (SIR at the detector input due to I/Q imbalance is derived. This offers a valuable analytical tool for assessing the I/Q imbalance effects in any STC-OFDM system, without lengthy data or system simulations. In addition, the impact of I/Q imbalances on the channel estimation in the STC-OFDM context is also analyzed analytically. Furthermore, based on the derived signal models, a practical pilot-based I/Q imbalance compensation scheme is also proposed, being able to jointly mitigate the effects of frequency-selective I/Q imbalances as well as channel estimation errors. The performance of the compensator is analyzed using extensive computer simulations, and it is shown to virtually reach the perfectly matched reference system performance with low pilot overhead.

  3. The Empathy Imbalance Hypothesis of Autism: A Theoretical Approach to Cognitive and Emotional Empathy in Autistic Development

    OpenAIRE

    Smith, A.

    2009-01-01

    There has been a widely held belief that people with autism spectrum disorders lack empathy. This article examines the empathy imbalance hypothesis (EIH) of autism. According to this account, people with autism have a deficit of cognitive empathy but a surfeit of emotional empathy. The behavioral characteristics of autism might be generated by this imbalance and a susceptibility to empathic overarousal. The EIH builds on the theory of mind account and provides an alternative to the extreme-ma...

  4. Duality in binocular rivalry: distinct sensitivity of percept sequence and percept duration to imbalance between monocular stimuli.

    Directory of Open Access Journals (Sweden)

    Chen Song

    Full Text Available BACKGROUND: Visual perception is usually stable and accurate. However, when the two eyes are simultaneously presented with conflicting stimuli, perception falls into a sequence of spontaneous alternations, switching between one stimulus and the other every few seconds. Known as binocular rivalry, this visual illusion decouples subjective experience from physical stimulation and provides a unique opportunity to study the neural correlates of consciousness. The temporal properties of this alternating perception have been intensively investigated for decades, yet the relationship between two fundamental properties - the sequence of percepts and the duration of each percept - remains largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Here we examine the relationship between the percept sequence and the percept duration by quantifying their sensitivity to the strength imbalance between two monocular stimuli. We found that the percept sequence is far more susceptible to the stimulus imbalance than does the percept duration. The percept sequence always begins with the stronger stimulus, even when the stimulus imbalance is too weak to cause a significant bias in the percept duration. Therefore, introducing a small stimulus imbalance affects the percept sequence, whereas increasing the imbalance affects the percept duration, but not vice versa. To investigate why the percept sequence is so vulnerable to the stimulus imbalance, we further measured the interval between the stimulus onset and the first percept, during which subjects experienced the fusion of two monocular stimuli. We found that this interval is dramatically shortened with increased stimulus imbalance. CONCLUSIONS/SIGNIFICANCE: Our study shows that in binocular rivalry, the strength imblanace between monocular stimuli has a much greater impact on the percept sequence than on the percept duration, and increasing this imbalance can accelerate the process responsible for the percept sequence.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Soybean Resistance Genes Specific for Different Pseudomonas Syringae Avirulence Genes Are Allelic, or Closely Linked, at the Rpg1 Locus

    OpenAIRE

    Ashfield, T.; Keen, N. T.; Buzzell, R. I.; Innes, R W

    1995-01-01

    RPG1 and RPM1 are disease resistance genes in soybean and Arabidopsis, respectively, that confer resistance to Pseudomonas syringae strains expressing the avirulence gene avrB. RPM1 has recently been demonstrated to have a second specificity, also conferring resistance to P. syringae strains expressing avrRpm1. Here we show that alleles, or closely linked genes, exist at the RPG1 locus in soybean that are specific for either avrB or avrRpm1 and thus can distinguish between these two avirulenc...

  7. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    International Nuclear Information System (INIS)

    Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines

  8. Work-life balance/imbalance: the dominance of the middle class and the neglect of the working class.

    Science.gov (United States)

    Warren, Tracey

    2015-12-01

    The paper was stimulated by the relative absence of the working class from work-life debates. The common conclusion from work-life studies is that work-life imbalance is largely a middle-class problem. It is argued here that this classed assertion is a direct outcome of a particular and narrow interpretation of work-life imbalance in which time is seen to be the major cause of difficulty. Labour market time, and too much of it, dominates the conceptualization of work-life and its measurement too. This heavy focus on too much labour market time has rendered largely invisible from dominant work-life discourses the types of imbalance that are more likely to impact the working class. The paper's analysis of large UK data-sets demonstrates a reduction in hours worked by working-class men, more part-time employment in working-class occupations, and a substantial growth in levels of reported financial insecurity amongst the working classes after the 2008-9 recession. It shows too that economic-based work-life imbalance is associated with lower levels of life satisfaction than is temporal imbalance. The paper concludes that the dominant conceptualization of work-life disregards the major work-life challenge experienced by the working class: economic precarity. The work-life balance debate needs to more fully incorporate economic-based work-life imbalance if it is to better represent class inequalities. PMID:26487574

  9. Disruption of germination and seedling development in Brassica napus by mutations causing severe seed hormonal imbalance

    Directory of Open Access Journals (Sweden)

    Tung eNguyen

    2016-03-01

    Full Text Available The Brassica napus (oilseed rape accession 1012-98 shows a disturbed germination phenotype that was thought to be associated with its lack of testa pigmentation and thin seed coat. Here we demonstrate that the disturbed germination and seedling development are actually due to independent mutations that disrupt the balance of hormone metabolites and their regulators in the seeds. High-throughput UPLC-MS/MS hormone profiling of seeds and seedlings before and after germination revealed that 1012-98 has a severely disturbed hormone balance with extremely atypical, excessive quantities of auxin and ABA metabolites. The resulting hypersensitivity to abscisic acid (ABA and a corresponding increase in dormancy often results in death of the embryo after imbibition or high frequencies of disturbed, often lethal developmental phenotypes, resembling Arabidopsis mutants for the auxin regulatory factor gene ARF10 or the auxin-overproducing transgenic line iaaM-OX. Molecular cloning of Brassica ARF10 orthologues revealed four loci in normal B. napus, two derived from the Brassica A genome and two from the C genome. On the other hand, the phenotypic mutant 1012-98 exhibited amplification of C-genome BnaC.ARF10 copy number along with a chimeric allele originating from recombination between homoeologous A and C genome loci which lead to minor increase of Bna.ARF10 transcription on the critical timepoint for seed germination, the indirect regulator of ABI3, the germinative inhibitor. Bna.GH3.5 expression was upregulated to conjugate free auxin to IAA-asp between 2-6 DAS. Functional amino acid changes were also found in important DNA binding domains of one BnaC.ARF10 locus, suggesting that regulatory changes in Bna.ARF10 are collectively responsible for the observed phenotpyes in 1012-98. To our knowledge, this study is the first to report disruption of germination and seedling development in Brassica napus caused by the crosstalk of auxin-ABA and the

  10. Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster

    OpenAIRE

    Deng, Xinxian; Hiatt, Joseph B.; Nguyen, Di Kim; Ercan, Sevinc; Sturgill, David; Hillier, Ladeana W; Schlesinger, Felix; Davis, Carrie A.; Reinke, Valerie J; Gingeras, Thomas R.; Shendure, Jay; Robert H Waterston; Oliver, Brian; Lieb, Jason D.; Disteche, Christine M

    2011-01-01

    Many animal species use a chromosome-based mechanism of sex determination, which has led to the coordinate evolution of dosage-compensation systems. Dosage compensation not only corrects the imbalance in the number of X chromosomes between the sexes but also is hypothesized to correct dosage imbalance within cells that is due to monoallelic X-linked expression and biallelic autosomal expression, by upregulating X-linked genes twofold (termed ‘Ohno’s hypothesis’). Although this hypothesis is w...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Frequency of Cry1F Non-Recessive Resistance Alleles in North Carolina Field Populations of Spodoptera frugiperda (Lepidoptera: Noctuidae.

    Directory of Open Access Journals (Sweden)

    Guoping Li

    Full Text Available Fall armyworm, Spodoptera frugiperda (J.E. Smith (Lepidoptera: Noctuidae, is a target species of transgenic corn (Zea mays L. that expresses single and pyramided Bacillus thuringiensis (Bt toxin. In 2014, S. frugiperda were collected from a light trap in North Carolina, and a total of 212 F1/F2 isofemale lines of S. frugiperda were screened for resistance to Bt and non-Bt corn. All of the 212 isolines were susceptible to corn tissue expressing Cry1A.105 + Cry2Ab, Cry1F + Cry1A.105 + Cry2Ab, and Cry1F + Cry1Ab + Vip3Aa20. Growth rate bioassays were performed to isolate non-recessive Bt resistance alleles. Seven individuals out of the 212 isofemale lines carried major non-recessive alleles conferring resistance to Cry1F. A pooled colony was created from the seven individuals. This colony was 151.21 times more resistant to Cry1F than a known-susceptible population and was also resistant to Cry1A.105, but was not resistant to Cry2Ab and Vip3Aa20. The results demonstrate that field populations of S. frugiperda collected from North Carolina are generally susceptible to Cry1F, but that some individuals carry resistant alleles. The data generated in this study can be used as baseline data for resistance monitoring.

  13. Early allelic selection in maize as revealed by ancient DNA.

    Science.gov (United States)

    Jaenicke-Després, Viviane; Buckler, Ed S; Smith, Bruce D; Gilbert, M Thomas P; Cooper, Alan; Doebley, John; Pääbo, Svante

    2003-11-14

    Maize was domesticated from teosinte, a wild grass, by approximately 6300 years ago in Mexico. After initial domestication, early farmers continued to select for advantageous morphological and biochemical traits in this important crop. However, the timing and sequence of character selection are, thus far, known only for morphological features discernible in corn cobs. We have analyzed three genes involved in the control of plant architecture, storage protein synthesis, and starch production from archaeological maize samples from Mexico and the southwestern United States. The results reveal that the alleles typical of contemporary maize were present in Mexican maize by 4400 years ago. However, as recently as 2000 years ago, allelic selection at one of the genes may not yet have been complete. PMID:14615538

  14. Mutant radiation-resistance alleles from the Escherichia coli Gamr444 mutant: Cloning and preliminary characterization

    International Nuclear Information System (INIS)

    Mutant alleles Gamr, which are able to increase the resistance to radiation of Escherichia coli wild-type cells, were cloned from the hyperradioresistant mutant Gamr444 on plasmid mini-Mu-vector MudII4042. The influence of recombinant plasmids on the sensitivity of wild-type and mutant (recA and htpR) cells to γ-irradiation was studied. It was shown that the enhanced resistance of the Gamr444 strain to radiation was caused by mutations of two different classes, dominant and recessive. The cloned recessive mutation gamr12 increases resistance to radiation only after homogenotization, that is, radiation-induced transfer from the plasmid to the chromosome, and it imposes constitutive expression of the heat-shock promoter htpG. Dominant mutant gamr alleles are active in the trans-position. A mutation-insertion into a chromosomal gene impaired by one of the dominant mutations, gamr18, was constructed. The insertion causes drastic cell radiosensitization on the recBC sbcB background and probably disturbs the RecF pathway of recombination and repair. Dominant plasmids of the second type lead to the RecA-independent inhibition of DNA postirradiation degradation. The radioprotective action of recessive and dominant gamr mutations is additive

  15. Site- and allele-specific polycomb dysregulation in T-cell leukaemia.

    Science.gov (United States)

    Navarro, Jean-Marc; Touzart, Aurore; Pradel, Lydie C; Loosveld, Marie; Koubi, Myriam; Fenouil, Romain; Le Noir, Sandrine; Maqbool, Muhammad Ahmad; Morgado, Ester; Gregoire, Claude; Jaeger, Sebastien; Mamessier, Emilie; Pignon, Charles; Hacein-Bey-Abina, Salima; Malissen, Bernard; Gut, Marta; Gut, Ivo G; Dombret, Hervé; Macintyre, Elizabeth A; Howe, Steven J; Gaspar, H Bobby; Thrasher, Adrian J; Ifrah, Norbert; Payet-Bornet, Dominique; Duprez, Estelle; Andrau, Jean-Christophe; Asnafi, Vahid; Nadel, Bertrand

    2015-01-01

    T-cell acute lymphoblastic leukaemias (T-ALL) are aggressive malignant proliferations characterized by high relapse rates and great genetic heterogeneity. TAL1 is amongst the most frequently deregulated oncogenes. Yet, over half of the TAL1(+) cases lack TAL1 lesions, suggesting unrecognized (epi)genetic deregulation mechanisms. Here we show that TAL1 is normally silenced in the T-cell lineage, and that the polycomb H3K27me3-repressive mark is focally diminished in TAL1(+) T-ALLs. Sequencing reveals that >20% of monoallelic TAL1(+) patients without previously known alterations display microinsertions or RAG1/2-mediated episomal reintegration in a single site 5' to TAL1. Using 'allelic-ChIP' and CrispR assays, we demonstrate that such insertions induce a selective switch from H3K27me3 to H3K27ac at the inserted but not the germline allele. We also show that, despite a considerable mechanistic diversity, the mode of oncogenic TAL1 activation, rather than expression levels, impact on clinical outcome. Altogether, these studies establish site-specific epigenetic desilencing as a mechanism of oncogenic activation. PMID:25615415

  16. Assessment of Quantitative and Allelic MGMT Methylation Patterns as a Prognostic Marker in Glioblastoma.

    Science.gov (United States)

    Kristensen, Lasse S; Michaelsen, Signe R; Dyrbye, Henrik; Aslan, Derya; Grunnet, Kirsten; Christensen, Ib J; Poulsen, Hans S; Grønbæk, Kirsten; Broholm, Helle

    2016-03-01

    Methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is a predictive and prognostic marker in newly diagnosed glioblastoma patients treated with temozolomide but how MGMT methylation should be assessed to ensure optimal detection accuracy is debated. We developed a novel quantitative methylation-specific PCR (qMSP) MGMT assay capable of providing allelic methylation data and analyzed 151 glioblastomas from patients receiving standard of care treatment (Stupp protocol). The samples were also analyzed by immunohistochemistry (IHC), standard bisulfite pyrosequencing, and genotyped for the rs1690252 MGMT promoter single nucleotide polymorphism. Monoallelic methylation was observed more frequently than biallelic methylation, and some cases with monoallelic methylation expressed the MGMT protein whereas others did not. The presence of MGMT methylation was associated with better overall survival (p = 0.006; qMSP and p = 0.002; standard pyrosequencing), and the presence of the protein was associated with worse overall survival (p = 0.009). Combined analyses of qMSP and standard pyrosequencing or IHC identified additional patients who benefited from temozolomide treatment. Finally, low methylation levels were also associated with better overall survival (p = 0.061; qMSP and p = 0.02; standard pyrosequencing). These data support the use of both MGMT methylation and MGMT IHC but not allelic methylation data as prognostic markers in patients with temozolomide-treated glioblastoma. PMID:26883115

  17. An ancestral allele of grapevine transcription factor MYB14 promotes plant defence.

    Science.gov (United States)

    Duan, Dong; Fischer, Sabine; Merz, Patrick; Bogs, Jochen; Riemann, Michael; Nick, Peter

    2016-04-01

    Stilbene synthase is a key enzyme for the production of the phytoalexin resveratrol. Some clones of Vitis sylvestris, a wild European grapevine species which is almost extinct, have been shown to accumulate more resveratrol in response to different forms of stress. In the current study, we asked whether the induction of stilbene synthase transcripts in Hoe29, one of the V. sylvestris clones with elevated stilbene inducibility, might result from the elevated induction of the transcription factor MYB14. The MYB14 promoter of Hoe29 and of Ke83 (a second stilbene-inducible genotype) harboured distinct regions and were applied to a promoter-reporter system. We show that stilbene synthase inducibility correlates with differences in the induction of MYB14 transcripts for these two genotypes. Both alleles were induced by UV in a promoter-reporter assay, but only the MYB14 promoter from Hoe29 was induced by flg22, consistent with the stilbene synthase expression of the donor genotypes, where both respond to UV but only Hoe29 is responsive to Plasmopara viticola during defence. We mapped upstream signals and found that a RboH-dependent oxidative burst, calcium influx, a MAPK cascade, and jasmonate activated the MYB14 promoter, whereas salicylic acid was ineffective. Our data suggest that the Hoe29 allele of the MYB14 promoter has potential as a candidate target for resistance breeding. PMID:26842984

  18. 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 ...

  19. 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...

  20. 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...

  1. Allelic diversity of the population of Phytophthora infestans in China

    OpenAIRE

    Li, Y; Huang, S.; Lee; Kessel, G.J.T.; Jacobsen, E.; Zhang, R.; Jin, G.; Lan, C.; Zhao, Z.; Kamoun, S

    2009-01-01

    Introduction of resistance genes from wild Solanum species into potato cultivars is considered the most promising and environmentally safe approach to achieve late blight resistance. An R-gene stacking breeding program using cisgenesis is planning to trial its products in China. To adapt this approach to local conditions, we propose to assess the allelic diversity of known avirulent genes of P. infestans from the intended introduction regions of the GM-potatoes in China. So far, we have a lar...

  2. 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....

  3. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots

    Czech Academy of Sciences Publication Activity Database

    Baker, C.L.; Petkova, P.; Walker, M.; Flachs, Petr; Mihola, Ondřej; Trachtulec, Zdeněk; Petkov, P.M.; Paigen, K.

    2015-01-01

    Roč. 11, č. 9 (2015), e1005512-e1005512. ISSN 1553-7390 R&D Projects: GA ČR GAP305/10/1931; GA ČR(CZ) GA14-20728S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : recombination * PRDM9 * allelic competition Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.528, year: 2014

  4. Demographic history and rare allele sharing among human populations

    OpenAIRE

    Henn, Brenna M.; Indap, Amit R.; Donnelly, Peter; Nickerson, Debbie A.; Peltonen, Leena; Deiros, David; Metzker, Mike; Li, Jingxiang; Jian, Min; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Wei; Zhang, Xiuqing; Zheng, Huisong

    2011-01-01

    High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, As...

  5. 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)

  6. Gain-of-Function Alleles in Caenorhabditis elegans Nuclear Hormone Receptor nhr-49 Are Functionally Distinct.

    Science.gov (United States)

    Lee, Kayoung; Goh, Grace Ying Shyen; Wong, Marcus Andrew; Klassen, Tara Leah; Taubert, Stefan

    2016-01-01

    Nuclear hormone receptors (NHRs) are transcription factors that regulate numerous physiological and developmental processes and represent important drug targets. NHR-49, an ortholog of Hepatocyte Nuclear Factor 4 (HNF4), has emerged as a key regulator of lipid metabolism and life span in the nematode worm Caenorhabditis elegans. However, many aspects of NHR-49 function remain poorly understood, including whether and how it regulates individual sets of target genes and whether its activity is modulated by a ligand. A recent study identified three gain-of-function (gof) missense mutations in nhr-49 (nhr-49(et7), nhr-49(et8), and nhr-49(et13), respectively). These substitutions all affect the ligand-binding domain (LBD), which is critical for ligand binding and protein interactions. Thus, these alleles provide an opportunity to test how three specific residues contribute to NHR-49 dependent gene regulation. We used computational and molecular methods to delineate how these mutations alter NHR-49 activity. We find that despite originating from a screen favoring the activation of specific NHR-49 targets, all three gof alleles cause broad upregulation of NHR-49 regulated genes. Interestingly, nhr-49(et7) and nhr-49(et8) exclusively affect nhr-49 dependent activation, whereas the nhr-49(et13) surprisingly affects both nhr-49 mediated activation and repression, implicating the affected residue as dually important. We also observed phenotypic non-equivalence of these alleles, as they unexpectedly caused a long, short, and normal life span, respectively. Mechanistically, the gof substitutions altered neither protein interactions with the repressive partner NHR-66 and the coactivator MDT-15 nor the subcellular localization or expression of NHR-49. However, in silico structural modeling revealed that NHR-49 likely interacts with small molecule ligands and that the missense mutations might alter ligand binding, providing a possible explanation for increased NHR-49 activity. In

  7. Tracing pastoralist migrations to southern Africa with lactase persistence alleles.

    Science.gov (United States)

    Macholdt, Enrico; Lede, Vera; Barbieri, Chiara; Mpoloka, Sununguko W; Chen, Hua; Slatkin, Montgomery; Pakendorf, Brigitte; Stoneking, Mark

    2014-04-14

    Although southern African Khoisan populations are often assumed to have remained largely isolated during prehistory, there is growing evidence for a migration of pastoralists from eastern Africa some 2,000 years ago, prior to the arrival of Bantu-speaking populations in southern Africa. Eastern Africa harbors distinctive lactase persistence (LP) alleles, and therefore LP alleles in southern African populations may be derived from this eastern African pastoralist migration. We sequenced the lactase enhancer region in 457 individuals from 18 Khoisan and seven Bantu-speaking groups from Botswana, Namibia, and Zambia and additionally genotyped four short tandem repeat (STR) loci that flank the lactase enhancer region. We found nine single-nucleotide polymorphisms, of which the most frequent is -14010(∗)C, which was previously found to be associated with LP in Kenya and Tanzania and to exhibit a strong signal of positive selection. This allele occurs in significantly higher frequency in pastoralist groups and in Khoe-speaking groups in our study, supporting the hypothesis of a migration of eastern African pastoralists that was primarily associated with Khoe speakers. Moreover, we find a signal of ongoing positive selection in all three pastoralist groups in our study, as well as (surprisingly) in two foraging groups. PMID:24704073

  8. The protease inhibitor PI*S allele and COPD

    DEFF Research Database (Denmark)

    Hersh, C P; Ly, N P; Berkey, C S; Silverman, E K; Nordestgaard, B G; Dahl, Morten; Dahl, M

    2005-01-01

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

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

    International Nuclear Information System (INIS)

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

  10. Lung ventilation-perfusion imbalance in pulmonary emphysema. Assessment with automated V/Q quotient SPECT

    International Nuclear Information System (INIS)

    Tc-99m-Technegas-macro-aggregated albumin (MAA) single photon emission computed tomography (SPECT)-derived ventilation (V)/perfusion (Q) quotient SPECT was used to assess lung V-Q imbalance in patients with pulmonary emphysema. V/Q quotient SPECT and V/Q profile were automatically built in 38 patients with pulmonary emphysema and 12 controls, and V/Q distribution and V/Q profile parameters were compared. V/Q distribution on V/Q quotient SPECT was correlated with low attenuation areas (LAA) on density-mask computed tomography (CT). Parameters of V/Q profile such as the median, standard deviation (SD), kurtosis and skewness were proposed to objectively evaluate the severity of lung V-Q imbalance. In contrast to uniform V/Q distribution on V/Q quotient SPECT and a sharp peak with symmetrical V/Q distribution on V/Q profile in controls, lung areas showing heterogeneously high or low V/Q and flattened peaks with broadened V/Q distribution were frequently seen in patients with emphysema, including lung areas with only slight LAA. V/Q distribution was also often asymmetric regardless of symmetric LAA. All the proposed parameters of V/Q profile in entire lungs of patients with emphysema showed large variations compared with controls; SD and kurtosis were significantly different from controls (P<0.0001 and P<0.001, respectively), and a significant correlation was found between SD and A-aDO2 (P<0.0001). V/Q quotient SPECT appears to be more sensitive to detect emphysematous lungs compared with morphologic CT in patients with emphysema. SD and kurtosis of V/Q profile can be adequate parameters to assess the severity of lung V-Q imbalance causing gas-exchange impairment in patients with emphysema. (author)

  11. Chromosomal imbalances in four new uterine cervix carcinoma derived cell lines

    Directory of Open Access Journals (Sweden)

    Vázquez Guelaguetza

    2003-03-01

    Full Text Available Abstract Background Uterine cervix carcinoma is the second most common female malignancy worldwide and a major health problem in Mexico, representing the primary cause of death among the Mexican female population. High risk human papillomavirus (HPV infection is considered to be the most important risk factor for the development of this tumor and cervical carcinoma derived cell lines are very useful models for the study of viral carcinogenesis. Comparative Genomic Hybridization (CGH experiments have detected a specific pattern of chromosomal imbalances during cervical cancer progression, indicating chromosomal regions that might contain genes that are important for cervical transformation. Methods We performed HPV detection and CGH analysis in order to initiate the genomic characterization of four recently established cervical carcinoma derived cell lines from Mexican patients. Results All the cell lines were HPV18 positive. The most prevalent imbalances in the cell lines were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2, this alteration present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter. Conclusions Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases. These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites. The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma.

  12. Framework for interpretation of trypsin-antitrypsin imbalance and genetic heterogeneity in pancreatitis

    Directory of Open Access Journals (Sweden)

    Kun Lin

    2015-01-01

    Full Text Available Early intracellular premature trypsinogen activation was interpreted as the key initiator of pancreatitis. When the balance in the homeostasis of trypsin and antitrypsin system is disequilibrated, elevated aggressive enzymes directly attack the pancreatic tissue, which leads to pancreatic destruction and inflammation. However, trypsin alone is not enough to cause complications in pancreatitis, which may play a crucial role in modulating signaling events in the initial phase of the disease. NFκB activation is the major inflammatory pathway involved in the occurrence and development of pancreatitis and it can be induced by intrapancreatic activation of trypsinogen. Synthesis of trypsinogen occurs in endoplasmic reticulum (ER, and ER stress is an important early acinar cell event. Components of ER stress response are known to be able to trigger cell death as well as NFκB signaling cascade. The strongest evidence supporting the trypsin-centered theory is that gene mutations, which lead to the generation of more trypsin, or reduce the activity of trypsin inhibitors or trypsin degradation, are associated with pancreatitis. Thus, trypsin–antitrypsin imbalance may be the first step leading to pancreatic autodigestion and inducing other pathways. Continued experimental studies are necessary to determine the specific relationships between trypsin–antitrypsin imbalance and genetic heterogeneity in pancreatitis. In this article, we review the latest advances that contributed to the understanding of the basic mechanisms behind the occurrence and development of pancreatitis with a focus on the interpretation of trypsin–antitrypsin imbalance and their relationships with other inflammation pathways. We additionally highlight genetic predispositions to pancreatitis and possible mechanisms associated with them.

  13. Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype.

    Science.gov (United States)

    Mastaglia, Frank L; Needham, Merrilee; Scott, Adrian; James, Ian; Zilko, Paul; Day, Timothy; Kiers, Lynette; Corbett, Alastair; Witt, Campbell S; Allcock, Richard; Laing, Nigel; Garlepp, Michael; Christiansen, Frank T

    2009-11-01

    Susceptibility to sIBM is strongly associated with the HLA-DRB1*03 allele and the 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB1*03) but little is known about the effects of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. HLA-A, B and DRB1 genotyping was performed in 80 Australian sIBM cases and the frequencies of different alleles and allele combinations were compared with those in a group of 190 healthy controls. Genotype-phenotype correlations were also investigated. Amongst carriers of the HLA-DRB1*03 allele, DRB1*03/*01 heterozygotes were over-represented in the sIBM group (pHLA-DRB1*03 allele and other alleles at the DRB1 locus can influence disease susceptibility and the clinical phenotype in sIBM. PMID:19720533

  14. Postural imbalance in non-treated adolescent idiopathic scoliosis at different periods of progression

    OpenAIRE

    Beaulieu, Marlene; Toulotte, Claire; Gatto, Laura; Rivard, Charles-H.; Teasdale, Normand; Simoneau, Martin; Allard, Paul

    2008-01-01

    The aim of this study was to test the hypothesis that imbalance in patients with a severe deformity of the spine is associated with an increase in the sensory integration disorder. This paper is a case comparison study. Patients were divided into three groups: able-bodied (n = 53), observation (n = 23), and pre-brace (n = 26) groups. Time domain parameters (sway area, position and displacement) and structural posturographic parameters [mean distance (MD) and mean peak (MP)] were calculated fr...

  15. Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Anna-Kaisa Niemi

    2014-01-01

    Full Text Available The pathophysiology of succinic semialdehyde dehydrogenase (SSADH deficiency is not completely understood. Oxidative stress, mitochondrial pathology, and low reduced glutathione levels have been demonstrated in mice, but no studies have been reported in humans. We report on a patient with SSADH deficiency in whom we found low levels of blood reduced glutathione (GSH, and elevations of dicarboxylic acids in urine, suggestive of possible redox imbalance and/or mitochondrial dysfunction. Thus, targeting the oxidative stress axis may be a potential therapeutic approach if our findings are confirmed in other patients.

  16. Quasiparticle Lifetime in Ultracold Fermionic Mixtures with Density and Mass Imbalance

    DEFF Research Database (Denmark)

    Lan, Zhihao; Bruun, Georg; Lobo, Carlos

    2013-01-01

    We show that atomic Fermi mixtures with density and mass imbalance exhibit a rich diversity of scaling laws for the quasiparticle decay rate beyond the quadratic energy and temperature dependence of conventional Fermi liquids. For certain densities and mass ratios, the decay rate is linear, whereas...... in other cases, it exhibits a plateau. Remarkably, this plateau extends from the deeply degenerate to the high temperature classical regime of the light species. Many of these scaling laws are analogous to what is found in very different systems, including dirty metals, liquid metals, and high...

  17. Oil price shocks and global imbalances: Lessons from a model with trade and financial interdependencies

    OpenAIRE

    Jean-Pierre Allegret; Valérie Mignon; Audrey Sallenave

    2014-01-01

    The aim of this paper is to investigate oil price shocks' effects and their associated transmission channels on global imbalances. To this end, we rely on a Global VAR approach that allows us to account for trade and Financial interdependencies between countries. Considering a sample of 30 oil-exporting and importing economies over the 1980-2011 period, we show that the nature of the shock-demand-driven or supply-driven matters in understanding the effects of oil price shocks on global imbala...

  18. Quantum Communication and Computing With Atomic Ensembles Using Light-Shift Imbalance Induced Blockade

    OpenAIRE

    Shahriar, M. S.; Pati, G. S.; Salit, K.

    2006-01-01

    Recently, we have shown that for conditions under which the so-called light-shift imbalance induced blockade (LSIIB) occurs, the collective excitation of an ensemble of a multi-level atom can be treated as a closed two level system. In this paper, we describe how such a system can be used as a quantum bit (qubit) for quantum communication and quantum computing. Specifically, we show how to realize a C-NOT gate using the collective qubit and an easily accessible ring cavity, via an extension o...

  19. Vortex-Core Structure in Neutral Fermion Superfluids with Population Imbalance

    International Nuclear Information System (INIS)

    Quantized vortex-core structure is theoretically investigated in fermion superfluids with population imbalance for two atom species of neutral atom clouds near a Feshbach resonance. In contrast with the vortex core in balance case where the quantum depletion makes a vortex visible through the density profile measurement, the vortex core is filled in and becomes less visible because the quantized discrete bound states are occupied exclusively by the majority species. Yet it is shown that the core can be visible through the minority density profile experiment using phase contrast imaging, revealing an interesting opportunity to examine low-lying fermionic core bound states unexplored so far

  20. FOXP3+Treg/Th17 cell imbalance in lung tissues of mice with asthma

    OpenAIRE

    Jiang, Hua; Wu, Xianbo; Zhu, Haiyan; Xie, Yiqiang; Tang, Songqi; Jiang, Yuji

    2015-01-01

    Immunocyte imbalances, particularly of Th1 and Th2 type helper T (Th) cells, have been implicated in the pathogenesis of chronic inflammatory diseases like asthma. Recent studies have suggested an important role for the balance between Th17 cells and FOXP3+ regulatory T cells (Treg). However, whether this balance is important in asthma remains unknown. This study sought to detect the populations of T cell subtypes (Th1, Th2, FOXP3+ Treg, Th17) in lung tissue of a mouse model of asthma to unde...