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Sample records for addition genes related

  1. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene.

    PubMed Central

    Plowman, G D; Whitney, G S; Neubauer, M G; Green, J M; McDonald, V L; Todaro, G J; Shoyab, M

    1990-01-01

    Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and amphiregulin are structurally and functionally related growth regulatory proteins. These secreted polypeptides all bind to the 170-kDa cell-surface EGF receptor, activating its intrinsic kinase activity. However, amphiregulin exhibits different activities than EGF and TGF-alpha in a number of biological assays. Amphiregulin only partially competes with EGF for binding EGF receptor, and amphiregulin does not induce anchorage-independent growth of normal rat kidney cells (NRK) in the presence of TGF-beta. Amphiregulin also appears to abrogate the stimulatory effect of TGF-alpha on the growth of several aggressive epithelial carcinomas that overexpress EGF receptor. These findings suggest that amphiregulin may interact with a separate receptor in certain cell types. Here we report the cloning of another member of the human EGF receptor (HER) family of receptor tyrosine kinases, which we have named "HER3/ERRB3." The cDNA was isolated from a human carcinoma cell line, and its 6-kilobase transcript was identified in various human tissues. We have generated peptide-specific antisera that recognizes the 160-kDa HER3 protein when transiently expressed in COS cells. These reagents will allow us to determine whether HER3 binds amphiregulin or other growth regulatory proteins and what role HER3 protein plays in the regulation of cell growth. Images PMID:2164210

  2. Supplementing High-Density SNP Microarrays for Additional Coverage of Disease-Related Genes: Addiction as a Paradigm

    SciTech Connect

    SacconePhD, Scott F; Chesler, Elissa J; Bierut, Laura J; Kalivas, Peter J; Lerman, Caryn; Saccone, Nancy L; Uhl, George R; Li, Chuan-Yun; Philip, Vivek M; Edenberg, Howard; Sherry, Steven; Feolo, Michael; Moyzis, Robert K; Rutter, Joni L

    2009-01-01

    Commercial SNP microarrays now provide comprehensive and affordable coverage of the human genome. However, some diseases have biologically relevant genomic regions that may require additional coverage. Addiction, for example, is thought to be influenced by complex interactions among many relevant genes and pathways. We have assembled a list of 486 biologically relevant genes nominated by a panel of experts on addiction. We then added 424 genes that showed evidence of association with addiction phenotypes through mouse QTL mappings and gene co-expression analysis. We demonstrate that there are a substantial number of SNPs in these genes that are not well represented by commercial SNP platforms. We address this problem by introducing a publicly available SNP database for addiction. The database is annotated using numeric prioritization scores indicating the extent of biological relevance. The scores incorporate a number of factors such as SNP/gene functional properties (including synonymy and promoter regions), data from mouse systems genetics and measures of human/mouse evolutionary conservation. We then used HapMap genotyping data to determine if a SNP is tagged by a commercial microarray through linkage disequilibrium. This combination of biological prioritization scores and LD tagging annotation will enable addiction researchers to supplement commercial SNP microarrays to ensure comprehensive coverage of biologically relevant regions.

  3. Supplementing High-Density SNP Microarrays for Additional Coverage of Disease-Related Genes: Addiction as a Paradigm

    PubMed Central

    Saccone, Scott F.; Bierut, Laura J.; Chesler, Elissa J.; Kalivas, Peter W.; Lerman, Caryn; Saccone, Nancy L.; Uhl, George R.; Li, Chuan-Yun; Philip, Vivek M.; Edenberg, Howard J.; Sherry, Stephen T.; Feolo, Michael; Moyzis, Robert K.; Rutter, Joni L.

    2009-01-01

    Commercial SNP microarrays now provide comprehensive and affordable coverage of the human genome. However, some diseases have biologically relevant genomic regions that may require additional coverage. Addiction, for example, is thought to be influenced by complex interactions among many relevant genes and pathways. We have assembled a list of 486 biologically relevant genes nominated by a panel of experts on addiction. We then added 424 genes that showed evidence of association with addiction phenotypes through mouse QTL mappings and gene co-expression analysis. We demonstrate that there are a substantial number of SNPs in these genes that are not well represented by commercial SNP platforms. We address this problem by introducing a publicly available SNP database for addiction. The database is annotated using numeric prioritization scores indicating the extent of biological relevance. The scores incorporate a number of factors such as SNP/gene functional properties (including synonymy and promoter regions), data from mouse systems genetics and measures of human/mouse evolutionary conservation. We then used HapMap genotyping data to determine if a SNP is tagged by a commercial microarray through linkage disequilibrium. This combination of biological prioritization scores and LD tagging annotation will enable addiction researchers to supplement commercial SNP microarrays to ensure comprehensive coverage of biologically relevant regions. PMID:19381300

  4. Transcriptome analysis of genes related to resistance against powdery mildew in wheat-Thinopyrum alien addition disomic line germplasm SN6306.

    PubMed

    Li, Quanquan; Niu, Zubiao; Bao, Yinguang; Tian, Qiuju; Wang, Honggang; Kong, Lingrang; Feng, Deshun

    2016-09-15

    Wheat powdery mildew, which is mainly caused by Blumeria graminis f. sp. tritici (Bgt), seriously damages wheat production. The wheat-Thinopyrum intermedium alien addition disomic line germplasm SN6306, being one of the important sources of genes for wheat resistance, is highly resistant to Bgt E09 and to many other powdery mildew physiological races. However, knowledge on the resistance mechanism of SN6306 remains limited. Our study employed high-throughput RNA sequencing based on next-generation sequencing technology (Illumina) to obtain an overview of the transcriptome characteristics of SN6306 and its parent wheat Yannong 15 (YN15) during Bgt infection. The sequencing generated 104,773 unigenes, 9909 of which showed varied expression levels. Among the 9909 unigenes, 1678 unigenes showed 0 reads in YN15. The expression levels in Bgt-inoculated SN6306 and YN15 of exactly 39 unigenes that showed 0 or considerably low reads in YN15 were validated to identify the genes involved in Bgt resistance. Among the 39 unigenes, 12 unigenes were upregulated in SN6306 by 3-45 times. These unigenes mainly encoded kinase, synthase, proteases, and signal transduction proteins, which may play an important role in the resistance against Bgt. To confirm whether the unigenes that showed 0 reads in YN15 are really unique to SN6306, 8 unigenes were cloned and sequenced. Results showed that the selected unigenes are more similar to SN6306 and Th. intermedium than to the wheat cultivar YN15. The sequencing results further confirmed that the unigenes showing 0 reads in YN15 are unique to SN6306 and are most likely derived from Th. intermedium (Host) Nevski. Thus, the genes from Th. intermedium most probably conferred the resistance of SN6306 to Bgt. PMID:27265028

  5. Refining Breast Cancer Risk Stratification: Additional Genes, Additional Information.

    PubMed

    Kurian, Allison W; Antoniou, Antonis C; Domchek, Susan M

    2016-01-01

    Recent advances in genomic technology have enabled far more rapid, less expensive sequencing of multiple genes than was possible only a few years ago. Advances in bioinformatics also facilitate the interpretation of large amounts of genomic data. New strategies for cancer genetic risk assessment include multiplex sequencing panels of 5 to more than 100 genes (in which rare mutations are often associated with at least two times the average risk of developing breast cancer) and panels of common single-nucleotide polymorphisms (SNPs), combinations of which are generally associated with more modest cancer risks (more than twofold). Although these new multiple-gene panel tests are used in oncology practice, questions remain about the clinical validity and the clinical utility of their results. To translate this increasingly complex genetic information for clinical use, cancer risk prediction tools are under development that consider the joint effects of all susceptibility genes, together with other established breast cancer risk factors. Risk-adapted screening and prevention protocols are underway, with ongoing refinement as genetic knowledge grows. Priority areas for future research include the clinical validity and clinical utility of emerging genetic tests; the accuracy of developing cancer risk prediction models; and the long-term outcomes of risk-adapted screening and prevention protocols, in terms of patients' experiences and survival. PMID:27249685

  6. Priming Addition Facts with Semantic Relations

    ERIC Educational Resources Information Center

    Bassok, Miriam; Pedigo, Samuel F.; Oskarsson, An T.

    2008-01-01

    Results from 2 relational-priming experiments suggest the existence of an automatic analogical coordination between semantic and arithmetic relations. Word pairs denoting object sets served as primes in a task that elicits "obligatory" activation of addition facts (5 + 3 activates 8; J. LeFevre, J. Bisanz, & L. Mrkonjic, 1988). Semantic relations…

  7. Priming addition facts with semantic relations.

    PubMed

    Bassok, Miriam; Pedigo, Samuel F; Oskarsson, An T

    2008-03-01

    Results from 2 relational-priming experiments suggest the existence of an automatic analogical coordination between semantic and arithmetic relations. Word pairs denoting object sets served as primes in a task that elicits "obligatory" activation of addition facts (5 + 3 activates 8; J. LeFevre, J. Bisanz, & L. Mrkonjic, 1988). Semantic relations between the priming words were either aligned or misaligned with the structure of addition (M. Bassok, V. M. Chase, & S. A. Martin, 1998). Obligatory activation of addition facts occurred when the digits were primed by categorically related words (tulips-daisies), which are aligned with addition, but did not occur when the digits were primed by unrelated words (hens-radios, Experiment 1) or by functionally related words (records-songs, Experiment 2), which are misaligned with addition. These findings lend support to the viability of automatic analogical priming (B. A. Spellman, K. J. Holyoak, & R. G. Morrison, 2001) and highlight the relevance of arithmetic applications to theoretical accounts of mental arithmetic. PMID:18315410

  8. Determining Semantically Related Significant Genes.

    PubMed

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement. PMID:26357049

  9. 21 CFR 170.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Tolerances for related food additives. 170.18... (CONTINUED) FOOD ADDITIVES General Provisions § 170.18 Tolerances for related food additives. (a) Food... food additives. (b) Tolerances established for such related food additives may limit the amount of...

  10. 21 CFR 570.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Tolerances for related food additives. 570.18... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES General Provisions § 570.18 Tolerances for related food additives. (a) Food additives that cause similar or related pharmacological...

  11. 21 CFR 570.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Tolerances for related food additives. 570.18... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES General Provisions § 570.18 Tolerances for related food additives. (a) Food additives that cause similar or related pharmacological...

  12. 21 CFR 570.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Tolerances for related food additives. 570.18... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES General Provisions § 570.18 Tolerances for related food additives. (a) Food additives that cause similar or related pharmacological...

  13. 21 CFR 570.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Tolerances for related food additives. 570.18... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES General Provisions § 570.18 Tolerances for related food additives. (a) Food additives that cause similar or related pharmacological...

  14. Prevalence of gene expression additivity in genetically stable wheat allohexaploids.

    PubMed

    Chelaifa, Houda; Chagué, Véronique; Chalabi, Smahane; Mestiri, Imen; Arnaud, Dominique; Deffains, Denise; Lu, Yunhai; Belcram, Harry; Huteau, Virginie; Chiquet, Julien; Coriton, Olivier; Just, Jérémy; Jahier, Joseph; Chalhoub, Boulos

    2013-02-01

    The reprogramming of gene expression appears as the major trend in synthetic and natural allopolyploids where expression of an important proportion of genes was shown to deviate from that of the parents or the average of the parents. In this study, we analyzed gene expression changes in previously reported, highly stable synthetic wheat allohexaploids that combine the D genome of Aegilops tauschii and the AB genome extracted from the natural hexaploid wheat Triticum aestivum. A comprehensive genome-wide analysis of transcriptional changes using the Affymetrix GeneChip Wheat Genome Array was conducted. Prevalence of gene expression additivity was observed where expression does not deviate from the average of the parents for 99.3% of 34,820 expressed transcripts. Moreover, nearly similar expression was observed (for 99.5% of genes) when comparing these synthetic and natural wheat allohexaploids. Such near-complete additivity has never been reported for other allopolyploids and, more interestingly, for other synthetic wheat allohexaploids that differ from the ones studied here by having the natural tetraploid Triticum turgidum as the AB genome progenitor. Our study gave insights into the dynamics of additive gene expression in the highly stable wheat allohexaploids. PMID:23278496

  15. 21 CFR 170.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Tolerances for related food additives. 170.18... (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES General Provisions § 170.18 Tolerances for related food additives. (a) Food additives that cause similar or related pharmacological effects will...

  16. 21 CFR 170.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Tolerances for related food additives. 170.18... (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES General Provisions § 170.18 Tolerances for related food additives. (a) Food additives that cause similar or related pharmacological effects will...

  17. 21 CFR 170.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Tolerances for related food additives. 170.18... (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES General Provisions § 170.18 Tolerances for related food additives. (a) Food additives that cause similar or related pharmacological effects will...

  18. 21 CFR 170.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Tolerances for related food additives. 170.18... (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES General Provisions § 170.18 Tolerances for related food additives. (a) Food additives that cause similar or related pharmacological effects will...

  19. Direct comparison between genomic constitution and flavonoid contents in Allium multiple alien addition lines reveals chromosomal locations of genes related to biosynthesis from dihydrokaempferol to quercetin glucosides in scaly leaf of shallot (Allium cepa L.).

    PubMed

    Masuzaki, S; Shigyo, M; Yamauchi, N

    2006-02-01

    The extrachromosome 5A of shallot (Allium cepa L., genomes AA) has an important role in flavonoid biosynthesis in the scaly leaf of Allium fistulosum-shallot monosomic addition lines (FF+nA). This study deals with the production and biochemical characterisation of A. fistulosum-shallot multiple alien addition lines carrying at least 5A to determine the chromosomal locations of genes for quercetin formation. The multiple alien additions were selected from the crossing between allotriploid FFA (female symbol) and A. fistulosum (male symbol). The 113 plants obtained from this cross were analysed by a chromosome 5A-specific PGI isozyme marker of shallot. Thirty plants were preliminarily selected for an alien addition carrying 5A. The chromosome numbers of the 30 plants varied from 18 to 23. The other extrachromosomes in 19 plants were completely identified by using seven other chromosome markers of shallot. High-performance liquid chromatography analyses of the 19 multiple additions were conducted to identify the flavonoid compounds produced in the scaly leaves. Direct comparisons between the chromosomal constitution and the flavonoid contents of the multiple alien additions revealed that a flavonoid 3'-hydroxylase (F3'H) gene for the synthesis of quercetin from kaempferol was located on 7A and that an anonymous gene involved in the glucosidation of quercetin was on 3A or 4A. As a result of supplemental SCAR analyses by using genomic DNAs from two complete sets of A. fistulosum-shallot monosomic additions, we have assigned F3'H to 7A and flavonol synthase to 4A. PMID:16411131

  20. 21 CFR 570.18 - Tolerances for related food additives.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tolerances for related food additives. 570.18 Section 570.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES General Provisions § 570.18...

  1. 78 FR 6272 - Rules Relating to Additional Medicare Tax; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ..., December 5, 2012 (77 FR 72268). The proposed regulations are relating to Additional Hospital Insurance Tax... proposed rulemaking and notice of public hearing (REG-130074-11), that was the subject of FR Doc. 2012... Internal Revenue Service 26 CFR Part 1 RIN 1545-BK54 Rules Relating to Additional Medicare Tax;...

  2. Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression.

    PubMed Central

    van der Krol, A R; Mur, L A; Beld, M; Mol, J N; Stuitje, A R

    1990-01-01

    To evaluate the effect of increased expression of genes involved in flower pigmentation, additional dihydroflavonol-4-reductase (DFR) or chalcone synthase (CHS) genes were transferred to petunia. In most transformants, the increased expression had no measurable effect on floral pigmentation. Surprisingly, however, in up to 25% of the transformants, a reduced floral pigmentation, accompanied by a dramatic reduction of DFR or CHS gene expression, respectively, was observed. This phenomenon was obtained with both chimeric gene constructs and intact CHS genomic clones. The reduction in gene expression was independent of the promoter driving transcription of the transgene and involved both the endogenous gene and the homologous transgene. The gene-specific collapse in expression was obtained even after introduction of only a single gene copy. The similarity between the sense transformants and regulatory CHS mutants suggests that this mechanism of gene silencing may operate in naturally occurring regulatory circuits. PMID:2152117

  3. Methods for detecting additional genes underlying Alzheimer disease

    SciTech Connect

    Locke, P.A.; Haines, J.L.; Ter-Minassian, M.

    1994-09-01

    Alzheimer`s disease (AD) is a complex inherited disorder with proven genetic heterogeneity. To date, genes on chromosome 21 (APP) and 14 (not yet identified) are associated with early-onset familial AD, while the APOE gene on chromosome 19 is associated with both late onset familial and sporadic AD and early onset sporadic AD. Although these genes likely account for the majority of AD, many familial cases cannot be traced to any of these genes. From a set of 127 late-onset multiplex families screened for APOE, 43 (34%) families have at least one affected individual with no APOE-4 allele, suggesting an alternative genetic etiology. Simulation studies indicated that additional loci could be identified through a genomic screen with a 10 cM sieve on a subset of 21 well documented, non-APOE-4 families. Given the uncertainties in the mode of inheritance, reliance on a single analytical method could result in a missed linkage. Therefore, we have developed a strategy of using multiple overlapping yet complementary methods to detect linkage. These include sib-pair analysis and affected-pedigree-member analysis, neither of which makes assumptions about mode of inheritance, and lod score analysis (using two predefined genetic models). In order for a marker to qualify for follow-up, it must fit at least two of three criteria. These are nominal P values of 0.05 or less for the non-parametric methods, and/or a lod score greater than 1.0. Adjacent markers each fulfilling a single criterion also warrant follow-up. To date, we have screened 61 markers on chromosomes 1, 2, 3, 18, 19, 21, and 22. One marker, D2S163, generated a lod score of 1.06 ({theta} = 0.15) and an APMT statistic of 3.68 (P < 0.001). This region is currently being investigated in more detail. Updated results of this region plus additional screening data will be presented.

  4. Additive genetic variation and evolvability of a multivariate trait can be increased by epistatic gene action.

    PubMed

    Griswold, Cortland K

    2015-12-21

    Epistatic gene action occurs when mutations or alleles interact to produce a phenotype. Theoretically and empirically it is of interest to know whether gene interactions can facilitate the evolution of diversity. In this paper, we explore how epistatic gene action affects the additive genetic component or heritable component of multivariate trait variation, as well as how epistatic gene action affects the evolvability of multivariate traits. The analysis involves a sexually reproducing and recombining population. Our results indicate that under stabilizing selection conditions a population with a mixed additive and epistatic genetic architecture can have greater multivariate additive genetic variation and evolvability than a population with a purely additive genetic architecture. That greater multivariate additive genetic variation can occur with epistasis is in contrast to previous theory that indicated univariate additive genetic variation is decreased with epistasis under stabilizing selection conditions. In a multivariate setting, epistasis leads to less relative covariance among individuals in their genotypic, as well as their breeding values, which facilitates the maintenance of additive genetic variation and increases a population׳s evolvability. Our analysis involves linking the combinatorial nature of epistatic genetic effects to the ancestral graph structure of a population to provide insight into the consequences of epistasis on multivariate trait variation and evolution. PMID:26431770

  5. Immunity-related genes and gene families in Anopheles gambiae.

    PubMed

    Christophides, George K; Zdobnov, Evgeny; Barillas-Mury, Carolina; Birney, Ewan; Blandin, Stephanie; Blass, Claudia; Brey, Paul T; Collins, Frank H; Danielli, Alberto; Dimopoulos, George; Hetru, Charles; Hoa, Ngo T; Hoffmann, Jules A; Kanzok, Stefan M; Letunic, Ivica; Levashina, Elena A; Loukeris, Thanasis G; Lycett, Gareth; Meister, Stephan; Michel, Kristin; Moita, Luis F; Müller, Hans-Michael; Osta, Mike A; Paskewitz, Susan M; Reichhart, Jean-Marc; Rzhetsky, Andrey; Troxler, Laurent; Vernick, Kenneth D; Vlachou, Dina; Volz, Jennifer; von Mering, Christian; Xu, Jiannong; Zheng, Liangbiao; Bork, Peer; Kafatos, Fotis C

    2002-10-01

    We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire. PMID:12364793

  6. 78 FR 6273 - Rules Relating to Additional Medicare Tax

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Parts 1 and 31 RIN 1545-BK54 Rules Relating to Additional Medicare Tax Correction In proposed rule document 2012-29237, appearing on pages 72268- 72277 in the issue of...

  7. Genes and gene networks implicated in aggression related behaviour.

    PubMed

    Malki, Karim; Pain, Oliver; Du Rietz, Ebba; Tosto, Maria Grazia; Paya-Cano, Jose; Sandnabba, Kenneth N; de Boer, Sietse; Schalkwyk, Leonard C; Sluyter, Frans

    2014-10-01

    Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a global transcriptomic characterization of the prefrontal cortex across all three genetic mouse models of aggression. A systems biology approach has been applied to transcriptomic data across the three pairs of selected inbred mouse strains (Turku Aggressive (TA) and Turku Non-Aggressive (TNA), Short Attack Latency (SAL) and Long Attack Latency (LAL) mice and North Carolina Aggressive (NC900) and North Carolina Non-Aggressive (NC100)), providing novel insight into the neurobiological mechanisms and genetics underlying aggression. First, weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly correlated genes associated with aggression. Probe sets belonging to gene modules uncovered by WGCNA were carried forward for network analysis using ingenuity pathway analysis (IPA). The RankProd non-parametric algorithm was then used to statistically evaluate expression differences across the genes belonging to modules significantly associated with aggression. IPA uncovered two pathways, involving NF-kB and MAPKs. The secondary RankProd analysis yielded 14 differentially expressed genes, some of which have previously been implicated in pathways associated with aggressive behaviour, such as Adrbk2. The results highlighted plausible candidate genes and gene networks implicated in aggression-related behaviour. PMID:25142712

  8. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  9. Gene Transfers Between Distantly Related Organisms

    NASA Technical Reports Server (NTRS)

    Doolittle, Russell F.

    2003-01-01

    With the completion of numerous microbial genome sequences, reports of individual gene transfers between distantly related prokaryotes have become commonplace. On the other hand, transfers between prokaryotes and eukaryotes still excite the imagination. Many of these claims may be premature, but some are certainly valid. In this chapter, the kinds of supporting data needed to propose transfers between distantly related organisms and cite some interesting examples are considered.

  10. Gene Ontology and KEGG Enrichment Analyses of Genes Related to Age-Related Macular Degeneration

    PubMed Central

    Zhang, Jian; Xing, ZhiHao; Ma, Mingming; Wang, Ning; Cai, Yu-Dong; Chen, Lei; Xu, Xun

    2014-01-01

    Identifying disease genes is one of the most important topics in biomedicine and may facilitate studies on the mechanisms underlying disease. Age-related macular degeneration (AMD) is a serious eye disease; it typically affects older adults and results in a loss of vision due to retina damage. In this study, we attempt to develop an effective method for distinguishing AMD-related genes. Gene ontology and KEGG enrichment analyses of known AMD-related genes were performed, and a classification system was established. In detail, each gene was encoded into a vector by extracting enrichment scores of the gene set, including it and its direct neighbors in STRING, and gene ontology terms or KEGG pathways. Then certain feature-selection methods, including minimum redundancy maximum relevance and incremental feature selection, were adopted to extract key features for the classification system. As a result, 720 GO terms and 11 KEGG pathways were deemed the most important factors for predicting AMD-related genes. PMID:25165703

  11. Relative Stabilities of Organic Compounds Using Benson's Additivity Rules.

    ERIC Educational Resources Information Center

    Vitale, Dale E.

    1986-01-01

    Shows how the structure-energy principle can be presented in organic chemistry (without having to resort to quantum mechanics) by use of Benson's Additive Rules. Examples of the application to several major classes of organic compounds are given.

  12. Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection

    PubMed Central

    Fitzmaurice, Karen; Hurst, Jacob; Dring, Megan; Rauch, Andri; McLaren, Paul J; Günthard, Huldrych F; Gardiner, Clair; Klenerman, Paul

    2015-01-01

    Background Chronic HCV infection is a leading cause of liver-related morbidity globally. The innate and adaptive immune responses are thought to be important in determining viral outcomes. Polymorphisms associated with the IFNL3 (IL28B) gene are strongly associated with spontaneous clearance and treatment outcomes. Objective This study investigates the importance of HLA genes in the context of genetic variation associated with the innate immune genes IFNL3 and KIR2DS3. Design We assess the collective influence of HLA and innate immune genes on viral outcomes in an Irish cohort of women (n=319) who had been infected from a single source as well as a more heterogeneous cohort (Swiss Cohort, n=461). In the Irish cohort, a number of HLA alleles are associated with different outcomes, and the impact of IFNL3-linked polymorphisms is profound. Results Logistic regression was performed on data from the Irish cohort, and indicates that the HLA-A*03 (OR 0.36 (0.15 to 0.89), p=0.027) -B*27 (OR 0.12 (0.03 to 0.45), p=<0.001), -DRB1*01:01 (OR 0.2 (0.07 to 0.61), p=0.005), -DRB1*04:01 (OR 0.31 (0.12 to 0.85, p=0.02) and the CC IFNL3 rs12979860 genotypes (OR 0.1 (0.04 to 0.23), p<0.001) are significantly associated with viral clearance. Furthermore, DQB1*02:01 (OR 4.2 (2.04 to 8.66), p=0.008), KIR2DS3 (OR 4.36 (1.62 to 11.74), p=0.004) and the rs12979860 IFNL3 ‘T’ allele are associated with chronic infection. This study finds no interactive effect between IFNL3 and these Class I and II alleles in relation to viral clearance. There is a clear additive effect, however. Data from the Swiss cohort also confirms independent and additive effects of HLA Class I, II and IFNL3 genes in their prediction of viral outcome. Conclusions This data supports a critical role for the adaptive immune response in the control of HCV in concert with the innate immune response. PMID:24996883

  13. [PRRT2 gene-related paroxysmal disorders].

    PubMed

    Li, Jin; Mao, Xiao; Wang, Junling; Li, Nan; Tang, Beisha

    2014-10-01

    Proline-rich transmembrane protein 2 (PRRT2), the causative gene of paroxysmal kinesigenic dyskinesias (PKD), benign familial infantile seizures (BFIS) and infantile convulsions with paroxysmal choreoathetosis (ICCA), also causes a variety of neurological paroxysmal disorders. These diseases share the same characteristics which may be due to the same genetic defect. We therefore propose to name them as PRRT2-related paroxysmal disorders (PRPDs) in order to assist clinical diagnosis, treatment and prognosis. This paper has reviewed the clinical phenotype, common features and pathogenesis of the PRPDs. PMID:25297589

  14. High presence/absence gene variability in defense-related gene clusters of Cucumis melo

    PubMed Central

    2013-01-01

    putative stress-response functions, were found to be particularly affected by PAV polymorphisms. As cucurbits are known to possess a significantly lower number of defense-related genes compared to other plant species, PAV variation may play an important role in generating new pathogen resistances at the subspecies level. In addition, these results show the limitations of single reference genome sequences as the only basis for characterization and cloning of resistance genes. PMID:24219589

  15. Detecting Horizontal Gene Transfer between Closely Related Taxa.

    PubMed

    Adato, Orit; Ninyo, Noga; Gophna, Uri; Snir, Sagi

    2015-10-01

    Horizontal gene transfer (HGT), the transfer of genetic material between organisms, is crucial for genetic innovation and the evolution of genome architecture. Existing HGT detection algorithms rely on a strong phylogenetic signal distinguishing the transferred sequence from ancestral (vertically derived) genes in its recipient genome. Detecting HGT between closely related species or strains is challenging, as the phylogenetic signal is usually weak and the nucleotide composition is normally nearly identical. Nevertheless, there is a great importance in detecting HGT between congeneric species or strains, especially in clinical microbiology, where understanding the emergence of new virulent and drug-resistant strains is crucial, and often time-sensitive. We developed a novel, self-contained technique named Near HGT, based on the synteny index, to measure the divergence of a gene from its native genomic environment and used it to identify candidate HGT events between closely related strains. The method confirms candidate transferred genes based on the constant relative mutability (CRM). Using CRM, the algorithm assigns a confidence score based on "unusual" sequence divergence. A gene exhibiting exceptional deviations according to both synteny and mutability criteria, is considered a validated HGT product. We first employed the technique to a set of three E. coli strains and detected several highly probable horizontally acquired genes. We then compared the method to existing HGT detection tools using a larger strain data set. When combined with additional approaches our new algorithm provides richer picture and brings us closer to the goal of detecting all newly acquired genes in a particular strain. PMID:26439115

  16. Detecting Horizontal Gene Transfer between Closely Related Taxa

    PubMed Central

    Adato, Orit; Ninyo, Noga; Gophna, Uri; Snir, Sagi

    2015-01-01

    Horizontal gene transfer (HGT), the transfer of genetic material between organisms, is crucial for genetic innovation and the evolution of genome architecture. Existing HGT detection algorithms rely on a strong phylogenetic signal distinguishing the transferred sequence from ancestral (vertically derived) genes in its recipient genome. Detecting HGT between closely related species or strains is challenging, as the phylogenetic signal is usually weak and the nucleotide composition is normally nearly identical. Nevertheless, there is a great importance in detecting HGT between congeneric species or strains, especially in clinical microbiology, where understanding the emergence of new virulent and drug-resistant strains is crucial, and often time-sensitive. We developed a novel, self-contained technique named Near HGT, based on the synteny index, to measure the divergence of a gene from its native genomic environment and used it to identify candidate HGT events between closely related strains. The method confirms candidate transferred genes based on the constant relative mutability (CRM). Using CRM, the algorithm assigns a confidence score based on “unusual” sequence divergence. A gene exhibiting exceptional deviations according to both synteny and mutability criteria, is considered a validated HGT product. We first employed the technique to a set of three E. coli strains and detected several highly probable horizontally acquired genes. We then compared the method to existing HGT detection tools using a larger strain data set. When combined with additional approaches our new algorithm provides richer picture and brings us closer to the goal of detecting all newly acquired genes in a particular strain. PMID:26439115

  17. The evolution of cancer-related genes in hominoids.

    PubMed

    Kang, Lin; Michalak, Pawel

    2015-01-01

    The evolution of cancer suppression is essential for the maintenance of multicellularity. The lack of correlation between body size and cancer risk across species, known as Peto's paradox, suggests that genetic variation in cancer resistance is sufficient to compensate for increases of cell numbers in bigger animals. To assess evolutionary dynamics of cancer-related genes, we analyzed Ka, Ks,and Ka/Ks values in 120 oncogenes and tumor suppressor genes (TSG) among seven hominoid species, including two extinct species, Neanderthal and Denisovan. Ka/Ks of tumor suppressor genes tended to be higher relative to that of oncogenes, consistent with relaxed purifying selection acting on the former. Ka/Ks values were positively correlated with TSG scores, but negatively correlated with oncogene scores, suggesting opposing selection pressures operating on the two groups of cancer-related genes. Additionally, we found 108 species-divergent substitutions that were prevalent germline genotypes in some species but in humans appeared only as somatic cancerous mutations. Better understanding the resistance to cancer may lead to new methods of cancer prevention in humans. PMID:25249249

  18. Calcitonin Gene-Related Peptide (CGRP)

    PubMed Central

    Russo, Andrew F.

    2015-01-01

    Migraine is a neurological disorder that manifests as a debilitating headache associated with altered sensory perception. The neuropeptide calcitonin gene-related peptide (CGRP) is now firmly established as a key player in migraine. Clinical trials carried out during the past decade have proved that CGRP receptor antagonists are effective for treating migraine, and antibodies to the receptor and CGRP are currently under investigation. Despite this progress in the clinical arena, the mechanisms by which CGRP triggers migraine remain uncertain. This review discusses mechanisms whereby CGRP enhances sensitivity to sensory input at multiple levels in both the periphery and central nervous system. Future studies on epistatic and epigenetic regulators of CGRP actions are expected to shed further light on CGRP actions in migraine. In conclusion, targeting CGRP represents an approachable therapeutic strategy for migraine. PMID:25340934

  19. Enhancement of aluminum tolerance in wheat by addition of chromosomes from the wild relative Leymus racemosus

    PubMed Central

    Mohammed, Yasir Serag Alnor; Eltayeb, Amin Elsadig; Tsujimoto, Hisashi

    2013-01-01

    Aluminum (Al) toxicity is the key factor limiting wheat production in acid soils. Soil liming has been used widely to increase the soil pH, but due to its high cost, breeding tolerant cultivars is more cost-effective mean to mitigate the problem. Tolerant cultivars could be developed by traditional breeding, genetic transformation or introgression of genes from wild relatives. We used 30 wheat alien chromosome addition lines to identify new genetic resources to improve wheat tolerance to Al and to identify the chromosomes harboring the tolerance genes. We evaluated these lines and their wheat background Chinese Spring for Al tolerance in hydroponic culture at various Al concentrations. We also investigated Al uptake, oxidative stress and cell membrane integrity. The L. racemosus chromosomes A and E significantly enhanced the Al tolerance of the wheat in term of relative root growth. At the highest Al concentration tested (200 μM), line E had the greatest tolerance. The introgressed chromosomes did not affect Al uptake of the tolerant lines. We attribute the improved tolerance conferred by chromosome E to improved cell membrane integrity. Chromosome engineering with these two lines could produce Al-tolerant wheat cultivars. PMID:24399913

  20. Enhancement of aluminum tolerance in wheat by addition of chromosomes from the wild relative Leymus racemosus.

    PubMed

    Mohammed, Yasir Serag Alnor; Eltayeb, Amin Elsadig; Tsujimoto, Hisashi

    2013-12-01

    Aluminum (Al) toxicity is the key factor limiting wheat production in acid soils. Soil liming has been used widely to increase the soil pH, but due to its high cost, breeding tolerant cultivars is more cost-effective mean to mitigate the problem. Tolerant cultivars could be developed by traditional breeding, genetic transformation or introgression of genes from wild relatives. We used 30 wheat alien chromosome addition lines to identify new genetic resources to improve wheat tolerance to Al and to identify the chromosomes harboring the tolerance genes. We evaluated these lines and their wheat background Chinese Spring for Al tolerance in hydroponic culture at various Al concentrations. We also investigated Al uptake, oxidative stress and cell membrane integrity. The L. racemosus chromosomes A and E significantly enhanced the Al tolerance of the wheat in term of relative root growth. At the highest Al concentration tested (200 μM), line E had the greatest tolerance. The introgressed chromosomes did not affect Al uptake of the tolerant lines. We attribute the improved tolerance conferred by chromosome E to improved cell membrane integrity. Chromosome engineering with these two lines could produce Al-tolerant wheat cultivars. PMID:24399913

  1. Senescence Mutants of Saccharomyces Cerevisiae with a Defect in Telomere Replication Identify Three Additional Est Genes

    PubMed Central

    Lendvay, T. S.; Morris, D. K.; Sah, J.; Balasubramanian, B.; Lundblad, V.

    1996-01-01

    The primary determinant for telomere replication is the enzyme telomerase, responsible for elongating the G-rich strand of the telomere. The only component of this enzyme that has been identified in Saccharomyces cerevisiae is the TLC1 gene, encoding the telomerase RNA subunit. However, a yeast strain defective for the EST1 gene exhibits the same phenotypes (progressively shorter telomeres and a senescence phenotype) as a strain deleted for TLC1, suggesting that EST1 encodes either a component of telomerase or some other factor essential for telomerase function. We designed a multitiered screen that led to the isolation of 22 mutants that display the same phenotypes as est1 and tlc1 mutant strains. These mutations mapped to four complementation groups: the previously identified EST1 gene and three additional genes, called EST2, EST3 and EST4. Cloning of the EST2 gene demonstrated that it encodes a large, extremely basic novel protein with no motifs that provide clues as to function. Epistasis analysis indicated that the four EST genes function in the same pathway for telomere replication as defined by the TLC1 gene, suggesting that the EST genes encode either components of telomerase or factors that positively regulate telomerase activity. PMID:8978029

  2. Ventromedial hypothalamic lesions change the expression of neuron-related genes and immune-related genes in rat liver.

    PubMed

    Kiba, Takayoshi; Kintaka, Yuri; Suzuki, Yoko; Nakata, Eiko; Ishigaki, Yasuhito; Inoue, Shuji

    2009-05-01

    There are no reports that hypothalamus can directly affect the expression of neuron-related genes and immune-related genes in liver. We identified genes of which expression profiles showed significant modulation in rat liver after ventromedial hypothalamic (VMH) lesions. Total RNA was extracted, and differences in the gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH lesioned rats were investigated using DNA microarray analysis. The result revealed that VMH lesions regulated the genes that were involved in functions related to neuronal development and immunofunction in the liver. Real-time PCR also confirmed that gene expression of SULT4A1 was upregulated, but expression of ACSL1 and CISH were downregulated at day 3 after VMH lesions. VMH lesions may change the expression of neuron-related genes and immune-related genes in rat liver. PMID:19429097

  3. Antagonistic control of a dual-input mammalian gene switch by food additives

    PubMed Central

    Xie, Mingqi; Ye, Haifeng; Hamri, Ghislaine Charpin-El; Fussenegger, Martin

    2014-01-01

    Synthetic biology has significantly advanced the design of mammalian trigger-inducible transgene-control devices that are able to programme complex cellular behaviour. Fruit-based benzoate derivatives licensed as food additives, such as flavours (e.g. vanillate) and preservatives (e.g. benzoate), are a particularly attractive class of trigger compounds for orthogonal mammalian transgene control devices because of their innocuousness, physiological compatibility and simple oral administration. Capitalizing on the genetic componentry of the soil bacterium Comamonas testosteroni, which has evolved to catabolize a variety of aromatic compounds, we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate. When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme. Additionally, the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch. Designer gene switches using licensed food additives as trigger compounds to achieve antagonistic dual-input expression profiles and provide novel control topologies and regulation dynamics may advance future gene- and cell-based therapies. PMID:25030908

  4. Leptin regulates gallbladder genes related to absorption and secretion.

    PubMed

    Swartz-Basile, Deborah A; Lu, Debao; Basile, David P; Graewin, Shannon J; Al-Azzawi, Hayder; Kiely, James M; Mathur, Abhishek; Yancey, Kyle; Pitt, Henry A

    2007-07-01

    Dysregulation of gallbladder ion and water absorption and/or secretion has been linked to cholesterol crystal and gallstone formation. We have recently demonstrated that obese, leptin-deficient (Lep(ob)) mice have enlarged gallbladder volumes and decreased gallbladder contractility and that leptin administration to these mice normalizes gallbladder function. However, the effect of leptin on gallbladder absorption/secretion is not known. Therefore, we sought to determine whether leptin would alter the expression of genes involved in water and ion transport across the gallbladder epithelium. Affymetrix oligonucleotide microarrays representing 39,000 transcripts were used to compare gallbladder gene-expression profiles from 12-wk-old control saline-treated Lep(ob) and from leptin-treated Lep(ob) female mice. Leptin administration to Lep(ob) mice decreased gallbladder volume, bile sodium concentration, and pH. Leptin repletion upregulated the expression of aquaporin 1 water channel by 1.3-fold and downregulated aquaporin 4 by 2.3-fold. A number of genes involved in sodium transport were also influenced by leptin replacement. Epithelial sodium channel-alpha and sodium hydrogen exchangers 1 and 3 were moderately downregulated by 2.0-, 1.6-, and 1.3-fold, respectively. Carbonic anhydrase-IV, which plays a role in the acidification of bile, was upregulated 3.7-fold. In addition, a number of inflammatory cytokines that are known to influence gallbladder epithelial cell absorption and secretion were upregulated. Thus leptin, an adipocyte-derived cytokine involved with satiety and energy balance, influences gallbladder bile volume, sodium, and pH as well as multiple inflammatory cytokine genes and genes related to water, sodium, chloride, and bicarbonate transport. PMID:17463181

  5. [The molecular evolution of rice stress-related genes].

    PubMed

    Song, Xiaojun; Xie, Kaibin; Zhang, Yanping; Jin, Ping

    2014-10-01

    In the processes of evolution, plants have formed a perfect regulation system to tolerate adverse environmental conditions. However, there has not been any report about the molecular evolution of rice stress-related genes. We derived a family of 22 stress-related genes in rice from Plant Stress Gene Database, and analyzed it by bioinformatics and comparative genome method. The results showed that these genes are relatively conservative in low organisms, and their copy numbers increase along with the environmental changes and the evolution. We also found four conserved sequence motifs and three other specific motifs. We propose that these motifs are closely associated with the function of rice stress-related genes. The analysis of selection pressure showed that about 50% rice stress-related genes have positive selection sites, although they were subject to a strong purifying selection. Positive selection sites might be very significant for plants to adapt to environmental changes. PMID:25406251

  6. A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme.

    PubMed Central

    Yasunami, M; Chen, C S; Yoshida, A

    1991-01-01

    The human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) gene family consists of five known loci (ADH1-ADH5), which have been mapped close together on chromosome 4 (4q21-25). ADH isozymes encoded by these genes are grouped in three distinct classes in terms of their enzymological properties. A moderate structural similarity is observed between the members of different classes. We isolated an additional member of the ADH gene family by means of cross-hybridization with the ADH2 (class I) cDNA probe. cDNA clones corresponding to this gene were derived from PCR-amplified libraries as well. The coding sequence of a 368-amino-acid-long open reading frame was interrupted by introns into eight exons and spanned approximately 17 kilobases on the genome. The gene contains a glucocorticoid response element at the 5' region. The transcript was detected in the stomach and liver. The deduced amino acid sequence of the open reading frame showed about 60% positional identity with known human ADHs. This extent of homology is comparable to interclass similarity in the human ADH family. Thus, the newly identified gene, which is designated ADH6, governs the synthesis of an enzyme that belongs to another class of ADHs presumably with a distinct physiological role. Images PMID:1881901

  7. Prostate Cancer Related JAZF1 Gene is Associated with Schizophrenia

    PubMed Central

    Wang, Ke-Sheng; Zuo, Lingjun; Owusu, Daniel; Pan, Yue; Luo, Xingguang

    2016-01-01

    Background Epidemiological studies have shown that there is a reduced risk of prostate cancer among persons diagnosed with schizophrenia (SCZ). However, the mechanism of such relationship is not clear. The reduced incidence of cancer observed in SCZ patients may be related to differences in genetic background. Recently, the JAZF1 gene is found to be associated with prostate cancer and type 2 diabetes. However, no study has focused on the association of JAZF1 with the risk of SCZ. Methods We examined genetic associations of 118 single-nucleotide polymorphisms (SNPs) within the JAZF1 gene with SCZ using one European American (EA) sample of 1,149 cases and 1,347 controls. Logistic regression analysis of SCZ as a binary trait was performed using PLINK software. Results The most significant association with SCZ was observed with rs10258132 (p = 0.0011); while the next best signal was rs17156259 (p = 0.0031). The third best associated SNP was rs7791865 (p = 0.00889). In addition, haplotype analyses revealed that the A-C haplotype from rs10244184 and rs10258132 was associated with SCZ (p = 0.00093); and the G-G haplotype from rs17156238 and rs17156259 was associated with SCZ (p = 0.00455). Conclusion These findings provide evidence of several genetic variants in JAZF1 gene influencing the risk of SCZ and will serve as a resource for replication in other populations.

  8. Combining Hierarchical and Associative Gene Ontology Relations with Textual Evidence in Estimating Gene and Gene Product Similarity

    SciTech Connect

    Sanfilippo, Antonio P.; Posse, Christian; Gopalan, Banu; Riensche, Roderick M.; Beagley, Nathaniel; Baddeley, Bob L.; Tratz, Stephen C.; Gregory, Michelle L.

    2007-03-01

    Gene and gene product similarity is a fundamental diagnostic measure in analyzing biological data and constructing predictive models for functional genomics. With the rising influence of the Gene Ontology, two complementary approaches have emerged where the similarity between two genes or gene products is obtained by comparing Gene Ontology (GO) annotations associated with the genes or gene products. One approach captures GO-based similarity in terms of hierarchical relations within each gene subontology. The other approach identifies GO-based similarity in terms of associative relations across the three gene subontologies. We propose a novel methodology where the two approaches can be merged with ensuing benefits in coverage and accuracy, and demonstrate that further improvements can be obtained by integrating textual evidence extracted from relevant biomedical literature.

  9. Characterizing Milk Production Related Genes in Holstein Using RNA-seq.

    PubMed

    Seo, Minseok; Lee, Hyun-Jeong; Kim, Kwondo; Caetano-Anolles, Kelsey; Jeong, Jin Young; Park, Sungkwon; Oh, Young Kyun; Cho, Seoae; Kim, Heebal

    2016-03-01

    Although the chemical, physical, and nutritional properties of bovine milk have been extensively studied, only a few studies have attempted to characterize milk-synthesizing genes using RNA-seq data. RNA-seq data was collected from 21 Holstein samples, along with group information about milk production ability; milk yield; and protein, fat, and solid contents. Meta-analysis was employed in order to generally characterize genes related to milk production. In addition, we attempted to investigate the relationship between milk related traits, parity, and lactation period. We observed that milk fat is highly correlated with lactation period; this result indicates that this effect should be considered in the model in order to accurately detect milk production related genes. By employing our developed model, 271 genes were significantly (false discovery rate [FDR] adjusted p-value<0.1) detected as milk production related differentially expressed genes. Of these genes, five (albumin, nitric oxide synthase 3, RNA-binding region (RNP1, RRM) containing 3, secreted and transmembrane 1, and serine palmitoyltransferase, small subunit B) were technically validated using quantitative real-time polymerase chain reaction (qRT-PCR) in order to check the accuracy of RNA-seq analysis. Finally, 83 gene ontology biological processes including several blood vessel and mammary gland development related terms, were significantly detected using DAVID gene-set enrichment analysis. From these results, we observed that detected milk production related genes are highly enriched in the circulation system process and mammary gland related biological functions. In addition, we observed that detected genes including caveolin 1, mammary serum amyloid A3.2, lingual antimicrobial peptide, cathelicidin 4 (CATHL4), cathelicidin 6 (CATHL6) have been reported in other species as milk production related gene. For this reason, we concluded that our detected 271 genes would be strong candidates for

  10. Characterizing Milk Production Related Genes in Holstein Using RNA-seq

    PubMed Central

    Seo, Minseok; Lee, Hyun-Jeong; Kim, Kwondo; Caetano-Anolles, Kelsey; Jeong, Jin Young; Park, Sungkwon; Oh, Young Kyun; Cho, Seoae; Kim, Heebal

    2016-01-01

    Although the chemical, physical, and nutritional properties of bovine milk have been extensively studied, only a few studies have attempted to characterize milk-synthesizing genes using RNA-seq data. RNA-seq data was collected from 21 Holstein samples, along with group information about milk production ability; milk yield; and protein, fat, and solid contents. Meta-analysis was employed in order to generally characterize genes related to milk production. In addition, we attempted to investigate the relationship between milk related traits, parity, and lactation period. We observed that milk fat is highly correlated with lactation period; this result indicates that this effect should be considered in the model in order to accurately detect milk production related genes. By employing our developed model, 271 genes were significantly (false discovery rate [FDR] adjusted p-value<0.1) detected as milk production related differentially expressed genes. Of these genes, five (albumin, nitric oxide synthase 3, RNA-binding region (RNP1, RRM) containing 3, secreted and transmembrane 1, and serine palmitoyltransferase, small subunit B) were technically validated using quantitative real-time polymerase chain reaction (qRT-PCR) in order to check the accuracy of RNA-seq analysis. Finally, 83 gene ontology biological processes including several blood vessel and mammary gland development related terms, were significantly detected using DAVID gene-set enrichment analysis. From these results, we observed that detected milk production related genes are highly enriched in the circulation system process and mammary gland related biological functions. In addition, we observed that detected genes including caveolin 1, mammary serum amyloid A3.2, lingual antimicrobial peptide, cathelicidin 4 (CATHL4), cathelicidin 6 (CATHL6) have been reported in other species as milk production related gene. For this reason, we concluded that our detected 271 genes would be strong candidates for

  11. Recombinase-mediated reprogramming and dystrophin gene addition in mdx mouse induced pluripotent stem cells.

    PubMed

    Zhao, Chunli; Farruggio, Alfonso P; Bjornson, Christopher R R; Chavez, Christopher L; Geisinger, Jonathan M; Neal, Tawny L; Karow, Marisa; Calos, Michele P

    2014-01-01

    A cell therapy strategy utilizing genetically-corrected induced pluripotent stem cells (iPSC) may be an attractive approach for genetic disorders such as muscular dystrophies. Methods for genetic engineering of iPSC that emphasize precision and minimize random integration would be beneficial. We demonstrate here an approach in the mdx mouse model of Duchenne muscular dystrophy that focuses on the use of site-specific recombinases to achieve genetic engineering. We employed non-viral, plasmid-mediated methods to reprogram mdx fibroblasts, using phiC31 integrase to insert a single copy of the reprogramming genes at a safe location in the genome. We next used Bxb1 integrase to add the therapeutic full-length dystrophin cDNA to the iPSC in a site-specific manner. Unwanted DNA sequences, including the reprogramming genes, were then precisely deleted with Cre resolvase. Pluripotency of the iPSC was analyzed before and after gene addition, and ability of the genetically corrected iPSC to differentiate into myogenic precursors was evaluated by morphology, immunohistochemistry, qRT-PCR, FACS analysis, and intramuscular engraftment. These data demonstrate a non-viral, reprogramming-plus-gene addition genetic engineering strategy utilizing site-specific recombinases that can be applied easily to mouse cells. This work introduces a significant level of precision in the genetic engineering of iPSC that can be built upon in future studies. PMID:24781921

  12. Transport of Magnesium by a Bacterial Nramp-Related Gene

    PubMed Central

    Rodionov, Dmitry A.; Freedman, Benjamin G.; Senger, Ryan S.; Winkler, Wade C.

    2014-01-01

    Magnesium is an essential divalent metal that serves many cellular functions. While most divalent cations are maintained at relatively low intracellular concentrations, magnesium is maintained at a higher level (∼0.5–2.0 mM). Three families of transport proteins were previously identified for magnesium import: CorA, MgtE, and MgtA/MgtB P-type ATPases. In the current study, we find that expression of a bacterial protein unrelated to these transporters can fully restore growth to a bacterial mutant that lacks known magnesium transporters, suggesting it is a new importer for magnesium. We demonstrate that this transport activity is likely to be specific rather than resulting from substrate promiscuity because the proteins are incapable of manganese import. This magnesium transport protein is distantly related to the Nramp family of proteins, which have been shown to transport divalent cations but have never been shown to recognize magnesium. We also find gene expression of the new magnesium transporter to be controlled by a magnesium-sensing riboswitch. Importantly, we find additional examples of riboswitch-regulated homologues, suggesting that they are a frequent occurrence in bacteria. Therefore, our aggregate data discover a new and perhaps broadly important path for magnesium import and highlight how identification of riboswitch RNAs can help shed light on new, and sometimes unexpected, functions of their downstream genes. PMID:24968120

  13. Transport of magnesium by a bacterial Nramp-related gene.

    PubMed

    Shin, Jung-Ho; Wakeman, Catherine A; Goodson, Jonathan R; Rodionov, Dmitry A; Freedman, Benjamin G; Senger, Ryan S; Winkler, Wade C

    2014-06-01

    Magnesium is an essential divalent metal that serves many cellular functions. While most divalent cations are maintained at relatively low intracellular concentrations, magnesium is maintained at a higher level (∼0.5-2.0 mM). Three families of transport proteins were previously identified for magnesium import: CorA, MgtE, and MgtA/MgtB P-type ATPases. In the current study, we find that expression of a bacterial protein unrelated to these transporters can fully restore growth to a bacterial mutant that lacks known magnesium transporters, suggesting it is a new importer for magnesium. We demonstrate that this transport activity is likely to be specific rather than resulting from substrate promiscuity because the proteins are incapable of manganese import. This magnesium transport protein is distantly related to the Nramp family of proteins, which have been shown to transport divalent cations but have never been shown to recognize magnesium. We also find gene expression of the new magnesium transporter to be controlled by a magnesium-sensing riboswitch. Importantly, we find additional examples of riboswitch-regulated homologues, suggesting that they are a frequent occurrence in bacteria. Therefore, our aggregate data discover a new and perhaps broadly important path for magnesium import and highlight how identification of riboswitch RNAs can help shed light on new, and sometimes unexpected, functions of their downstream genes. PMID:24968120

  14. Odd-skipped related 2 regulates genes related to proliferation and development

    SciTech Connect

    Kawai, Shinji; Abiko, Yoshimitsu; Amano, Atsuo

    2010-07-23

    Cell proliferation is a biological process in which chromosomes replicate in one cell and equally divide into two daughter cells. Our previous findings suggested that Odd-skipped related 2 (Osr2) plays an important role in cellular quiescence and proliferation under epigenetic regulation. However, the mechanism used by Osr2 to establish and maintain proliferation is unknown. To examine the functional role of Osr2 in cell proliferation, we analyzed its downstream target genes using microarray analysis following adenovirus-induced overexpression of Osr2 as well as knockdown with Osr2 siRNA, which showed that Osr2 regulates a multitude of genes involved in proliferation and the cell cycle, as well as development. Additional proliferation assays also indicated that Osr2 likely functions to elicit cell proliferation. Together, these results suggest that Osr2 plays important roles in proliferation and development.

  15. Identifying Novel Candidate Genes Related to Apoptosis from a Protein-Protein Interaction Network

    PubMed Central

    Wang, Baoman; Yuan, Fei; Kong, Xiangyin; Hu, Lan-Dian; Cai, Yu-Dong

    2015-01-01

    Apoptosis is the process of programmed cell death (PCD) that occurs in multicellular organisms. This process of normal cell death is required to maintain the balance of homeostasis. In addition, some diseases, such as obesity, cancer, and neurodegenerative diseases, can be cured through apoptosis, which produces few side effects. An effective comprehension of the mechanisms underlying apoptosis will be helpful to prevent and treat some diseases. The identification of genes related to apoptosis is essential to uncover its underlying mechanisms. In this study, a computational method was proposed to identify novel candidate genes related to apoptosis. First, protein-protein interaction information was used to construct a weighted graph. Second, a shortest path algorithm was applied to the graph to search for new candidate genes. Finally, the obtained genes were filtered by a permutation test. As a result, 26 genes were obtained, and we discuss their likelihood of being novel apoptosis-related genes by collecting evidence from published literature. PMID:26543496

  16. CoMAGC: a corpus with multi-faceted annotations of gene-cancer relations

    PubMed Central

    2013-01-01

    Background In order to access the large amount of information in biomedical literature about genes implicated in various cancers both efficiently and accurately, the aid of text mining (TM) systems is invaluable. Current TM systems do target either gene-cancer relations or biological processes involving genes and cancers, but the former type produces information not comprehensive enough to explain how a gene affects a cancer, and the latter does not provide a concise summary of gene-cancer relations. Results In this paper, we present a corpus for the development of TM systems that are specifically targeting gene-cancer relations but are still able to capture complex information in biomedical sentences. We describe CoMAGC, a corpus with multi-faceted annotations of gene-cancer relations. In CoMAGC, a piece of annotation is composed of four semantically orthogonal concepts that together express 1) how a gene changes, 2) how a cancer changes and 3) the causality between the gene and the cancer. The multi-faceted annotations are shown to have high inter-annotator agreement. In addition, we show that the annotations in CoMAGC allow us to infer the prospective roles of genes in cancers and to classify the genes into three classes according to the inferred roles. We encode the mapping between multi-faceted annotations and gene classes into 10 inference rules. The inference rules produce results with high accuracy as measured against human annotations. CoMAGC consists of 821 sentences on prostate, breast and ovarian cancers. Currently, we deal with changes in gene expression levels among other types of gene changes. The corpus is available at http://biopathway.org/CoMAGCunder the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0). Conclusions The corpus will be an important resource for the development of advanced TM systems on gene-cancer relations. PMID:24225062

  17. Isolation of tumor suppressor genes from MEN-1 related neoplasms

    SciTech Connect

    Yavari, R.; Kinder, B.; Bale, A.E.

    1994-09-01

    Multiple Endocrine Neoplasia type 1 (MEN 1) is a cancer predisposition syndrome marked by the development of tumors in specific endocrine tissues such as the pituitary, parathyroid and pancreatic islets. Genetic linkage studies have mapped the MEN 1 gene to 11q13, and allelic loss in related tumors suggests that the gene is a tumor suppressor. Because inactivation of tumor suppressors may be accompanied by underexpression, subtractive hybridization was used to isolate potential candidate genes underexpressed in MEN 1 tumors. cDNA was synthesized from tumor and normal parathyroid tissue by RT-PCR. Biotinylated tumor cDNA was used as a driver and normal cDNA as a tester in subtractive hybridization. Following annealing of the driver and tester amplicons, the biotinylated strands were removed with streptavidin. The subtracted material was then used as a probe to isolate clones from a normal pancreatic islet library. Screening 2 x 10{sup 5} plaques yielded 14 positive clones. Of 6 clones analyzed, 3 were confirmed to be underexpressed in parathyroid tumors. Sequence analysis identified 2 clones as human ribosomal protein S10 (RPS10, chromosome 6) and 1 as the islet amyloid polypeptide (1AP, chromosome 12). The precise function of human RPS10 is not known but the related RPS6 functions as a tumor suppressor in Drosophila. 1AP has been implicated in modulation of G protein activity. The remaining positive clones will be mapped to determine if any fall on chromosome 11q13, and additional subtractions with parathyroid and pancreatic islet neoplasms are underway.

  18. Fine Mapping of Two Additive Effect Genes for Awn Development in Rice (Oryza sativa L.).

    PubMed

    Li, Ben; Zhang, Yanpei; Li, Jinjie; Yao, Guoxin; Pan, Huiqiao; Hu, Guanglong; Chen, Chao; Zhang, Hongliang; Li, Zichao

    2016-01-01

    Awns, important domestication and agronomic traits in rice (Oryza sativa L.), are conferred by polygenes and the environment. Near isogenic line (NIL) pairs BM33 and BM38 were constructed from crosses between awnless japonica cv Nipponbare as recurrent parent, and lines SLG or Funingxiaohongmang (awned japonica accessions), respectively, as donors. In order to study the genetic and molecular mechanism of awning, two unknown, independent genes with additive effects were identified in a cross between the NILs. To map and clone the two genes, a BC4F4 population of 8,103 individuals and a BC4F6 population of 11,206 individuals were constructed. Awn3-1 was fine mapped to a 101.13 kb genomic region between Indel marker In316 and SNP marker S9-1 on chromosome 3. Nine predicted genes in the interval were annotated in the Rice Annotation Project Database (RAP-DB), and Os03g0418600 was identified as the most likely candidate for Awn3-1 through sequence comparisons and RT-PCR assays. Awn4-2 was fine mapped to a 62.4 kb genomic region flanked by simple sequence repeat (SSR) marker M1126 and Indel maker In73 on chromosome 4L. This region contained the previously reported gene An-1 that regulates awn development. Thus, An-1 may be the candidate gene of Awn4-2. These results will facilitate cloning of the awn genes and thereby provide an understanding of the molecular basis of awn development. PMID:27494628

  19. Fine Mapping of Two Additive Effect Genes for Awn Development in Rice (Oryza sativa L.)

    PubMed Central

    Li, Jinjie; Yao, Guoxin; Pan, Huiqiao; Hu, Guanglong; Chen, Chao; Zhang, Hongliang; Li, Zichao

    2016-01-01

    Awns, important domestication and agronomic traits in rice (Oryza sativa L.), are conferred by polygenes and the environment. Near isogenic line (NIL) pairs BM33 and BM38 were constructed from crosses between awnless japonica cv Nipponbare as recurrent parent, and lines SLG or Funingxiaohongmang (awned japonica accessions), respectively, as donors. In order to study the genetic and molecular mechanism of awning, two unknown, independent genes with additive effects were identified in a cross between the NILs. To map and clone the two genes, a BC4F4 population of 8,103 individuals and a BC4F6 population of 11,206 individuals were constructed. Awn3-1 was fine mapped to a 101.13 kb genomic region between Indel marker In316 and SNP marker S9-1 on chromosome 3. Nine predicted genes in the interval were annotated in the Rice Annotation Project Database (RAP-DB), and Os03g0418600 was identified as the most likely candidate for Awn3-1 through sequence comparisons and RT-PCR assays. Awn4-2 was fine mapped to a 62.4 kb genomic region flanked by simple sequence repeat (SSR) marker M1126 and Indel maker In73 on chromosome 4L. This region contained the previously reported gene An-1 that regulates awn development. Thus, An-1 may be the candidate gene of Awn4-2. These results will facilitate cloning of the awn genes and thereby provide an understanding of the molecular basis of awn development. PMID:27494628

  20. Network analysis of EtOH-related candidate genes.

    PubMed

    Guo, An-Yuan; Sun, Jingchun; Jia, Peilin; Zhao, Zhongming

    2010-05-01

    Recently, we collected many large-scale datasets for alcohol dependence and EtOH response in five organisms and deposited them in our EtOH-related gene resource database (ERGR, http://bioinfo.mc.vanderbilt.edu/ERGR/). Based on multidimensional evidence among these datasets, we prioritized 57 EtOH-related candidate genes. To explore their biological roles, and the molecular mechanisms of EtOH response and alcohol dependence, we examined the features of these genes by the Gene Ontology (GO) term-enrichment test and network/pathway analysis. Our analysis revealed that these candidate genes were highly enriched in alcohol dependence/alcoholism and highly expressed in brain or liver tissues. All the significantly enriched GO terms were related to neurotransmitter systems or EtOH metabolic processes. Using the Ingenuity Pathway Analysis system, we found that these genes were involved in networks of neurological disease, cardiovascular disease, inflammatory response, and small molecular metabolism. Many key genes in signaling pathways were in the central position of these networks. Furthermore, our protein-protein interaction (PPI) network analysis suggested some novel candidate genes which also had evidence in the ERGR database. This study demonstrated that our candidate gene selection is effective and our network/pathway analysis is useful for uncovering the molecular mechanisms of EtOH response and alcohol dependence. This approach can be applied to study the features of candidate genes of other complex traits/phenotypes. PMID:20491071

  1. Increased drought tolerance through the suppression of ESKMO1 gene and overexpression of CBF-related genes in Arabidopsis.

    PubMed

    Xu, Fuhui; Liu, Zhixue; Xie, Hongyan; Zhu, Jian; Zhang, Juren; Kraus, Josef; Blaschnig, Tasja; Nehls, Reinhard; Wang, Hong

    2014-01-01

    Improved drought tolerance is always a highly desired trait for agricultural plants. Significantly increased drought tolerance in Arabidopsis thaliana (Columbia-0) has been achieved in our work through the suppression of ESKMO1 (ESK1) gene expression with small-interfering RNA (siRNA) and overexpression of CBF genes with constitutive gene expression. ESK1 has been identified as a gene linked to normal development of the plant vascular system, which is assumed directly related to plant drought response. By using siRNA that specifically targets ESK1, the gene expression has been reduced and drought tolerance of the plant has been enhanced dramatically in the work. However, the plant response to external abscisic acid application has not been changed. ICE1, CBF1, and CBF3 are genes involved in a well-characterized plant stress response pathway, overexpression of them in the plant has demonstrated capable to increase drought tolerance. By overexpression of these genes combining together with suppression of ESK1 gene, the significant increase of plant drought tolerance has been achieved in comparison to single gene manipulation, although the effect is not in an additive way. Accompanying the increase of drought tolerance via suppression of ESK1 gene expression, the negative effect has been observed in seeds yield of transgenic plants in normal watering conditions comparing with wide type plant. PMID:25184213

  2. Amplification of a Gene Related to Mammalian mdr Genes in Drug-Resistant Plasmodium falciparum

    NASA Astrophysics Data System (ADS)

    Wilson, Craig M.; Serrano, Adelfa E.; Wasley, Annemarie; Bogenschutz, Michael P.; Shankar, Anuraj H.; Wirth, Dyann F.

    1989-06-01

    The malaria parasite Plasmodium falciparum contains at least two genes related to the mammalian multiple drug resistance genes, and at least one of the P. falciparum genes is expressed at a higher level and is present in higher copy number in a strain that is resistant to multiple drugs than in a strain that is sensitive to the drugs.

  3. Gene Therapy for Age-Related Macular Degeneration.

    PubMed

    Constable, Ian Jeffery; Blumenkranz, Mark Scott; Schwartz, Steven D; Barone, Sam; Lai, Chooi-May; Rakoczy, Elizabeth Piroska

    2016-01-01

    The purpose of this article was to evaluate safety and signals of efficacy of gene therapy with subretinal rAAV.sFlt-1 for wet age-related macular degeneration (wet AMD). A phase 1 dose-escalating single-center controlled unmasked human clinical trial was followed up by extension of the protocol to a phase 2A single-center trial. rAAV.sFlt-1 vector was used to deliver a naturally occurring anti-vascular endothelial growth factor agent, sFlt-1, into the subretinal space. In phase 1, step 1 randomized 3 subjects to low-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm; step 2 randomized an additional 3 subjects to treatment with high-dose rAAV.sFlt-1 (1 × 10 vector genomes) and 1 subject to the control arm. Follow-up studies demonstrated that rAAV.sFlt-1 was well tolerated with a favorable safety profile in these elderly subjects with wet AMD. Subretinal injection was highly reproducible, and no drug-related adverse events were reported. Procedure-related adverse events were mild and self-resolving. Two phakic patients developed cataract and underwent cataract surgery. Four of the 6 patients responded better than the small control group in this study and historical controls in terms of maintaining vision and a relatively dry retina with zero ranibizumab retreatments per annum. Two patients required 1 ranibizumab injection over the 52-week follow-up period. rAAV.sFlt-1 gene therapy may prove to be a potential adjunct or alternative to conventional intravitreal injection for patients with wet AMD by providing extended delivery of a naturally occurring antiangiogenic protein. PMID:27488071

  4. Microarray analysis of relative gene expression stability for selection of internal reference genes in the rhesus macaque brain

    PubMed Central

    2010-01-01

    Background Normalization of gene expression data refers to the comparison of expression values using reference standards that are consistent across all conditions of an experiment. In PCR studies, genes designated as "housekeeping genes" have been used as internal reference genes under the assumption that their expression is stable and independent of experimental conditions. However, verification of this assumption is rarely performed. Here we assess the use of gene microarray analysis to facilitate selection of internal reference sequences with higher expression stability across experimental conditions than can be expected using traditional selection methods. We recently demonstrated that relative gene expression from qRT-PCR data normalized using GAPDH, ALG9 and RPL13A expression values mirrored relative expression using quantile normalization in Robust Multichip Analysis (RMA) on the Affymetrix® GeneChip® rhesus Macaque Genome Array. Having shown that qRT-PCR and Affymetrix® GeneChip® data from the same hormone replacement therapy (HRT) study yielded concordant results, we used quantile-normalized gene microarray data to identify the most stably expressed among probe sets for prospective internal reference genes across three brain regions from the HRT study and an additional study of normally menstruating rhesus macaques (cycle study). Gene selection was limited to 575 previously published human "housekeeping" genes. Twelve animals were used per study, and three brain regions were analyzed from each animal. Gene expression stabilities were determined using geNorm, NormFinder and BestKeeper software packages. Results Sequences co-annotated for ribosomal protein S27a (RPS27A), and ubiquitin were among the most stably expressed under all conditions and selection criteria used for both studies. Higher annotation quality on the human GeneChip® facilitated more targeted analysis than could be accomplished using the rhesus GeneChip®. In the cycle study, multiple

  5. Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases

    PubMed Central

    Moehle, Erica A.; Rock, Jeremy M.; Lee, Ya-Li; Jouvenot, Yann; DeKelver, Russell C.; Gregory, Philip D.; Urnov, Fyodor D.; Holmes, Michael C.

    2007-01-01

    Efficient incorporation of novel DNA sequences into a specific site in the genome of living human cells remains a challenge despite its potential utility to genetic medicine, biotechnology, and basic research. We find that a precisely placed double-strand break induced by engineered zinc finger nucleases (ZFNs) can stimulate integration of long DNA stretches into a predetermined genomic location, resulting in high-efficiency site-specific gene addition. Using an extrachromosomal DNA donor carrying a 12-bp tag, a 900-bp ORF, or a 1.5-kb promoter-transcription unit flanked by locus-specific homology arms, we find targeted integration frequencies of 15%, 6%, and 5%, respectively, within 72 h of treatment, and with no selection for the desired event. Importantly, we find that the integration event occurs in a homology-directed manner and leads to the accurate reconstruction of the donor-specified genotype at the endogenous chromosomal locus, and hence presumably results from synthesis-dependent strand annealing repair of the break using the donor DNA as a template. This site-specific gene addition occurs with no measurable increase in the rate of random integration. Remarkably, we also find that ZFNs can drive the addition of an 8-kb sequence carrying three distinct promoter-transcription units into an endogenous locus at a frequency of 6%, also in the absence of any selection. These data reveal the surprising versatility of the specialized polymerase machinery involved in double-strand break repair, illuminate a powerful approach to mammalian cell engineering, and open the possibility of ZFN-driven gene addition therapy for human genetic disease. PMID:17360608

  6. Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases.

    PubMed

    Moehle, Erica A; Moehle, E A; Rock, Jeremy M; Rock, J M; Lee, Ya-Li; Lee, Y L; Jouvenot, Yann; Jouvenot, Y; DeKelver, Russell C; Dekelver, R C; Gregory, Philip D; Gregory, P D; Urnov, Fyodor D; Urnov, F D; Holmes, Michael C; Holmes, M C

    2007-02-27

    Efficient incorporation of novel DNA sequences into a specific site in the genome of living human cells remains a challenge despite its potential utility to genetic medicine, biotechnology, and basic research. We find that a precisely placed double-strand break induced by engineered zinc finger nucleases (ZFNs) can stimulate integration of long DNA stretches into a predetermined genomic location, resulting in high-efficiency site-specific gene addition. Using an extrachromosomal DNA donor carrying a 12-bp tag, a 900-bp ORF, or a 1.5-kb promoter-transcription unit flanked by locus-specific homology arms, we find targeted integration frequencies of 15%, 6%, and 5%, respectively, within 72 h of treatment, and with no selection for the desired event. Importantly, we find that the integration event occurs in a homology-directed manner and leads to the accurate reconstruction of the donor-specified genotype at the endogenous chromosomal locus, and hence presumably results from synthesis-dependent strand annealing repair of the break using the donor DNA as a template. This site-specific gene addition occurs with no measurable increase in the rate of random integration. Remarkably, we also find that ZFNs can drive the addition of an 8-kb sequence carrying three distinct promoter-transcription units into an endogenous locus at a frequency of 6%, also in the absence of any selection. These data reveal the surprising versatility of the specialized polymerase machinery involved in double-strand break repair, illuminate a powerful approach to mammalian cell engineering, and open the possibility of ZFN-driven gene addition therapy for human genetic disease. PMID:17360608

  7. 78 FR 17612 - Rules Relating to Additional Medicare Tax; Hearing Cancellation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-22

    ... public hearing that appeared in the Federal Register on Wednesday, December 5, 2012 (77 FR 72268... Internal Revenue Service 26 CFR Parts 1 and 31 RIN 1545-BK54 Rules Relating to Additional Medicare Tax...; relating to the Additional Hospital Insurance Tax on income above threshold amounts as added by...

  8. 31 CFR 561.204 - Additional petroleum-related sanctions on certain foreign financial institutions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Additional petroleum-related sanctions... TREASURY IRANIAN FINANCIAL SANCTIONS REGULATIONS Prohibitions § 561.204 Additional petroleum-related... Iran Sanctions Act of 1996 (Pub. L. 104-172) (50 U.S.C. 1701 note), as amended, are refined...

  9. 31 CFR 561.204 - Additional petroleum-related sanctions on certain foreign financial institutions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Additional petroleum-related sanctions... TREASURY IRANIAN FINANCIAL SANCTIONS REGULATIONS Prohibitions § 561.204 Additional petroleum-related... Iran Sanctions Act of 1996 (Pub. L. 104-172) (50 U.S.C. 1701 note), as amended, are refined...

  10. 48 CFR 1337.110-71 - Additional DOC clauses related to service contracting.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Additional DOC clauses related to service contracting. 1337.110-71 Section 1337.110-71 Federal Acquisition Regulations System....110-71 Additional DOC clauses related to service contracting. (a) Insert a clause...

  11. 48 CFR 1337.110-71 - Additional DOC clauses related to service contracting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Additional DOC clauses related to service contracting. 1337.110-71 Section 1337.110-71 Federal Acquisition Regulations System....110-71 Additional DOC clauses related to service contracting. (a) Insert a clause...

  12. 48 CFR 1337.110-71 - Additional DOC clauses related to service contracting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Additional DOC clauses related to service contracting. 1337.110-71 Section 1337.110-71 Federal Acquisition Regulations System....110-71 Additional DOC clauses related to service contracting. (a) Insert a clause...

  13. 48 CFR 1337.110-71 - Additional DOC clauses related to service contracting.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Additional DOC clauses related to service contracting. 1337.110-71 Section 1337.110-71 Federal Acquisition Regulations System....110-71 Additional DOC clauses related to service contracting. (a) Insert a clause...

  14. 48 CFR 1337.110-71 - Additional DOC clauses related to service contracting.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Additional DOC clauses related to service contracting. 1337.110-71 Section 1337.110-71 Federal Acquisition Regulations System....110-71 Additional DOC clauses related to service contracting. (a) Insert a clause...

  15. Genome-Wide Gene Expression in relation to Age in Large Laboratory Cohorts of Drosophila melanogaster

    PubMed Central

    Carlson, Kimberly A.; Gardner, Kylee; Pashaj, Anjeza; Carlson, Darby J.; Yu, Fang; Eudy, James D.; Zhang, Chi; Harshman, Lawrence G.

    2015-01-01

    Aging is a complex process characterized by a steady decline in an organism's ability to perform life-sustaining tasks. In the present study, two cages of approximately 12,000 mated Drosophila melanogaster females were used as a source of RNA from individuals sampled frequently as a function of age. A linear model for microarray data method was used for the microarray analysis to adjust for the box effect; it identified 1,581 candidate aging genes. Cluster analyses using a self-organizing map algorithm on the 1,581 significant genes identified gene expression patterns across different ages. Genes involved in immune system function and regulation, chorion assembly and function, and metabolism were all significantly differentially expressed as a function of age. The temporal pattern of data indicated that gene expression related to aging is affected relatively early in life span. In addition, the temporal variance in gene expression in immune function genes was compared to a random set of genes. There was an increase in the variance of gene expression within each cohort, which was not observed in the set of random genes. This observation is compatible with the hypothesis that D. melanogaster immune function genes lose control of gene expression as flies age. PMID:26090231

  16. Covariation of Branch Lengths in Phylogenies of Functionally Related Genes

    PubMed Central

    Li, Wai Lok Sibon; Rodrigo, Allen G.

    2009-01-01

    Recent studies have shown evidence for the coevolution of functionally-related genes. This coevolution is a result of constraints to maintain functional relationships between interacting proteins. The studies have focused on the correlation in gene tree branch lengths of proteins that are directly interacting with each other. We here hypothesize that the correlation in branch lengths is not limited only to proteins that directly interact, but also to proteins that operate within the same pathway. Using generalized linear models as a basis of identifying correlation, we attempted to predict the gene ontology (GO) terms of a gene based on its gene tree branch lengths. We applied our method to a dataset consisting of proteins from ten prokaryotic species. We found that the degree of accuracy to which we could predict the function of the proteins from their gene tree varied substantially with different GO terms. In particular, our model could accurately predict genes involved in translation and certain ribosomal activities with the area of the receiver-operator curve of up to 92%. Further analysis showed that the similarity between the trees of genes labeled with similar GO terms was not limited to genes that physically interacted, but also extended to genes functioning within the same pathway. We discuss the relevance of our findings as it relates to the use of phylogenetic methods in comparative genomics. PMID:20041191

  17. Extracellular complementation and the identification of additional genes involved in aerial mycelium formation in Streptomyces coelicolor.

    PubMed Central

    Nodwell, J R; Yang, M; Kuo, D; Losick, R

    1999-01-01

    Morphogenesis in the bacterium Streptomyces coelicolor involves the formation of a lawn of hair-like aerial hyphae on the colony surface that stands up in the air and differentiates into chains of spores. bld mutants are defective in the formation of this aerial mycelium and grow as smooth, hairless colonies. When certain pairs of bld mutants are grown close to one another on rich sporulation medium, they exhibit extracellular complementation such that one mutant restores aerial mycelium formation to the other. The extracellular complementation relationships of most of the previously isolated bld mutants placed them in a hierarchy of extracellular complementation groups. We have screened for further bld mutants with precautions intended to maximize the discovery of additional genes. Most of the 50 newly isolated mutant strains occupy one of three of the previously described positions in the hierarchy, behaving like bldK, bldC, or bldD mutants. We show that the mutations in some of the strains that behave like bldK are bldK alleles but that others fall in a cluster at a position on the chromosome distinct from that of any known bld gene. We name this locus bldL. By introducing cloned genes into the strains that exhibit bldC or bldD-like extracellular complementation phenotypes, we show that most of these strains are likely to contain mutations in genes other than bldC or bldD. These results indicate that the genetic control of aerial mycelium formation is more complex than previously recognized and support the idea that a high proportion of bld genes are directly or indirectly involved in the production of substances that are exchanged between cells during morphological differentiation. PMID:9927452

  18. Extracellular complementation and the identification of additional genes involved in aerial mycelium formation in Streptomyces coelicolor.

    PubMed

    Nodwell, J R; Yang, M; Kuo, D; Losick, R

    1999-02-01

    Morphogenesis in the bacterium Streptomyces coelicolor involves the formation of a lawn of hair-like aerial hyphae on the colony surface that stands up in the air and differentiates into chains of spores. bld mutants are defective in the formation of this aerial mycelium and grow as smooth, hairless colonies. When certain pairs of bld mutants are grown close to one another on rich sporulation medium, they exhibit extracellular complementation such that one mutant restores aerial mycelium formation to the other. The extracellular complementation relationships of most of the previously isolated bld mutants placed them in a hierarchy of extracellular complementation groups. We have screened for further bld mutants with precautions intended to maximize the discovery of additional genes. Most of the 50 newly isolated mutant strains occupy one of three of the previously described positions in the hierarchy, behaving like bldK, bldC, or bldD mutants. We show that the mutations in some of the strains that behave like bldK are bldK alleles but that others fall in a cluster at a position on the chromosome distinct from that of any known bld gene. We name this locus bldL. By introducing cloned genes into the strains that exhibit bldC or bldD-like extracellular complementation phenotypes, we show that most of these strains are likely to contain mutations in genes other than bldC or bldD. These results indicate that the genetic control of aerial mycelium formation is more complex than previously recognized and support the idea that a high proportion of bld genes are directly or indirectly involved in the production of substances that are exchanged between cells during morphological differentiation. PMID:9927452

  19. Age-related regulation of genes: slow homeostatic changes and age-dimension technology

    NASA Astrophysics Data System (ADS)

    Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

    2002-11-01

    Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

  20. The identification of additional zebrafish DICP genes reveals haplotype variation and linkage to MHC class I genes.

    PubMed

    Rodriguez-Nunez, Ivan; Wcisel, Dustin J; Litman, Ronda T; Litman, Gary W; Yoder, Jeffrey A

    2016-04-01

    Bony fish encode multiple multi-gene families of membrane receptors that are comprised of immunoglobulin (Ig) domains and are predicted to function in innate immunity. One of these families, the diverse immunoglobulin (Ig) domain-containing protein (DICP) genes, maps to three chromosomal loci in zebrafish. Most DICPs possess one or two Ig ectodomains and include membrane-bound and secreted forms. Membrane-bound DICPs include putative inhibitory and activating receptors. Recombinant DICP Ig domains bind lipids with varying specificity, a characteristic shared with mammalian CD300 and TREM family members. Numerous DICP transcripts amplified from different lines of zebrafish did not match the zebrafish reference genome sequence suggesting polymorphic and haplotypic variation. The expression of DICPs in three different lines of zebrafish has been characterized employing PCR-based strategies. Certain DICPs exhibit restricted expression in adult tissues whereas others are expressed ubiquitously. Transcripts of a subset of DICPs can be detected during embryonic development suggesting roles in embryonic immunity or other developmental processes. Transcripts representing 11 previously uncharacterized DICP sequences were identified. The assignment of two of these sequences to an unplaced genomic scaffold resulted in the identification of an alternative DICP haplotype that is linked to a MHC class I Z lineage haplotype on zebrafish chromosome 3. The linkage of DICP and MHC class I genes also is observable in the genomes of the related grass carp (Ctenopharyngodon idellus) and common carp (Cyprinus carpio) suggesting that this is a shared character with the last common Cyprinidae ancestor. PMID:26801775

  1. Mining for Candidate Genes Related to Pancreatic Cancer Using Protein-Protein Interactions and a Shortest Path Approach

    PubMed Central

    Yuan, Fei; Zhang, Yu-Hang; Wan, Sibao; Wang, ShaoPeng; Kong, Xiang-Yin

    2015-01-01

    Pancreatic cancer (PC) is a highly malignant tumor derived from pancreas tissue and is one of the leading causes of death from cancer. Its molecular mechanism has been partially revealed by validating its oncogenes and tumor suppressor genes; however, the available data remain insufficient for medical workers to design effective treatments. Large-scale identification of PC-related genes can promote studies on PC. In this study, we propose a computational method for mining new candidate PC-related genes. A large network was constructed using protein-protein interaction information, and a shortest path approach was applied to mine new candidate genes based on validated PC-related genes. In addition, a permutation test was adopted to further select key candidate genes. Finally, for all discovered candidate genes, the likelihood that the genes are novel PC-related genes is discussed based on their currently known functions. PMID:26613085

  2. Sex chromosome complement regulates expression of mood-related genes

    PubMed Central

    2013-01-01

    Background Studies on major depressive and anxiety disorders suggest dysfunctions in brain corticolimbic circuits, including altered gamma-aminobutyric acid (GABA) and modulatory (serotonin and dopamine) neurotransmission. Interestingly, sexual dimorphisms in GABA, serotonin, and dopamine systems are also reported. Understanding the mechanisms behind these sexual dimorphisms may help unravel the biological bases of the heightened female vulnerability to mood disorders. Here, we investigate the contribution of sex-related factors (sex chromosome complement, developmental gonadal sex, or adult circulating hormones) to frontal cortex expression of selected GABA-, serotonin-, and dopamine-related genes. Methods As gonadal sex is determined by sex chromosome complement, the role of sex chromosomes cannot be investigated individually in humans. Therefore, we used the Four Core Genotypes (FCG) mouse model, in which sex chromosome complement and gonadal sex are artificially decoupled, to examine the expression of 13 GABA-related genes, 6 serotonin- and dopamine-related genes, and 8 associated signal transduction genes under chronic stress conditions. Results were analyzed by three-way ANOVA (sex chromosome complement × gonadal sex × circulating testosterone). A global perspective of gene expression changes was provided by heatmap representation and gene co-expression networks to identify patterns of transcriptional activities related to each main factor. Results We show that under chronic stress conditions, sex chromosome complement influenced GABA/serotonin/dopamine-related gene expression in the frontal cortex, with XY mice consistently having lower gene expression compared to XX mice. Gonadal sex and circulating testosterone exhibited less pronounced, more complex, and variable control over gene expression. Across factors, male conditions were associated with a tightly co-expressed set of signal transduction genes. Conclusions Under chronic stress conditions

  3. Evolutionary analysis of the jacalin-related lectin family genes in 11 fishes.

    PubMed

    Cao, Jun; Lv, Yueqing

    2016-09-01

    Jacalin-related lectins are a type of carbohydrate-binding proteins, which are distributed across a wide variety of organisms and involved in some important biological processes. The evolution of this gene family in fishes is unknown. Here, 47 putative jacalin genes in 11 fish species were identified and divided into 4 groups through phylogenetic analysis. Conserved gene organization and motif distribution existed in each group, suggesting their functional conservation. Some fishes have eleven jacalin genes, while others have only one or zero gene in their genomes, suggesting dynamic changes in the number of jacalin genes during the evolution of fishes. Intragenic recombination played a key role in the evolution of jacalin genes. Synteny analyses of jacalin genes in some fishes implied conserved and dynamic evolution characteristics of this gene family and related genome segments. Moreover, a few functional divergence sites were identified within each group pairs. Divergent expression profiles of the zebra fish jacalin genes were further investigated in different stresses. The results provided a foundation for exploring the characterization of the jacalin genes in fishes and will offer insights for additional functional studies. PMID:27514782

  4. Relating significance and relations of differentially expressed genes in response to Aspergillus flavus infection in maize.

    PubMed

    Asters, Matthew C; Williams, W Paul; Perkins, Andy D; Mylroie, J Erik; Windham, Gary L; Shan, Xueyan

    2014-01-01

    Aspergillus flavus is a pathogenic fungus infecting maize and producing aflatoxins that are health hazards to humans and animals. Characterizing host defense mechanism and prioritizing candidate resistance genes are important to the development of resistant maize germplasm. We investigated methods amenable for the analysis of the significance and relations among maize candidate genes based on the empirical gene expression data obtained by RT-qPCR technique from maize inbred lines. We optimized a pipeline of analysis tools chosen from various programs to provide rigorous statistical analysis and state of the art data visualization. A network-based method was also explored to construct the empirical gene expression relational structures. Maize genes at the centers in the network were considered as important candidate genes for maize DNA marker studies. The methods in this research can be used to analyze large RT-qPCR datasets and establish complex empirical gene relational structures across multiple experimental conditions. PMID:24770700

  5. Relating significance and relations of differentially expressed genes in response to Aspergillus flavus infection in maize

    PubMed Central

    Asters, Matthew C.; Williams, W. Paul; Perkins, Andy D.; Mylroie, J. Erik; Windham, Gary L.; Shan, Xueyan

    2014-01-01

    Aspergillus flavus is a pathogenic fungus infecting maize and producing aflatoxins that are health hazards to humans and animals. Characterizing host defense mechanism and prioritizing candidate resistance genes are important to the development of resistant maize germplasm. We investigated methods amenable for the analysis of the significance and relations among maize candidate genes based on the empirical gene expression data obtained by RT-qPCR technique from maize inbred lines. We optimized a pipeline of analysis tools chosen from various programs to provide rigorous statistical analysis and state of the art data visualization. A network-based method was also explored to construct the empirical gene expression relational structures. Maize genes at the centers in the network were considered as important candidate genes for maize DNA marker studies. The methods in this research can be used to analyze large RT-qPCR datasets and establish complex empirical gene relational structures across multiple experimental conditions. PMID:24770700

  6. Molecular functions of genes related to grain shape in rice

    PubMed Central

    Zheng, Jia; Zhang, Yadong; Wang, Cailin

    2015-01-01

    Because grain shape is an important component of rice grain yield, the discovery of genes related to rice grain shape has attracted much attention of rice breeding programs. In recent years, some of these genes have been cloned and studied. They have been found not only regulate grain shape by changing the shape of the spikelet hull, but also regulate endosperm development through control of cell division using different molecular mechanisms. In this paper, we review the recent research on genes related to rice grain shape and their possible regulatory mechanisms. PMID:26069441

  7. DRUMS: a human disease related unique gene mutation search engine.

    PubMed

    Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

    2011-10-01

    With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html. PMID:21913285

  8. Beyond the Call of Duty: A Qualitative Study of Teachers' Additional Responsibilities Related to Sexuality Education

    ERIC Educational Resources Information Center

    Eisenberg, Marla E.; Madsen, Nikki; Oliphant, Jennifer A.; Resnick, Michael

    2011-01-01

    Seven focus groups were conducted with sexuality educators in Minnesota to explore ways that teaching sexuality education differs from teaching other health education content and to determine if additional supports or resources are needed for sexuality educators. Teachers described many specific additional responsibilities or concerns related to…

  9. Review of Literature: Genes Related to Postaxial Polydactyly

    PubMed Central

    Verma, Prashant Kumar; El-Harouni, Ashraf A.

    2015-01-01

    Background: Postaxial polydactyly (PAP) is one of the commonest congenital malformations and usually is associated to several syndromes. There is no primary investigational strategy for PAP cases with single gene disorder in literature. PAP cases with single gene disorder can be classified according to common pathways and molecular basis. Molecular classification may help in diagnostic approach. Materials and Methods: All single gene disorders associated with PAP reported on PubMed and OMIM are analyzed and classified according to molecular basis. Results: Majority of genes related to cilia structure and functions are associated with PAP, so we classified them as ciliopathies and non-ciliopathies groups. Genes related to Shh–Gli3 pathway was the commonest group in non-ciliopathies. Conclusion: Genes related to cilia are most commonly related to PAP due to their indirect relationship to Shh–Gli3 signaling pathway. Initially, PAP may be the only clinical finding with ciliopathies so those cases need follow up. Proper diagnosis is helpful for management and genetic counseling. Molecular approach may help to define pleiotropy. PMID:25717468

  10. 36 CFR 223.52 - Market-related contract term additions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Market-related contract term... Provisions § 223.52 Market-related contract term additions. (a) Contract provision. (1) Except as provided in... the Forest Service has determined that adverse wood products market conditions have resulted in...

  11. NERI: network-medicine based integrative approach for disease gene prioritization by relative importance

    PubMed Central

    2015-01-01

    Background Complex diseases are characterized as being polygenic and multifactorial, so this poses a challenge regarding the search for genes related to them. With the advent of high-throughput technologies for genome sequencing, gene expression measurements (transcriptome), and protein-protein interactions, complex diseases have been sistematically investigated. Particularly, Protein-Protein Interaction (PPI) networks have been used to prioritize genes related to complex diseases according to its topological features. However, PPI networks are affected by ascertainment bias, in which more studied proteins tend to have more connections, degrading the results quality. Additionally, methods using only PPI networks can provide only static and non-specific results, since the topologies of these networks are not specific of a given disease. Results The goal of this work is to develop a methodology that integrates PPI networks with disease specific data sources, such as GWAS and gene expression, to find genes more specific of a given complex disease. After the integration of PPI networks and gene expression data, the resulting network is used to connect genes related to the disease through the shortest paths that have the greatest concordance between their gene expressions. Both case and control expression data are used separately and, at the end, the most altered genes between the two conditions are selected. To evaluate the method, schizophrenia was adopted as case study. Conclusion Results show that the proposed method successfully retrieves differentially coexpressed genes in two conditions, while avoiding the bias from literature. Moreover we were able to achieve a greater concordance in the selection of important genes from different microarray studies of the same disease and to produce a more specific gene set related to the studied disease. PMID:26696568

  12. Sparse Additive Ordinary Differential Equations for Dynamic Gene Regulatory Network Modeling.

    PubMed

    Wu, Hulin; Lu, Tao; Xue, Hongqi; Liang, Hua

    2014-04-01

    The gene regulation network (GRN) is a high-dimensional complex system, which can be represented by various mathematical or statistical models. The ordinary differential equation (ODE) model is one of the popular dynamic GRN models. High-dimensional linear ODE models have been proposed to identify GRNs, but with a limitation of the linear regulation effect assumption. In this article, we propose a sparse additive ODE (SA-ODE) model, coupled with ODE estimation methods and adaptive group LASSO techniques, to model dynamic GRNs that could flexibly deal with nonlinear regulation effects. The asymptotic properties of the proposed method are established and simulation studies are performed to validate the proposed approach. An application example for identifying the nonlinear dynamic GRN of T-cell activation is used to illustrate the usefulness of the proposed method. PMID:25061254

  13. A complex network analysis of hypertension-related genes

    NASA Astrophysics Data System (ADS)

    Wang, Huan; Xu, Chuan-Yun; Hu, Jing-Bo; Cao, Ke-Fei

    2014-01-01

    In this paper, a network of hypertension-related genes is constructed by analyzing the correlations of gene expression data among the Dahl salt-sensitive rat and two consomic rat strains. The numerical calculations show that this sparse and assortative network has small-world and scale-free properties. Further, 16 key hub genes (Col4a1, Lcn2, Cdk4, etc.) are determined by introducing an integrated centrality and have been confirmed by biological/medical research to play important roles in hypertension.

  14. Consequences of recurrent gene flow from crops to wild relatives.

    PubMed Central

    Haygood, Ralph; Ives, Anthony R; Andow, David A

    2003-01-01

    Concern about gene flow from crops to wild relatives has become widespread with the increasing cultivation of transgenic crops. Possible consequences of such gene flow include genetic assimilation, wherein crop genes replace wild ones, and demographic swamping, wherein hybrids are less fertile than their wild parents, and wild populations shrink. Using mathematical models of a wild population recurrently receiving pollen from a genetically fixed crop, we find that the conditions for genetic assimilation are not stringent, and progress towards replacement can be fast, even for disfavoured crop genes. Demographic swamping and genetic drift relax the conditions for genetic assimilation and speed progress towards replacement. Genetic assimilation can involve thresholds and hysteresis, such that a small increase in immigration can lead to fixation of a disfavoured crop gene that had been maintained at a moderate frequency, even if the increase in immigration is cancelled before the gene fixes. Demographic swamping can give rise to 'migrational meltdown', such that a small increase in immigration can lead to not only fixation of a disfavoured crop gene but also drastic shrinkage of the wild population. These findings suggest that the spread of crop genes in wild populations should be monitored more closely. PMID:14561300

  15. Consequences of recurrent gene flow from crops to wild relatives.

    PubMed

    Haygood, Ralph; Ives, Anthony R; Andow, David A

    2003-09-22

    Concern about gene flow from crops to wild relatives has become widespread with the increasing cultivation of transgenic crops. Possible consequences of such gene flow include genetic assimilation, wherein crop genes replace wild ones, and demographic swamping, wherein hybrids are less fertile than their wild parents, and wild populations shrink. Using mathematical models of a wild population recurrently receiving pollen from a genetically fixed crop, we find that the conditions for genetic assimilation are not stringent, and progress towards replacement can be fast, even for disfavoured crop genes. Demographic swamping and genetic drift relax the conditions for genetic assimilation and speed progress towards replacement. Genetic assimilation can involve thresholds and hysteresis, such that a small increase in immigration can lead to fixation of a disfavoured crop gene that had been maintained at a moderate frequency, even if the increase in immigration is cancelled before the gene fixes. Demographic swamping can give rise to 'migrational meltdown', such that a small increase in immigration can lead to not only fixation of a disfavoured crop gene but also drastic shrinkage of the wild population. These findings suggest that the spread of crop genes in wild populations should be monitored more closely. PMID:14561300

  16. Cross-Ontological Analytics: Combining Associative and Hierarchical Relations in the Gene Ontologies to Assess Gene Product Similarity

    SciTech Connect

    Posse, Christian; Sanfilippo, Antonio P.; Gopalan, Banu; Riensche, Roderick M.; Beagley, Nathaniel; Baddeley, Bob L.

    2006-05-28

    Gene and gene product similarity is a fundamental diagnostic measure in analyzing biological data and constructing predictive models for functional genomics. With the rising influence of the gene ontologies, two complementary approaches have emerged where the similarity between two genes/gene products is obtained by comparing gene ontology (GO) annotations associated with the gene/gene products. One approach captures GO-based similarity in terms of hierarchical relations within each gene ontology. The other approach identifies GO-based similarity in terms of associative relations across the three gene ontologies. We propose a novel methodology where the two approaches can be merged with ensuing benefits in coverage and accuracy.

  17. Evolution of xyloglucan-related genes in green plants

    PubMed Central

    2010-01-01

    Background The cell shape and morphology of plant tissues are intimately related to structural modifications in the primary cell wall that are associated with key processes in the regulation of cell growth and differentiation. The primary cell wall is composed mainly of cellulose immersed in a matrix of hemicellulose, pectin, lignin and some structural proteins. Xyloglucan is a hemicellulose polysaccharide present in the cell walls of all land plants (Embryophyta) and is the main hemicellulose in non-graminaceous angiosperms. Results In this work, we used a comparative genomic approach to obtain new insights into the evolution of the xyloglucan-related enzymatic machinery in green plants. Detailed phylogenetic analyses were done for enzymes involved in xyloglucan synthesis (xyloglucan transglycosylase/hydrolase, α-xylosidase, β-galactosidase, β-glucosidase and α-fucosidase) and mobilization/degradation (β-(1→4)-glucan synthase, α-fucosyltransferases, β-galactosyltransferases and α-xylosyl transferase) based on 12 fully sequenced genomes and expressed sequence tags from 29 species of green plants. Evidence from Chlorophyta and Streptophyta green algae indicated that part of the Embryophyta xyloglucan-related machinery evolved in an aquatic environment, before land colonization. Streptophyte algae have at least three enzymes of the xyloglucan machinery: xyloglucan transglycosylase/hydrolase, β-(1→4)-glucan synthase from the celullose synthase-like C family and α-xylosidase that is also present in chlorophytes. Interestingly, gymnosperm sequences orthologs to xyloglucan transglycosylase/hydrolases with exclusively hydrolytic activity were also detected, suggesting that such activity must have emerged within the last common ancestor of spermatophytes. There was a positive correlation between the numbers of founder genes within each gene family and the complexity of the plant cell wall. Conclusions Our data support the idea that a primordial xyloglucan

  18. Caste-specific expression patterns of immune response and chemosensory related genes in the leaf-cutting ant, Atta vollenweideri.

    PubMed

    Koch, Sarah I; Groh, Katrin; Vogel, Heiko; Hansson, Bill S; Hannson, Bill S; Kleineidam, Christoph J; Grosse-Wilde, Ewald

    2013-01-01

    Leaf-cutting ants are evolutionary derived social insects with elaborated division of labor and tremendous colony sizes with millions of workers. Their social organization is mainly based on olfactory communication using different pheromones and is promoted by a pronounced size-polymorphism of workers that perform different tasks within the colony. The size polymorphism and associated behaviors are correlated to distinct antennal lobe (AL) phenotypes. Two worker phenotypes differ in number of olfactory glomeruli in the AL and the presence or absence of an extremely large glomerulus (macroglomerulus), involved in trail-pheromone reception. The males' AL contains three macroglomeruli which are presumably involved in detection of sex-pheromone components. We investigated the antennal transcriptome data of all major castes (males, queens and workers) and two worker subcastes (large and tiny workers). In order to identify putative odorant receptor genes involved in pheromone detection, we identified differentially expressed odorant receptor genes (OR-genes) using custom microarrays. In total, we found 185 OR-gene fragments that are clearly related to ORs and we identified orthologs for 70 OR-genes. Among them one OR-gene differs in relative expression between the two worker subcastes by a factor of >3 and thus is a very promising candidate gene for the trail-pheromone receptor. Using the relative expression of OR-genes in males versus queens, we identified 2 candidates for sex-pheromone receptor genes in males. In addition, we identified genes from all other chemosensory related gene families (13 chemosensory protein genes, 8 odorant binding protein genes, 2 sensory-neuron membrane protein genes, 7 ionotropic receptor genes, 2 gustatory receptor genes), and we found ant-specific expansions in the chemosensory protein gene family. In addition, a large number of genes involved in immune defense exhibited differential expression across the three different castes, and some

  19. Caste-Specific Expression Patterns of Immune Response and Chemosensory Related Genes in the Leaf-Cutting Ant, Atta vollenweideri

    PubMed Central

    Koch, Sarah I.; Groh, Katrin; Vogel, Heiko; Hannson, Bill S.; Kleineidam, Christoph J.; Grosse-Wilde, Ewald

    2013-01-01

    Leaf-cutting ants are evolutionary derived social insects with elaborated division of labor and tremendous colony sizes with millions of workers. Their social organization is mainly based on olfactory communication using different pheromones and is promoted by a pronounced size-polymorphism of workers that perform different tasks within the colony. The size polymorphism and associated behaviors are correlated to distinct antennal lobe (AL) phenotypes. Two worker phenotypes differ in number of olfactory glomeruli in the AL and the presence or absence of an extremely large glomerulus (macroglomerulus), involved in trail-pheromone reception. The males' AL contains three macroglomeruli which are presumably involved in detection of sex-pheromone components. We investigated the antennal transcriptome data of all major castes (males, queens and workers) and two worker subcastes (large and tiny workers). In order to identify putative odorant receptor genes involved in pheromone detection, we identified differentially expressed odorant receptor genes (OR-genes) using custom microarrays. In total, we found 185 OR-gene fragments that are clearly related to ORs and we identified orthologs for 70 OR-genes. Among them one OR-gene differs in relative expression between the two worker subcastes by a factor of >3 and thus is a very promising candidate gene for the trail-pheromone receptor. Using the relative expression of OR-genes in males versus queens, we identified 2 candidates for sex-pheromone receptor genes in males. In addition, we identified genes from all other chemosensory related gene families (13 chemosensory protein genes, 8 odorant binding protein genes, 2 sensory-neuron membrane protein genes, 7 ionotropic receptor genes, 2 gustatory receptor genes), and we found ant-specific expansions in the chemosensory protein gene family. In addition, a large number of genes involved in immune defense exhibited differential expression across the three different castes, and some

  20. Identification and Expression Profiles of Sex Pheromone Biosynthesis and Transport Related Genes in Spodoptera litura.

    PubMed

    Zhang, Ya-Nan; Zhu, Xiu-Yun; Fang, Li-Ping; He, Peng; Wang, Zhi-Qiang; Chen, Geng; Sun, Liang; Ye, Zhan-Feng; Deng, Dao-Gui; Li, Jin-Bu

    2015-01-01

    Although the general pathway of sex pheromone synthesis in moth species has been established, the molecular mechanisms remain poorly understood. The common cutworm Spodoptera litura is an important agricultural pest worldwide and causes huge economic losses annually. The female sex pheromone of S. litura comprises Z9,E11-14:OAc, Z9,E12-14:OAc, Z9-14:OAc, and E11-14:OAc. By sequencing and analyzing the transcriptomic data of the sex pheromone glands, we identified 94 candidate genes related to pheromone biosynthesis (55 genes) or chemoreception (39 genes). Gene expression patterns and phylogenetic analysis revealed that two desaturase genes (SlitDes5 and SlitDes11) and one fatty acyl reductase gene (SlitFAR3) showed pheromone gland (PG) biased or specific expression, and clustered with genes known to be involved in pheromone synthesis in other moth species. Furthermore, 4 chemoreception related genes (SlitOBP6, SlitOBP11, SlitCSP3, and SlitCSP14) also showed higher expression in the PG, and could be additional candidate genes involved in sex pheromone transport. This study provides the first solid background information that should facilitate further elucidation of sex pheromone biosynthesis and transport, and indicates potential targets to disrupt sexual communication in S. litura for a novel pest management strategy. PMID:26445454

  1. Identification and Expression Profiles of Sex Pheromone Biosynthesis and Transport Related Genes in Spodoptera litura

    PubMed Central

    Zhang, Ya-Nan; Zhu, Xiu-Yun; Fang, Li-Ping; He, Peng; Wang, Zhi-Qiang; Chen, Geng; Sun, Liang; Ye, Zhan-Feng; Deng, Dao-Gui; Li, Jin-Bu

    2015-01-01

    Although the general pathway of sex pheromone synthesis in moth species has been established, the molecular mechanisms remain poorly understood. The common cutworm Spodoptera litura is an important agricultural pest worldwide and causes huge economic losses annually. The female sex pheromone of S. litura comprises Z9,E11-14:OAc, Z9,E12-14:OAc, Z9-14:OAc, and E11-14:OAc. By sequencing and analyzing the transcriptomic data of the sex pheromone glands, we identified 94 candidate genes related to pheromone biosynthesis (55 genes) or chemoreception (39 genes). Gene expression patterns and phylogenetic analysis revealed that two desaturase genes (SlitDes5 and SlitDes11) and one fatty acyl reductase gene (SlitFAR3) showed pheromone gland (PG) biased or specific expression, and clustered with genes known to be involved in pheromone synthesis in other moth species. Furthermore, 4 chemoreception related genes (SlitOBP6, SlitOBP11, SlitCSP3, and SlitCSP14) also showed higher expression in the PG, and could be additional candidate genes involved in sex pheromone transport. This study provides the first solid background information that should facilitate further elucidation of sex pheromone biosynthesis and transport, and indicates potential targets to disrupt sexual communication in S. litura for a novel pest management strategy. PMID:26445454

  2. Identification of genes related to Parkinson's disease using expressed sequence tags.

    PubMed

    Kim, Jeong-Min; Lee, Kyu-Hwa; Jeon, Yeo-Jin; Oh, Jung-Hwa; Jeong, So-Young; Song, In-Sung; Kim, Jin-Man; Lee, Dong-Seok; Kim, Nam-Soon

    2006-12-31

    In a search for novel target genes related to Parkinson's disease (PD), two full-length cDNA libraries were constructed from a human normal substantia nigra (SN) and a PD patient's SN. An analysis of the gene expression profiles between them was done using the expressed sequence tags (ESTs) frequency. Data for the differently expressed genes were verified by quantitative real-time RT-PCR, immunohistochemical analysis and a cell death assay. Among the 76 genes identified with a significant difference (P > 0.9), 21 upregulated genes and 13 downregulated genes were confirmed to be differentially expressed in human PD tissues and/or in an MPTP-treated mice model by quantitative real-time RT-PCR. Among those genes, an immunohistochemical analysis using an MPTP mice model for alpha-tubulin including TUBA3 and TUBA6 showed that the protein levels are downregulated, as well as the RNA levels. In addition, MBP, PBP and GNAS were confirmed to accelerate cell death activity, whereas SPP1 and TUBA3 to retard this process. Using an analysis of ESTs frequency, it was possible to identify a large number of genes related to human PD. These new genes, MBP, PBP, GNAS, SPP1 and TUBA3 in particular, represent potential biomarkers for PD and could serve as useful targets for elucidating the molecular mechanisms associated with PD. PMID:17213182

  3. Heritability of heterozygosity offers a new way of understanding why dominant gene action contributes to additive genetic variance.

    PubMed

    Nietlisbach, Pirmin; Hadfield, Jarrod D

    2015-07-01

    Whenever allele frequencies are unequal, nonadditive gene action contributes to additive genetic variance and therefore the resemblance between parents and offspring. The reason for this has not been easy to understand. Here, we present a new single-locus decomposition of additive genetic variance that may give greater intuition about this important result. We show that the contribution of dominant gene action to parent-offspring resemblance only depends on the degree to which the heterozygosity of parents and offspring covary. Thus, dominant gene action only contributes to additive genetic variance when heterozygosity is heritable. Under most circumstances this is the case because individuals with rare alleles are more likely to be heterozygous, and because they pass rare alleles to their offspring they also tend to have heterozygous offspring. When segregating alleles are at equal frequency there are no rare alleles, the heterozygosities of parents and offspring are uncorrelated and dominant gene action does not contribute to additive genetic variance. PMID:26100570

  4. Age-related macular degeneration: Evidence of a major gene

    SciTech Connect

    Bhatt, S.; Warren, C.; Yang, H.

    1994-09-01

    Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.

  5. Comparative and functional analysis of cardiovascular-related genes

    SciTech Connect

    Cheng, Jan-Fang; Pennacchio, Len A.

    2003-09-01

    The ability to detect putative cis-regulatory elements in cardiovascular-related genes has been accelerated by the availability of genomic sequence data from numerous vertebrate species and the recent development of comparative genomic tools. This improvement is anticipated to lead to a better understanding of the complex regulatory architecture of cardiovascular (CV) genes and how genetic variants in these non-coding regions can potentially play a role in cardiovascular disease. This manuscript reviews a recently established database dedicated to the comparative sequence analysis of 250 human CV genes of known importance, 37 of which currently contain sequence comparison data for organisms beyond those of human, mouse and rat. These data have provided a glimpse into the variety of possible insights from deep vertebrate sequence comparisons and the identification of putative gene regulatory elements.

  6. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms.

    PubMed

    Dondeti, Mahmoud Fathy; El-Maadawy, Eman Anwar; Talaat, Roba Mohamed

    2016-08-14

    Hepatocellular carcinoma (HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC. PMID:27570418

  7. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms

    PubMed Central

    Dondeti, Mahmoud Fathy; El-Maadawy, Eman Anwar; Talaat, Roba Mohamed

    2016-01-01

    Hepatocellular carcinoma (HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC. PMID:27570418

  8. Visually Relating Gene Expression and in vivo DNA Binding Data

    SciTech Connect

    Huang, Min-Yu; Mackey, Lester; Ker?,; nen, Soile V. E.; Weber, Gunther H.; Jordan, Michael I.; Knowles, David W.; Biggin, Mark D.; Hamann, Bernd

    2011-09-20

    Gene expression and in vivo DNA binding data provide important information for understanding gene regulatory networks: in vivo DNA binding data indicate genomic regions where transcription factors are bound, and expression data show the output resulting from this binding. Thus, there must be functional relationships between these two types of data. While visualization and data analysis tools exist for each data type alone, there is a lack of tools that can easily explore the relationship between them. We propose an approach that uses the average expression driven by multiple of ciscontrol regions to visually relate gene expression and in vivo DNA binding data. We demonstrate the utility of this tool with examples from the network controlling early Drosophila development. The results obtained support the idea that the level of occupancy of a transcription factor on DNA strongly determines the degree to which the factor regulates a target gene, and in some cases also controls whether the regulation is positive or negative.

  9. Gene-Environment Interactions in Stress Response Contribute Additively to a Genotype-Environment Interaction

    PubMed Central

    Matsui, Takeshi; Ehrenreich, Ian M.

    2016-01-01

    How combinations of gene-environment interactions collectively give rise to genotype-environment interactions is not fully understood. To shed light on this problem, we genetically dissected an environment-specific poor growth phenotype in a cross of two budding yeast strains. This phenotype is detectable when certain segregants are grown on ethanol at 37°C (‘E37’), a condition that differs from the standard culturing environment in both its carbon source (ethanol as opposed to glucose) and temperature (37°C as opposed to 30°C). Using recurrent backcrossing with phenotypic selection, we identified 16 contributing loci. To examine how these loci interact with each other and the environment, we focused on a subset of four loci that together can lead to poor growth in E37. We measured the growth of all 16 haploid combinations of alleles at these loci in all four possible combinations of carbon source (ethanol or glucose) and temperature (30 or 37°C) in a nearly isogenic population. This revealed that the four loci act in an almost entirely additive manner in E37. However, we also found that these loci have weaker effects when only carbon source or temperature is altered, suggesting that their effect magnitudes depend on the severity of environmental perturbation. Consistent with such a possibility, cloning of three causal genes identified factors that have unrelated functions in stress response. Thus, our results indicate that polymorphisms in stress response can show effects that are intensified by environmental stress, thereby resulting in major genotype-environment interactions when multiple of these variants co-occur. PMID:27437938

  10. Localization of eight additional genes in the human major histocompatibility complex, including the gene encoding the casein kinase II {beta} subunit (CSNK2B)

    SciTech Connect

    Albertella, M.R.; Jones, H.; Thomson, W.

    1996-09-01

    A wide range of autoimmune and other diseases are known to be associated with the major histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility antigens in the class I and class II regions, but some appear to be more strongly associated with genes in the central 1100-kb class III region, making it important to characterize this region fully for the presence of novel genes. An {approximately}220-kb segment of DNA in the class III region separating the Hsp70 (HSPA1L) and BAT1 (D6S8IE) genes, which was previously known to contain 14 genes. Genomic DNA fragments spanning the gaps between the known genes were used as probes to isolate cDNAs corresponding to five new genes within this region. Evidence from Northern blot analysis and exon trapping experiments that suggested the presence of at least two more new genes was also obtained. Partial cDNA and complete exonic genomic sequencing of one of the new genes has identified it as the casein kinase II{beta} subunit (CSNK2B). Two of the other novel genes lie within a region syntenic to that implicated in susceptibility to experimental allergic orchitis in the mouse, an autoimmune disease of the testis, and represent additional candidates for the Orch-1 locus associated with this disease. In addition, characterization of the 13-kb intergenic gap separating the RD (D6545) and G11 (D6S60E) genes has revealed the presence of a gene encoding a 1246-amino-acid polypeptide that shows significant sequence similarity to the yeast anti-viral Ski2p gene product. 49 refs., 8 figs.

  11. A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease

    PubMed Central

    Holmans, Peter; Moskvina, Valentina; Jones, Lesley; Sharma, Manu; Vedernikov, Alexey; Buchel, Finja; Sadd, Mohamad; Bras, Jose M.; Bettella, Francesco; Nicolaou, Nayia; Simón-Sánchez, Javier; Mittag, Florian; Gibbs, J. Raphael; Schulte, Claudia; Durr, Alexandra; Guerreiro, Rita; Hernandez, Dena; Brice, Alexis; Stefánsson, Hreinn; Majamaa, Kari; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Martinez, Maria; Singleton, Andrew B.; Nalls, Michael A.; Hardy, John; Morris, Huw R.; Williams, Nigel M.; Arepalli, Sampath; Barker, Roger; Barrett, Jeffrey; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M.A.; Biffi, Alessandro; Bloem, Bas; Brice, Alexis; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, Jonathan M.; Corvol, Jen-Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean Francois; Deloukas, Panagiotis; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Durr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gasser, Thomas; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Ómar; Hardy, John; Harris, Clare; Hernandez, Dena G.; Heutink, Peter; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holmans, Peter; Holton, Janice; Hu, Michele; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Langford, Cordelia; Lees, Andrew; Lesage, Suzanne; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; Martinez, Maria; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw; Morrison, Karen E.; Moskvina, Valentina; Mudanohwo, Ese; Nalls, Michael A.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Plagnol, Vincent; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Saad, Mohamad; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Sharma, Manu; Shaw, Karen; Sheerin, Una-Marie; Shoulson, Ira; Schulte, Claudia; Sidransky, Ellen; Simón-Sánchez, Javier; Singleton, Andrew B.; Smith, Colin; Stefánsson, Hreinn; Stefánsson, Kári; Steinberg, Stacy; Stockton, Joanna D.; Sveinbjornsdottir, Sigurlaug; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Wood, Nicholas

    2013-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1–2% in people >60 and 3–4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 × 10−16) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched for genes containing variants associated with PD. Analysing two independent GWA studies, we identified that both had a significant excess in the number of functional categories enriched for PD-associated genes (minimum P = 0.014 and P = 0.006, respectively). Moreover, 58 categories were significantly enriched for associated genes in both GWA studies (P < 0.001), implicating genes involved in the ‘regulation of leucocyte/lymphocyte activity’ and also ‘cytokine-mediated signalling’ as conferring an increased susceptibility to PD. These results were unaltered by the exclusion of all 178 genes that were present at the 18 genomic regions previously reported to be strongly associated with PD (including the HLA locus). Our findings, therefore, provide independent support to the strong association signal at the HLA locus and imply that the immune-related genetic susceptibility to PD is likely to be more widespread in the genome than previously appreciated. PMID:23223016

  12. 36 CFR 223.52 - Market-related contract term additions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Market-related contract term additions. 223.52 Section 223.52 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER, SPECIAL FOREST PRODUCTS, AND FOREST...

  13. 36 CFR 223.52 - Market-related contract term additions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 2 2013-07-01 2013-07-01 false Market-related contract term additions. 223.52 Section 223.52 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER, SPECIAL FOREST PRODUCTS, AND FOREST...

  14. 36 CFR 223.52 - Market-related contract term additions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false Market-related contract term additions. 223.52 Section 223.52 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER, SPECIAL FOREST PRODUCTS, AND FOREST...

  15. 36 CFR 223.52 - Market-related contract term additions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 2 2014-07-01 2014-07-01 false Market-related contract term additions. 223.52 Section 223.52 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER, SPECIAL FOREST PRODUCTS, AND FOREST...

  16. Sexual Dimorphism in the Expression of Mitochondria-Related Genes in Rat Heart at Different Ages

    PubMed Central

    Vijay, Vikrant; Han, Tao; Moland, Carrie L.; Kwekel, Joshua C.; Fuscoe, James C.; Desai, Varsha G.

    2015-01-01

    Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Moreover, sex and age are considered major risk factors in the development of CVDs. Mitochondria are vital for normal cardiac function, and regulation of mitochondrial structure and function may impact susceptibility to CVD. To identify potential role of mitochondria in sex-related differences in susceptibility to CVD, we analyzed the basal expression levels of mitochondria-related genes in the hearts of male and female rats. Whole genome expression profiling was performed in the hearts of young (8-week), adult (21-week), and old (78-week) male and female Fischer 344 rats and the expression of 670 unique genes related to various mitochondrial functions was analyzed. A significant (p<0.05) sexual dimorphism in expression levels of 46, 114, and 41 genes was observed in young, adult and old rats, respectively. Gene Ontology analysis revealed the influence of sex on various biological pathways related to cardiac energy metabolism at different ages. The expression of genes involved in fatty acid metabolism was significantly different between the sexes in young and adult rat hearts. Adult male rats also showed higher expression of genes associated with the pyruvate dehydrogenase complex compared to females. In young and adult hearts, sexual dimorphism was not noted in genes encoding oxidative phosphorylation. In old rats, however, a majority of genes involved in oxidative phosphorylation had higher expression in females compared to males. Such basal differences between the sexes in cardiac expression of genes associated with energy metabolism may indicate a likely involvement of mitochondria in susceptibility to CVDs. In addition, female rats showed lower expression levels of apoptotic genes in hearts compared to males at all ages, which may have implications for better preservation of cardiac mass in females than in males. PMID:25615628

  17. APOLIPOPROTEIN E GENE AND EARLY AGE-RELATED MACULOPATHY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and early age-related maculopathy (ARM) in middle-aged persons. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants from the Atherosclerosis Risk in Communities Study (n = 10139; age range, 49-73 ye...

  18. How should we measure proportionality on relative gene expression data?

    PubMed

    Erb, Ionas; Notredame, Cedric

    2016-06-01

    Correlation is ubiquitously used in gene expression analysis although its validity as an objective criterion is often questionable. If no normalization reflecting the original mRNA counts in the cells is available, correlation between genes becomes spurious. Yet the need for normalization can be bypassed using a relative analysis approach called log-ratio analysis. This approach can be used to identify proportional gene pairs, i.e. a subset of pairs whose correlation can be inferred correctly from unnormalized data due to their vanishing log-ratio variance. To interpret the size of non-zero log-ratio variances, a proposal for a scaling with respect to the variance of one member of the gene pair was recently made by Lovell et al. Here we derive analytically how spurious proportionality is introduced when using a scaling. We base our analysis on a symmetric proportionality coefficient (briefly mentioned in Lovell et al.) that has a number of advantages over their statistic. We show in detail how the choice of reference needed for the scaling determines which gene pairs are identified as proportional. We demonstrate that using an unchanged gene as a reference has huge advantages in terms of sensitivity. We also explore the link between proportionality and partial correlation and derive expressions for a partial proportionality coefficient. A brief data-analysis part puts the discussed concepts into practice. PMID:26762323

  19. Inferring gene transcriptional modulatory relations: a genetical genomics approach

    SciTech Connect

    Li, Hongqiang; Lu, Lu; Manly, Kenneth; Chesler, Elissa J; Bao, Lei; Wang, Jintao; Zhou, Mi; Williams, Robert; Cui, Yan

    2005-01-01

    Bayesian network modeling is a promising approach to define and evaluate gene expression circuits in diverse tissues and cell types under different experimental conditions. The power and practicality of this approach can be improved by restricting the number of potential interactions among genes and by defining causal relations before evaluating posterior probabilities for billions of networks. A newly developed genetical genomics method that combines transcriptome profiling with complex trait analysis now provides strong constraints on network architecture. This method detects those chromosomal intervals responsible for differences in mRNA expression using quantitative trait locus (QTL) mapping. We have developed an efficient Bayesian approach that exploits the genetical genomics method to focus computational effort on the most plausible gene modulatory networks. We exploit a dense marker map for a genetic reference population (GRP) that consists of 32 BXD strains of mice made by intercrossing two progenitor strains- C57BL/6J and DBA/2J. These progenitors differ at 1.3 million known single nucleotide polymorphisms (SNPs), all of which can be exploited to estimate the probability that a gene contains functional polymorphisms that segregate within the GRP. We constructed 66 candidate networks that include all the candidate modulator genes located in the 209 statistically significant trans-acting QTL regions. SNPs that distinguish between the two progenitor strains were used to further winnow the list of candidate modulators. Bayesian network was then used to identify the genetic modulatory relations that best explain the microarray data.

  20. A human TAPBP (TAPASIN)-related gene, TAPBP-R.

    PubMed

    Teng, Michelle S; Stephens, Richard; Du Pasquier, Louis; Freeman, Tom; Lindquist, Jonathan A; Trowsdale, John

    2002-04-01

    TAPASIN, a V-C1 (variable-constant) immunoglobulin superfamily (IgSF) molecule that links MHC class I molecules to the transporter associated with antigen processing (TAP) in the endoplasmic reticulum (ER) is encoded by the TAPBP gene, located near to the MHC at 6p21.3. A related gene was identified at chromosome position 12p13.3 between the CD27 and VAMP1 genes near a group of MHC-paralogous loci. The gene, which we have called TAPBP-R (R for related), also encodes a member of the IgSF, TAPASIN-R. Its putative product contains similar structural motifs to TAPASIN, with some marked differences, especially in the V domain, transmembrane and cytoplasmic regions. By using the mouse ortholog to screen tissue, we revealed that the TAPBP-R gene was broadly expressed. Sub-cellular localization showed that the bulk of TAPASIN-R is located within the ER but biotinylation experiments were consistent with some expression at thecell surface. TAPASIN-R lacks an obvious ER retention signal. The function of TAPASIN-R will be of interest in regards to the evolution of the immune system as well as antigen processing. PMID:11920573

  1. Identification of Gene Expression Signatures in the Chicken Intestinal Intraepithelial Lymphocytes in Response to Herb Additive Supplementations.

    PubMed

    Won, Kyeong-Hye; Song, Ki-Duk; Park, Jong-Eun; Kim, Duk-Kyung; Na, Chong-Sam

    2016-10-01

    Anethole and garlic have an immune modulatory effects on avian coccidiosis, and these effects are correlated with gene expression changes in intestinal epithelial lymphocytes (IELs). In this study, we integrated gene expression datasets from two independent experiments and investigated gene expression profile changes by anethole and garlic respectively, and identified gene expression signatures, which are common targets of these herbs as they might be used for the evaluation of the effect of plant herbs on immunity toward avian coccidiosis. We identified 4,382 and 371 genes, which were differentially expressed in IELs of chickens supplemented with garlic and anethole respectively. The gene ontology (GO) term of differentially expressed genes (DEGs) from garlic treatment resulted in the biological processes (BPs) related to proteolysis, e.g., "modification-dependent protein catabolic process", "proteolysis involved in cellular protein catabolic process", "cellular protein catabolic process", "protein catabolic process", and "ubiquitin-dependent protein catabolic process". In GO analysis, one BP term, "Proteolysis", was obtained. Among DEGs, 300 genes were differentially regulated in response to both garlic and anethole, and 234 and 59 genes were either up- or down-regulated in supplementation with both herbs. Pathway analysis resulted in enrichment of the pathways related to digestion such as "Starch and sucrose metabolism" and "Insulin signaling pathway". Taken together, the results obtained in the present study could contribute to the effective development of evaluation system of plant herbs based on molecular signatures related with their immunological functions in chicken IELs. PMID:26954117

  2. Gene-environment interactions of circadian-related genes for cardiometabolic traits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs1...

  3. Associations between DNA methylation and schizophrenia-related intermediate phenotypes a gene set enrichment analysis

    PubMed Central

    Hass, Johanna; Walton, Esther; Wright, Carrie; Beyer, Andreas; Scholz, Markus; Turner, Jessica; Liu, Jingyu; Smolka, Michael N.; Roessner, Veit; Sponheim, Scott R.; Gollub, Randy L.; Calhoun, Vince D.; Ehrlich, Stefan

    2015-01-01

    Multiple genetic approaches have identified microRNAs as key effectors in psychiatric disorders as they post-transcriptionally regulate expression of thousands of target genes. However, their role in specific psychiatric diseases remains poorly understood. In addition, epigenetic mechanisms such as DNA methylation, which affect the expression of both microRNAs and coding genes, are critical for our understanding of molecular mechanisms in schizophrenia. Using clinical, imaging, genetic, and epigenetic data of 103 patients with schizophrenia and 111 healthy controls of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia, we conducted gene set enrichment analysis to identify markers for schizophrenia-associated intermediate phenotypes. Genes were ranked based on the correlation between DNA methylation patterns and each phenotype, and then searched for enrichment in 221 predicted microRNA target gene sets. We found the predicted hsa-miR-219a-5p target gene set to be significantly enriched for genes (EPHA4, PKNOX1, ESR1, amongst others) whose methylation status is correlated with hippocampal volume independent of disease status. Our results were strengthened by significant associations between hsa-miR-219a-5p target gene methylation patterns and hippocampus-related neuropsychological variables. IPA pathway analysis of the respective predicted hsa-miR-219a-5p target genes revealed associated network functions in behaviour and developmental disorders. Altered methylation patterns of predicted hsa-miR-219a-5p target genes are associated with a structural aberration of the brain that has been proposed as a possible biomarker for schizophrenia. The (dys)regulation of microRNA target genes by epigenetic mechanisms may confer additional risk for developing psychiatric symptoms. Further study is needed to understand possible interactions between microRNAs and epigenetic changes and their impact on risk for brain-based disorders such as schizophrenia. PMID

  4. Gene expression profiles of autophagy-related genes in multiple sclerosis.

    PubMed

    Igci, Mehri; Baysan, Mehmet; Yigiter, Remzi; Ulasli, Mustafa; Geyik, Sirma; Bayraktar, Recep; Bozgeyik, İbrahim; Bozgeyik, Esra; Bayram, Ali; Cakmak, Ecir Ali

    2016-08-15

    Multiple sclerosis (MS) is an imflammatory disease of central nervous system caused by genetic and environmental factors that remain largely unknown. Autophagy is the process of degradation and recycling of damaged cytoplasmic organelles, macromolecular aggregates, and long-lived proteins. Malfunction of autophagy contributes to the pathogenesis of neurological diseases, and autophagy genes may modulate the T cell survival. We aimed to examine the expression levels of autophagy-related genes. The blood samples of 95 unrelated patients (aged 17-65years, 37 male, 58 female) diagnosed as MS and 95 healthy controls were used to extract the RNA samples. After conversion to single stranded cDNA using polyT priming: the targeted genes were pre-amplified, and 96×78 (samples×primers) qRT-PCR reactions were performed for each primer pair on each sample on a 96.96 array of Fluidigm BioMark™. Compared to age- and sex-matched controls, gene expression levels of ATG16L2, ATG9A, BCL2, FAS, GAA, HGS, PIK3R1, RAB24, RGS19, ULK1, FOXO1, HTT were significantly altered (false discovery rate<0.05). Thus, altered expression levels of several autophagy related genes may affect protein levels, which in turn would influence the activity of autophagy, or most probably, those genes might be acting independent of autophagy and contributing to MS pathogenesis as risk factors. The indeterminate genetic causes leading to alterations in gene expressions require further analysis. PMID:27125224

  5. Prospects for cost reductions from relaxing additional cross-border measures related to livestock trade.

    PubMed

    Hop, G E; Mourits, M C M; Slager, R; Oude Lansink, A G J M; Saatkamp, H W

    2013-05-01

    Compared with the domestic trade in livestock, intra-communal trade across the European Union (EU) is subject to costly, additional veterinary measures. Short-distance transportation just across a border requires more measures than long-distance domestic transportation, while the need for such additional cross-border measures can be questioned. This study examined the prospects for cost reductions from relaxing additional cross-border measures related to trade within the cross-border region of the Netherlands (NL) and Germany (GER); that is, North Rhine Westphalia and Lower Saxony. The study constructed a deterministic spread-sheet cost model to calculate the costs of both routine veterinary measures (standard measures that apply to both domestic and cross-border transport) and additional cross-border measures (extra measures that only apply to cross-border transport) as applied in 2010. This model determined costs by stakeholder, region and livestock sector, and studied the prospects for cost reduction by calculating the costs after the relaxation of additional cross-border measures. The selection criteria for relaxing these measures were (1) a low expected added value on preventing contagious livestock diseases, (2) no expected additional veterinary risks in case of relaxation of measures and (3) reasonable cost-saving possibilities. The total cost of routine veterinary measures and additional cross-border measures for the cross-border region was €22.1 million, 58% (€12.7 million) of which came from additional cross-border measures. Two-thirds of this €12.7 million resulted from the trade in slaughter animals. The main cost items were veterinary checks on animals (twice in the case of slaughter animals), export certification and control of export documentation. Four additional cross-border measures met the selection criteria for relaxation. The relaxation of these measures could save €8.2 million (€5.0 million for NL and €3.2 million for GER) annually

  6. An Additional Motor-Related Field in the Lateral Frontal Cortex of Squirrel Monkeys

    PubMed Central

    Duric, Vanja; Barbay, Scott; Frost, Shawn B.; Stylianou, Antonis; Nudo, Randolph J.

    2008-01-01

    Our earlier efforts to document the cortical connections of the ventral premotor cortex (PMv) revealed dense connections with a field rostral and lateral to PMv, an area we called the frontal rostral field (FR). Here, we present data collected in FR using electrophysiological and anatomical methods. Results show that FR contains an isolated motor representation of the forelimb that can be differentiated from PMv based on current thresholds and latencies to evoke electromyographic activity using intracortical microstimulation techniques. In addition, FR has a different pattern of cortical connections compared with PMv. Together, these data support that FR is an additional, previously undescribed motor-related area in squirrel monkeys. PMID:18424778

  7. Combinatorial gene regulation by modulation of relative pulse timing

    PubMed Central

    Lin, Yihan; Sohn, Chang Ho; Dalal, Chiraj K.; Cai, Long; Elowitz, Michael B.

    2015-01-01

    Studies of individual living cells have revealed that many transcription factors activate in dynamic, and often stochastic, pulses within the same cell. However, it has remained unclear whether cells might modulate the relative timing of these pulses to control gene expression. Here, using quantitative single-cell time-lapse imaging of Saccharomyces cerevisiae, we show that the pulsatile transcription factors Msn2 and Mig1 combinatorially regulate their target genes through modulation of their relative pulse timing. The activator Msn2 and repressor Mig1 pulsed in either a temporally overlapping or non-overlapping manner during their transient response to different inputs, with only the non-overlapping dynamics efficiently activating target gene expression. Similarly, under constant environmental conditions, where Msn2 and Mig1 exhibit sporadic pulsing, glucose concentration modulated the temporal overlap between pulses of the two factors. Together, these results reveal a time-based mode of combinatorial gene regulation. Regulation through relative signal timing is common in engineering and neurobiology, and these results suggest that it could also function broadly within the signaling and regulatory systems of the cell. PMID:26466562

  8. Titanium nanotubes activate genes related to bone formation in vitro

    PubMed Central

    Pozio, Alfonso; Palmieri, Annalisa; Girardi, Ambra; Cura, Francesca; Carinci, Francesco

    2012-01-01

    Background: Titanium is used worldwide to make osseointegrable devices, thanks to its favorable characteristics as mechanical proprieties and biocompatibility, demonstrated by in vivo studies with animal models and clinical trials over a forty-year period. However, the exact genetic effect of the titanium layer on cells is still not well characterized. Materials and Methods: To investigate how titanium nanotubes stimulate osteoblasts differentiation and proliferation, some osteoblast genes (SP7, RUNX2, COL3A1, COL1A1, ALPL, SPP1 and FOSL1) were analyzed by quantitative Real Time RT- PCR. Results: After 15 days, osteoblasts cultivated on titanium naotube showed the up-regulation of bone related genes SP7, ENG, FOSL1 and SPP1 and the down-regulation of RUNX2, COL3A1, COL1A1, and ALPL. After 30 days of treatment, the bone related genes SP7, ENG, FOSL1 and RUNX2 were up-regulated while COL3A1, COL1A1, ALPL and SPP1 were down-regulated. Conclusions: Our results, demonstrates that titanium nanotubes can lead to osteoblast differentiation and extracellular matrix deposition and mineralization in dental pulp stem cells by the activation of osteoblast related genes SPP1, FOSL1 and RUNX2. PMID:23814577

  9. Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

    PubMed Central

    Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

    2014-01-01

    Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)–related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

  10. Genotype relative risks: methods for design and analysis of candidate-gene association studies.

    PubMed Central

    Schaid, D J; Sommer, S S

    1993-01-01

    Design and analysis methods are presented for studying the association of a candidate gene with a disease by using parental data in place of nonrelated controls. This alternative design eliminates spurious differences in allele frequencies between cases and nonrelated controls resulting from different ethnic origins and population stratification for these two groups. We present analysis methods which are based on two genetic relative risks: (1) the relative risk of disease for homozygotes with two copies of the candidate gene versus homozygotes without the candidate gene and (2) the relative risk for heterozygotes with one copy of the candidate gene versus homozygotes without the candidate gene. In addition to estimating the magnitude of these relative risks, likelihood methods allow specific hypotheses to be tested, namely, a test for overall association of the candidate gene with disease, as well as specific genetic hypotheses, such as dominant or recessive inheritance. Two likelihood methods are presented: (1) a likelihood method appropriate when Hardy-Weinberg equilibrium holds and (2) a likelihood method in which we condition on parental genotype data when Hardy-Weinberg equilibrium does not hold. The results for the relative efficiency of these two methods suggest that the conditional approach may at times be preferable, even when equilibrium holds. Sample-size and power calculations are presented for a multitiered design. The purpose of tier 1 is to detect the presence of an abnormal sequence for a postulated candidate gene among a small group of cases. The purpose of tier 2 is to test for association of the abnormal variant with disease, such as by the likelihood methods presented. The purpose of tier 3 is to confirm positive results from tier 2. Results indicate that required sample sizes are smaller when expression of disease is recessive, rather than dominant, and that, for recessive disease and large relative risks, necessary sample sizes may be

  11. Tamoxifen Induces Expression of Immune Response-Related Genes in Cultured Normal Human Mammary Epithelial Cells

    PubMed Central

    Schild-Hay, Laura J.; Leil, Tarek A.; Divi, Rao L.; Olivero, Ofelia, A.; Weston, Ainsley; Poirier, Miriam C.

    2008-01-01

    Use of tamoxifen (TAM) is associated with a 50% reduction in breast cancer incidence and an increase in endometrial cancer incidence. Here, we documented TAM-induced gene expression changes in cultured normal human mammary epithelial cells (NHMEC strains numbered 5, 16 and 40), established from tissue taken at reduction mammoplasty from 3 individuals. Cells exposed to 0, 10 or 50 μM TAM for 48 hours were evaluated for (E)-α-(deoxyguanosin-N2-yl)-tamoxifen (dG-N2-TAM) adduct formation by TAM-DNA (DNA modified with dG-N2-TAM) chemiluminescence immunoassay (CIA), gene expression changes using NCI DNA-oligonucleotide microarray, and real time (RT)-PCR. At 48 hr, cells exposed to 10 μM and 50 μM TAM were 85.6% and 48.4% viable, respectively, and there were no measurable dG-N2-TAM adducts. For microarray, cells were exposed to 10 μM TAM and genes with expression changes of ≥ 3-fold were as follows: thirteen genes up-regulated and one down-related for strain 16; seventeen genes up-regulated for strain 5; and eleven genes up-regulated for strain 40. Interferon-inducible genes (IFITM1, IFIT1, IFNA1, MXI and GIP3), and a potassium ion channel (KCNJ1) were up-regulated in all 3 strains. No significant expression changes were found for genes related to estrogen or xenobiotic metabolism. RT-PCR revealed up-regulation of interferon α (IFNA1) and confirmed the TAM-induced up-regulation of the genes identified by microarray, with the exception of GIP3 and MX1, which were not up-regulated in strain 40. Induction of interferon-related genes in the three NHMEC strains suggests that, in addition to hormonal effects, TAM exposure may enhance immune response in normal breast tissue. PMID:19155303

  12. Temporal expression analysis of angiogenesis-related genes in brain development

    PubMed Central

    2012-01-01

    Background The current knowledge on molecular pathogenesis of cerebral vascular malformations (CVM), which are believed to arise during development, is very limited. To unravel the molecular mechanisms involved in CVMs, a detailed understanding of the brain vascular development at molecular level is crucial. In this study, we aimed to explore the temporal and comparative expression profile of angiogenesis-related genes in the establishment of brain vasculature. Methods Expression of a total of 113 angiogenesis-related genes during murine brain development has been analyzed using low-density array systems designed for angiogenesis-related genes. Bai1 (brain specific angiogenesis inhibitor-1), a recently identified novel anti-angiogenic gene, has been selected for further characterization. Results We found that 62 out of 113 analyzed genes have expression in brain development at varying levels. Nineteen of these were differentially expressed between embryonic and postnatal stages (>1.5 fold). Bai1 is strongly expressed on growing blood vessels of cerebral cortex and hippocampus, partially expressed in the lateral regions of striatum, but mostly absent on the thalamus. Conclusion By showing the comparative expression analysis of angiogenesis-related genes throughout brain development, the data presented here will be a crucial addition to further functional studies on cerebrovascular research. PMID:23020941

  13. Age-Related Macular Degeneration: Insights into Inflammatory Genes

    PubMed Central

    Ragazzo, Michele; Missiroli, Filippo; Borgiani, Paola; Angelucci, Francesco; Marsella, Luigi Tonino; Cusumano, Andrea; Novelli, Giuseppe; Ricci, Federico; Giardina, Emiliano

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old). AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension). In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species) have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2) that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines), immune cells (macrophages), and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression. PMID:25478207

  14. Genetic Association Analysis of 30 Genes Related to Obesity in a European American Population

    PubMed Central

    Li, Peng; Tiwari, Hemant K.; Lin, Wan-Yu; Allison, David B.; Chung, Wendy K.; Leibel, Rudolph L.; Yi, Nengjun; Liu, Nianjun

    2013-01-01

    Objective Obesity, which is frequently associated with diabetes, hypertension, and cardiovascular diseases, is primarily the result of a net excess of caloric intake over energy expenditure. Human obesity is highly heritable, but the specific genes mediating susceptibility in non-syndromic obesity remain unclear. We tested candidate genes in pathways related to food intake and energy expenditure for association with body mass index (BMI). Methods We re-analyzed 355 common genetic variants of 30 candidate genes in 7 molecular pathways related to obesity in 1,982 unrelated European Americans from the New York Health Project. Data were analyzed by using a Bayesian hierarchical generalized linear model. The BMIs were log-transformed and then adjusted for covariates including age, age2, gender, and diabetes status. The single nucleotide polymorphisms (SNPs) were modeled as additive effects. Results With the stipulated adjustments, nine SNPs in eight genes were significantly associated with BMI: GHRL (rs35683), AGRP (rs5030980), CPE (rs1946816 and rs4481204), GLP1R (rs2268641), HTR2A (rs912127), NPY5R (Y5R1c52), SOCS3 (rs4969170), and STAT3 (rs4796793). We also found a gender-by-SNP interaction (rs1745837 in HTR2A), which indicated that variants in the gene HTR2A had a stronger association with BMI in males. In addition, NPY1R was detected as having a significant gene effect even though none of the SNPs in this gene was significant. Conclusion Variations in genes AGRP, CPE, GHRL, GLP1R, HTR2A, NPY1R, NPY5R, SOCS3, and STAT3 showed modest associations with BMI in European Americans. The pathways in which these genes participate regulate energy intake and thus these associations are mechanistically plausible in this context. PMID:23900445

  15. A patient with PMP22-related hereditary neuropathy and DBH-gene-related dysautonomia.

    PubMed

    Bartoletti-Stella, Anna; Chiaro, Giacomo; Calandra-Buonaura, Giovanna; Contin, Manuela; Scaglione, Cesa; Barletta, Giorgio; Cecere, Annagrazia; Garagnani, Paolo; Tieri, Paolo; Ferrarini, Alberto; Piras, Silvia; Franceschi, Claudio; Delledonne, Massimo; Cortelli, Pietro; Capellari, Sabina

    2015-10-01

    Recurrent focal neuropathy with liability to pressure palsies is a relatively frequent autosomal-dominant demyelinating neuropathy linked to peripheral myelin protein 22 (PMP22) gene deletions. The combination of PMP22 gene mutations with other genetic variants is known to cause a more severe phenotype than expected. We present the case of a patient with severe orthostatic hypotension since 12 years of age, who inherited a PMP22 gene deletion from his father. Genetic double trouble was suspected because of selective sympathetic autonomic disturbances. Through exome-sequencing analysis, we identified two novel mutations in the dopamine beta hydroxylase gene. Moreover, with interactome analysis, we excluded a further influence on the origin of the disease by variants in other genes. This case increases the number of unique patients presenting with dopamine-β-hydroxylase deficiency and of cases with genetically proven double trouble. Finding the right, complete diagnosis is crucial to obtain adequate medical care and appropriate genetic counseling. PMID:26410747

  16. Genes related to high temperature tolerance during maize seed germination.

    PubMed

    Dutra, S M F; Von Pinho, E V R; Santos, H O; Lima, A C; Von Pinho, R G; Carvalho, M L M

    2015-01-01

    The identification of genes related to heat tolerance is fundamental for the development of high-quality seeds that are tolerant to heat stress condition. The objective of this study was to evaluate maize lineages and the gene expression involved in high temperature tolerance during germination using physiological tests, proteomics, and transcriptome analysis. Seeds from six maize lineages (30, 44, 54, 63, 64, and 91) with different levels of tolerance to high temperatures were used. Lineages 54 and 91 were observed to be more tolerant to high temperature conditions. The highest expression of α-amylase was observed in maize seeds from lineages 30 and 91 that were subjected to controlled deterioration. The highest expression of α-amylase was observed in maize seeds from lineages 30 and 91 that were subjected to controlled deterioration; with the controlled deterioration, the highest level of gene expression did not occur in the most tolerant materials; the association of lower expression of genes involved in heat-resistant protein systems was observed in seeds from lineage 44, which were more susceptible to high temperatures, and the highest gene expression of LEA D-34, ZmAN13, and AOX-1 was observed in seeds from lineage 64 when submitted to controlled deterioration. PMID:26782452

  17. Identifying novel genes and chemicals related to nasopharyngeal cancer in a heterogeneous network.

    PubMed

    Li, Zhandong; An, Lifeng; Li, Hao; Wang, ShaoPeng; Zhou, You; Yuan, Fei; Li, Lin

    2016-01-01

    Nasopharyngeal cancer or nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The factors that induce nasopharyngeal cancer are still not clear. Additional information about the chemicals or genes related to nasopharyngeal cancer will promote a better understanding of the pathogenesis of this cancer and the factors that induce it. Thus, a computational method NPC-RGCP was proposed in this study to identify the possible relevant chemicals and genes based on the presently known chemicals and genes related to nasopharyngeal cancer. To extensively utilize the functional associations between proteins and chemicals, a heterogeneous network was constructed based on interactions of proteins and chemicals. The NPC-RGCP included two stages: the searching stage and the screening stage. The former stage is for finding new possible genes and chemicals in the heterogeneous network, while the latter stage is for screening and removing false discoveries and selecting the core genes and chemicals. As a result, five putative genes, CXCR3, IRF1, CDK1, GSTP1, and CDH2, and seven putative chemicals, iron, propionic acid, dimethyl sulfoxide, isopropanol, erythrose 4-phosphate, β-D-Fructose 6-phosphate, and flavin adenine dinucleotide, were identified by NPC-RGCP. Extensive analyses provided confirmation that the putative genes and chemicals have significant associations with nasopharyngeal cancer. PMID:27149165

  18. Identifying novel genes and chemicals related to nasopharyngeal cancer in a heterogeneous network

    PubMed Central

    Li, Zhandong; An, Lifeng; Li, Hao; Wang, ShaoPeng; Zhou, You; Yuan, Fei; Li, Lin

    2016-01-01

    Nasopharyngeal cancer or nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The factors that induce nasopharyngeal cancer are still not clear. Additional information about the chemicals or genes related to nasopharyngeal cancer will promote a better understanding of the pathogenesis of this cancer and the factors that induce it. Thus, a computational method NPC-RGCP was proposed in this study to identify the possible relevant chemicals and genes based on the presently known chemicals and genes related to nasopharyngeal cancer. To extensively utilize the functional associations between proteins and chemicals, a heterogeneous network was constructed based on interactions of proteins and chemicals. The NPC-RGCP included two stages: the searching stage and the screening stage. The former stage is for finding new possible genes and chemicals in the heterogeneous network, while the latter stage is for screening and removing false discoveries and selecting the core genes and chemicals. As a result, five putative genes, CXCR3, IRF1, CDK1, GSTP1, and CDH2, and seven putative chemicals, iron, propionic acid, dimethyl sulfoxide, isopropanol, erythrose 4-phosphate, β-D-Fructose 6-phosphate, and flavin adenine dinucleotide, were identified by NPC-RGCP. Extensive analyses provided confirmation that the putative genes and chemicals have significant associations with nasopharyngeal cancer. PMID:27149165

  19. Eukaryotic operon-like transcription of functionally related genes in Drosophila

    PubMed Central

    Ben-Shahar, Yehuda; Nannapaneni, Kishore; Casavant, Thomas L.; Scheetz, Todd E.; Welsh, Michael J.

    2007-01-01

    Complex biological processes require coordinated function of many genes. One evolutionary solution to the problem of coordinately expressing functionally related genes in bacteria and nematodes is organization of genes in operons. Surprisingly, eukaryotic operons are considered rare outside the nematode lineage. In Drosophila melanogaster, we found lounge lizard (llz), which encodes a degenerin/ENaC cation channel, cotranscribed with CheB42a, a nonhomologous gene of unknown function residing <100 bp upstream. These two genes were transcribed from a single promoter as one primary transcript and were processed posttranscriptionally to generate individual mRNAs. The mechanism did not involve alternative splicing, and it differed from the trans splicing used in nematode operons. Both genes were expressed in the same tissues, and previous work suggested that both may be involved in courtship behavior. A bioinformatic approach identified numerous additional loci as potential Drosophila operons. These data reveal eukaryotic operon-like transcription of functionally related genes in Drosophila. The results also suggest that operon-based transcription may be more common in eukaryotes than previously appreciated. PMID:17190802

  20. Globin gene expression in correlation with G protein-related genes during erythroid differentiation

    PubMed Central

    2013-01-01

    Background The guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) regulate cell growth, proliferation and differentiation. G proteins are also implicated in erythroid differentiation, and some of them are expressed principally in hematopoietic cells. GPCRs-linked NO/cGMP and p38 MAPK signaling pathways already demonstrated potency for globin gene stimulation. By analyzing erythroid progenitors, derived from hematopoietic cells through in vitro ontogeny, our study intends to determine early markers and signaling pathways of globin gene regulation and their relation to GPCR expression. Results Human hematopoietic CD34+ progenitors are isolated from fetal liver (FL), cord blood (CB), adult bone marrow (BM), peripheral blood (PB) and G-CSF stimulated mobilized PB (mPB), and then differentiated in vitro into erythroid progenitors. We find that growth capacity is most abundant in FL- and CB-derived erythroid cells. The erythroid progenitor cells are sorted as 100% CD71+, but we did not find statistical significance in the variations of CD34, CD36 and GlyA antigens and that confirms similarity in maturation of studied ontogenic periods. During ontogeny, beta-globin gene expression reaches maximum levels in cells of adult blood origin (176 fmol/μg), while gamma-globin gene expression is consistently up-regulated in CB-derived cells (60 fmol/μg). During gamma-globin induction by hydroxycarbamide, we identify stimulated GPCRs (PTGDR, PTGER1) and GPCRs-coupled genes known to be activated via the cAMP/PKA (ADIPOQ), MAPK pathway (JUN) and NO/cGMP (PRPF18) signaling pathways. During ontogeny, GPR45 and ARRDC1 genes have the most prominent expression in FL-derived erythroid progenitor cells, GNL3 and GRP65 genes in CB-derived cells (high gamma-globin gene expression), GPR110 and GNG10 in BM-derived cells, GPR89C and GPR172A in PB-derived cells, and GPR44 and GNAQ genes in mPB-derived cells (high beta-globin gene expression). Conclusions These results

  1. Obtain osteoarthritis related molecular signature genes through regulation network.

    PubMed

    Li, Yawei; Wang, Bing; Lv, Guohua; Xiong, Guangzhong; Liu, Wei Dong; Li, Lei

    2012-01-01

    Osteoarthritis (OA), also known as degenerative joint disease or osteoarthrosis, is the most common form of arthritis. OA occurs when cartilage in the joints wears down over time. We used the GSE1919 series to identify potential genes that correlated to OA. The aim of our study was to obtain a molecular signature of OA through the regulation network based on differentially expressed genes. From the result of regulation network construction in OA, a number of transcription factors (TFs) and pathways closely related to OA were linked by our method. Peroxisome proliferator-activated receptor γ also arises as hub nodes in our transcriptome network and certain TFs containing CEBPD, EGR2 and ETS2 were shown to be related to OA by a previous study. PMID:21946934

  2. B.E.A.R. GeneInfo: A tool for identifying gene-related biomedical publications through user modifiable queries

    PubMed Central

    Zhou, Guohui; Wen, Xinyu; Liu, Hang; Schlicht, Michael J; Hessner, Martin J; Tonellato, Peter J; Datta, Milton W

    2004-01-01

    Background Once specific genes are identified through high throughput genomics technologies there is a need to sort the final gene list to a manageable size for validation studies. The triaging and sorting of genes often relies on the use of supplemental information related to gene structure, metabolic pathways, and chromosomal location. Yet in disease states where the genes may not have identifiable structural elements, poorly defined metabolic pathways, or limited chromosomal data, flexible systems for obtaining additional data are necessary. In these situations having a tool for searching the biomedical literature using the list of identified genes while simultaneously defining additional search terms would be useful. Results We have built a tool, BEAR GeneInfo, that allows flexible searches based on the investigators knowledge of the biological process, thus allowing for data mining that is specific to the scientist's strengths and interests. This tool allows a user to upload a series of GenBank accession numbers, Unigene Ids, Locuslink Ids, or gene names. BEAR GeneInfo takes these IDs and identifies the associated gene names, and uses the lists of gene names to query PubMed. The investigator can add additional modifying search terms to the query. The subsequent output provides a list of publications, along with the associated reference hyperlinks, for reviewing the identified articles for relevance and interest. An example of the use of this tool in the study of human prostate cancer cells treated with Selenium is presented. Conclusions This tool can be used to further define a list of genes that have been identified through genomic or genetic studies. Through the use of targeted searches with additional search terms the investigator can limit the list to genes that match their specific research interests or needs. The tool is freely available on the web at [1], and the authors will provide scripts and database components if requested mdatta@mcw.edu PMID

  3. Transcriptome expression analysis of candidate milk genes affecting cheese-related traits in 2 sheep breeds.

    PubMed

    Suárez-Vega, A; Gutiérrez-Gil, B; Arranz, J J

    2016-08-01

    Because ewe milk is principally used for cheese making, its quality is related to its content of total solids and the way in which milk constituents influence cheese yield and determine the technological and organoleptic characteristics of dairy products. Therefore, an in-depth knowledge of the expression levels of milk genes influencing cheese-related traits is essential. In the present study, the milk transcriptome data set of 2 dairy sheep breeds, Assaf and Spanish Churra, was used to evaluate the expression levels of 77 transcripts related to cheese yield and quality traits. For the comparison between both breeds, we selected the RNA sequencing (RNA-Seq) data at d 10 of lactation because this is the time point at which within and between breed differences due to lactation length are minimal. The evaluated genes encode major milk proteins (caseins and whey proteins), endogenous proteases, and enzymes related to fatty acid metabolism and citrate content. Through this analysis, we identified the genes predominantly expressed in each of the analyzed pathways that appear to be key genes for traits related to sheep milk cheese. Among the highly expressed genes in both breeds were the genes encoding caseins and whey proteins (CSN2, CSN3, CSN1S1, ENSOARG00000005099/PAEP, CSN1S2, LALBA), genes related to lipid metabolism (BTN1A1, XDH, FASN, ADFP, SCD, H-FABP, ACSS2), and one endogenous protease (CTSB). Moreover, a differential expression analysis between Churra and Assaf sheep allowed us to identify 7 genes that are significantly differentially expressed between the 2 breeds. These genes were mainly linked to endogenous protease activity (CTSL, CTSK, KLK10, KLK6, SERPINE2). Additionally, there were 2 differentially expressed genes coding for an intracellular fatty acid transporter (FABP4), an intermediate molecule of the citric acid cycle (SUCNR1), and 2 heat shock proteins (HSP70, HSPB8) that could be related to high protein production. The differential expression of

  4. Reduction of dioxin-like toxicity in effluents by additional wastewater treatment and related effects in fish.

    PubMed

    Maier, Diana; Benisek, Martin; Blaha, Ludek; Dondero, Francesco; Giesy, John P; Köhler, Heinz-R; Richter, Doreen; Scheurer, Marco; Triebskorn, Rita

    2016-10-01

    Efficiency of advanced wastewater treatment technologies to reduce micropollutants which mediate dioxin-like toxicity was investigated. Technologies compared included ozonation, powdered activated carbon and granular activated carbon. In addition to chemical analyses in samples of effluents, surface waters, sediments, and fish, (1) dioxin-like potentials were measured in paired samples of effluents, surface waters, and sediments by use of an in vitro biotest (reporter gene assay) and (2) dioxin-like effects were investigated in exposed fish by use of in vivo activity of the mixed-function, monooxygenase enzyme, ethoxyresorufin O-deethylase (EROD) in liver. All advanced technologies studied, based on degradation or adsorption, significantly reduced dioxin-like potentials in samples and resulted in lesser EROD activity in livers of fish. Results of in vitro and in vivo biological responses were not clearly related to quantification of targeted analytes by use of instrumental analyses. PMID:27262214

  5. Genotype relative risks: Methods for design and analysis of candidate-gene association studies

    SciTech Connect

    Shaid, D.J.; Sommer, S.S. )

    1993-11-01

    Design and analysis methods are presented for studying the association of a candidate gene with a disease by using parental data in place of nonrelated controls. This alternating design eliminates spurious differences in allele frequencies between cases and nonrelated controls resulting from different ethnic origins and population stratification for these two groups. The authors present analysis methods which are based on two genetic relative risks: (1) the relative risk of disease for homozygotes with two copies of the candidate gene versus homozygotes without the candidate gene and (2) the relative risk for heterozygotes with one copy of the candidate gene versus homozygotes without the candidate gene. In addition to estimating the magnitude of these relative risks, likelihood methods allow specific hypotheses to be tested, namely, a test for overall association of the candidate gene with disease, as well as specific genetic hypotheses, such as dominant or recessive inheritance. Two likelihood methods are presented: (1) a likelihood method appropriate when Hardy-Weinberg equilibrium holds and (2) a likelihood method in which the authors condition on parental genotype data when Hardy-Weinberg equilibrium does not hold. The results for the relative efficiency of these two methods suggest that the conditional approach may at times be preferable, even when equilibrium holds. Sample-size and power calculations are presented for a multitiered design. Tier 1 detects the presence of an abnormal sequence for a postulated candidate gene among a small group of cases. Tier 2 tests for association of the abnormal variant with disease, such as by the likelihood methods presented. Tier 3 confirms positive results from tier 2. Results indicate that required sample sizes are smaller when expression of disease is recessive, rather than dominant, and that, for recessive disease and large relative risks, necessary sample sizes may be feasible. 19 refs., 2 figs., 2 tabs.

  6. Tributyltin increases the expression of apoptosis- and adipogenesis-related genes in rat ovaries

    PubMed Central

    Lee, Hyojin; Lim, Sojeong; Yun, Sujin; Yoon, Ayoung; Park, Gayoung

    2012-01-01

    Objective Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease ovarian function by causing apoptosis in the ovary, but the mechanism is not fully understood. Therefore, we examined whether TBT increases the expression of adipogenesis-related genes in the ovary and the increased expression of these genes is associated with apoptosis induction. Methods Three-week-old Sprague-Dawley rats were orally administered TBT (1 or 10 mg/kg body weight) or sesame oil as a control for 7 days. The ovaries were obtained and weighed on day 8, and then they were fixed for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or frozen for RNA extraction. Using the total RNA of the ovaries, adipogenesis- and apoptosis-related genes were analyzed by real-time polymerase chain reaction (PCR). Results The ovarian weight was significantly decreased in rats administered 10 mg/kg TBT compared to that in control rats. As determined by the TUNEL assay, the number of apoptotic follicles in ovary was significantly increased in rats administered 10 mg/kg TBT. The real-time PCR results showed that the expression of adipogenesis-related genes such as PPARγ, aP2, CD36, and PEPCK was increased after TBT administration. In addition, apoptosis-related genes such as TNFα and TNFR1 were expressed more in the TBT-administered rats compared with the control rats. Conclusion The present study demonstrates that TBT induces the expression of adipogenesis- and apoptosis-related genes in the ovary leading to apoptosis in the ovarian follicles. These results suggest that the increased expression of adipogenesis-related genes in the ovary by TBT exposure might induce apoptosis resulting in a loss of ovarian function. PMID:22563546

  7. Expression and interaction analysis of Arabidopsis Skp1-related genes.

    PubMed

    Takahashi, Naoki; Kuroda, Hirofumi; Kuromori, Takashi; Hirayama, Takashi; Seki, Motoaki; Shinozaki, Kazuo; Shimada, Hiroaki; Matsui, Minami

    2004-01-01

    Specific protein degradation has been observed in several aspects of development and differentiation in many organisms. One example of such proteolysis is regulated by protein polyubiquitination that is promoted by the SCF complex consisting of Skp1, cullin, and an F-box protein. We examined the activities of the Arabidopsis Skp1-related proteins (ASKs). Among 19 annotated ASK genes, we isolated 16 of the corresponding cDNAs (ASK1, 2, 3, 4, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19), and examined their gene products for interactions with 24 representatives of F-box proteins carrying various classes of the C-terminal domains using the yeast two-hybrid system. As a result, we found diverse binding specificities: ASK1, ASK2, ASK11 and ASK12 interacted well with COI1, FKF1, UFO-like protein, LRR-containing F-box proteins, and other F-box proteins with unknown C-terminal motifs. We also observed specific interaction between F-box proteins and ASK3, ASK9, ASK13, ASK14, ASK16 and ASK18. In contrast, we detected no interaction between any of the 12 ASK proteins and F-box proteins containing CRFA, CRFB or CRFC domains. Both histochemical and RT-PCR analysis of eight ASK genes expression revealed unique expression patterns for the respective genes. PMID:14749489

  8. Relating protein adduction to gene expression changes: a systems approach

    PubMed Central

    Zhang, Bing; Shi, Zhiao; Duncan, Dexter T; Prodduturi, Naresh; Marnett, Lawrence J; Liebler, Daniel C

    2013-01-01

    Modification of proteins by reactive electrophiles such as the 4-hydroxy-2-nonenal (HNE) plays a critical role in oxidant-associated human diseases. However, little is known about protein adduction and the mechanism by which protein damage elicits adaptive effects and toxicity. We developed a systems approach for relating protein adduction to gene expression changes through the integration of protein adduction, gene expression, protein-DNA interaction, and protein-protein interaction data. Using a random walk strategy, we expanded a list of responsive transcription factors inferred from gene expression studies to upstream signaling networks, which in turn allowed overlaying protein adduction data on the network for the prediction of stress sensors and their associated regulatory mechanisms. We demonstrated the general applicability of transcription factor-based signaling network inference using 103 known pathways. Applying our workflow on gene expression and protein adduction data from HNE-treatment not only rediscovered known mechanisms of electrophile stress but also generated novel hypotheses regarding protein damage sensors. Although developed for analyzing protein adduction data, the framework can be easily adapted for phosphoproteomics and other types of protein modification data. PMID:21594272

  9. The Drosophila gene escargot encodes a zinc finger motif found in snail-related genes.

    PubMed

    Whiteley, M; Noguchi, P D; Sensabaugh, S M; Odenwald, W F; Kassis, J A

    1992-02-01

    Two independent P-element enhancer detection lines were obtained that express lacZ in a pattern of longitudinal stripes early in germband elongation. In this paper, molecular and genetic characterization of a gene located near these transposons is presented. Sequence analysis of a cDNA clone from the region reveals that this gene has a high degree of similarity with the Drosophila snail gene (Boulay et al., 1987). The sequence similarity extends over 400 nucleotides, and includes a region encoding five tandem zinc finger motifs (72% nucleotide identity; 76% amino acid identity). This region is also conserved in the snail homologue from Xenopus laevis (76% nucleotide identity; 83% amino acid identity) (Sargent and Bennett, 1990). We have named the Drosophila snail-related gene escargot (esg), and the region of sequence conservation common to all three genes the 'snailbox'. A number of Drosophila genomic DNA fragments cross-hybridize to a probe from the snailbox region suggesting that snail and escargot are members of a multigene family. The expression pattern of escargot is dynamic and complex. Early in germband elongation, escargot RNA is expressed in a pattern of longitudinal stripes identical to the one observed in the two enhancer detection lines. Later in development, escargot is expressed in cells that will form the larval imaginal tissues, escargot is allelic with l(2)35Ce, an essential gene located near snail in the genome. PMID:1571289

  10. Differential regulation of the 70K heat shock gene and related genes in Saccharomyces cerevisiae.

    PubMed Central

    Ellwood, M S; Craig, E A

    1984-01-01

    Saccharomyces cerevisiae contains a family of genes related to Hsp70, the major heat shock gene of Drosophila melanogaster. The transcription of three of these genes, which show no conservation of sequences 5' to the protein-coding region, was analyzed. The 5' flanking regions from the three genes were fused to the Escherichia coli beta-galactosidase structural gene and introduced into yeasts on multicopy plasmids, putting the beta-galactosidase production under yeast promoter control. Analysis of beta-galactosidase mRNA and protein production in these transformed strains revealed that transcription from the three promoters is differentially regulated. The number of transcripts from one promoter is vastly increased for a brief period after heat shock, whereas mRNA from another declines. Transcripts from a third gene are slightly enhanced upon heat shock; however, multiple 5' ends of the mRNA are found, and a minor species increases in amount after heat shock. Transcription of these promoters in their native state on the chromosome appears to be modulated in the same manner. Images PMID:6436685

  11. Molecular cloning of allelopathy related genes and their relation to HHO in Eupatorium adenophorum.

    PubMed

    Guo, Huiming; Pei, Xixiang; Wan, Fanghao; Cheng, Hongmei

    2011-10-01

    In this study, conserved sequence regions of HMGR, DXR, and CHS (encoding 3-hydroxy-3-methylglutaryl-CoA reductase, 1-deoxyxylulose-5-phosphate reductoisomerase and chalcone synthase, respectively) were amplified by reverse transcriptase (RT)-PCR from Eupatorium adenophorum. Quantitative real-time PCR showed that the expression of CHS was related to the level of HHO, an allelochemical isolated from E. adenophorum. Semi-quantitative RT-PCR showed that there was no significant difference in expression of genes among three different tissues, except for CHS. Southern blotting indicated that at least three CHS genes are present in the E. adenophorum genome. A full-length cDNA from CHS genes (named EaCHS1, GenBank ID: FJ913888) was cloned. The 1,455 bp cDNA contained an open reading frame (1,206 bp) encoding a protein of 401 amino acids. Preliminary bioinformatics analysis of EaCHS1 revealed that EaCHS1 was a member of CHS family, the subcellular localization predicted that EaCHS1 was a cytoplasmic protein. To the best of our knowledge, this is the first report of conserved sequences of these genes and of a full-length EaCHS1 gene in E. adenophorum. The results indicated that CHS gene is related to allelopathy of E. adenophorum. PMID:21127986

  12. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption.

    PubMed

    Pirastu, Nicola; Kooyman, Maarten; Robino, Antonietta; van der Spek, Ashley; Navarini, Luciano; Amin, Najaf; Karssen, Lennart C; Van Duijn, Cornelia M; Gasparini, Paolo

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID:27561104

  13. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Robino, Antonietta; van der Spek, Ashley; Navarini, Luciano; Amin, Najaf; Karssen, Lennart C.; Van Duijn, Cornelia M; Gasparini, Paolo

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID:27561104

  14. Four additional mouse crosses improve the lipid QTL landscape and identify Lipg as a QTL gene.

    PubMed

    Su, Zhiguang; Ishimori, Naoki; Chen, Yaoyu; Leiter, Edward H; Churchill, Gary A; Paigen, Beverly; Stylianou, Ioannis M

    2009-10-01

    To identify genes controlling plasma HDL and triglyceride levels, quantitative trait locus (QTL) analysis was performed in one backcross, (NZO/H1Lt x NON/LtJ) x NON/LtJ, and three intercrosses, C57BL/6J x DBA/2J, C57BL/6J x C3H/HeJ, and NZB/B1NJ x NZW/LacJ. HDL concentrations were affected by 25 QTL distributed on most chromosomes (Chrs); those on Chrs 1, 8, 12, and 16 were newly identified, and the remainder were replications of previously identified QTL. Triglyceride concentrations were controlled by nine loci; those on Chrs 1, 2, 3, 7, 16, and 18 were newly identified QTL, and the remainder were replications. Combining mouse crosses with haplotype analysis for the HDL QTL on Chr 18 reduced the list of candidates to six genes. Further expression analysis, sequencing, and quantitative complementation testing of these six genes identified Lipg as the HDL QTL gene on distal Chr 18. The data from these crosses further increase the ability to perform haplotype analyses that can lead to the identification of causal lipid genes. PMID:19436067

  15. Impact of obesity-related genes in Spanish population

    PubMed Central

    2013-01-01

    Background The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis. Results Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%). Conclusion The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population. PMID:24267414

  16. Cloning and characterization of temperature-related gene TRS1.

    PubMed

    Han, X-B; Zhou, X-C; Hu, Z-Y; Zhang, Z-H; Liu, Y-X

    2002-01-01

    To investigate the mechanism of spermatogenesis arrest derived from heat treatment and to screen temperature-related genes involved in spermatogenesis, the authors analyzed the differences in gene expression between cryptorchid and scrotal testes in rats, and cloned a full-length cDNA named TRS1. In situ hybridization showed that TRS1 mRNA was mainly expressed in spermatocyte and round spermatids in testis. The expression level decreased in cryptorchid testis, suggesting that the lower scrotal temperature is a key factor in keeping the normal expression of TRS1. At the N-terminal of TRS1, there was a plecstrin homology (PH) domain signature. This PH domain has high similarity to that in PEPP2, a homosapien protein, which has a characteristic of binding phosphatidylinositol 3-phosphate via its PH domain in vitro. These findings suggest that TRS1 may be important in spermatogenesis and give clues for further research on the function of TRS1. PMID:12137588

  17. Identification of Novel Cholesteatoma-Related Gene Expression Signatures Using Full-Genome Microarrays

    PubMed Central

    Klenke, Christin; Janowski, Sebastian; Borck, Daniela; Widera, Darius; Ebmeyer, Jörg; Kalinowski, Jörn; Leichtle, Anke; Hofestädt, Ralf; Upile, Tahwinder; Kaltschmidt, Christian; Kaltschmidt, Barbara; Sudhoff, Holger

    2012-01-01

    Background Cholesteatoma is a gradually expanding destructive epithelial lesion within the middle ear. It can cause extensive local tissue destruction in the temporal bone and can initially lead to the development of conductive hearing loss via ossicular erosion. As the disease progresses, sensorineural hearing loss, vertigo or facial palsy may occur. Cholesteatoma may promote the spread of infection through the tegmen of the middle ear and cause meningitis or intracranial infections with abscess formation. It must, therefore, be considered as a potentially life-threatening middle ear disease. Methods and Findings In this study, we investigated differentially expressed genes in human cholesteatomas in comparison to regular auditory canal skin using Whole Human Genome Microarrays containing 19,596 human genes. In addition to already described up-regulated mRNAs in cholesteatoma, such as MMP9, DEFB2 and KRT19, we identified 3558 new cholesteatoma-related transcripts. 811 genes appear to be significantly differentially up-regulated in cholesteatoma. 334 genes were down-regulated more than 2-fold. Significantly regulated genes with protein metabolism activity include matrix metalloproteinases as well as PI3, SERPINB3 and SERPINB4. Genes like SPP1, KRT6B, PRPH, SPRR1B and LAMC2 are known as genes with cell growth and/or maintenance activity. Transport activity genes and signal transduction genes are LCN2, GJB2 and CEACAM6. Three cell communication genes were identified; one CDH19 and two from the S100 family. Conclusions This study demonstrates that the expression profile of cholesteatoma is similar to a metastatic tumour and chronically inflamed tissue. Based on the investigated profiles we present novel protein-protein interaction and signal transduction networks, which include cholesteatoma-regulated transcripts and may be of great value for drug targeting and therapy development. PMID:23285167

  18. EST sequencing and gene expression profiling of defence-related genes from Persea americana infected with Phytophthora cinnamomi

    PubMed Central

    2011-01-01

    Background Avocado (Persea americana) belongs to the Lauraceae family and is an important commercial fruit crop in over 50 countries. The most serious pathogen affecting avocado production is Phytophthora cinnamomi which causes Phytophthora root rot (PRR). Root pathogens such as P. cinnamomi and their interactions with hosts are poorly understood and despite the importance of both the avocado crop and the effect Phytophthora has on its cultivation, there is a lack of molecular knowledge underpinning our understanding of defence strategies against the pathogen. In order to initiate a better understanding of host-specific defence we have generated EST data using 454 pyrosequencing and profiled nine defence-related genes from Pc-infected avocado roots. Results 2.0 Mb of data was generated consisting of ~10,000 reads on a single lane of the GS FLX platform. Using the Newbler assembler 371 contigs were assembled, of which 367 are novel for Persea americana. Genes were classified according to Gene Ontology terms. In addition to identifying root-specific ESTs we were also able to identify and quantify the expression of nine defence-related genes that were differentially regulated in response to P. cinnamomi. Genes such as metallothionein, thaumatin and the pathogenesis related PsemI, mlo and profilin were found to be differentially regulated. Conclusions This is the first study in elucidating the avocado root transcriptome as well as identifying defence responses of avocado roots to the root pathogen P. cinnamomi. Our data is currently the only EST data that has been generated for avocado rootstocks, and the ESTs identified in this study have already been useful in identifying defence-related genes as well as providing gene information for other studies looking at processes such as ROS regulation as well as hypoxia in avocado roots. Our EST data will aid in the elucidation of the avocado transcriptome and identification of markers for improved rootstock breeding and

  19. A gene and protein expression study on four porcine genes related to intramuscular fat deposition.

    PubMed

    Zappaterra, Martina; Deserti, Marzia; Mazza, Roberta; Braglia, Silvia; Zambonelli, Paolo; Davoli, Roberta

    2016-11-01

    Intramuscular fat (IMF) content has a prominent role in meat quality, affecting sensory attributes such as flavour and texture. In the present research, we studied in samples of porcine Semimembranosus muscle four genes related to lipid metabolism and whose gene expressions have been associated to IMF deposition: FASN, SCD, LIPE and LPL. We analysed both mRNA and protein expressions in two groups of Italian Large White pigs divergent for Semimembranosus IMF deposition, with the aim of comparing the levels of four genes and enzymes between the two groups and identifying possible coexpression links. The obtained results suggest a prominent role of LIPE enzyme in IMF hydrolysis, as the samples with low IMF deposition show a significantly higher amount of this lipase. Finally, a poorly known correlation was found between LIPE and FASN enzymes only in female individuals. These results provide new information for the understanding of IMF deposition. PMID:27236338

  20. Augmented Annotation of the Schizosaccharomyces pombe Genome Reveals Additional Genes Required for Growth and Viability

    PubMed Central

    Bitton, Danny A.; Wood, Valerie; Scutt, Paul J.; Grallert, Agnes; Yates, Tim; Smith, Duncan L.; Hagan, Iain M.; Miller, Crispin J.

    2011-01-01

    Genome annotation is a synthesis of computational prediction and experimental evidence. Small genes are notoriously difficult to detect because the patterns used to identify them are often indistinguishable from chance occurrences, leading to an arbitrary cutoff threshold for the length of a protein-coding gene identified solely by in silico analysis. We report a systematic reappraisal of the Schizosaccharomyces pombe genome that ignores thresholds. A complete six-frame translation was compared to a proteome data set, the Pfam domain database, and the genomes of six other fungi. Thirty-nine novel loci were identified. RT-PCR and RNA-Seq confirmed transcription at 38 loci; 33 novel gene structures were delineated by 5′ and 3′ RACE. Expression levels of 14 transcripts fluctuated during meiosis. Translational evidence for 10 genes, evolutionary conservation data supporting 35 predictions, and distinct phenotypes upon ORF deletion (one essential, four slow-growth, two delayed-division phenotypes) suggest that all 39 predictions encode functional proteins. The popularity of S. pombe as a model organism suggests that this augmented annotation will be of interest in diverse areas of molecular and cellular biology, while the generality of the approach suggests widespread applicability to other genomes. PMID:21270388

  1. Detection of additional genes of the patulin biosynthetic pathway in Penicillium griseofulvum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genes in the patulin biosynthetic pathway are likely to be arranged in a cluster as has been found for biosynthetic pathways of other mycotoxins. The mycotoxin patulin, common in apples and apple juice, is most often associated with Penicillium expansum. However, of 15 fungal species capable of sy...

  2. Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals

    PubMed Central

    Gao, Jianjun; Roy, Shantanu; Tong, Lin; Argos, Maria; Jasmine, Farzana; Rahaman, Ronald; Rakibuz-Zaman, Muhammad; Parvez, Faruque; Ahmed, Alauddin; Hore, Samar K; Sarwar, Golam; Slavkovich, Vesna; Yunus, Mohammad; Rahman, Mahfuzar; Baron, John A.; Graziano, Joseph H.; Ahsan, Habibul; Pierce, Brandon L.

    2014-01-01

    Background Inorganic arsenic is a carcinogen whose mode of action may involve telomere dysfunction. Recent epidemiological studies suggest that chronic arsenic exposure is associated with longer telomeres and altered expression of telomere-related genes in peripheral blood. In this study, we evaluated the association of urinary arsenic concentration with expression of telomere-related genes and telomere length in Bangladeshi individuals with a wide range of arsenic exposure through naturally contaminated drinking water. Methods We used linear regression models to estimate associations between urinary arsenic and array-based expression measures for 69 telomere related genes using mononuclear cell RNA samples from 1,799 individuals. Association between arsenic exposure and a qPCR-based telomere length was assessed among 167 individuals. Results Urinary arsenic was possitively associated with expression of WRN, and negatively associated with TERF2, DKC1, TERF2IP and OBFC1 (all P < 0.00035, Bonferroni correction threshold). We detected interaction between urinary arsenic and arsenic metabolism efficiency in relation to expression of WRN (P for interaction = 0.00008). In addition, we observed that very high arsenic exposure was associated with longer telomeres compared to very low exposure (P=0.02). Discussion Our findings suggest that arsenic’s carcinogenic mode of action may involve alteration of telomere maintenance and/or telomere damage. This study extends our knowledge regarding the effect of arsenic on telomere length and expression of telomere-related genes. PMID:25460668

  3. Tenm, a Drosophila gene related to tenascin, is a new pair-rule gene.

    PubMed Central

    Baumgartner, S; Martin, D; Hagios, C; Chiquet-Ehrismann, R

    1994-01-01

    We describe the molecular characterization of the Drosophila gene tenm, a large transcription unit spanning > 110 kb of DNA. tenm encodes a large extracellular protein of 2515 amino acids related to the extracellular matrix molecule tenascin. The Tenm protein is found in seven stripes during the blastoderm stage, and each stripe overlaps with the even-skipped stripes. tenm mutants show a phenotype resembling that of odd-paired (opa), a member of the pair-rule class of segmentation genes. Thus, Tenm is the first example of a pair-rule gene product acting from outside the cell. While the Tenm protein is under the control of fushi tarazu and even-skipped, but not of opa, at least two pair-rule genes, paired (prd) and sloppy paired (slp), and all segment-polarity genes analysed to date are under the control of tenm. Our data suggest that Tenm initiates a signal transduction cascade which acts, via or in concert with opa, on downstream targets such as prd, slp, gooseberry, engrailed and wingless, leading to an opa-like phenotype. Images PMID:8070401

  4. Modulation of adipogenesis-related gene expression by estrogen-related receptor gamma during adipocytic differentiation.

    PubMed

    Kubo, Mayumi; Ijichi, Nobuhiro; Ikeda, Kazuhiro; Horie-Inoue, Kuniko; Takeda, Satoru; Inoue, Satoshi

    2009-02-01

    Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in oxidative metabolism and mitochondrial biogenesis in brown adipose tissue and heart. However, the physiological role of ERRgamma in adipogenesis and the development of white adipose tissue has not been well studied. Here we show that ERRgamma was up-regulated in murine mesenchyme-derived cells, especially in ST2 and C3H10T1/2 cells, at mRNA levels under the adipogenic differentiation condition including the inducer of cAMP, glucocorticoid, and insulin. The up-regulation of ERRgamma mRNA was also observed in inguinal white adipose and brown adipose tissues of mice fed a high-fat diet. Gene knockdown by ERRgamma-specific siRNA results in mRNA down-regulation of adipogenic marker genes including fatty acid binding protein 4, PPARgamma, and PGC-1beta in a preadipocyte cell line 3T3-L1 preadipocytes and mesenchymal ST2 and C3H10T1/2 cells in the adipogenesis medium. In contrast, stable expression of ERRgamma in 3T3-L1 cells resulted in up-regulation of these adipogenic marker genes under the adipogenic condition. These results suggest that ERRgamma positively regulate the adipocyte differentiation with modulating the expression of various adipogenesis-related genes. PMID:18809516

  5. Genes related to chromate resistance by Pseudomonas aeruginosa PAO1.

    PubMed

    Rivera, Sonia L; Vargas, Eréndira; Ramírez-Díaz, Martha I; Campos-García, Jesús; Cervantes, Carlos

    2008-08-01

    Chromate-hypersensitive mutants of the Pseudomonas aeruginosa PAO1 strain were isolated using transposon-insertion mutagenesis. Comparison of the nucleotide sequences of the regions interrupted in the mutants with the PAO1 genome revealed that the genes affected in three mutant strains were oprE (ORF PA0291), rmlA (ORF PA5163), and ftsK (ORF PA2615), respectively. A relationship of these genes with chromate tolerance has not been previously reported. No other phenotypic changes were observed in the oprE mutant but its resistance to chromate was not fully restored by expressing the ChrA protein, which extrudes chromate ions from the cytoplasm to the periplasmic space. These data suggest that OprE participates in the efflux of chromate from the periplasm to the outside. Increased susceptibility of the rmlA mutant to the metals cadmium and mercury and to the anion-superoxide generator paraquat suggests a protective role of LPS against chromate toxicity. A higher susceptibility of the ftsK mutant to compounds affecting DNA structure (ciprofloxacin, tellurite, mitomycin C) suggests a role of FtsK in the recombinational repair of DNA damage caused by chromate. In conclusion, the P. aeruginosa genome contains diverse genes related to its intrinsic resistance to chromate. Systems pertaining to the outer membrane (OprE), the cell wall (LPS), and the cytoplasm (FtsK) were identified in this work as involved in chromate protection mechanisms. PMID:18446454

  6. Identification and expression analysis of chitinase genes related to biotic stress resistance in Brassica.

    PubMed

    Ahmed, Nasar Uddin; Park, Jong-In; Seo, Mi-Suk; Kumar, Thamilarasan Senthil; Lee, In-Ho; Park, Beom-Seok; Nou, Ill-Sup

    2012-04-01

    Brassica is a very important vegetable group because of its contribution to human nutrition and consequent economic benefits. However, biotic stress is a major concern for these crops and molecular biology techniques offer the most efficient of approaches to address this concern. Chitinase is an important biotic stress resistance-related gene. We identified three genes designated as Brassica chitinase like protein (BrCLP1), BrCLP2 and BrCLP3 from a full-length cDNA library of Brassica rapa cv. Osome. Sequence analysis of these genes confirmed that BrCLP1 was a class IV chitinase, and BrCLP2 and BrCLP3 were class VII chitinases. Also, these genes showed a high degree of homology with other biotic stress resistance-related plant chitinases. In expression analysis, organ-specific expression of all three genes was high except BrCLP1 in all the organs tested and BrCLP2 showed the highest expression compared to the other genes in flower buds. All these genes also showed expression during all developmental growth stages of Chinese cabbage. In addition, BrCLP1 was up-regulated with certain time of infection by Pectobacterium carotovorum subsp. carotovorum in Chinese cabbage plants during microarray expression analysis. On the other hand, expression of BrCLP2 and BrCLP3 were increased after 6 h post inoculation (hpi) but decreased from 12 hpi. All these data suggest that these three chitinase genes may be involved in plant resistance against biotic stresses. PMID:21720758

  7. Age and work environment characteristics in relation to sleep: Additive, interactive and curvilinear effects.

    PubMed

    Parkes, Katharine R

    2016-05-01

    Although additive combinations of age and work environment characteristics have been found to predict sleep impairment, possible age x work environment interactions have been largely disregarded. The present study examined linear and curvilinear interactions of age with work environment measures in relation to sleep quality and duration. Survey data were collected from offshore day-shift personnel (N = 901). Main effects and interactions of the age terms with work environment measures (job demand, control, and social support, physical environment and strenuous work) were evaluated. Sleep duration was predicted by a curvilinear interaction, age(2)x job demand (p < .005), and by the age x social support interaction (p < .002); sleep quality was predicted by age x job demand (p < .002). Job control and physical environment showed significant additive effects. At a time when older employees are encouraged to remain in the workforce, the findings serve to increase understanding of how ageing and work demands jointly contribute to sleep impairment. PMID:26851463

  8. Influence of oxygen partial pressure and silver additions on microstructure and related properties of YBCO superconductors

    SciTech Connect

    Singh, J.P.; Joo, J.; Guttschow, R.; Poeppel, R.B.

    1992-02-01

    Microstructure has a great influence on the mechanical and superconducting properties of YBCO. Mechanical properties of YBCO can be improved by both modifying the monolithic microstructure and developing composites of YBCO with silver (Ag). When monolithic YBCO was sintered to high densities ({approx} 91%) at a relatively low temperature ({approx} 910{degrees}C) by controlling oxygen partial pressure during sintering, the result was a small-grain microstructure (average grain size {approx} 5 {mu}m) and hence a high strength of 191 {plus minus} 7 MPa. Addition of Ag as a second phase further improved the strength of YBCO. Composites of YBCO with 10 to 15 vol % Ag has a strength of 225 {plus minus} 6 MPa and a fracture toughness of 3.3 {plus minus} 0.2 MPa{radical}m. These improvements are believed to be due to compressive stresses in the YBCO matrix as a result of thermal mismatch between the YBCO and Ag phases. Furthermore, the Ag particles may provide increased resistance to crack propagation by pinning the crack. On the other hand, addition of Ag as a dopant to substitute for Cu sites in YBCO has a profound but nonmonotonic effect on grain microstructure and the resulting critical current density.

  9. Influence of oxygen partial pressure and silver additions on microstructure and related properties of YBCO superconductors

    SciTech Connect

    Singh, J.P.; Joo, J.; Guttschow, R.; Poeppel, R.B.

    1992-02-01

    Microstructure has a great influence on the mechanical and superconducting properties of YBCO. Mechanical properties of YBCO can be improved by both modifying the monolithic microstructure and developing composites of YBCO with silver (Ag). When monolithic YBCO was sintered to high densities ({approx} 91%) at a relatively low temperature ({approx} 910{degrees}C) by controlling oxygen partial pressure during sintering, the result was a small-grain microstructure (average grain size {approx} 5 {mu}m) and hence a high strength of 191 {plus_minus} 7 MPa. Addition of Ag as a second phase further improved the strength of YBCO. Composites of YBCO with 10 to 15 vol % Ag has a strength of 225 {plus_minus} 6 MPa and a fracture toughness of 3.3 {plus_minus} 0.2 MPa{radical}m. These improvements are believed to be due to compressive stresses in the YBCO matrix as a result of thermal mismatch between the YBCO and Ag phases. Furthermore, the Ag particles may provide increased resistance to crack propagation by pinning the crack. On the other hand, addition of Ag as a dopant to substitute for Cu sites in YBCO has a profound but nonmonotonic effect on grain microstructure and the resulting critical current density.

  10. Characterization of the rainbow trout spleen transcriptome and identification of immune-related genes

    PubMed Central

    Ali, Ali; Rexroad, Caird E.; Thorgaard, Gary H.; Yao, Jianbo; Salem, Mohamed

    2014-01-01

    Resistance against diseases affects profitability of rainbow trout. Limited information is available about functions and mechanisms of teleost immune pathways. Immunogenomics provides powerful tools to determine disease resistance genes/gene pathways and develop genetic markers for genomic selection. RNA-Seq sequencing of the rainbow trout spleen yielded 93,532,200 reads (100 bp). High quality reads were assembled into 43,047 contigs. 26,333 (61.17%) of the contigs had hits to the NR protein database and 7024 (16.32%) had hits to the KEGG database. Gene ontology showed significant percentages of transcripts assigned to binding (51%), signaling (7%), response to stimuli (9%) and receptor activity (4%) suggesting existence of many immune-related genes. KEGG annotation revealed 2825 sequences belonging to “organismal systems” with the highest number of sequences, 842 (29.81%), assigned to immune system. A number of sequences were identified for the first time in rainbow trout belonging to Toll-like receptor signaling (35), B cell receptor signaling pathway (44), T cell receptor signaling pathway (56), chemokine signaling pathway (73), Fc gamma R-mediated phagocytosis (52), leukocyte transendothelial migration (60) and NK cell mediated cytotoxicity (42). In addition, 51 transcripts were identified as spleen-specific genes. The list includes 277 full-length cDNAs. The presence of a large number of immune-related genes and pathways similar to other vertebrates suggests that innate and adaptive immunity in fish are conserved. This study provides deep-sequence data of rainbow trout spleen transcriptome and identifies many new immune-related genes and full-length cDNAs. This data will help identify allelic variations suitable for genomic selection and genetic manipulation in aquaculture. PMID:25352861

  11. Characterization of the rainbow trout spleen transcriptome and identification of immune-related genes.

    PubMed

    Ali, Ali; Rexroad, Caird E; Thorgaard, Gary H; Yao, Jianbo; Salem, Mohamed

    2014-01-01

    Resistance against diseases affects profitability of rainbow trout. Limited information is available about functions and mechanisms of teleost immune pathways. Immunogenomics provides powerful tools to determine disease resistance genes/gene pathways and develop genetic markers for genomic selection. RNA-Seq sequencing of the rainbow trout spleen yielded 93,532,200 reads (100 bp). High quality reads were assembled into 43,047 contigs. 26,333 (61.17%) of the contigs had hits to the NR protein database and 7024 (16.32%) had hits to the KEGG database. Gene ontology showed significant percentages of transcripts assigned to binding (51%), signaling (7%), response to stimuli (9%) and receptor activity (4%) suggesting existence of many immune-related genes. KEGG annotation revealed 2825 sequences belonging to "organismal systems" with the highest number of sequences, 842 (29.81%), assigned to immune system. A number of sequences were identified for the first time in rainbow trout belonging to Toll-like receptor signaling (35), B cell receptor signaling pathway (44), T cell receptor signaling pathway (56), chemokine signaling pathway (73), Fc gamma R-mediated phagocytosis (52), leukocyte transendothelial migration (60) and NK cell mediated cytotoxicity (42). In addition, 51 transcripts were identified as spleen-specific genes. The list includes 277 full-length cDNAs. The presence of a large number of immune-related genes and pathways similar to other vertebrates suggests that innate and adaptive immunity in fish are conserved. This study provides deep-sequence data of rainbow trout spleen transcriptome and identifies many new immune-related genes and full-length cDNAs. This data will help identify allelic variations suitable for genomic selection and genetic manipulation in aquaculture. PMID:25352861

  12. Heme-related gene expression signatures of meat intakes in lung cancer tissues

    PubMed Central

    Lam, Tram Kim; Rotunno, Melissa; Ryan, Brid M.; Pesatori, Angela C.; Bertazzi, Pier Alberto; Spitz, Margaret; Caporaso, Neil E.; Landi, Maria Teresa

    2014-01-01

    Lung cancer causes more deaths worldwide than any other cancer. In addition to cigarette smoking, dietary factors may contribute to lung carcinogenesis. Epidemiologic studies, including the Environment and Genetics in Lung cancer Etiology (EAGLE), have reported increased consumption of red/processed meats to be associated with higher risk of lung cancer. Heme-iron toxicity may link meat intake with cancer. We investigated this hypothesis in meat-related lung carcinogenesis using whole genome expression. We measured genome-wide expression (HG-U133A) in 49 tumor and 42 non-involved fresh frozen lung tissues of 64 adenocarcinoma EAGLE patients. We studied gene expression profiles by high-versus-low meat consumption, with and without adjustment by sex, age, and smoking. Threshold for significance was a False Discovery Rate (FDR) ≤0.15. We studied whether the identified genes played a role in heme-iron related processes by means of manually curated literature search and gene ontology-based pathway analysis. We found that gene expression of 232 annotated genes in tumor tissue significantly distinguished lung adenocarcinoma cases who consumed above/below the median intake of fresh red meats (FDR=0.12). Sixty-three (~28%) of the 232 identified genes (12 expected by chance, p-value<0.001) were involved in heme binding, absorption, transport, and Wnt signaling pathway (e.g., CYPs, TPO, HPX, HFE, SLCs, WNTs). We also identified several genes involved in lipid metabolism (e.g., NCR1, TNF, UCP3) and oxidative stress (e.g., TPO, SGK2, MTHFR) that may be indirectly related to heme-toxicity. The study’s results provide preliminary evidence that heme-iron toxicity might be one underlying mechanism linking fresh red meat intake and lung cancer. PMID:23681825

  13. Heme-related gene expression signatures of meat intakes in lung cancer tissues.

    PubMed

    Lam, Tram Kim; Rotunno, Melissa; Ryan, Brid M; Pesatori, Angela C; Bertazzi, Pier Alberto; Spitz, Margaret; Caporaso, Neil E; Landi, Maria Teresa

    2014-07-01

    Lung cancer causes more deaths worldwide than any other cancer. In addition to cigarette smoking, dietary factors may contribute to lung carcinogenesis. Epidemiologic studies, including the environment and genetics in lung cancer etiology (EAGLE), have reported increased consumption of red/processed meats to be associated with higher risk of lung cancer. Heme-iron toxicity may link meat intake with cancer. We investigated this hypothesis in meat-related lung carcinogenesis using whole genome expression. We measured genome-wide expression (HG-U133A) in 49 tumor and 42 non-involved fresh frozen lung tissues of 64 adenocarcinoma EAGLE patients. We studied gene expression profiles by high-versus-low meat consumption, with and without adjustment by sex, age, and smoking. Threshold for significance was a false discovery rate (FDR) ≤ 0.15. We studied whether the identified genes played a role in heme-iron related processes by means of manually curated literature search and gene ontology-based pathway analysis. We found that gene expression of 232 annotated genes in tumor tissue significantly distinguished lung adenocarcinoma cases who consumed above/below the median intake of fresh red meats (FDR = 0.12). Sixty-three (∼ 28%) of the 232 identified genes (12 expected by chance, P-value < 0.001) were involved in heme binding, absorption, transport, and Wnt signaling pathway (e.g., CYPs, TPO, HPX, HFE, SLCs, and WNTs). We also identified several genes involved in lipid metabolism (e.g., NCR1, TNF, and UCP3) and oxidative stress (e.g., TPO, SGK2, and MTHFR) that may be indirectly related to heme-toxicity. The study's results provide preliminary evidence that heme-iron toxicity might be one underlying mechanism linking fresh red meat intake and lung cancer. PMID:23681825

  14. Inflammatory mediators release calcitonin gene-related peptide from dorsal root ganglion neurons of the rat.

    PubMed

    Averbeck, B; Izydorczyk, I; Kress, M

    2000-01-01

    The interactions between the inflammatory mediators bradykinin, serotonin, prostaglandin E(2) and acid pH were studied in rat dorsal root ganglion neurons in culture. For this purpose, the cultures were stimulated by inflammatory mediators (bradykinin, serotonin, prostaglandin E(2), 10(-5)M each) or acid solution (pH 6.1) for 5 min and the content of calcitonin gene-related peptide was determined in the supernatant before, during and after stimulation, using an enzyme immunoassay. Acid solution resulted in a threefold increase of the basal calcitonin gene-related peptide release which was entirely dependent on the presence of extracellular calcium. The release could not be blocked by the addition of the capsaicin antagonist capsazepine (10(-5)M). Bradykinin (10(-5)M) caused a 50% increase of the basal calcitonin gene-related peptide release which was again dependent on the presence of extracellular calcium, whereas serotonin and prostaglandin E(2) were each ineffective at 10(-5)M concentration. The combination of bradykinin, serotonin and prostaglandin E(2) led to a fivefold increase of the calcitonin gene-related peptide release which could not be further enhanced by acidification. The competitive capsaicin receptor antagonist capsazepine (10(-5)M) significantly reduced the release induced by the combination of bradykinin, serotonin and prostaglandin E(2). It is suggested that the inflammatory mediators co-operate and together may act as endogenous agonists at the capsaicin receptor to cause calcium influx and consecutive neuropeptide release. PMID:10858619

  15. [Construction of nervous system relative protein and gene secondary database].

    PubMed

    Wang, Pan; Chen, Xinhao; Liu, Xiangming

    2007-10-01

    Along with the rapid research of neural molecular biology, abundant data are produced so that the collection and coordination of high-throughout data about nervous system relative proteins and genes are imperative. Through analyzing the biological primary databases maintained by NCBI and RCSB as the main data source and designing a new data model, a local specialized secondary database is constructed, which mainly includes nucleotide sequences, protein sequences and protein structures, and is established on Sun Blade 2000 System and Oracle 9i. All programs are developed by Java technology. A method of web information automatic retrieval with XML is proposed for sequence data collection and submission to the database. JSP + JavaBean technology is used to support data promulgation on Internet. The establishment of this database provides an excellent platform for the research of neural molecular biology and the pathogenesis of related diseases. PMID:18027688

  16. Six family of homeobox genes and related mechanisms in tumorigenesis protocols.

    PubMed

    Armat, Marzieh; Ramezani, Fatemeh; Molavi, Ommoleila; Sabzichi, Mehdi; Samadi, Nasser

    2016-06-01

    In recent years, the homeobox gene superfamily has been introduced as a master regulator in downstream target genes related to cell development and proliferation. An indispensable role of this family involved in organogenesis development has been widely demonstrated since expression of Six family led to a distinct increase in development of various organs. These functions of Six family genes are primarily based on structure as well as regulatory role in response to external or internal stimuli. In addition to these roles, mutation or aberrant expression of Six family plays a fundamental role in initiation of carcinogenesis, a multistep process including transformation, proliferation, angiogenesis, migration, and metastasis. This suggests that the Six superfamily members can be considered as novel target molecules to inhibit tumor growth and progression. This review focuses on the structure, function, and mechanisms of the Six family in cancer processes and possible strategies to apply these family members for diagnostic, prognostic, and therapeutic purposes. PMID:27056337

  17. Gene expression suggests conserved aspects of Hox gene regulation in arthropods and provides additional support for monophyletic Myriapoda.

    PubMed

    Janssen, Ralf; Budd, Graham E

    2010-01-01

    Antisense transcripts of Ultrabithorax (aUbx) in the millipede Glomeris and the centipede Lithobius are expressed in patterns complementary to that of the Ubx sense transcripts. A similar complementary expression pattern has been described for non-coding RNAs (ncRNAs) of the bithoraxoid (bxd) locus in Drosophila, in which the transcription of bxd ncRNAs represses Ubx via transcriptional interference. We discuss our findings in the context of possibly conserved mechanisms of Ubx regulation in myriapods and the fly.Bicistronic transcription of Ubx and Antennapedia (Antp) has been reported previously for a myriapod and a number of crustaceans. In this paper, we show that Ubx/Antp bicistronic transcripts also occur in Glomeris and an onychophoran, suggesting further conserved mechanisms of Hox gene regulation in arthropods.Myriapod monophyly is supported by the expression of aUbx in all investigated myriapods, whereas in other arthropod classes, including the Onychophora, aUbx is not expressed. Of the two splice variants of Ubx/Antp only one could be isolated from myriapods, representing a possible further synapomorphy of the Myriapoda. PMID:20849647

  18. Evolution of the CD4 family: teleost fish possess two divergent forms of CD4 in addition to lymphocyte activation gene-3

    USGS Publications Warehouse

    Laing, K.J.; Zou, J.J.; Purcell, M.K.; Phillips, R.; Secombes, C.J.; Hansen, J.D.

    2006-01-01

    The T cell coreceptor CD4 is a transmembrane glycoprotein belonging to the Ig superfamily and is essential for cell-mediated immunity. Two different genes were identified in rainbow trout that resemble mammalian CD4. One (trout CD4) encodes four extracellular Ig domains reminiscent off mammalian CD4, whereas the other (CD4REL) codes for two Ig domains. Structural motifs within the amino acid sequences suggest that the two Ig domains of CD4REL duplicated to generate the four-domain molecule of CD4 and the related gene, lymphocyte activation gene-3. Here we present evidence that both of these molecules in trout are homologous to mammalian CD4 and that teleosts encode an additional CD4 family member, lymphocyte activation gene-3, which is a marker for activated T cells. The syntenic relationships of similar genes in other teleost and non-fish genomes provide evidence for the likely evolution of CD4-related molecules in vertebrates, with CD4REL likely representing the primordial form in fish. Expression of both CD4 genes is highest in the thymus and spleen, and mRNA expression of these genes is limited to surface IgM- lymphocytes, consistent with a role for T cell functionality. Finally, the intracellular regions of both CD4 and CD4REL possess the canonical CXC motif involved in the interaction off CD4 with p56LCK, implying that similar mechanisms for CD4 + T cell activation are present in all vertebrates. Our results therefore raise new questions about T cell development and functionality in lower vertebrates that cannot be answered by current mammalian models and, thus, is of fundamental importance for understanding the evolution of cell-mediated immunity in gnathosomes. Copyright ?? 2006 by The American Association of Immunologists, Inc.

  19. Apoptosis-Related Gene Expression in an Adult Cohort with Crimean-Congo Hemorrhagic Fever

    PubMed Central

    Guler, Nil; Eroglu, Cafer; Yilmaz, Hava; Karadag, Adil; Alacam, Hasan; Sunbul, Mustafa; Fletcher, Tom E.; Leblebicioglu, Hakan

    2016-01-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended. PMID:27304063

  20. Apoptosis-Related Gene Expression in an Adult Cohort with Crimean-Congo Hemorrhagic Fever.

    PubMed

    Guler, Nil; Eroglu, Cafer; Yilmaz, Hava; Karadag, Adil; Alacam, Hasan; Sunbul, Mustafa; Fletcher, Tom E; Leblebicioglu, Hakan

    2016-01-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended. PMID:27304063

  1. Identifying aging-related genes in mouse hippocampus using gateway nodes

    PubMed Central

    2014-01-01

    Background High-throughput studies continue to produce volumes of metadata representing valuable sources of information to better guide biological research. With a stronger focus on data generation, analysis models that can readily identify actual signals have not received the same level of attention. This is due in part to high levels of noise and data heterogeneity, along with a lack of sophisticated algorithms for mining useful information. Networks have emerged as a powerful tool for modeling high-throughput data because they are capable of representing not only individual biological elements but also different types of relationships en masse. Moreover, well-established graph theoretic methodology can be applied to network models to increase efficiency and speed of analysis. In this project, we propose a network model that examines temporal data from mouse hippocampus at the transcriptional level via correlation of gene expression. Using this model, we formally define the concept of “gateway” nodes, loosely defined as nodes representing genes co-expressed in multiple states. We show that the proposed network model allows us to identify target genes implicated in hippocampal aging-related processes. Results By mining gateway genes related to hippocampal aging from networks made from gene expression in young and middle-aged mice, we provide a proof-of-concept of existence and importance of gateway nodes. Additionally, these results highlight how network analysis can act as a supplement to traditional statistical analysis of differentially expressed genes. Finally, we use the gateway nodes identified by our method as well as functional databases and literature to propose new targets for study of aging in the mouse hippocampus. Conclusions This research highlights the need for methods of temporal comparison using network models and provides a systems biology approach to extract information from correlation networks of gene expression. Our results identify a

  2. Breast and Prostate Cancer and Hormone-Related Gene Variant Study

    Cancer.gov

    The Breast and Prostate Cancer and Hormone-Related Gene Variant Study allows large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism.

  3. Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort.

    PubMed

    Nakamura, Ryoichi; Sone, Jun; Atsuta, Naoki; Tohnai, Genki; Watanabe, Hazuki; Yokoi, Daichi; Nakatochi, Masahiro; Watanabe, Hirohisa; Ito, Mizuki; Senda, Jo; Katsuno, Masahisa; Tanaka, Fumiaki; Li, Yuanzhe; Izumi, Yuishin; Morita, Mitsuya; Taniguchi, Akira; Kano, Osamu; Oda, Masaya; Kuwabara, Satoshi; Abe, Koji; Aiba, Ikuko; Okamoto, Koichi; Mizoguchi, Kouichi; Hasegawa, Kazuko; Aoki, Masashi; Hattori, Nobutaka; Tsuji, Shoji; Nakashima, Kenji; Kaji, Ryuji; Sobue, Gen

    2016-03-01

    We investigated the frequency and contribution of variants of the 28 known amyotrophic lateral sclerosis (ALS)-related genes in Japanese ALS patients. We designed a multiplex, polymerase chain reaction-based primer panel to amplify the coding regions of the 28 ALS-related genes and sequenced DNA samples from 257 Japanese ALS patients using an Ion Torrent PGM sequencer. We also performed exome sequencing and identified variants of the 28 genes in an additional 251 ALS patients using an Illumina HiSeq 2000 platform. We identified the known ALS pathogenic variants and predicted the functional properties of novel nonsynonymous variants in silico. These variants were confirmed by Sanger sequencing. Known pathogenic variants were identified in 19 (48.7%) of the 39 familial ALS patients and 14 (3.0%) of the 469 sporadic ALS patients. Thirty-two sporadic ALS patients (6.8%) harbored 1 or 2 novel nonsynonymous variants of ALS-related genes that might be deleterious. This study reports the first extensive genetic screening of Japanese ALS patients. These findings are useful for developing genetic screening and counseling strategies for such patients. PMID:26742954

  4. Ethanol-related alterations in gene expression patterns in the developing murine hippocampus.

    PubMed

    Mandal, Chanchal; Park, Kyoung Sun; Jung, Kyoung Hwa; Chai, Young Gyu

    2015-08-01

    It is well known that consuming alcohol prior to and during pregnancy can cause harm to the developing fetus. Fetal alcohol spectrum disorder is a term commonly used to describe a range of disabilities that may arise from prenatal alcohol exposure such as fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol-related neurodevelopmental disorders, and alcohol-related birth defects. Here, we report that maternal binge alcohol consumption alters several important genes that are involved in nervous system development in the mouse hippocampus at embryonic day 18. Microarray analysis revealed that Nova1, Ntng1, Gal, Neurog2, Neurod2, and Fezf2 gene expressions are altered in the fetal hippocampus. Pathway analysis also revealed the association of the calcium signaling pathway in addition to other pathways with the differentially expressed genes during early brain development. Alteration of such important genes and dynamics of the signaling pathways may cause neurodevelopmental disorders. Our findings offer insight into the molecular mechanism involved in neurodevelopmental disorders associated with alcohol-related defects. PMID:26063602

  5. Systematic cloning and analysis of autophagy-related genes from the silkworm Bombyx mori

    PubMed Central

    Zhang, Xuan; Hu, Zhan-Ying; Li, Wei-Fang; Li, Qing-Rong; Deng, Xiao-Juan; Yang, Wan-Ying; Cao, Yang; Zhou, Cong-Zhao

    2009-01-01

    Background Through the whole life of eukaryotes, autophagy plays an important role in various biological events including development, differentiation and determination of lifespan. A full set of genes and their encoded proteins of this evolutionarily conserved pathway have been identified in many eukaryotic organisms from yeast to mammals. However, this pathway in the insect model organism, the silkworm Bombyx mori, remains poorly investigated. Results Based on the autophagy pathway in several model organisms and a series of bioinformatic analyses, we have found more than 20 autophagy-related genes from the current database of the silkworm Bombyx mori. These genes could be further classified into the signal transduction pathway and two ubiquitin-like pathways. Using the mRNA extracted from the silkgland, we cloned the full length cDNA fragments of some key genes via reverse transcription PCR and 3' rapid amplification of cDNA ends (RACE). In addition, we found that the transcription levels of two indicator genes BmATG8 and BmATG12 in the silkgland tend to be increased from 1st to 8th day of the fifth instar larvae. Conclusion Bioinformatics in combination with RT-PCR enable us to remodel a preliminary pathway of autophagy in the silkworm. Amplification and cloning of most autophagy-related genes from the silkgland indicated autophagy is indeed an activated process. Furthermore, the time-course transcriptional profiles of BmATG8 and BmATG12 revealed that both genes are up-regulated along the maturation of the silkgland during the fifth instar. These findings suggest that the autophagy should play an important role in Bombyx mori silkgland. PMID:19470186

  6. Identification of pathogenicity‐related genes in Fusarium oxysporum f. sp. cepae

    PubMed Central

    Vágány, Viktória; Jackson, Alison C.; Harrison, Richard J.; Rainoni, Alessandro; Clarkson, John P.

    2016-01-01

    Summary Pathogenic isolates of Fusarium oxysporum, distinguished as formae speciales (f. spp.) on the basis of their host specificity, cause crown rots, root rots and vascular wilts on many important crops worldwide. Fusarium oxysporum f. sp. cepae (FOC) is particularly problematic to onion growers worldwide and is increasing in prevalence in the UK. We characterized 31 F. oxysporum isolates collected from UK onions using pathogenicity tests, sequencing of housekeeping genes and identification of effectors. In onion seedling and bulb tests, 21 isolates were pathogenic and 10 were non‐pathogenic. The molecular characterization of these isolates, and 21 additional isolates comprising other f. spp. and different Fusarium species, was carried out by sequencing three housekeeping genes. A concatenated tree separated the F. oxysporum isolates into six clades, but did not distinguish between pathogenic and non‐pathogenic isolates. Ten putative effectors were identified within FOC, including seven Secreted In Xylem (SIX) genes first reported in F. oxysporum f. sp. lycopersici. Two highly homologous proteins with signal peptides and RxLR motifs (CRX1/CRX2) and a gene with no previously characterized domains (C5) were also identified. The presence/absence of nine of these genes was strongly related to pathogenicity against onion and all were shown to be expressed in planta. Different SIX gene complements were identified in other f. spp., but none were identified in three other Fusarium species from onion. Although the FOC SIX genes had a high level of homology with other f. spp., there were clear differences in sequences which were unique to FOC, whereas CRX1 and C5 genes appear to be largely FOC specific. PMID:26609905

  7. Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy.

    PubMed

    Hicks, Debbie; Farsani, Golara Torabi; Laval, Steven; Collins, James; Sarkozy, Anna; Martoni, Elena; Shah, Ashoke; Zou, Yaqun; Koch, Manuel; Bönnemann, Carsten G; Roberts, Mark; Lochmüller, Hanns; Bushby, Kate; Straub, Volker

    2014-05-01

    Bethlem myopathy (BM) [MIM 158810] is a slowly progressive muscle disease characterized by contractures and proximal weakness, which can be caused by mutations in one of the collagen VI genes (COL6A1, COL6A2 and COL6A3). However, there may be additional causal genes to identify as in ∼50% of BM cases no mutations in the COL6 genes are identified. In a cohort of -24 patients with a BM-like phenotype, we first sequenced 12 candidate genes based on their function, including genes for known binding partners of collagen VI, and those enzymes involved in its correct post-translational modification, assembly and secretion. Proceeding to whole-exome sequencing (WES), we identified mutations in the COL12A1 gene, a member of the FACIT collagens (fibril-associated collagens with interrupted triple helices) in five individuals from two families. Both families showed dominant inheritance with a clinical phenotype resembling classical BM. Family 1 had a single-base substitution that led to the replacement of one glycine residue in the triple-helical domain, breaking the Gly-X-Y repeating pattern, and Family 2 had a missense mutation, which created a mutant protein with an unpaired cysteine residue. Abnormality at the protein level was confirmed in both families by the intracellular retention of collagen XII in patient dermal fibroblasts. The mutation in Family 2 leads to the up-regulation of genes associated with the unfolded protein response (UPR) pathway and swollen, dysmorphic rough-ER. We conclude that the spectrum of causative genes in extracellular matrix (ECM)-related myopathies be extended to include COL12A1. PMID:24334769

  8. Identification of pathogenicity-related genes in Fusarium oxysporum f. sp. cepae.

    PubMed

    Taylor, Andrew; Vágány, Viktória; Jackson, Alison C; Harrison, Richard J; Rainoni, Alessandro; Clarkson, John P

    2016-09-01

    Pathogenic isolates of Fusarium oxysporum, distinguished as formae speciales (f. spp.) on the basis of their host specificity, cause crown rots, root rots and vascular wilts on many important crops worldwide. Fusarium oxysporum f. sp. cepae (FOC) is particularly problematic to onion growers worldwide and is increasing in prevalence in the UK. We characterized 31 F. oxysporum isolates collected from UK onions using pathogenicity tests, sequencing of housekeeping genes and identification of effectors. In onion seedling and bulb tests, 21 isolates were pathogenic and 10 were non-pathogenic. The molecular characterization of these isolates, and 21 additional isolates comprising other f. spp. and different Fusarium species, was carried out by sequencing three housekeeping genes. A concatenated tree separated the F. oxysporum isolates into six clades, but did not distinguish between pathogenic and non-pathogenic isolates. Ten putative effectors were identified within FOC, including seven Secreted In Xylem (SIX) genes first reported in F. oxysporum f. sp. lycopersici. Two highly homologous proteins with signal peptides and RxLR motifs (CRX1/CRX2) and a gene with no previously characterized domains (C5) were also identified. The presence/absence of nine of these genes was strongly related to pathogenicity against onion and all were shown to be expressed in planta. Different SIX gene complements were identified in other f. spp., but none were identified in three other Fusarium species from onion. Although the FOC SIX genes had a high level of homology with other f. spp., there were clear differences in sequences which were unique to FOC, whereas CRX1 and C5 genes appear to be largely FOC specific. PMID:26609905

  9. Calcitonin Gene-Related Peptide: Physiology and Pathophysiology

    PubMed Central

    Russell, F. A.; King, R.; Smillie, S.-J.; Kodji, X.; Brain, S. D.

    2014-01-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two major forms (α and β). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule. PMID:25287861

  10. Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells

    PubMed Central

    Xu, Hong; Xian, Jian; Vire, Emmanuelle; McKinney, Steven; Wong, Jason; Wei, Vivien; Tong, Rebecca; Kouzarides, Tony; Caldas, Carlos; Aparicio, Samuel

    2016-01-01

    BRCA2 mutations are significantly associated with early onset breast cancer, and the tumour suppressing function of BRCA2 has been attributed to its involvement in homologous recombination [1]-mediated DNA repair. In order to identify additional functions of BRCA2, we generated BRCA2-knockout HCT116 human colorectal carcinoma cells. Using genome-wide microarray analyses, we have discovered a link between the loss of BRCA2 and the up-regulation of a subset of interferon (IFN)-related genes, including APOBEC3F and APOBEC3G. The over-expression of IFN-related genes was confirmed in different human BRCA2−/− and mouse Brca2−/− tumour cell lines, and was independent of either senescence or apoptosis. In isogenic wild type BRCA2 cells, we observed over-expression of IFN-related genes after treatment with DNA-damaging agents, and following ionizing radiation. Cells with endogenous DNA damage because of defective BRCA1 or RAD51 also exhibited over-expression of IFN-related genes. Transcriptional activity of the IFN-stimulated response element (ISRE) was increased in BRCA2 knockout cells, and the expression of BRCA2 greatly decreased IFN-α stimulated ISRE reporter activity, suggesting that BRCA2 directly represses the expression of IFN-related genes through the ISRE. Finally, the colony forming capacity of BRCA2 knockout cells was significantly reduced in the presence of either IFN-β or IFN-γ, suggesting that IFNs may have potential as therapeutic agents in cancer cells with BRCA2 mutations. PMID:25043256

  11. Additional experiments relative to the shelf life of Li(Si)/FeS2 thermal batteries

    NASA Astrophysics Data System (ADS)

    Searcy, J. Q.; Armijo, J. R.

    1985-02-01

    A continuing effort to develop a new thermal battery technology based on the Li(Si)/FeS2 electrochemical couple is reported. The results relate to the long shelf life requirement for thermal batteries designed by Sandia, and include topics relevant to leakage through the hermetic seal and accelerated aging experiments with materials new to the technology. Conclusions relevant to leakage through the hermetic seal are that the maximum leak rate must not exceed 1.8 x 10(-7) w, where w is the grams of Li(Si) contained by a battery, and that a bomb type leak test can be designed that is adequate for most Li(Si)/FeS2 batteries. Conclusions relevant to long term compatibility of new materials include the following: nickel is not compatible with the iron disulfide in the cathode; the CaSi2 additive used to suppress the initial voltage transient does not react or degrade during accelerated aging experiments, but the use of that material can lead to an increase in the variability of the activated lives, especially for long life batteries; Grafoil current collectors used with the cathode do not degrade in accelerated aging experiments.

  12. Gene Therapies for Neovascular Age-Related Macular Degeneration.

    PubMed

    Pechan, Peter; Wadsworth, Samuel; Scaria, Abraham

    2015-07-01

    Pathological neovascularization is a key component of the neovascular form (also known as the wet form) of age-related macular degeneration (AMD) and proliferative diabetic retinopathy. Several preclinical studies have shown that antiangiogenesis strategies are effective for treating neovascular AMD in animal models. Vascular endothelial growth factor (VEGF) is one of the main inducers of ocular neovascularization, and several clinical trials have shown the benefits of neutralizing VEGF in patients with neovascular AMD or diabetic macular edema. In this review, we summarize several preclinical and early-stage clinical trials with intraocular gene therapies, which have the potential to reduce or eliminate the repeated intravitreal injections that are currently required for the treatment of neovascular AMD. PMID:25524721

  13. Genome-wide meta-analysis of maize heterosis reveals the potential role of additive gene expression at pericentromeric loci

    PubMed Central

    2014-01-01

    Background The identification of QTL involved in heterosis formation is one approach to unravel the not yet fully understood genetic basis of heterosis - the improved agronomic performance of hybrid F1 plants compared to their inbred parents. The identification of candidate genes underlying a QTL is important both for developing markers and determining the molecular genetic basis of a trait, but remains difficult owing to the large number of genes often contained within individual QTL. To address this problem in heterosis analysis, we applied a meta-analysis strategy for grain yield (GY) of Zea mays L. as example, incorporating QTL-, hybrid field-, and parental gene expression data. Results For the identification of genes underlying known heterotic QTL, we made use of tight associations between gene expression pattern and the trait of interest, identified by correlation analyses. Using this approach genes strongly associated with heterosis for GY were discovered to be clustered in pericentromeric regions of the complex maize genome. This suggests that expression differences of sequences in recombination-suppressed regions are important in the establishment of heterosis for GY in F1 hybrids and also in the conservation of heterosis for GY across genotypes. Importantly functional analysis of heterosis-associated genes from these genomic regions revealed over-representation of a number of functional classes, identifying key processes contributing to heterosis for GY. Based on the finding that the majority of the analyzed heterosis-associated genes were addtitively expressed, we propose a model referring to the influence of cis-regulatory variation on heterosis for GY by the compensation of fixed detrimental expression levels in parents. Conclusions The study highlights the utility of a meta-analysis approach that integrates phenotypic and multi-level molecular data to unravel complex traits in plants. It provides prospects for the identification of genes relevant for

  14. The retinoid-related orphan receptor alpha (RORA) gene and fear-related psychopathology

    PubMed Central

    Miller, Mark W.; Wolf, Erika J.; Logue, Mark W.; Baldwin, Clinton T.

    2013-01-01

    Background This study followed on findings from a recent genome-wide association study of PTSD that implicated the retinoid-related orphan receptor alpha (RORA) gene (Logue et al, 2012) by examining its relationship to broader array of disorders. Methods Using data from the same cohort (N = 540), we analyzed patterns of association between 606 single nucleotide polymorphisms (SNPs) spanning the RORA gene and comorbidity factors termed fear, distress (i.e., internalizing factors) and externalizing. Results Results showed that rs17303244 was associated with the fear component of internalizing (i.e., defined by symptoms of panic, agoraphobia, specific phobia, and obsessive-compulsive disorder) at a level of significance that withstood correction for gene-wide multiple testing. Limitations The primary limitations were the modest size of the cohort and the absence of a replication sample. Conclusions Results add to a growing literature implicating the RORA gene in a wide range of neuropsychiatric disorders and offer new insight into possible molecular mechanisms of the effects of traumatic stress on the brain and the role of genetic factors in those processes. PMID:24007783

  15. Estrogen-related receptor {alpha} modulates the expression of adipogenesis-related genes during adipocyte differentiation

    SciTech Connect

    Ijichi, Nobuhiro; Ikeda, Kazuhiro; Horie-Inoue, Kuniko; Yagi, Ken; Okazaki, Yasushi; Inoue, Satoshi . E-mail: INOUE-GER@h.u-tokyo.ac.jp

    2007-07-06

    Estrogen-related receptor {alpha} (ERR{alpha}) is an orphan nuclear receptor that regulates cellular energy metabolism by modulating gene expression involved in fatty acid oxidation and mitochondrial biogenesis in brown adipose tissue. However, the physiological role of ERR{alpha} in adipogenesis and white adipose tissue development has not been well studied. Here, we show that ERR{alpha} and ERR{alpha}-related transcriptional coactivators, peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) coactivator-1{alpha} (PGC-1{alpha}) and PGC-1{beta}, can be up-regulated in 3T3-L1 preadipocytes at mRNA levels under the adipogenic differentiation condition including the inducer of cAMP, glucocorticoid, and insulin. Gene knockdown by ERR{alpha}-specific siRNA results in mRNA down-regulation of fatty acid binding protein 4, PPAR{gamma}, and PGC-1{alpha} in 3T3-L1 cells in the adipogenesis medium. ERR{alpha} and PGC-1{beta} mRNA expression can be also up-regulated in another preadipocyte lineage DFAT-D1 cells and a pluripotent mesenchymal cell line C3H10T1/2 under the differentiation condition. Furthermore, stable expression of ERR{alpha} in 3T3-L1 cells up-regulates adipogenic marker genes and promotes triglyceride accumulation during 3T3-L1 differentiation. These results suggest that ERR{alpha} may play a critical role in adipocyte differentiation by modulating the expression of various adipogenesis-related genes.

  16. GeneMesh: a web-based microarray analysis tool for relating differentially expressed genes to MeSH terms

    PubMed Central

    2010-01-01

    Background An important objective of DNA microarray-based gene expression experimentation is determining inter-relationships that exist between differentially expressed genes and biological processes, molecular functions, cellular components, signaling pathways, physiologic processes and diseases. Results Here we describe GeneMesh, a web-based program that facilitates analysis of DNA microarray gene expression data. GeneMesh relates genes in a query set to categories available in the Medical Subject Headings (MeSH) hierarchical index. The interface enables hypothesis driven relational analysis to a specific MeSH subcategory (e.g., Cardiovascular System, Genetic Processes, Immune System Diseases etc.) or unbiased relational analysis to broader MeSH categories (e.g., Anatomy, Biological Sciences, Disease etc.). Genes found associated with a given MeSH category are dynamically linked to facilitate tabular and graphical depiction of Entrez Gene information, Gene Ontology information, KEGG metabolic pathway diagrams and intermolecular interaction information. Expression intensity values of groups of genes that cluster in relation to a given MeSH category, gene ontology or pathway can be displayed as heat maps of Z score-normalized values. GeneMesh operates on gene expression data derived from a number of commercial microarray platforms including Affymetrix, Agilent and Illumina. Conclusions GeneMesh is a versatile web-based tool for testing and developing new hypotheses through relating genes in a query set (e.g., differentially expressed genes from a DNA microarray experiment) to descriptors making up the hierarchical structure of the National Library of Medicine controlled vocabulary thesaurus, MeSH. The system further enhances the discovery process by providing links between sets of genes associated with a given MeSH category to a rich set of html linked tabular and graphic information including Entrez Gene summaries, gene ontologies, intermolecular interactions

  17. Lipids, Lipid Genes and Incident Age-Related Macular Degeneration: The Three Continent Age-Related Macular Degeneration Consortium

    PubMed Central

    Klein, Ronald; Myers, Chelsea E.; Buitendijk, Gabriëlle H. S.; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T. V. M.; Sivakumaran, Theru A.; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K.; Lee, Kristine E.; Stricker, Bruno H.; Vingerling, Johannes R.; Mitchell, Paul; Klein, Barbara E. K.; Klaver, Caroline C. W.; Wang, Jie Jin

    2014-01-01

    Purpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods Setting Three population-based cohorts. Population 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). Observation Procedures Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios (HRs) associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. Main Outcome Measures Incidence of AMD. Results The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the three studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. Conclusion In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. PMID:24879949

  18. Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex.

    PubMed

    Chen, Shi; Huang, Xi; Zhou, Xiufen; Bai, Linquan; He, Jing; Jeong, Ki Jun; Lee, Sang Yup; Deng, Zixin

    2003-11-01

    The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans 137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a modular PKS and 15 additional genes. The extensive similarity to the partially characterized candicidin gene cluster in Streptomyces griseus IMRU3570, especially for genes involved in mycosamine biosynthesis, prompted us to compare the compounds produced by Streptomyces sp. FR-008 and Streptomyces griseus IMRU3570, and we found that FR-008 and candicidin complex are identical. A model for biosynthesis of a set of four structurally related FR-008/candicidin compounds was proposed. Deletion of the putative regulatory genes abolished antibiotic production, while disruption of putative glycosyltransferase and GDP-ketosugar aminotransferase functionalities led to the productions of a set of nonmycosaminated aglycones and a novel polyene complex with attachment of altered sugar moiety, respectively. PMID:14652074

  19. Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma

    PubMed Central

    Rosas-Salazar, Christian; James, Kristina; Escobar, Gabriel; Gebretsadik, Tebeb; Li, Sherian Xu; Carroll, Kecia N.; Walsh, Eileen; Mitchel, Edward; Das, Suman; Kumar, Rajesh; Yu, Chang; Dupont, William D.; Hartert, Tina V.

    2016-01-01

    Background Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma. Methods We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated. Results Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal

  20. Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery.

    PubMed

    Verstraeten, Aline; Alaerts, Maaike; Van Laer, Lut; Loeys, Bart

    2016-06-01

    Marfan syndrome (MFS) is a rare, autosomal-dominant, multisystem disorder, presenting with skeletal, ocular, skin, and cardiovascular symptoms. Significant clinical overlap with other systemic connective tissue diseases, including Loeys-Dietz syndrome (LDS), Shprintzen-Goldberg syndrome (SGS), and the MASS phenotype, has been documented. In MFS and LDS, the cardiovascular manifestations account for the major cause of patient morbidity and mortality, rendering them the main target for therapeutic intervention. Over the past decades, gene identification studies confidently linked the aforementioned syndromes, as well as nonsyndromic aneurysmal disease, to genetic defects in proteins related to the transforming growth factor (TGF)-β pathway, greatly expanding our knowledge on the disease mechanisms and providing us with novel therapeutic targets. As a result, the focus of the developing pharmacological treatment strategies is shifting from hemodynamic stress management to TGF-β antagonism. In this review, we discuss the insights that have been gained in the molecular biology of MFS and related disorders over the past 25 years. PMID:26919284

  1. Soybean root growth in acid subsoils in relation to magnesium additions and soil solution ionic strength

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydroponic studies with soybean [Glycine max (L.) Merr.] have shown that µM additions of Mg2+ were as effective in ameliorating Al rhizotoxicity as additions of Ca2+ in the mM concentration range. The objectives of this study were to assess ameliorative effects of Mg on soybean root growth in acidic...

  2. Deciphering causal and statistical relations of molecular aberrations and gene expressions in NCI-60 cell lines

    PubMed Central

    2011-01-01

    Background Cancer cells harbor a large number of molecular alterations such as mutations, amplifications and deletions on DNA sequences and epigenetic changes on DNA methylations. These aberrations may dysregulate gene expressions, which in turn drive the malignancy of tumors. Deciphering the causal and statistical relations of molecular aberrations and gene expressions is critical for understanding the molecular mechanisms of clinical phenotypes. Results In this work, we proposed a computational method to reconstruct association modules containing driver aberrations, passenger mRNA or microRNA expressions, and putative regulators that mediate the effects from drivers to passengers. By applying the module-finding algorithm to the integrated datasets of NCI-60 cancer cell lines, we found that gene expressions were driven by diverse molecular aberrations including chromosomal segments' copy number variations, gene mutations and DNA methylations, microRNA expressions, and the expressions of transcription factors. In-silico validation indicated that passenger genes were enriched with the regulator binding motifs, functional categories or pathways where the drivers were involved, and co-citations with the driver/regulator genes. Moreover, 6 of 11 predicted MYB targets were down-regulated in an MYB-siRNA treated leukemia cell line. In addition, microRNA expressions were driven by distinct mechanisms from mRNA expressions. Conclusions The results provide rich mechanistic information regarding molecular aberrations and gene expressions in cancer genomes. This kind of integrative analysis will become an important tool for the diagnosis and treatment of cancer in the era of personalized medicine. PMID:22051105

  3. The Association of Peroxisome Proliferator-Activated Receptor δ and Additional Gene-Gene Interaction with C-Reactive Protein in Chinese Population

    PubMed Central

    Ding, Xiao-Ying; Yuan, Hao-Zheng; Gu, Ru; Gao, Yan-Feng; Liu, Xiao-Gang; Gao, Ya

    2016-01-01

    Aims. To examine the association between 4 single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors δ (PPARδ) polymorphisms and C-reactive protein (CRP) level and additional gene-gene interaction. Methods. Line regression analysis was performed to verify polymorphism association between SNP and CRP levels. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction. Results. A total of 1028 subjects (538 men, 490 women) were selected. The carriers of the C allele (TC or CC) of rs2016520 were associated with a significant decreased level of CRP, regression coefficients was −0.338, and standard error was 0.104 (p = 0.001). The carriers of the G allele (CG or GG) of rs9794 were also significantly associated with decreased level of CRP, regression coefficients was −0.219, and standard error was 0.114 (p = 0.012). We also found a potential gene-gene interaction between rs2016520 and rs9794. Subjects with rs2016520-TC or CC, rs9794-CG or GG genotypes have lowest CRP level, difference (95% CI) = −0.50 (−0.69 to −0.21) (p < 0.001), compared to subjects with rs2016520-TT and rs9794-CC genotypes. Conclusions. rs2016520 and rs9794 minor allele of PPARδ and combined effect between the two SNP were associated with decreased CRP level. PMID:26884762

  4. The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene.

    PubMed

    Paço, Ana; Brígido, Clarisse; Alexandre, Ana; Mateos, Pedro F; Oliveira, Solange

    2016-01-01

    The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra-copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under

  5. Contributions of 18 Additional DNA Sequence Variations in the Gene Encoding Apolipoprotein E to Explaining Variation in Quantitative Measures of Lipid Metabolism

    PubMed Central

    Stengård, Jari H.; Clark, Andrew G.; Weiss, Kenneth M.; Kardia, Sharon; Nickerson, Deborah A.; Salomaa, Veikko; Ehnholm, Christian; Boerwinkle, Eric; Sing, Charles F.

    2002-01-01

    Apolipoprotein E (ApoE) is a major constituent of many lipoprotein particles. Previous genetic studies have focused on six genotypes defined by three alleles, denoted ε2, ε3, and ε4, encoded by two variable exonic sites that segregate in most populations. We have reported studies of the distribution of alleles of 20 biallelic variable sites in the gene encoding the ApoE molecule within and among samples, ascertained without regard to health, from each of three populations: African Americans from Jackson, Miss.; Europeans from North Karelia, Finland; and non-Hispanic European Americans from Rochester, Minn. Here we ask (1) how much variation in blood levels of ApoE (lnApoE), of total cholesterol (TC), of high-density lipoprotein cholesterol (HDL-C), and of triglyceride (lnTG) is statistically explained by variation among APOE genotypes defined by the ε2, ε3, and ε4 alleles; (2) how much additional variation in these traits is explained by genotypes defined by combining the two variable sites that define these three alleles with one or more additional variable sites; and (3) what are the locations and relative allele frequencies of the sites that define multisite genotypes that significantly improve the statistical explanation of variation beyond that provided by the genotypes defined by the ε2, ε3, and ε4 alleles, separately for each of the six gender-population strata. This study establishes that the use of only genotypes defined by the ε2, ε3, and ε4 alleles gives an incomplete picture of the contribution that the variation in the APOE gene makes to the statistical explanation of interindividual variation in blood measurements of lipid metabolism. The addition of variable sites to the genotype definition significantly improved the ability to explain variation in lnApoE and in TC and resulted in the explanation of variation in HDL-C and in lnTG. The combination of additional sites that explained the greatest amount of trait variation was different for

  6. Array-Based Transcript Profiling and Limiting-Dilution Reverse Transcription-PCR Analysis Identify Additional Latent Genes in Kaposi's Sarcoma-Associated Herpesvirus▿ †

    PubMed Central

    Chandriani, Sanjay; Ganem, Don

    2010-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a B-lymphotropic herpesvirus strongly linked to both lymphoproliferative diseases and Kaposi's sarcoma. The viral latency program of KSHV is central to persistent infection and plays important roles in the pathogenesis of KSHV-related tumors. Up to six polypeptides and 18 microRNAs are known to be expressed in latency, but it is unclear if all major latency genes have been identified. Here, we have employed array-based transcript profiling and limiting-dilution reverse transcription-PCR (RT-PCR) methodologies to explore this issue in several KSHV-infected cell lines. Our results show that RNAs encoding the K1 protein are found at low levels in most latently infected cell lines. The gene encoding v-IL-6 is also expressed as a latent transcript in some contexts. Both genes encode powerful signaling molecules with particular relevance to B cell biology: K1 mimics signaling through the B cell receptor, and v-IL-6 promotes B cell survival. These data resolve earlier controversies about K1 and v-IL-6 expression and indicate that, in addition to core latency genes, some transcripts can be expressed in KSHV latency in a context-dependent manner. PMID:20219929

  7. Identification of Hub Genes Related to the Recovery Phase of Irradiation Injury by Microarray and Integrated Gene Network Analysis

    PubMed Central

    Zhang, Jing; Yang, Yue; Wang, Yin; Zhang, Jinyuan; Wang, Zejian; Yin, Ming; Shen, Xudong

    2011-01-01

    Background Irradiation commonly causes long-term bone marrow injury charactertized by defective HSC self-renewal and a decrease in HSC reserve. However, the effect of high-dose IR on global gene expression during bone marrow recovery remains unknown. Methodology Microarray analysis was used to identify differentially expressed genes that are likely to be critical for bone marrow recovery. Multiple bioinformatics analyses were conducted to identify key hub genes, pathways and biological processes. Principal Findings 1) We identified 1302 differentially expressed genes in murine bone marrow at 3, 7, 11 and 21 days after irradiation. Eleven of these genes are known to be HSC self-renewal associated genes, including Adipoq, Ccl3, Ccnd1, Ccnd2, Cdkn1a, Cxcl12, Junb, Pten, Tal1, Thy1 and Tnf; 2) These 1302 differentially expressed genes function in multiple biological processes of immunity, including hematopoiesis and response to stimuli, and cellular processes including cell proliferation, differentiation, adhesion and signaling; 3) Dynamic Gene Network analysis identified a subgroup of 25 core genes that participate in immune response, regulation of transcription and nucleosome assembly; 4) A comparison of our data with known irradiation-related genes extracted from literature showed 42 genes that matched the results of our microarray analysis, thus demonstrated consistency between studies; 5) Protein-protein interaction network and pathway analyses indicated several essential protein-protein interactions and signaling pathways, including focal adhesion and several immune-related signaling pathways. Conclusions Comparisons to other gene array datasets indicate that global gene expression profiles of irradiation damaged bone marrow show significant differences between injury and recovery phases. Our data suggest that immune response (including hematopoiesis) can be considered as a critical biological process in bone marrow recovery. Several critical hub genes that are

  8. BRONCO: Biomedical entity Relation ONcology COrpus for extracting gene-variant-disease-drug relations

    PubMed Central

    Lee, Kyubum; Lee, Sunwon; Park, Sungjoon; Kim, Sunkyu; Kim, Suhkyung; Choi, Kwanghun; Tan, Aik Choon; Kang, Jaewoo

    2016-01-01

    Comprehensive knowledge of genomic variants in a biological context is key for precision medicine. As next-generation sequencing technologies improve, the amount of literature containing genomic variant data, such as new functions or related phenotypes, rapidly increases. Because numerous articles are published every day, it is almost impossible to manually curate all the variant information from the literature. Many researchers focus on creating an improved automated biomedical natural language processing (BioNLP) method that extracts useful variants and their functional information from the literature. However, there is no gold-standard data set that contains texts annotated with variants and their related functions. To overcome these limitations, we introduce a Biomedical entity Relation ONcology COrpus (BRONCO) that contains more than 400 variants and their relations with genes, diseases, drugs and cell lines in the context of cancer and anti-tumor drug screening research. The variants and their relations were manually extracted from 108 full-text articles. BRONCO can be utilized to evaluate and train new methods used for extracting biomedical entity relations from full-text publications, and thus be a valuable resource to the biomedical text mining research community. Using BRONCO, we quantitatively and qualitatively evaluated the performance of three state-of-the-art BioNLP methods. We also identified their shortcomings, and suggested remedies for each method. We implemented post-processing modules for the three BioNLP methods, which improved their performance. Database URL: http://infos.korea.ac.kr/bronco PMID:27074804

  9. BRONCO: Biomedical entity Relation ONcology COrpus for extracting gene-variant-disease-drug relations.

    PubMed

    Lee, Kyubum; Lee, Sunwon; Park, Sungjoon; Kim, Sunkyu; Kim, Suhkyung; Choi, Kwanghun; Tan, Aik Choon; Kang, Jaewoo

    2016-01-01

    Comprehensive knowledge of genomic variants in a biological context is key for precision medicine. As next-generation sequencing technologies improve, the amount of literature containing genomic variant data, such as new functions or related phenotypes, rapidly increases. Because numerous articles are published every day, it is almost impossible to manually curate all the variant information from the literature. Many researchers focus on creating an improved automated biomedical natural language processing (BioNLP) method that extracts useful variants and their functional information from the literature. However, there is no gold-standard data set that contains texts annotated with variants and their related functions. To overcome these limitations, we introduce a Biomedical entity Relation ONcology COrpus (BRONCO) that contains more than 400 variants and their relations with genes, diseases, drugs and cell lines in the context of cancer and anti-tumor drug screening research. The variants and their relations were manually extracted from 108 full-text articles. BRONCO can be utilized to evaluate and train new methods used for extracting biomedical entity relations from full-text publications, and thus be a valuable resource to the biomedical text mining research community. Using BRONCO, we quantitatively and qualitatively evaluated the performance of three state-of-the-art BioNLP methods. We also identified their shortcomings, and suggested remedies for each method. We implemented post-processing modules for the three BioNLP methods, which improved their performance.Database URL:http://infos.korea.ac.kr/bronco. PMID:27074804

  10. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality. PMID:26515667

  11. Selection of Reference Genes for Gene Expression Studies Related to Intramuscular Fat Deposition in Capra hircus Skeletal Muscle

    PubMed Central

    Zhu, Wuzheng; Lin, Yaqiu; Liao, Honghai; Wang, Yong

    2015-01-01

    The identification of suitable reference genes is critical for obtaining reliable results from gene expression studies using quantitative real-time PCR (qPCR) because the expression of reference genes may vary considerably under different experimental conditions. In most cases, however, commonly used reference genes are employed in data normalization without proper validation, which may lead to incorrect data interpretation. Here, we aim to select a set of optimal reference genes for the accurate normalization of gene expression associated with intramuscular fat (IMF) deposition during development. In the present study, eight reference genes (PPIB, HMBS, RPLP0, B2M, YWHAZ, 18S, GAPDH and ACTB) were evaluated by three different algorithms (geNorm, NormFinder and BestKeeper) in two types of muscle tissues (longissimus dorsi muscle and biceps femoris muscle) across different developmental stages. All three algorithms gave similar results. PPIB and HMBS were identified as the most stable reference genes, while the commonly used reference genes 18S and GAPDH were the most variably expressed, with expression varying dramatically across different developmental stages. Furthermore, to reveal the crucial role of appropriate reference genes in obtaining a reliable result, analysis of PPARG expression was performed by normalization to the most and the least stable reference genes. The relative expression levels of PPARG normalized to the most stable reference genes greatly differed from those normalized to the least stable one. Therefore, evaluation of reference genes must be performed for a given experimental condition before the reference genes are used. PPIB and HMBS are the optimal reference genes for analysis of gene expression associated with IMF deposition in skeletal muscle during development. PMID:25794179

  12. New type IV pili-related genes involved in early stages of Ralstonia solanacearum potato infection.

    PubMed

    Siri, María Inés; Sanabria, Analía; Boucher, Christian; Pianzzola, María Julia

    2014-07-01

    This study provides insights into the pathogenesis of Ralstonia solanacearum, in particular with regards to strains belonging to phylotype IIB, sequevar 1 (IIB-1) and their interaction with potato, its natural host. We performed a comparative genomic analysis among IIB-1 R. solanacearum strains with different levels of virulence in order to identify candidate virulence genes. With this approach, we identified a 33.7-kb deletion in a strain showing reduced virulence on potato. This region contains a cluster of six genes putatively involved in type IV pili (Tfp) biogenesis. Functional analysis suggests that these proteins contribute to several Tfp-related functions such as twitching motility and biofilm formation. In addition, this genetic cluster was found to contribute to early bacterial wilt pathogenesis and colonization fitness of potato roots. PMID:24625029

  13. Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration

    MedlinePlus

    ... macular degeneration Three studies point to same risk gene for age-related macular degeneration NIH-funded research ... in Nature Genetics have converged on the same gene as a rare, but powerful risk factor for ...

  14. Polyphenol Oxidase Gene Structure in Wheat and Related Species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since PPO is known to be the major cause of browning reactions that discolour Asian noodles and other wheat products, a better understanding of PPO gene structure should contribute to minimizing the deleterious effects of PPO via wheat breeding and improvement. A PPO gene model has emerged that iden...

  15. Mechanism-based biomarker gene sets for glutathione depletion-related hepatotoxicity in rats

    SciTech Connect

    Gao Weihua; Mizukawa, Yumiko; Nakatsu, Noriyuki; Minowa, Yosuke; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

    2010-09-15

    Chemical-induced glutathione depletion is thought to be caused by two types of toxicological mechanisms: PHO-type glutathione depletion [glutathione conjugated with chemicals such as phorone (PHO) or diethyl maleate (DEM)], and BSO-type glutathione depletion [i.e., glutathione synthesis inhibited by chemicals such as L-buthionine-sulfoximine (BSO)]. In order to identify mechanism-based biomarker gene sets for glutathione depletion in rat liver, male SD rats were treated with various chemicals including PHO (40, 120 and 400 mg/kg), DEM (80, 240 and 800 mg/kg), BSO (150, 450 and 1500 mg/kg), and bromobenzene (BBZ, 10, 100 and 300 mg/kg). Liver samples were taken 3, 6, 9 and 24 h after administration and examined for hepatic glutathione content, physiological and pathological changes, and gene expression changes using Affymetrix GeneChip Arrays. To identify differentially expressed probe sets in response to glutathione depletion, we focused on the following two courses of events for the two types of mechanisms of glutathione depletion: a) gene expression changes occurring simultaneously in response to glutathione depletion, and b) gene expression changes after glutathione was depleted. The gene expression profiles of the identified probe sets for the two types of glutathione depletion differed markedly at times during and after glutathione depletion, whereas Srxn1 was markedly increased for both types as glutathione was depleted, suggesting that Srxn1 is a key molecule in oxidative stress related to glutathione. The extracted probe sets were refined and verified using various compounds including 13 additional positive or negative compounds, and they established two useful marker sets. One contained three probe sets (Akr7a3, Trib3 and Gstp1) that could detect conjugation-type glutathione depletors any time within 24 h after dosing, and the other contained 14 probe sets that could detect glutathione depletors by any mechanism. These two sets, with appropriate scoring

  16. Increased Missense Mutation Burden of Fatty Acid Metabolism Related Genes in Nunavik Inuit Population

    PubMed Central

    Zhou, Sirui; Xiong, Lan; Xie, Pingxing; Ambalavanan, Amirthagowri; Bourassa, Cynthia V.; Dionne-Laporte, Alexandre; Spiegelman, Dan; Turcotte Gauthier, Maude; Henrion, Edouard; Diallo, Ousmane; Dion, Patrick A.; Rouleau, Guy A.

    2015-01-01

    Background Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism. Methods Exome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals. Results Altogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians. Conclusion The increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit. PMID:26010953

  17. 47 CFR 5.311 - Additional requirements related to safety of the public.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... safety of the public. In addition to the notification requirements of § 5.309, for experiments that may... bands and geographic area as the planned experiment and, as appropriate, their end users; (b) Rapid identification, and elimination, of any harm the experiment may cause; and (c) Identifying an alternate means...

  18. 47 CFR 5.311 - Additional requirements related to safety of the public.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... safety of the public. In addition to the notification requirements of § 5.309, for experiments that may... bands and geographic area as the planned experiment and, as appropriate, their end users; (b) Rapid identification, and elimination, of any harm the experiment may cause; and (c) Identifying an alternate means...

  19. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P.

    1998-01-01

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  20. Isolation and characterization of Agouti: a diabetes/obesity related gene

    DOEpatents

    Woychik, Richard P.

    2000-06-27

    The present invention relates to the cloning and expression of the Agouti gene and analogous genes in transformed, transfected and transgenic mice. The present invention provides an animal model for the study of diabetes, obesity and tumors for the testing of potential therapeutic agents. The present invention provides oligonucleotide probes for the detection of the Agouti gene and mutations in the gene. The present invention also relates to the isolation and recombinant production of the Agouti gene product, production of antibodies to the Agouti gene product and their use as diagnostic and therapeutic agents.

  1. Effects of Chlorine Stress on Pseudomonas aeruginosa Biofilm and Analysis of Related Gene Expressions.

    PubMed

    Kekeç, Özge; Gökalsın, Barış; Karaltı, İskender; Kayhan, Figen Esin; Sesal, Nüzhet Cenk

    2016-08-01

    Chlorine is deployed worldwide to clean waters and prevent water-originated illnesses. However, chlorine has a limited disinfection capacity against biofilms. Microorganisms form biofilms to protect themselves from biological threats such as disinfectant chemicals. Pseudomonas aeruginosa is an opportunistic pathogen and its biofilm form attaches to surfaces, living buried into exopolysaccharides, can be present in all watery environments including tap water and drinking water. This research aimed to study the biofilm trigger mechanism of the opportunistic pathogen P. aeruginosa PAO1 strain, which is known to form biofilm in water supply systems and human body, under chlorine stress levels. In addition to biofilm staining, certain genes that are relevant to the stress condition were selected for gene expression analysis. The bacteria cultures were grown under chlorine stress with concentrations of 0.5, 0.7 and 1 mg/l. Six gene regions were determined related to biofilm and stress response: rpoS, bifA, migA, katB, soxR, and algC. Biofilm formation was analyzed by basic fuchsin staining, and gene expressions were quantified by quantitative real-time PCR. According to the results, highest biofilm production was observed in P. aeruginosa PAO1 wild strain under no stress conditions. Higher biofilm amounts were observed for bacteria under 0.5 and 0.7 mg/l chlorine stress compared to 1 mg/l chlorine stress. PMID:27146505

  2. Structure of the mouse calcitonin/calcitonin gene-related peptide alpha and beta genes.

    PubMed

    Thomas, P M; Nasonkin, I; Zhang, H; Gagel, R F; Cote, G J

    2001-01-01

    We report the cloning, genomic organization and sequence of the mouse alpha-CALC and beta-CALC genes. The two genes share extensive sequence homology. The transcription units of both genes contain 6 exons. Transcripts of the alpha-CALC gene were found to alternatively include exon 4 or exons 5 and 6. For the beta-CALC gene exon 4 was not detected in transcripts derived from this gene. The predicted mouse alpha-CGRP was found to be identical to rat alpha-CGRP, however, beta-CGRP predicted amino acid sequences revealed three amino acid differences suggesting these residues are not critical to CGRP function. PMID:11761712

  3. Expression analysis of autophagy-related genes in the hard tick Haemaphysalis longicornis.

    PubMed

    Umemiya-Shirafuji, Rika; Galay, Remil Linggatong; Maeda, Hiroki; Kawano, Suguru; Tanaka, Tetsuya; Fukumoto, Shinya; Suzuki, Hiroshi; Tsuji, Naotoshi; Fujisaki, Kozo

    2014-03-17

    Ticks are obligate hematophagous arthropods with unique life cycles characterized by relatively short feeding periods and long non-feeding periods. They ambush a suitable host animal while staying in a pasture without any food source for up to several months. To understand the molecular mechanisms underlying their exceptional viability, we focused on autophagy, a proteolysis system via the lysosomes that is induced by starvation in eukaryotes. We hypothesized that starved conditions facilitate autophagy during host-seeking periods in the life cycle of the tick. To date, homologues of five autophagy-related (ATG) genes, ATG3, ATG4, ATG6, ATG8, and ATG12, have been identified from the hard tick Haemaphysalis longicornis. We showed previously that the mRNA levels of H. longicornis ATG (HlATG) genes were higher during the non-feeding period than the feeding period in the nymphal to adult stages. In addition, the expressions of HlATG3, HlATG4, HlATG8 and HlATG12 were highest in the egg compared to the other developmental stages in the same tick. In the present study, we used real-time polymerase chain reaction to examine the expression profiles of HlATG genes in the embryonic stage, larval to nymphal stages, and in internal organs of female ticks. We found that the HlATG genes were expressed at the highest levels in developing eggs on day 0 after oviposition. The levels of HlATG4 and HlATG8 were higher during the non-feeding period than the feeding period in the larval to nymphal stages. In the adults, the unfed condition appeared to be associated with the increased expression of HlATG genes in the fat body and midgut, which are nutrient storage organs; however, the expression patterns of HlATG genes varied in other organs. These results suggest that an up-regulation of HlATG genes is not always induced in different organs of unfed female ticks. Taken together, our findings raise the new possibility that HlATG genes play distinct biological roles in eggs, unfed ticks

  4. Placental genetic variations in circadian clock-related genes increase the risk of placental abruption

    PubMed Central

    Qiu, Chunfang; Gelaye, Bizu; Denis, Marie; Tadesse, Mahlet G; Enquobahrie, Daniel A; Ananth, Cande V; Pacora, Percy N; Salazar, Manuel; Sanchez, Sixto E; Williams, Michelle A

    2016-01-01

    The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to estimate odds ratios (ORs). The combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score. We examined independent and joint associations of wGRS derived from placental and maternal genomes with PA. Seven SNPs in five genes (ARNTL2, CRY2, DEC1, PER3 and RORA), in the placental genome, were associated with PA risk. Each copy of the minor allele (G) of a SNP in the RORA gene (rs2899663) was associated with a 30% reduced odds of PA (95% CI 0.52-0.95). The odds of PA increased with increasing placental-wGRS (Ptrend<0.001). The ORs were 1.00, 2.16, 3.24 and 4.48 across quartiles. Associations persisted after the maternal-wGRS was included in the model. There was evidence of an additive contribution of placental and maternal genetic contributions to PA risk. Participants with placental- and maternal-wGRS in the highest quartile, compared with those in the lowest quartile, had a 15.57-fold (95% CI 3.34-72.60) increased odds of PA. Placental variants in circadian clock-related genes are associated with PA risk; and the association persists after control of genetic variants in the maternal genome. PMID:27186326

  5. De novo transcriptome sequencing and discovery of genes related to copper tolerance in Paeonia ostii.

    PubMed

    Wang, Yanjie; Dong, Chunlan; Xue, Zeyun; Jin, Qijiang; Xu, Yingchun

    2016-01-15

    Paeonia ostii, an important ornamental and medicinal plant, grows normally on copper (Cu) mines with widespread Cu contamination of soils, and it has the ability to lower Cu contents in the Cu-contaminated soils. However, very little molecular information concerned with Cu resistance of P. ostii is available. In this study, high-throughput de novo transcriptome sequencing was carried out for P. ostii with and without Cu treatment using Illumina HiSeq 2000 platform. A total of 77,704 All-unigenes were obtained with a mean length of 710 bp. Of these unigenes, 47,461 were annotated with public databases based on sequence similarities. Comparative transcript profiling allowed the discovery of 4324 differentially expressed genes (DEGs), with 2207 up-regulated and 2117 down-regulated unigenes in Cu-treated library as compared to the control counterpart. Based on these DEGs, Gene Ontology (GO) enrichment analysis indicated Cu stress-relevant terms, such as 'membrane' and 'antioxidant activity'. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis uncovered some important pathways, including 'biosynthesis of secondary metabolites' and 'metabolic pathways'. In addition, expression patterns of 12 selected DEGs derived from quantitative real-time polymerase chain reaction (qRT-PCR) were consistent with their transcript abundance changes obtained by transcriptomic analyses, suggesting that all the 12 genes were authentically involved in Cu tolerance in P. ostii. This is the first report to identify genes related to Cu stress responses in P. ostii, which could offer valuable information on the molecular mechanisms of Cu resistance, and provide a basis for further genomics research on this and related ornamental species for phytoremediation. PMID:26435192

  6. Relations among Parental Alcoholism, Eating Disorders, and Substance Abuse in Nonclinical College Women: Additional Evidence against the Uniformity Myth.

    ERIC Educational Resources Information Center

    Mintz, Laurie B.; And Others

    1995-01-01

    The relationship of parental alcoholism to eating disorder symptomology and substance abuse in a nonclinical sample of college women was examined. In addition, differences among adult children of alcoholics (ACOAs) related to level of distress concerning parental alcohol use was examined. Results add additional evidence to the notion that not all…

  7. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells

    SciTech Connect

    Heneweer, Marjoke . E-mail: M.Heneweer@iras.uu.nl; Muusse, Martine; Berg, Martin van den; Sanderson, J. Thomas

    2005-10-15

    In order to protect consumers from ultraviolet (UV) radiation and enhance light stability of the product, three to eight UV filters are usually added to consumer sunscreen products. High lipophilicity of the UV filters has been shown to cause bioaccumulation in fish and humans, leading to environmental levels of UV filters that are similar to those of PCBs and DDT. In this paper, estrogen-regulated pS2 gene transcription in the human mammary tumor cell line MCF-7 was used as a measure of estrogenicity of four individual UV filters. Since humans are exposed to more than one UV filter at a time, an equipotent binary mixture of 2-hydroxy-4-methoxy-benzophenone (BP-3) and its metabolite 2,4-dihydroxy benzophenone (BP-1), as well as an equipotent multi-component mixture of BP-1, BP-3, octyl methoxy cinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC), were also evaluated for their ability to induce pS2 gene transcription in order to examine additivity. An estrogen receptor-mediated mechanism of action was expected for all UV filters. Therefore, our null-hypothesis was that combined estrogenic responses, measured as increased pS2 gene transcription in MCF-7 cells after exposure to mixtures of UV filters, are additive, according to a concentration-addition model. Not all UV filters produced a full concentration-response curve within the concentration range tested (100 nM-1 {mu}M). Therefore, instead of using EC{sub 50} values for comparison, the concentration at which each compound caused a 50% increase of basal pS2 gene transcription was defined as the C50 value for that compound and used to calculate relative potencies. For comparison, the EC{sub 50} value of a compound is the concentration at which the compound elicits an effect that is 50% of its maximal effect. Individual UV filters increased pS2 gene transcription concentration-dependently with C50 values of 0.12 {mu}M, 0.5 {mu}M, 1.9 {mu}M, and 1.0 {mu}M for BP-1, BP-3, 4-MBC and OMC, respectively. Estradiol

  8. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells.

    PubMed

    Heneweer, Marjoke; Muusse, Martine; van den Berg, Martin; Sanderson, J Thomas

    2005-10-15

    In order to protect consumers from ultraviolet (UV) radiation and enhance light stability of the product, three to eight UV filters are usually added to consumer sunscreen products. High lipophilicity of the UV filters has been shown to cause bioaccumulation in fish and humans, leading to environmental levels of UV filters that are similar to those of PCBs and DDT. In this paper, estrogen-regulated pS2 gene transcription in the human mammary tumor cell line MCF-7 was used as a measure of estrogenicity of four individual UV filters. Since humans are exposed to more than one UV filter at a time, an equipotent binary mixture of 2-hydroxy-4-methoxy-benzophenone (BP-3) and its metabolite 2,4-dihydroxy benzophenone (BP-1), as well as an equipotent multi-component mixture of BP-1, BP-3, octyl methoxy cinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC), were also evaluated for their ability to induce pS2 gene transcription in order to examine additivity. An estrogen receptor-mediated mechanism of action was expected for all UV filters. Therefore, our null-hypothesis was that combined estrogenic responses, measured as increased pS2 gene transcription in MCF-7 cells after exposure to mixtures of UV filters, are additive, according to a concentration-addition model. Not all UV filters produced a full concentration-response curve within the concentration range tested (100 nM-1 microM). Therefore, instead of using EC50 values for comparison, the concentration at which each compound caused a 50% increase of basal pS2 gene transcription was defined as the C50 value for that compound and used to calculate relative potencies. For comparison, the EC50 value of a compound is the concentration at which the compound elicits an effect that is 50% of its maximal effect. Individual UV filters increased pS2 gene transcription concentration-dependently with C50 values of 0.12 microM, 0.5 microM, 1.9 microM, and 1.0 microM for BP-1, BP-3, 4-MBC and OMC, respectively. Estradiol (E2

  9. Organization of the flaFG gene cluster and identification of two additional genes involved in flagellum biogenesis in Caulobacter crescentus.

    PubMed Central

    Schoenlein, P V; Gallman, L S; Ely, B

    1989-01-01

    In Caulobacter crescentus, mutations have been isolated in more than 30 flagellar genes (fla, flb, and flg) which are required in the cell cycle event of flagellum biogenesis. The flaF and flaG mutations and two newly identified mutations, flbT and flbA (P.V. Schoenlein and B. Ely, J. Bacteriol. 171:000-000, 1989), have been localized to the flaFG region. In this study, the genetic and physical organization of this region was analyzed, using the cloned 4.0-kilobase flaFG region in the recombinant plasmid pPLG727. Plasmid pPLG727 complemented flaF, flaG, flbA, and flbT mutations. Further complementation studies with pPLG727 derivatives indicated that flaF and flbT are unique but overlapping transcription units, whereas flbA and flaG constitute a single transcription unit. To determine the direction of transcription of the putative flbA-flaG operon, the promoterless chloramphenicol transacetylase gene was inserted into various positions in the flbA-flaG region, and merodiploid strains containing these transcriptional fusions were assayed for gene function and expression of chloramphenicol resistance. These studies showed that transcription proceeds from flbA to flaG. To confirm the complementation analysis, Southern analyses were performed on chromosomal DNAs isolated from strains containing insertion and deletion mutations. Taken together, these studies defined the relative gene order at one end of the flaYG flagellar gene cluser as flgL-flaF-flbT-flbA-flaG. PMID:2921244

  10. Feed- and feed additives-related aspects of gut health and development in weanling pigs.

    PubMed

    Pluske, John R

    2013-01-01

    The development of new/different management and feeding strategies to stimulate gut development and health in newly-weaned pigs, in order to improve growth performance while minimizing the use of antimicrobial compounds such as antibiotic growth promotants (AGP) and heavy mineral compounds, is essential for the long-term sustainability of the pig industry. Factors including the sub-optimal intake of nutrients and energy, inappropriate microbiota biomass and (or) balance, immature and compromised immune function, and psychosomatic factors caused by weaning can compromise both the efficiency of digestion and absorption and intestinal barrier function through mucosal damage and alteration of tight junction integrity. As a consequence, pigs at weaning are highly susceptible to pathogenic enteric conditions such as post-weaning diarrhea that may be caused by serotypes of enterotoxigenic Escherichia coli. Many dietary components, e.g., protein, fiber, feed additives and minerals, are known to influence microbial growth in the gastrointestinal tract that in turn can impact upon pig growth and health, although the relationships between these are sometimes not necessarily apparent or obvious. In a world climate of increased scrutiny over the use of antibiotics per se in pig production, certain feed additives are seen as alternatives/replacements to antibiotics, and have evolved in some cases to have important roles in everyday commercial pig nutrition. Nevertheless and in general, there remains inconsistency and variability in the efficacy of some feed additives and in cases of severe disease outbreaks, for example, therapeutic antibiotics and/or heavy minerals such as zinc oxide (ZnO) are generally relied upon. If feed ingredients and (or) feed additives are to be used with greater regularity and reliability, then it is necessary to better understand the mechanisms whereby antibiotics and minerals such as ZnO influence animal physiology, in conjunction with the use of

  11. Feed- and feed additives-related aspects of gut health and development in weanling pigs

    PubMed Central

    2013-01-01

    The development of new/different management and feeding strategies to stimulate gut development and health in newly-weaned pigs, in order to improve growth performance while minimizing the use of antimicrobial compounds such as antibiotic growth promotants (AGP) and heavy mineral compounds, is essential for the long-term sustainability of the pig industry. Factors including the sub-optimal intake of nutrients and energy, inappropriate microbiota biomass and (or) balance, immature and compromised immune function, and psychosomatic factors caused by weaning can compromise both the efficiency of digestion and absorption and intestinal barrier function through mucosal damage and alteration of tight junction integrity. As a consequence, pigs at weaning are highly susceptible to pathogenic enteric conditions such as post-weaning diarrhea that may be caused by serotypes of enterotoxigenic Escherichia coli. Many dietary components, e.g., protein, fiber, feed additives and minerals, are known to influence microbial growth in the gastrointestinal tract that in turn can impact upon pig growth and health, although the relationships between these are sometimes not necessarily apparent or obvious. In a world climate of increased scrutiny over the use of antibiotics per se in pig production, certain feed additives are seen as alternatives/replacements to antibiotics, and have evolved in some cases to have important roles in everyday commercial pig nutrition. Nevertheless and in general, there remains inconsistency and variability in the efficacy of some feed additives and in cases of severe disease outbreaks, for example, therapeutic antibiotics and/or heavy minerals such as zinc oxide (ZnO) are generally relied upon. If feed ingredients and (or) feed additives are to be used with greater regularity and reliability, then it is necessary to better understand the mechanisms whereby antibiotics and minerals such as ZnO influence animal physiology, in conjunction with the use of

  12. Problems Related to the Use of Food Additives in the United States

    PubMed Central

    Oser, Bernard L.

    1966-01-01

    Major problems encountered by enforcement agencies and by regulated industries, respectively, in implementing and conforming to recent food additive laws are reviewed. Decisions as to which substances fall within the broad terms of the legal definition, and which escape by virtue of “generally recognized as safe” (GRAS) status, are often difficult and complex. Distinctions cannot be made solely on the basis of whether substances are old or new, natural or synthetic. Registration of pesticides on a “no residue” basis and establishment of “zero tolerances” for food additives have created an anomalous situation as a result of improvements in sensitivity of analytical techniques which revealed the presence of minute amounts of substances where none were believed to exist. A solution has been recommended by a specially appointed committee of the National Academy of Sciences-National Research Council (U.S.A.). Enforcement of the new food additive laws warrants revision of present labelling requirements to provide for designating chemical ingredients by functional categories rather than by confusing chemical terminology.

  13. Calcitonin Gene-Related Peptide: Key Regulator of Cutaneous Immunity

    PubMed Central

    Granstein, Richard D.; Wagner, John A.; Stohl, Lori L.; Ding, Wanhong

    2014-01-01

    Calcitonin gene-related peptide (CGRP) has been viewed as a neuropeptide and vasodilator. However, CGRP is more appropriately thought of as a pleiotropic signaling molecule. Indeed, CGRP has key regulatory functions on immune and inflammatory processes within the skin. CGRP-containing nerves are intimately associated with epidermal LCs and CGRP has profound regulatory effects on Langerhans cell antigen-presenting capability. When LCs are exposed to CGRP in vitro, their ability to present antigen for in vivo priming of naïve mice or elicitation of delayed-type hypersensitivity is inhibited in at least some situations. Administration of CGRP intradermally inhibits acquisition of immunity to Th1-dominant haptens applied to the injected site while augmenting immunity to Th2-dominant haptens, although the cellular targets of activity in these experiments remains unclear. Although CGRP can be a pro-inflammatory agent, several studies have demonstrated that administration of CGRP can inhibit the elicitation of inflammation by inflammatory stimuli in vivo. In this regard, CGRP inhibits the release of certain chemokines by stimulated endothelial cells. This is likely to be physiologically relevant since cutaneous blood vessels are innervated by sensory nerves. Exciting new studies suggest a significant role for CGRP in the pathogenesis of psoriasis and, most strikingly, that CGRP inhibit the ability of LCs to transmit the human immunodeficiency virus 1 to T lymphocytes. A more complete understanding of the role of CGRP in the skin immune system may lead to new and novel approaches for the therapy of immune mediated skin disorders. PMID:25534428

  14. Identification of Immunity-related Genes in Arabidopsis and Cassava Using Genomic Data

    PubMed Central

    Leal, Luis Guillermo; Perez, Álvaro; Quintero, Andrés; Bayona, Ángela; Ortiz, Juan Felipe; Gangadharan, Anju; Mackey, David; López, Camilo; López-Kleine, Liliana

    2013-01-01

    Recent advances in genomic and post-genomic technologies have provided the opportunity to generate a previously unimaginable amount of information. However, biological knowledge is still needed to improve the understanding of complex mechanisms such as plant immune responses. Better knowledge of this process could improve crop production and management. Here, we used holistic analysis to combine our own microarray and RNA-seq data with public genomic data from Arabidopsis and cassava in order to acquire biological knowledge about the relationships between proteins encoded by immunity-related genes (IRGs) and other genes. This approach was based on a kernel method adapted for the construction of gene networks. The obtained results allowed us to propose a list of new IRGs. A putative function in the immunity pathway was predicted for the new IRGs. The analysis of networks revealed that our predicted IRGs are either well documented or recognized in previous co-expression studies. In addition to robust relationships between IRGs, there is evidence suggesting that other cellular processes may be also strongly related to immunity. PMID:24316329

  15. Discovering Implicit Entity Relation with the Gene-Citation-Gene Network

    PubMed Central

    Song, Min; Han, Nam-Gi; Kim, Yong-Hwan; Ding, Ying; Chambers, Tamy

    2013-01-01

    In this paper, we apply the entitymetrics model to our constructed Gene-Citation-Gene (GCG) network. Based on the premise there is a hidden, but plausible, relationship between an entity in one article and an entity in its citing article, we constructed a GCG network of gene pairs implicitly connected through citation. We compare the performance of this GCG network to a gene-gene (GG) network constructed over the same corpus but which uses gene pairs explicitly connected through traditional co-occurrence. Using 331,411 MEDLINE abstracts collected from 18,323 seed articles and their references, we identify 25 gene pairs. A comparison of these pairs with interactions found in BioGRID reveal that 96% of the gene pairs in the GCG network have known interactions. We measure network performance using degree, weighted degree, closeness, betweenness centrality and PageRank. Combining all measures, we find the GCG network has more gene pairs, but a lower matching rate than the GG network. However, combining top ranked genes in both networks produces a matching rate of 35.53%. By visualizing both the GG and GCG networks, we find that cancer is the most dominant disease associated with the genes in both networks. Overall, the study indicates that the GCG network can be useful for detecting gene interaction in an implicit manner. PMID:24358368

  16. Discovering implicit entity relation with the gene-citation-gene network.

    PubMed

    Song, Min; Han, Nam-Gi; Kim, Yong-Hwan; Ding, Ying; Chambers, Tamy

    2013-01-01

    In this paper, we apply the entitymetrics model to our constructed Gene-Citation-Gene (GCG) network. Based on the premise there is a hidden, but plausible, relationship between an entity in one article and an entity in its citing article, we constructed a GCG network of gene pairs implicitly connected through citation. We compare the performance of this GCG network to a gene-gene (GG) network constructed over the same corpus but which uses gene pairs explicitly connected through traditional co-occurrence. Using 331,411 MEDLINE abstracts collected from 18,323 seed articles and their references, we identify 25 gene pairs. A comparison of these pairs with interactions found in BioGRID reveal that 96% of the gene pairs in the GCG network have known interactions. We measure network performance using degree, weighted degree, closeness, betweenness centrality and PageRank. Combining all measures, we find the GCG network has more gene pairs, but a lower matching rate than the GG network. However, combining top ranked genes in both networks produces a matching rate of 35.53%. By visualizing both the GG and GCG networks, we find that cancer is the most dominant disease associated with the genes in both networks. Overall, the study indicates that the GCG network can be useful for detecting gene interaction in an implicit manner. PMID:24358368

  17. Identification of Reproduction-Related Gene Polymorphisms Using Whole Transcriptome Sequencing in the Large White Pig Population

    PubMed Central

    Fischer, Daniel; Laiho, Asta; Gyenesei, Attila; Sironen, Anu

    2015-01-01

    Recent developments in high-throughput sequencing techniques have enabled large-scale analysis of genetic variations and gene expression in different tissues and species, but gene expression patterns and genetic variations in livestock are not well-characterized. In this study, we have used high-throughput transcriptomic sequencing of the Finnish Large White to identify gene expression patterns and coding polymorphisms within the breed in the testis and oviduct. The main objective of this study was to identify polymorphisms within genes that are highly and specifically expressed in male and/or female reproductive organs. The differential expression (DE) analysis underlined 1234 genes highly expressed in the testis and 1501 in the oviduct. Furthermore, we used a novel in-house R-package hoardeR for the identification of novel genes and their orthologs, which underlined 55 additional DE genes based on orthologs in the human, cow, and sheep. Identification of polymorphisms in the dataset resulted in a total of 29,973 variants, of which 10,704 were known coding variants. Fifty-seven nonsynonymous SNPs were present among genes with high expression in the testis and 67 were present in the oviduct, underlining possible influential genes for reproduction traits. Seven genes (PGR, FRAS1, TCF4, ADAT1, SPAG6, PIWIL2, and DNAH8) with polymorphisms were highlighted as reproduction-related based on their biological function. The expression and SNPs of these genes were confirmed using RT-PCR and Sanger sequencing. The identified nonsynonymous mutations within genes highly expressed in the testis or oviduct provide a list of candidate genes for reproduction traits within the pig population and enable identification of biomarkers for sow and boar fertility. PMID:25917919

  18. Age-related gene expression change of GABAergic system in visual cortex of rhesus macaque.

    PubMed

    Liao, Chenghong; Han, Qian; Ma, Yuanye; Su, Bing

    2016-09-30

    Degradation of visual function is a common phenomenon during aging and likely mediated by change in the impaired central visual pathway. Treatment with GABA or its agonist could recover the ability of visual neurons in the primary visual cortex of senescent macaques. However, little is known about how GABAergic system change is related to the aged degradation of visual function in nonhuman primate. With the use of quantitative PCR method, we measured the expression change of 24 GABA related genes in the primary visual cortex (Brodmann's 17) of different age groups. In this study, both of mRNA and protein of glutamic acid decarboxylase (GAD65) were measured by real-time RT-PCR and Western blot, respectively. Results revealed that the level of GAD65 message was not significantly altered, but the proteins were significantly decreased in the aged monkey. As GAD65 plays an important role in GABA synthesis, the down-regulation of GAD65 protein was likely the key factor leading to the observed GABA reduction in the primary visual cortex of the aged macaques. In addition, 7 of 14 GABA receptor genes were up-regulated and one GABA receptor gene was significantly reduced during aging process even after Banjamini correction for multiple comparisons (P<0.05). These results suggested that the dysregulation of GAD65 protein might contribute to some age-related neural visual dysfunctions and most of GABA receptor genes induce a clear indication of compensatory effect for the reduced GABA release in the healthy aged monkey cortex. PMID:27196061

  19. Gibberellin-induced expression of Fe uptake-related genes in Arabidopsis.

    PubMed

    Matsuoka, Keita; Furukawa, Jun; Bidadi, Haniyeh; Asahina, Masashi; Yamaguchi, Shinjiro; Satoh, Shinobu

    2014-01-01

    In dicots, iron (Fe) is acquired from the soil by IRT1 (IRON-REGULATED TRANSPORTER 1) and FRO2 (FERRIC REDUCTION OXIDASE 2) that are localized at the root epidermis. IRT1 and FRO2 expression is induced by local and systemic signals under Fe-deficient conditions in Arabidopsis thaliana. In this study, the expression of IRT1, FRO2, bHLH038 and bHLH39 (the latter two of which control IRT1 and FRO2 expression) was promoted by GA4 treatment of gibberellin (GA) deficient ga3ox1 ga3ox2 mutants. In contrast, the expression of FIT, which encodes a transcription factor necessary for IRT1 and FRO2 induction under Fe deficiency, was not induced by the application of GA4. The induction of those genes triggered by shoot-applied GA4 was observed, even in the fit-2 mutant which had reduced endogenous GA levels caused by treatment with paclobutrazol (PBZ), a GA biosynthesis inhibitor. These results suggested that FIT was not a key regulator in the GA responses under Fe-sufficient conditions. On the other hand, among Fe uptake-related genes, the expression of IRT1, bHLH038 and bHLH39 was lower in ga3ox1 ga3ox2 compared with the wild type (WT) under Fe-sufficient conditions, but the expression of all Fe uptake-related genes decreased under Fe-deficient conditions. Additionally, the PBZ treatment decreased IRT1 expression in the WT under Fe-deficient conditions, but not in the fit-2 mutant. These data suggest the contribution of GA to the induction of Fe uptake-related genes under Fe-sufficient and Fe-deficient conditions, possibly in FIT-independent and FIT-dependent manners, respectively. PMID:24192296

  20. 36 CFR 1237.14 - What are the additional scheduling requirements for audiovisual, cartographic, and related records?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... creation (see also 36 CFR part 1235). See § 1235.42 of this subchapter for specifications and standards for... scheduling requirements for audiovisual, cartographic, and related records? 1237.14 Section 1237.14 Parks..., CARTOGRAPHIC, AND RELATED RECORDS MANAGEMENT § 1237.14 What are the additional scheduling requirements...

  1. 26 CFR 1.6033-3 - Additional provisions relating to private foundations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... foundations. 1.6033-3 Section 1.6033-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... provisions relating to private foundations. (a) In general. The foundation managers (as defined in section... treated as) a private foundation (as defined in section 509) the assets of which are at least $5,000...

  2. 26 CFR 1.6033-3 - Additional provisions relating to private foundations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... foundations. 1.6033-3 Section 1.6033-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... provisions relating to private foundations. (a) In general. The foundation managers (as defined in section... treated as) a private foundation (as defined in section 509) the assets of which are at least $5,000...

  3. 26 CFR 1.6033-3 - Additional provisions relating to private foundations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... foundations. 1.6033-3 Section 1.6033-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... provisions relating to private foundations. (a) In general. The foundation managers (as defined in section... treated as) a private foundation (as defined in section 509) the assets of which are at least $5,000...

  4. 26 CFR 1.6033-3 - Additional provisions relating to private foundations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... foundations. 1.6033-3 Section 1.6033-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... provisions relating to private foundations. (a) In general. The foundation managers (as defined in section... treated as) a private foundation (as defined in section 509) the assets of which are at least $5,000...

  5. EFFECT OF RELATIVE HUMIDITY AND ADDITIVES ON THE REACTION OF SULFUR DIOXIDE WITH CALCIUM HYDROXIDE

    EPA Science Inventory

    The paper gives results of a study of the reaction of SO2 with Ca(OH)2 at conditions similar to those of commercial-scale bag filters: 19-74 percent relative humidity (RH), 30.4-95 C, and 300-4000 ppm SO2. The study was carried out in a bench-scale reactor with powder reagent Ca(...

  6. The clustering of functionally related genes contributes to CNV-mediated disease

    PubMed Central

    Andrews, Tallulah; Honti, Frantisek; Pfundt, Rolph; de Leeuw, Nicole; Hehir-Kwa, Jayne; Vulto-van Silfhout, Anneke; de Vries, Bert; Webber, Caleb

    2015-01-01

    Clusters of functionally related genes can be disrupted by a single copy number variant (CNV). We demonstrate that the simultaneous disruption of multiple functionally related genes is a frequent and significant characteristic of de novo CNVs in patients with developmental disorders (P = 1 × 10−3). Using three different functional networks, we identified unexpectedly large numbers of functionally related genes within de novo CNVs from two large independent cohorts of individuals with developmental disorders. The presence of multiple functionally related genes was a significant predictor of a CNV's pathogenicity when compared to CNVs from apparently healthy individuals and a better predictor than the presence of known disease or haploinsufficient genes for larger CNVs. The functionally related genes found in the de novo CNVs belonged to 70% of all clusters of functionally related genes found across the genome. De novo CNVs were more likely to affect functional clusters and affect them to a greater extent than benign CNVs (P = 6 × 10−4). Furthermore, such clusters of functionally related genes are phenotypically informative: Different patients possessing CNVs that affect the same cluster of functionally related genes exhibit more similar phenotypes than expected (P < 0.05). The spanning of multiple functionally similar genes by single CNVs contributes substantially to how these variants exert their pathogenic effects. PMID:25887030

  7. Transcriptome profiling analysis of naked carp (Gymnocypris przewalskii) provides insights into the immune-related genes in highland fish.

    PubMed

    Tong, Chao; Zhang, Cunfang; Zhang, Renyi; Zhao, Kai

    2015-10-01

    The naked carp, Gymnocypris przewalskii, is one of the dominant aquaculture fish species in Qinghai Province, China. Its wild stocks have severely suffered from overfishing, and the farming species are vulnerable to various pathogens infections. Here we report the first immune-related tissues transcriptome of a wild naked carp using a deep sequencing approach. A total of 158,087 unigenes are generated, 2687 gill-specific gene and 3215 kidney-specific genes are identified, respectively. Gene ontology analysis shows that 51,671 unigenes are involved in three major functional categories: biological process, cellular component, and molecular function. Further analysis shows that numerous consensus sequences are homologous to known immune-related genes. Pathways mapping annotate 56,270 unigenes and identify a large number of immune-related pathways. In addition, we focus on the immune-related genes and gene family in Toll-like receptor signaling pathway involved in innate immunity, including toll-like receptors (TLRs), interferon regulatory factors (IRFs), interleukins (ILs) and tumor necrosis factors (TNFs). Eventually, we identify 5 TLRs, 4 IRFs, 3 ILs and 2 TNFs with a completed coding sequence though mining the transcriptome data. Phylogeny analysis shows these genes of naked carp are mostly close to zebrafish. Protein domain and selection pressure analyses together show that all these genes are highly conserved in gene sequence and protein domain structure with other species, and purifying selection underwent in these genes, implied functionally important features are conserved in the genes above. Intriguingly, we detect positive selection signals in naked carp TLR4, and significant divergence occurred among tested species TLR4, suggested that naked carp TLR4 function may be affected. Finally, we identify 23,867 simple sequence repeat (SSR) marks in this transcriptome. Taken together, this study not only contributes a large number of candidate genes in naked carp

  8. Sieve-based relation extraction of gene regulatory networks from biological literature

    PubMed Central

    2015-01-01

    Background Relation extraction is an essential procedure in literature mining. It focuses on extracting semantic relations between parts of text, called mentions. Biomedical literature includes an enormous amount of textual descriptions of biological entities, their interactions and results of related experiments. To extract them in an explicit, computer readable format, these relations were at first extracted manually from databases. Manual curation was later replaced with automatic or semi-automatic tools with natural language processing capabilities. The current challenge is the development of information extraction procedures that can directly infer more complex relational structures, such as gene regulatory networks. Results We develop a computational approach for extraction of gene regulatory networks from textual data. Our method is designed as a sieve-based system and uses linear-chain conditional random fields and rules for relation extraction. With this method we successfully extracted the sporulation gene regulation network in the bacterium Bacillus subtilis for the information extraction challenge at the BioNLP 2013 conference. To enable extraction of distant relations using first-order models, we transform the data into skip-mention sequences. We infer multiple models, each of which is able to extract different relationship types. Following the shared task, we conducted additional analysis using different system settings that resulted in reducing the reconstruction error of bacterial sporulation network from 0.73 to 0.68, measured as the slot error rate between the predicted and the reference network. We observe that all relation extraction sieves contribute to the predictive performance of the proposed approach. Also, features constructed by considering mention words and their prefixes and suffixes are the most important features for higher accuracy of extraction. Analysis of distances between different mention types in the text shows that our choice

  9. RECENT ADDITIONS OF CRITICALITY SAFETY RELATED INTEGRAL BENCHMARK DATA TO THE ICSBEP AND IRPHEP HANDBOOKS

    SciTech Connect

    J. Blair Briggs; Lori Scott; Yolanda Rugama; Enrico Sartori

    2009-09-01

    High-quality integral benchmark experiments have always been a priority for criticality safety. However, interest in integral benchmark data is increasing as efforts to quantify and reduce calculational uncertainties accelerate to meet the demands of future criticality safety needs to support next generation reactor and advanced fuel cycle concepts. The importance of drawing upon existing benchmark data is becoming more apparent because of dwindling availability of critical facilities worldwide and the high cost of performing new experiments. Integral benchmark data from the International Handbook of Evaluated Criticality Safety Benchmark Experiments and the International Handbook of Reactor Physics Benchmark Experiments are widely used. Benchmark data have been added to these two handbooks since the last Nuclear Criticality Safety Division Topical Meeting in Knoxville, Tennessee (September 2005). This paper highlights these additions.

  10. Hot Jupiters with relatives: discovery of additional planets in orbit around WASP-41 and WASP-47

    NASA Astrophysics Data System (ADS)

    Neveu-VanMalle, M.; Queloz, D.; Anderson, D. R.; Brown, D. J. A.; Collier Cameron, A.; Delrez, L.; Díaz, R. F.; Gillon, M.; Hellier, C.; Jehin, E.; Lister, T.; Pepe, F.; Rojo, P.; Ségransan, D.; Triaud, A. H. M. J.; Turner, O. D.; Udry, S.

    2016-02-01

    We report the discovery of two additional planetary companions to WASP-41 and WASP-47. WASP-41 c is a planet of minimum mass 3.18 ± 0.20 MJup and eccentricity 0.29 ± 0.02, and it orbits in 421 ± 2 days. WASP-47 c is a planet of minimum mass 1.24 ± 0.22 MJup and eccentricity 0.13 ± 0.10, and it orbits in 572 ± 7 days. Unlike most of the planetary systems that include a hot Jupiter, these two systems with a hot Jupiter have a long-period planet located at only ~1 au from their host star. WASP-41 is a rather young star known to be chromospherically active. To differentiate its magnetic cycle from the radial velocity effect induced by the second planet, we used the emission in the Hα line and find this indicator well suited to detecting the stellar activity pattern and the magnetic cycle. The analysis of the Rossiter-McLaughlin effect induced by WASP-41 b suggests that the planet could be misaligned, though an aligned orbit cannot be excluded. WASP-47 has recently been found to host two additional transiting super Earths. With such an unprecedented architecture, the WASP-47 system will be very important for understanding planetary migration. Using data collected at ESO's La Silla Observatory, Chile: HARPS on the ESO 3.6 m (Prog ID 087.C-0649 & 089.C-0151), the Swiss Euler Telescope, TRAPPIST, the 1.54-m Danish telescope (Prog CN2013A-159), and at the LCOGT's Faulkes Telescope South.Photometric lightcurve and RV tables are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/586/A93

  11. Retinoic Acid Induced 1, RAI1: A Dosage Sensitive Gene Related to Neurobehavioral Alterations Including Autistic Behavior

    PubMed Central

    Carmona-Mora, Paulina; Walz, Katherina

    2010-01-01

    Genomic structural changes, such as gene Copy Number Variations (CNVs) are extremely abundant in the human genome. An enormous effort is currently ongoing to recognize and catalogue human CNVs and their associations with abnormal phenotypic outcomes. Recently, several reports related neuropsychiatric diseases (i.e. autism spectrum disorders, schizophrenia, mental retardation, behavioral problems, epilepsy) with specific CNV. Moreover, for some conditions, both the deletion and duplication of the same genomic segment are related to the phenotype. Syndromes associated with CNVs (microdeletion and microduplication) have long been known to display specific neurobehavioral traits. It is important to note that not every gene is susceptible to gene dosage changes and there are only a few dosage sensitive genes. Smith-Magenis (SMS) and Potocki-Lupski (PTLS) syndromes are associated with a reciprocal microdeletion and microduplication within chromosome 17p11.2. in humans. The dosage sensitive gene responsible for most phenotypes in SMS has been identified: the Retinoic Acid Induced 1 (RAI1). Studies on mouse models and humans suggest that RAI1 is likely the dosage sensitive gene responsible for clinical features in PTLS. In addition, the human RAI1 gene has been implicated in several neurobehavioral traits as spinocerebellar ataxia (SCA2), schizophrenia and non syndromic autism. In this review we discuss the evidence of RAI1 as a dosage sensitive gene, its relationship with different neurobehavioral traits, gene structure and mutations, and what is known about its molecular and cellular function, as a first step in the elucidation of the mechanisms that relate dosage sensitive genes with abnormal neurobehavioral outcomes. PMID:21629438

  12. Characterization and expression analysis of a Retinoblastoma-related gene from Chinese wild Vitis pseudoreticulata

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Retinoblastoma-related (RBR) genes, a conserved gene family in higher eukaryotes, plays an important role in cell differentiation, development and mammalian cell death in animals; however, little is known about its function in plants. In this study, an RBR gene was isolated from the Chinese wild gr...

  13. Characterization of rainbow trout (Oncorhynchus mykiss) spleen transcriptome and identification of immune-related genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resistance against specific diseases is affecting profitability in fish production systems including rainbow trout. Limited information is known about functions and mechanisms of the immune gene pathways in teleosts. Immunogenomics are powerful tools to determine immune-related genes/gene pathways a...

  14. Evolution in the Fast Lane: Rapidly Evolving Sex-Related Genes in Drosophila

    PubMed Central

    Haerty, Wilfried; Jagadeeshan, Santosh; Kulathinal, Rob J.; Wong, Alex; Ravi Ram, Kristipati; Sirot, Laura K.; Levesque, Lisa; Artieri, Carlo G.; Wolfner, Mariana F.; Civetta, Alberto; Singh, Rama S.

    2007-01-01

    A large portion of the annotated genes in Drosophila melanogaster show sex-biased expression, indicating that sex and reproduction-related genes (SRR genes) represent an appreciable component of the genome. Previous studies, in which subsets of genes were compared among few Drosophila species, have found that SRR genes exhibit unusual evolutionary patterns. Here, we have used the newly released genome sequences from 12 Drosophila species, coupled to a larger set of SRR genes, to comprehensively test the generality of these patterns. Among 2505 SRR genes examined, including ESTs with biased expression in reproductive tissues and genes characterized as involved in gametogenesis, we find that a relatively high proportion of SRR genes have experienced accelerated divergence throughout the genus Drosophila. Several testis-specific genes, male seminal fluid proteins (SFPs), and spermatogenesis genes show lineage-specific bursts of accelerated evolution and positive selection. SFP genes also show evidence of lineage-specific gene loss and/or gain. These results bring us closer to understanding the details of the evolutionary dynamics of SRR genes with respect to species divergence. PMID:18039869

  15. Megakaryocyte- and megakaryocyte precursor–related gene therapies

    PubMed Central

    2016-01-01

    Hematopoietic stem cells (HSCs) can be safely collected from the body, genetically modified, and re-infused into a patient with the goal to express the transgene product for an individual’s lifetime. Hematologic defects that can be corrected with an allogeneic bone marrow transplant can theoretically also be treated with gene replacement therapy. Because some genetic disorders affect distinct cell lineages, researchers are utilizing HSC gene transfer techniques using lineage-specific endogenous gene promoters to confine transgene expression to individual cell types (eg, ITGA2B for inherited platelet defects). HSCs appear to be an ideal target for platelet gene therapy because they can differentiate into megakaryocytes which are capable of forming several thousand anucleate platelets that circulate within blood vessels to establish hemostasis by repairing vascular injury. Platelets play an essential role in other biological processes (immune response, angiogenesis) as well as diseased states (atherosclerosis, cancer, thrombosis). Thus, recent advances in genetic manipulation of megakaryocytes could lead to new and improved therapies for treating a variety of disorders. In summary, genetic manipulation of megakaryocytes has progressed to the point where clinically relevant strategies are being developed for human trials for genetic disorders affecting platelets. Nevertheless, challenges still need to be overcome to perfect this field; therefore, strategies to increase the safety and benefit of megakaryocyte gene therapy will be discussed. PMID:26787735

  16. ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients

    PubMed Central

    Vargas, Teodoro; Moreno-Rubio, Juan; Herranz, Jesús; Cejas, Paloma; Molina, Susana; González-Vallinas, Margarita; Mendiola, Marta; Burgos, Emilio; Aguayo, Cristina; Custodio, Ana B.; Machado, Isidro; Ramos, David; Gironella, Meritxell; Espinosa-Salinas, Isabel; Ramos, Ricardo; Martín-Hernández, Roberto; Risueño, Alberto; De Las Rivas, Javier; Reglero, Guillermo; Yaya, Ricardo; Fernández-Martos, Carlos; Aparicio, Jorge; Maurel, Joan; Feliu, Jaime; de Molina, Ana Ramírez

    2015-01-01

    Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group. PMID:25749516

  17. Understanding the Role of Housekeeping and Stress-Related Genes in Transcription-Regulatory Networks

    NASA Astrophysics Data System (ADS)

    Heath, Allison; Kavraki, Lydia; Balázsi, Gábor

    2008-03-01

    Despite the increasing number of completely sequenced genomes, much remains to be learned about how living cells process environmental information and respond to changes in their surroundings. Accumulating evidence indicates that eukaryotic and prokaryotic genes can be classified in two distinct categories that we will call class I and class II. Class I genes are housekeeping genes, often characterized by stable, noise resistant expression levels. In contrast, class II genes are stress-related genes and often have noisy, unstable expression levels. In this work we analyze the large scale transcription-regulatory networks (TRN) of E. coli and S. cerevisiae and preliminary data on H. sapien. We find that stable, housekeeping genes (class I) are preferentially utilized as transcriptional inputs while stress related, unstable genes (class II) are utilized as transcriptional integrators. This might be the result of convergent evolution that placed the appropriate genes in the appropriate locations within transcriptional networks according to some fundamental principles that govern cellular information processing.

  18. A multigene phylogeny of the fly superfamily Asiloidea (Insecta): Taxon sampling and additional genes reveal the sister-group to all higher flies (Cyclorrhapha).

    PubMed

    Trautwein, Michelle D; Wiegmann, Brian M; Yeates, David K

    2010-09-01

    Asiloidea are a group of 9 lower brachyceran fly families, considered to be the closest relative to the large Metazoan radiation Eremoneura (Cyclorrhapha+Empidoidea). The evidence for asiloid monophyly is limited, and few characters define the relationships between the families of Asiloidea and Eremoneura. Additionally, enigmatic genera, Hilarimorpha and Apystomyia, retain morphological characters of both asiloids and higher flies. We use the nuclear protein-coding gene CAD and 28S rDNA to test the monophyly of Asiloidea and to resolve its relationship to Eremoneura. We explore the effects of taxon sampling on support values and topological stability, the resolving power of additional genes, and hypothesis testing using four-cluster likelihood mapping. We find that: (1) the 'asiloid' genus Apystomyia is sister to Cyclorrhapha, (2) the remaining asiloids are monophyletic at the exclusion of the family Bombyliidae, and (3) our best estimate of relationships places the asiloid flies excluding Bombyliidae as the sister-group to Eremoneura, though high support is lacking. PMID:20399874

  19. Applying the Fisher score to identify Alzheimer's disease-related genes.

    PubMed

    Yang, J; Liu, Y L; Feng, C S; Zhu, G Q

    2016-01-01

    Biologists and scientists can use the data from Alzheimer's disease (AD) gene expression microarrays to mine AD disease-related genes. Because of disadvantages such as small sample sizes, high dimensionality, and a high level of noise, it is difficult to obtain accurate and meaningful biological information from gene expression profiles. In this paper, we present a novel approach for utilizing AD microarray data to identify the morbigenous genes. The Fisher score, a classical feature selection method, is utilized to evaluate the importance of each gene. Genes with a large between-classes variance and small within-class variance are selected as candidate morbigenous genes. The results using an AD dataset show that the proposed approach is effective for gene selection. Satisfactory accuracy can be achieved by using only a small number of selected genes. PMID:27420981

  20. A Hybrid Computational Method for the Discovery of Novel Reproduction-Related Genes

    PubMed Central

    Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Guohua; Huang, Tao; Cai, Yu-Dong

    2015-01-01

    Uncovering the molecular mechanisms underlying reproduction is of great importance to infertility treatment and to the generation of healthy offspring. In this study, we discovered novel reproduction-related genes with a hybrid computational method, integrating three different types of method, which offered new clues for further reproduction research. This method was first executed on a weighted graph, constructed based on known protein-protein interactions, to search the shortest paths connecting any two known reproduction-related genes. Genes occurring in these paths were deemed to have a special relationship with reproduction. These newly discovered genes were filtered with a randomization test. Then, the remaining genes were further selected according to their associations with known reproduction-related genes measured by protein-protein interaction score and alignment score obtained by BLAST. The in-depth analysis of the high confidence novel reproduction genes revealed hidden mechanisms of reproduction and provided guidelines for further experimental validations. PMID:25768094

  1. Fatty Acid Profiles and Stearoyl-CoA Desaturase Gene Expression in Longissimus dorsi Muscle of Growing Lambs Influenced by Addition of Tea Saponins and Soybean Oil

    PubMed Central

    Mao, H. L.; Wang, J. K.; Lin, J.; Liu, J. X.

    2012-01-01

    This study was conducted to determine the effects of dietary addition of tea saponins (TS) and soybean oil (SO) on fatty acid profile and gene expression of stearoyl-CoA desaturase (SCD) in longissimus dorsi (LD) muscle of growing lambs. Thirty-two Huzhou lambs were assigned to four dietary treatments in a 2×2 factorial arrangement with main effects of TS (0 or 3 g/d) and SO (0 or 30 g/kg of diet DM). The diet without additives was considered as NTNS (no TS or SO). After a feeding trial for 60 d, four lambs of each treatment were slaughtered to collect the samples of LD muscle. Percentage of trans-11 vaccenic acid was enhanced (p<0.05) in muscle of lambs fed TS and SO. The proportion of total conjugated linoleic acid (CLA) was increased (p<0.05) by SO, but decreased (p<0.05) by TS in LD muscle. The percentage of total saturated fatty acids in muscle was decreased (p<0.05) by addition of TS and SO, while addition of SO increased (p<0.05) the percentage of total polyunsaturated fatty acids. The ratio of cis-9, trans-11 CLA to tran-11 vaccenic acid was decreased (p<0.05) by TS, but increased (p<0.05) by SO. The same effects were observed in SCD mRNA expression. From these results it is indicated that including TS and SO in the diet of growing lambs affect the fatty acid profiles of LD muscle and that the proportion of cis-9, trans-11 CLA in the muscle influenced by TS and SO may be related to the SCD gene expression. PMID:25049609

  2. Selection of Reference Genes for Gene Expression Studies related to lung injury in a preterm lamb model

    PubMed Central

    Pereira-Fantini, Prue M.; Rajapaksa, Anushi E.; Oakley, Regina; Tingay, David G.

    2016-01-01

    Preterm newborns often require invasive support, however even brief periods of supported ventilation applied inappropriately to the lung can cause injury. Real-time quantitative reverse transcriptase-PCR (qPCR) has been extensively employed in studies of ventilation-induced lung injury with the reference gene 18S ribosomal RNA (18S RNA) most commonly employed as the internal control reference gene. Whilst the results of these studies depend on the stability of the reference gene employed, the use of 18S RNA has not been validated. In this study the expression profile of five candidate reference genes (18S RNA, ACTB, GAPDH, TOP1 and RPS29) in two geographical locations, was evaluated by dedicated algorithms, including geNorm, Normfinder, Bestkeeper and ΔCt method and the overall stability of these candidate genes determined (RefFinder). Secondary studies examined the influence of reference gene choice on the relative expression of two well-validated lung injury markers; EGR1 and IL1B. In the setting of the preterm lamb model of lung injury, RPS29 reference gene expression was influenced by tissue location; however we determined that individual ventilation strategies influence reference gene stability. Whilst 18S RNA is the most commonly employed reference gene in preterm lamb lung studies, our results suggest that GAPDH is a more suitable candidate. PMID:27210246

  3. Identification of Potential Cold-Related Genes in Listeria monocytogenes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes is a foodborne pathogen with the atypical ability to grow at refrigeration temperatures. One approach to identifying genes and proteins involved in growth in the cold is through creation of cold-sensitive mutants by transposon mutagenesis. L. monocytogenes strain 10403S was ra...

  4. R gene expression changes related to Cercospora hydrangeae L.

    PubMed

    Kafantaris, Ioannis; Woodrow, Pasqualina; Carillo, Petronia

    2013-07-01

    Nursery growing as well as common landscape hydrangeas are all susceptible to leaf spot fungus Cercospora hydrangeae. Warm and rainy weather causes the fungal spores to germinate quickly and spread over the plant leaves forming small purple or brown spots. Although Hydrangea plants are not killed by leaf spot, it detracts from the value of plants through the reduction of flowering and plant vigor. The aim of our study was to isolate, characterize and investigate the expression profile of Hydrangea macrophylla resistance (R) gene transcripts under C. hydrangeae fungus infection and examine their evolutionary relationships by phylogenetic analysis. R-genes are thought to be one of the components of the genetic resistance in plants and most of them encode nucleotide binding site-leucine rich repeat (NBS-LRR) proteins. A cDNA-NBS strategy was carried out using as template cDNAs isolated from control and infected plant leaves. The cDNA-NBS profiling gave an excellent bands reproducibility. Twenty new transcripts corresponding to NBS-LRR proteins were identified only in infected plants. The extent of positivity between the aminoacid sequences at NBS region varied from 45 to 90 %, which indicates the diversity among the RGAs. The results of this paper will provide a genomic framework for the further isolation of candidate disease resistance NBS-encoding genes in Hortensia, and contribute to the understanding of the evolutionary mode of NBS-encoding genes in Hydrangeaceae crops. PMID:23644981

  5. Les Liaisons Dangereuses: Cancer-Related Genes and Neurodegenerative Diseases

    NASA Astrophysics Data System (ADS)

    Ghetti, Bernardino; Buonaguro, Franco M.

    2014-07-01

    The following sections are included: * INTRODUCTION * MUTATIONS IN THE CSF1R GENE ASSOCIATED WITH DIFFUSE LEUKOENCEPHALOPATHY WITH SPHEROIDS AND HUMAN CANCERS. * A SPECIAL LINK HAS BEEN SHOWN BETWEEN PTEN AND AD. * ACETYLCHOLINE DEFICIENCY AND PATHOGENESIS OF AD. * MIRNAS AND COMMON PATHWAYS IN CANCER AND NEURODEGENERATIVE DISEASE. * SUMMARY * REFERENCES

  6. Addition by Subtraction: The Relation Between Dropout Rates and School-Level Academic Achievement

    PubMed Central

    GLENNIE, ELIZABETH; BONNEAU, KARA; VANDELLEN, MICHELLE; DODGE, KENNETH A.

    2013-01-01

    Background/Context Efforts to improve student achievement should increase graduation rates. However, work investigating the effects of student-level accountability has consistently demonstrated that increases in the standards for high school graduation are correlated with increases in dropout rates. The most favored explanation for this finding is that high-stakes testing policies that mandate grade repetition and high school exit exams may be the tipping point for students who are already struggling academically. These extra demands may, in fact, push students out of school. Purpose/Objective/Focus This article examines two hypotheses regarding the relation between school-level accountability and dropout rates. The first posits that improvements in school performance lead to improved success for everyone. If school-level accountability systems improve a school for all students, then the proportion of students performing at grade level increases, and the dropout rate decreases. The second hypothesis posits that schools facing pressure to improve their overall accountability score may pursue this increase at the cost of other student outcomes, including dropout rate. Research Design Our approach focuses on the dynamic relation between school-level academic achievement and dropout rates over time—that is, between one year’s achievement and the subsequent year’s dropout rate, and vice versa. This article employs longitudinal data of records on all students in North Carolina public schools over an 8-year period. Analyses employ fixed-effects models clustering schools and districts within years and controls each year for school size, percentage of students who were free/reduced-price lunch eligible, percentage of students who are ethnic minorities, and locale. Findings/Results This study finds partial evidence that improvements in school-level academic performance will lead to improvements (i.e., decreases) in school-level dropout rates. Schools with improved

  7. Differential Expression of Genes of the Calvin-Benson Cycle and its Related Genes During Leaf Development in Rice.

    PubMed

    Yamaoka, Chihiro; Suzuki, Yuji; Makino, Amane

    2016-01-01

    To understand how the machinery for photosynthetic carbon assimilation is formed and maintained during leaf development, changes in the mRNA levels of the Calvin-Benson cycle enzymes, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activase and two key enzymes for sucrose synthesis were determined in rice (Oryza sativa L.). According to the patterns of changes in the mRNA levels, these genes were categorized into three groups. Group 1 included most of the genes involved in the carboxylation and reduction phases of the Calvin-Benson cycle, as well as three genes in the regeneration phase. The mRNA levels increased and reached maxima during leaf expansion and then rapidly declined, although there were some variations in the residual mRNA levels in senescent leaves. Group 2 included a number of genes involved in the regeneration phase, one gene in the reduction phase of the Calvin-Benson cycle and one gene in sucrose synthesis. The mRNA levels increased and almost reached maxima before full expansion and then gradually declined. Group 3 included Rubisco activase, one gene involved in the regeneration phase and one gene in sucrose synthesis. The overall pattern was similar to that in group 2 genes except that the mRNA levels reached maxima after the stage of full expansion. Thus, genes of the Calvin-Benson cycle and its related genes were differentially expressed during leaf development in rice, suggesting that such differential gene expression is necessary for formation and maintenance of the machinery of photosynthetic carbon assimilation. PMID:26615032

  8. Transcriptome-Wide Differential Gene Expression in Bicyclus anynana Butterflies: Female Vision-Related Genes Are More Plastic.

    PubMed

    Macias-Muñoz, Aide; Smith, Gilbert; Monteiro, Antónia; Briscoe, Adriana D

    2016-01-01

    Vision is energetically costly to maintain. Consequently, over time many cave-adapted species downregulate the expression of vision genes or even lose their eyes and associated eye genes entirely. Alternatively, organisms that live in fluctuating environments, with different requirements for vision at different times, may evolve phenotypic plasticity for expression of vision genes. Here, we use a global transcriptomic and candidate gene approach to compare gene expression in the heads of a polyphenic butterfly. Bicyclus anynana have two seasonal forms that display sexual dimorphism and plasticity in eye morphology, and female-specific plasticity in opsin gene expression. Nonchoosy dry season females downregulate opsin expression, consistent with the high physiological cost of vision. To identify other genes associated with sexually dimorphic and seasonally plastic differences in vision, we analyzed RNA-sequencing data from whole head tissues. We identified two eye development genes (klarsicht and warts homologs) and an eye pigment biosynthesis gene (henna) differentially expressed between seasonal forms. By comparing sex-specific expression across seasonal forms, we found that klarsicht, warts, henna, and another eye development gene (domeless) were plastic in a female-specific manner. In a male-only analysis, white (w) was differentially expressed between seasonal forms. Reverse transcription polymerase chain reaction confirmed that warts and white are expressed in eyes only, whereas klarsicht, henna and domeless are expressed in both eyes and brain. We find that differential expression of eye development and eye pigment genes is associated with divergent eye phenotypes in B. anynana seasonal forms, and that there is a larger effect of season on female vision-related genes. PMID:26371082

  9. Transcriptional Profiles of Drought-Related Genes in Modulating Metabolic Processes and Antioxidant Defenses in Lolium multiflorum

    PubMed Central

    Pan, Ling; Zhang, Xinquan; Wang, Jianping; Ma, Xiao; Zhou, Meiliang; Huang, LinKai; Nie, Gang; Wang, Pengxi; Yang, Zhongfu; Li, Ji

    2016-01-01

    Drought is a major environmental stress that limits growth and development of cool-season annual grasses. Drought transcriptional profiles of resistant and susceptible lines were studied to understand the molecular mechanisms of drought tolerance in annual ryegrass (Lolium multiflorum L.). A total of 4718 genes exhibited significantly differential expression in two L. multiflorum lines. Additionally, up-regulated genes associated with drought response in the resistant lines were compared with susceptible lines. Gene ontology enrichment and pathway analyses revealed that genes partially encoding drought-responsive proteins as key regulators were significantly involved in carbon metabolism, lipid metabolism, and signal transduction. Comparable gene expression was used to identify the genes that contribute to the high drought tolerance in resistant lines of annual ryegrass. Moreover, we proposed the hypothesis that short-term drought have a beneficial effect on oxidation stress, which may be ascribed to a direct effect on the drought tolerance of annual ryegrass. Evidence suggests that some of the genes encoding antioxidants (HPTs, GGT, AP, 6-PGD, and G6PDH) function as antioxidant in lipid metabolism and signal transduction pathways, which have indispensable and promoting roles in drought resistance. This study provides the first transcriptome data on the induction of drought-related gene expression in annual ryegrass, especially via modulation of metabolic homeostasis, signal transduction, and antioxidant defenses to improve drought tolerance response to short-term drought stress. PMID:27200005

  10. Whole Exome Sequencing of Distant Relatives in Multiplex Families Implicates Rare Variants in Candidate Genes for Oral Clefts

    PubMed Central

    Bureau, Alexandre; Parker, Margaret M.; Ruczinski, Ingo; Taub, Margaret A.; Marazita, Mary L.; Murray, Jeffrey C.; Mangold, Elisabeth; Noethen, Markus M.; Ludwig, Kirsten U.; Hetmanski, Jacqueline B.; Bailey-Wilson, Joan E.; Cropp, Cheryl D.; Li, Qing; Szymczak, Silke; Albacha-Hejazi, Hasan; Alqosayer, Khalid; Field, L. Leigh; Wu-Chou, Yah-Huei; Doheny, Kimberly F.; Ling, Hua; Scott, Alan F.; Beaty, Terri H.

    2014-01-01

    A dozen genes/regions have been confirmed as genetic risk factors for oral clefts in human association and linkage studies, and animal models argue even more genes may be involved. Genomic sequencing studies should identify specific causal variants and may reveal additional genes as influencing risk to oral clefts, which have a complex and heterogeneous etiology. We conducted a whole exome sequencing (WES) study to search for potentially causal variants using affected relatives drawn from multiplex cleft families. Two or three affected second, third, and higher degree relatives from 55 multiplex families were sequenced. We examined rare single nucleotide variants (SNVs) shared by affected relatives in 348 recognized candidate genes. Exact probabilities that affected relatives would share these rare variants were calculated, given pedigree structures, and corrected for the number of variants tested. Five novel and potentially damaging SNVs shared by affected distant relatives were found and confirmed by Sanger sequencing. One damaging SNV in CDH1, shared by three affected second cousins from a single family, attained statistical significance (P = 0.02 after correcting for multiple tests). Family-based designs such as the one used in this WES study offer important advantages for identifying genes likely to be causing complex and heterogeneous disorders. PMID:24793288

  11. Age-related changes in relative expression stability of commonly used housekeeping genes in selected porcine tissues

    PubMed Central

    2011-01-01

    Background Gene expression analysis using real-time RT-PCR (qRT-PCR) is increasingly important in biological research due to the high-throughput and accuracy of qRT-PCR. For accurate and reliable gene expression analysis, normalization of gene expression data against housekeeping genes or internal control genes is required. The stability of reference genes has a tremendous effect on the results of relative quantification of gene expression by qRT-PCR. The expression stability of reference genes could vary according to tissues, age of individuals and experimental conditions. In the pig however, very little information is available on the expression stability of reference genes. The aim of this research was therefore to develop a new set of reference genes which can be used for normalization of mRNA expression data of genes expressed in varieties of porcine tissues at different ages. Results The mRNA expression stability of nine commonly used reference genes (B2M, BLM, GAPDH, HPRT1, PPIA, RPL4, SDHA, TBP and YWHAZ) was determined in varieties of tissues collected from newborn, young and adult pigs. geNorm, NormFinder and BestKeeper software were used to rank the genes according to their stability. geNorm software revealed that RPL4, PPIA and YWHAZ showed high stability in newborn and adult pigs, while B2M, YWHAZ and SDHA showed high stability in young pigs. In all cases, GAPDH showed the least stability in geNorm. NormFinder revealed that TBP was the most stable gene in newborn and young pigs, while PPIA was most stable in adult pigs. Moreover, geNorm software suggested that the geometric mean of three most stable gene would be the suitable combination for accurate normalization of gene expression study. Conclusions Although, there was discrepancy in the ranking order of reference genes obtained by different analysing software methods, the geometric mean of the RPL4, PPIA and YWHAZ seems to be the most appropriate combination of housekeeping genes for accurate

  12. Ventromedial hypothalamic lesions change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets

    PubMed Central

    Kiba, Takayoshi; Ishigaki, Yasuhito

    2014-01-01

    Studies in normal rats and ob/ob mice indicated that islet neogenesis does not occur in the intact rodent pancreas. We previously reported that ventromedial hypothalamic (VMH) lesions stimulated cell proliferation of rat pancreatic islet B and acinar cells primarily through a cholinergic receptor mechanism and examined how gene families involved in cell proliferation in total pancreatic tissue are regulated after VMH lesions formation. This study examined how gene families involved in cell proliferation in pancreatic islets alone are regulated after VMH lesions formation. Pancreatic islet RNA was extracted, and differences in gene expression profiles between rats at day 3 after VMH lesioning and sham-VMH-lesioned rats were investigated using DNA microarray and real-time polymerase chain reaction. VMH lesions regulated genes that were involved in functions related to cell cycle and differentiation, growth, binding, apoptosis and morphology in pancreas islets. Real-time polymerase chain reaction also confirmed that gene expression of polo-like kinase 1 (Plk1) and topoisomerase (DNA) II α 170 kDa (Top2a), and stanniocalcin 1 (Stc1) were upregulated at day 3 after the VMH lesions. Ventromedial hypothalamic lesions may change the expression of cell proliferation-related genes and morphology-related genes in rat pancreatic islets. PMID:25658146

  13. Gene-to-gene interaction between sodium channel-related genes in determining the risk of antiepileptic drug resistance.

    PubMed

    Jang, Sin-Young; Kim, Myeong-Kyu; Lee, Kee-Ra; Park, Man-Seok; Kim, Byeong-Chae; Cho, Ki-Hyun; Lee, Min-Cheol; Kim, Yo-Sik

    2009-02-01

    The pathogenesis of antiepileptic drug (AED) resistance is multifactorial. However, most candidate gene association studies typically assess the effects of candidate genes independently of each other, which is partly because of the limitations of the parametric-statistical methods for detecting the gene-to-gene interactions. A total of 200 patients with drug-resistant epilepsy and 200 patients with drug-responsive epilepsy were genotyped for 3 representative the single nucleotide polymorphisms (SNPs) of the voltage-gated sodium channel genes (SCN1A, SCN1B, and SCN2A) by polymerase chain reaction and direct sequencing analysis. Besides the typical parametric statistical method, a new statistical method (multifactor dimensionality reduction [MDR]) was used to determine whether gene-to-gene interactions increase the risk of AED resistance. None of the individual genotypes or alleles tested in the present study showed a significant association with AED resistance, regardless of their theoretical functional value. With the MDR method, of three possible 2-locus genotype combinations, the combination of SCN2A-PM with SCN1B-PM was the best model for predicting susceptibility to AED resistance, with a p value of 0.0547. MDR, as an analysis paradigm for investigating multi-locus effects in complex disorders, may be a useful statistical method for determining the role of gene-to-gene interactions in the pathogenesis of AED resistance. PMID:19270815

  14. Identification of genes related to beak deformity of chickens using digital gene expression profiling.

    PubMed

    Bai, Hao; Zhu, Jing; Sun, Yanyan; Liu, Ranran; Liu, Nian; Li, Dongli; Wen, Jie; Chen, Jilan

    2014-01-01

    Frequencies of up to 3% of beak deformity (normally a crossed beak) occur in some indigenous chickens in China, such as and Beijing-You. Chickens with deformed beaks have reduced feed intake, growth rate, and abnormal behaviors. Beak deformity represents an economic as well as an animal welfare problem in the poultry industry. Because the genetic basis of beak deformity remains incompletely understood, the present study sought to identify important genes and metabolic pathways involved in this phenotype. Digital gene expression analysis was performed on deformed and normal beaks collected from Beijing-You chickens to detect global gene expression differences. A total of >11 million cDNA tags were sequenced, and 5,864,499 and 5,648,877 clean tags were obtained in the libraries of deformed and normal beaks, respectively. In total, 1,156 differentially expressed genes (DEG) were identified in the deformed beak with 409 being up-regulated and 747 down-regulated in the deformed beaks. qRT-PCR using eight genes was performed to verify the results of DGE profiling. Gene ontology (GO) analysis highlighted that genes of the keratin family on GGA25 were abundant among the DEGs. Pathway analysis showed that many DEGs were linked to the biosynthesis of unsaturated fatty acids and glycerolipid metabolism. Combining the analyses, 11 genes (MUC, LOC426217, BMP4, ACAA1, LPL, ALDH7A1, GLA, RETSAT, SDR16C5, WWOX, and MOGAT1) were highlighted as potential candidate genes for beak deformity in chickens. Some of these genes have been identified previously, while others have unknown function with respect to thus phenotype. To the best of our knowledge, this is the first genome-wide study to investigate the transcriptome differences in the deformed and normal beaks of chickens. The DEGs identified here are worthy of further functional characterization. PMID:25198128

  15. Early and sustained altered expression of aging-related genes in young 3xTg-AD mice

    PubMed Central

    Gatta, V; D'Aurora, M; Granzotto, A; Stuppia, L; Sensi, S L

    2014-01-01

    Alzheimer's disease (AD) is a multifactorial neurological condition associated with a genetic profile that is still not completely understood. In this study, using a whole gene microarray approach, we investigated age-dependent gene expression profile changes occurring in the hippocampus of young and old transgenic AD (3xTg-AD) and wild-type (WT) mice. The aim of the study was to assess similarities between aging- and AD-related modifications of gene expression and investigate possible interactions between the two processes. Global gene expression profiles of hippocampal tissue obtained from 3xTg-AD and WT mice at 3 and 12 months of age (m.o.a.) were analyzed by hierarchical clustering. Interaction among transcripts was then studied with the Ingenuity Pathway Analysis (IPA) software, a tool that discloses functional networks and/or pathways associated with sets of specific genes of interest. Cluster analysis revealed the selective presence of hundreds of upregulated and downregulated transcripts. Functional analysis showed transcript involvement mainly in neuronal death and autophagy, mitochondrial functioning, intracellular calcium homeostasis, inflammatory response, dendritic spine formation, modulation of synaptic functioning, and cognitive decline. Thus, overexpression of AD-related genes (such as mutant APP, PS1, and hyperphosphorylated tau, the three genes that characterize our model) appears to favor modifications of additional genes that are involved in AD development and progression. The study also showed overlapping changes in 3xTg-AD at 3 m.o.a. and WT mice at 12 m.o.a., thereby suggesting altered expression of aging-related genes that occurs earlier in 3xTg-AD mice. PMID:24525730

  16. Gene Risk Factors for Age-Related Brain Disorders May Affect Immune System Function

    MedlinePlus

    ... for age-related brain disorders may affect immune system function June 17, 2014 Scientists have discovered gene ... factors for age-related neurological disorders to immune system functions, such as inflammation, offers new insights into ...

  17. A Genome-Wide Screen Indicates Correlation between Differentiation and Expression of Metabolism Related Genes

    PubMed Central

    Shende, Akhilesh; Singh, Anupama; Meena, Anil; Ghosal, Ritika; Ranganathan, Madhav; Bandyopadhyay, Amitabha

    2013-01-01

    Differentiated tissues may be considered as materials with distinct properties. The differentiation program of a given tissue ensures that it acquires material properties commensurate with its function. It may be hypothesized that some of these properties are acquired through production of tissue-specific metabolites synthesized by metabolic enzymes. To establish correlation between metabolism and organogenesis we have carried out a genome-wide expression study of metabolism related genes by RNA in-situ hybridization. 23% of the metabolism related genes studied are expressed in a tissue-restricted but not tissue-exclusive manner. We have conducted the screen on whole mount chicken (Gallus gallus) embryos from four distinct developmental stages to correlate dynamic changes in expression patterns of metabolic enzymes with spatio-temporally unique developmental events. Our data strongly suggests that unique combinations of metabolism related genes, and not specific metabolic pathways, are upregulated during differentiation. Further, expression of metabolism related genes in well established signaling centers that regulate different aspects of morphogenesis indicates developmental roles of some of the metabolism related genes. The database of tissue-restricted expression patterns of metabolism related genes, generated in this study, should serve as a resource for systematic identification of these genes with tissue-specific functions during development. Finally, comprehensive understanding of differentiation is not possible unless the downstream genes of a differentiation cascade are identified. We propose, metabolic enzymes constitute a significant portion of these downstream target genes. Thus our study should help elucidate different aspects of tissue differentiation. PMID:23717462

  18. EpilepsyGene: a genetic resource for genes and mutations related to epilepsy.

    PubMed

    Ran, Xia; Li, Jinchen; Shao, Qianzhi; Chen, Huiqian; Lin, Zhongdong; Sun, Zhong Sheng; Wu, Jinyu

    2015-01-01

    Epilepsy is one of the most prevalent chronic neurological disorders, afflicting about 3.5-6.5 per 1000 children and 10.8 per 1000 elderly people. With intensive effort made during the last two decades, numerous genes and mutations have been published to be associated with the disease. An organized resource integrating and annotating the ever-increasing genetic data will be imperative to acquire a global view of the cutting-edge in epilepsy research. Herein, we developed EpilepsyGene (http://61.152.91.49/EpilepsyGene). It contains cumulative to date 499 genes and 3931 variants associated with 331 clinical phenotypes collected from 818 publications. Furthermore, in-depth data mining was performed to gain insights into the understanding of the data, including functional annotation, gene prioritization, functional analysis of prioritized genes and overlap analysis focusing on the comorbidity. An intuitive web interface to search and browse the diversified genetic data was also developed to facilitate access to the data of interest. In general, EpilepsyGene is designed to be a central genetic database to provide the research community substantial convenience to uncover the genetic basis of epilepsy. PMID:25324312

  19. EpilepsyGene: a genetic resource for genes and mutations related to epilepsy

    PubMed Central

    Ran, Xia; Li, Jinchen; Shao, Qianzhi; Chen, Huiqian; Lin, Zhongdong; Sun, Zhong Sheng; Wu, Jinyu

    2015-01-01

    Epilepsy is one of the most prevalent chronic neurological disorders, afflicting about 3.5–6.5 per 1000 children and 10.8 per 1000 elderly people. With intensive effort made during the last two decades, numerous genes and mutations have been published to be associated with the disease. An organized resource integrating and annotating the ever-increasing genetic data will be imperative to acquire a global view of the cutting-edge in epilepsy research. Herein, we developed EpilepsyGene (http://61.152.91.49/EpilepsyGene). It contains cumulative to date 499 genes and 3931 variants associated with 331 clinical phenotypes collected from 818 publications. Furthermore, in-depth data mining was performed to gain insights into the understanding of the data, including functional annotation, gene prioritization, functional analysis of prioritized genes and overlap analysis focusing on the comorbidity. An intuitive web interface to search and browse the diversified genetic data was also developed to facilitate access to the data of interest. In general, EpilepsyGene is designed to be a central genetic database to provide the research community substantial convenience to uncover the genetic basis of epilepsy. PMID:25324312

  20. The PMP22 gene and its related diseases.

    PubMed

    Li, Jun; Parker, Brett; Martyn, Colin; Natarajan, Chandramohan; Guo, Jiasong

    2013-04-01

    Peripheral myelin protein-22 (PMP22) is primarily expressed in the compact myelin of the peripheral nervous system. Levels of PMP22 have to be tightly regulated since alterations of PMP22 levels by mutations of the PMP22 gene are responsible for >50 % of all patients with inherited peripheral neuropathies, including Charcot-Marie-Tooth type-1A (CMT1A) with trisomy of PMP22, hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of PMP22, and CMT1E with point mutations of PMP22. While overexpression and point-mutations of the PMP22 gene may produce gain-of-function phenotypes, deletion of PMP22 results in a loss-of-function phenotype that reveals the normal physiological functions of the PMP22 protein. In this article, we will review the basic genetics, biochemistry and molecular structure of PMP22, followed by discussion of the current understanding of pathogenic mechanisms involving in the inherited neuropathies with mutations in PMP22 gene. PMID:23224996

  1. The PMP22 Gene and Its Related Diseases

    PubMed Central

    Li, Jun; Parker, Brett; Martyn, Colin; Natarajan, Chandramohan; Guo, Jiasong

    2012-01-01

    Peripheral myelin protein-22 (PMP22) is primarily expressed in the compact myelin of the peripheral nervous system. Levels of PMP22 have to be tightly regulated since alterations of PMP22 levels by mutations of the PMP22 gene are responsible for >50% of all patients with inherited peripheral neuropathies, including Charcot-Marie-Tooth type-1A (CMT1A) with trisomy of PMP22, hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of PMP22, and CMT1E with point mutations of PMP22. While over-expression and point-mutations of the PMP22 gene may produce gain-of-function phenotypes, deletion of PMP22 results in a loss-of-function phenotype that reveals the normal physiological functions of the PMP22 protein. In this article, we will review the basic genetics, biochemistry and molecular structure of PMP22, followed by discussion of the current understanding of pathogenic mechanisms involving in the inherited neuropathies with mutations in PMP22 gene. PMID:23224996

  2. Identification of Cancer Related Genes Using a Comprehensive Map of Human Gene Expression

    PubMed Central

    Lukk, Margus; Xue, Vincent; Parkinson, Helen; Rung, Johan; Brazma, Alvis

    2016-01-01

    Rapid accumulation and availability of gene expression datasets in public repositories have enabled large-scale meta-analyses of combined data. The richness of cross-experiment data has provided new biological insights, including identification of new cancer genes. In this study, we compiled a human gene expression dataset from ∼40,000 publicly available Affymetrix HG-U133Plus2 arrays. After strict quality control and data normalisation the data was quantified in an expression matrix of ∼20,000 genes and ∼28,000 samples. To enable different ways of sample grouping, existing annotations where subjected to systematic ontology assisted categorisation and manual curation. Groups like normal tissues, neoplasmic tissues, cell lines, homoeotic cells and incompletely differentiated cells were created. Unsupervised analysis of the data confirmed global structure of expression consistent with earlier analysis but with more details revealed due to increased resolution. A suitable mixed-effects linear model was used to further investigate gene expression in solid tissue tumours, and to compare these with the respective healthy solid tissues. The analysis identified 1,285 genes with systematic expression change in cancer. The list is significantly enriched with known cancer genes from large, public, peer-reviewed databases, whereas the remaining ones are proposed as new cancer gene candidates. The compiled dataset is publicly available in the ArrayExpress Archive. It contains the most diverse collection of biological samples, making it the largest systematically annotated gene expression dataset of its kind in the public domain. PMID:27322383

  3. Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes

    SciTech Connect

    Elferink, M.G.L.; Olinga, P.; van Leeuwen, E.M.; Bauerschmidt, S.; Polman, J.; Schoonen, W.G.; Heisterkamp, S.H.; Groothuis, G.M.M.

    2011-05-15

    In the process of drug development it is of high importance to test the safety of new drugs with predictive value for human toxicity. A promising approach of toxicity testing is based on shifts in gene expression profiling of the liver. Toxicity screening based on animal liver cells cannot be directly extrapolated to humans due to species differences. The aim of this study was to evaluate precision-cut human liver slices as in vitro method for the prediction of human specific toxicity by toxicogenomics. The liver slices contain all cell types of the liver in their natural architecture. This is important since drug-induced toxicity often is a multi-cellular process. Previously we showed that toxicogenomic analysis of rat liver slices is highly predictive for rat in vivo toxicity. In this study we investigated the levels of gene expression during incubation up to 24 h with Affymetrix microarray technology. The analysis was focused on a broad spectrum of genes related to stress and toxicity, and on genes encoding for phase-I, -II and -III metabolizing enzymes and transporters. Observed changes in gene expression were associated with cytoskeleton remodeling, extracellular matrix and cell adhesion, but for the ADME-Tox related genes only minor changes were observed. PCA analysis showed that changes in gene expression were not associated with age, sex or source of the human livers. Slices treated with acetaminophen showed patterns of gene expression related to its toxicity. These results indicate that precision-cut human liver slices are relatively stable during 24 h of incubation and represent a valuable model for human in vitro hepatotoxicity testing despite the human inter-individual variability.

  4. 78 FR 57505 - World Trade Center Health Program; Addition of Prostate Cancer to the List of WTC-Related Health...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-19

    ...On May 2, 2013, the Administrator of the World Trade Center (WTC) Health Program received a petition (Petition 002) requesting the addition of prostate cancer to the List of WTC-Related Health Conditions (List) covered in the WTC Health Program. In this final rule, the Administrator adds malignant neoplasm of the prostate (prostate cancer) to the List in the WTC Health Program...

  5. [Screening genes related to 'black' character in wu-ding chicken by delta differential display].

    PubMed

    Wu, Ge-Min; Liu, Xiao-Chun; Lou, Yi-Zhou; Shi, Qi-Shun

    2005-01-01

    The 'black' character is a cardinal character of black chicken that is very important to the medical value and economical value of black chicken. The study compared gene expression between black chicken and non-black chicken by delta differential display method, and obtained twenty-nine expressed sequence tags(ESTs) by extraction, amplification, purification, northern blotting, cloning and sequencing of gel-embedded DNA. Of twenty-nine ESTs, eight ESTs have high similarity rate with known gene in chicken-beta-trepomyosin gene, cardiac myosin alkali light chain gene, insertionally activated c-Ha-ras oncogene, fra-2 oncogene, 16S rRNA gene and mitochondrion genome sequence, respectively, with similarity rate 97%,100%, 98%, 98%, 98%, 99%, 99% and 97%. Five ESTs have high similarity rate with human TTN gene, human phosphoglucomutase 5 gene, human or mouse signal recongnition particle 54 kD gene, human or mouse ribonuclease/angiogenin inhibitor gene, respectively, with similarity rate 82%, 82%, 87%, 99% and 99%. Their homologous genes in chicken are still not cloned. Thirteen ESTs are novel gene fragments. Of thirteen ESTs, nine ESTs have high similarity with ESTs in database. Four ESTs have not high similarity with any EST in database. The results of gene expression analysis show that one known gene (insertionally activated c-Ha-ras oncogene) fragment and one novel gene fragment are expressed in all non-black chicken and are not expressed in all black chicken, and that one known gene (signal recongnition particle 54 kD gene) fragment is expressed in all black chicken and is not expressed in all non-black chicken. According to these results, we conclude that the expression of insertionally activated c-Ha-ras oncogene, signal recongnition particle 54 kD gene and one novel gene are related to the 'black' character in chicken. PMID:15715435

  6. Large-scale cDNA transfection screening for genes related to cancer development and progression

    PubMed Central

    Wan, Dafang; Gong, Yi; Qin, Wenxin; Zhang, Pingping; Li, Jinjun; Wei, Lin; Zhou, Xiaomei; Li, Hongnian; Qiu, Xiaokun; Zhong, Fei; He, Liping; Yu, Jian; Yao, Genfu; Jiang, Huiqiu; Qian, Lianfang; Yu, Ye; Shu, Huiqun; Chen, Xianlian; Xu, Huili; Guo, Minglei; Pan, Zhimei; Chen, Yan; Ge, Chao; Yang, Shengli; Gu, Jianren

    2004-01-01

    A large-scale assay was performed by transfecting 29,910 individual cDNA clones derived from human placenta, fetus, and normal liver tissues into human hepatoma cells and 22,926 cDNA clones into mouse NIH 3T3 cells. Based on the results of colony formation in hepatoma cells and foci formation in NIH 3T3 cells, 3,806 cDNA species (8,237 clones) were found to possess the ability of either stimulating or inhibiting cell growth. Among them, 2,836 (6,958 clones) were known genes, 372 (384 clones) were previously unrecognized genes, and 598 (895 clones) were unigenes of uncharacterized structure and function. A comprehensive analysis of the genes and the potential mechanisms for their involvement in the regulation of cell growth is provided. The genes were classified into four categories: I, genes related to the basic cellular mechanism for growth and survival; II, genes related to the cellular microenvironment; III, genes related to host-cell systemic regulation; and IV, genes of miscellaneous function. The extensive growth-regulatory activity of genes with such highly diversified functions suggests that cancer may be related to multiple levels of cellular and systemic controls. The present assay provides a direct genomewide functional screening method. It offers a better understanding of the basic machinery of oncogenesis, including previously undescribed systemic regulatory mechanisms, and also provides a tool for gene discovery with potential clinical applications. PMID:15498874

  7. Identification of a conserved family of Meis1-related homeobox genes.

    PubMed

    Steelman, S; Moskow, J J; Muzynski, K; North, C; Druck, T; Montgomery, J C; Huebner, K; Daar, I O; Buchberg, A M

    1997-02-01

    Meis1 locus was isolated as a common site of viral integration involved in myeloid leukemia in BXH-2 mice. Meis1 encodes a novel homeobox protein belonging to the TALE (three amino acid loop extension) family of homeodomain-containing proteins. The homeodomain of Meis1 is the only known motif within the entire 390-amino-acid protein. Southern blot analyses using the Meis1 homeodomain as a probe revealed the existence family of Meis1-related genes (Mrgs) in several diverged species. In addition, the 3' untranslated region (UTR) Meis1 was remarkably conserved in evolution. To gain a further understanding of the role Meis1 plays in leukemia and development, as well as to identify conserved regions of the protein that might reveal function, we cloned and characterized Mrgs from the mouse and human genomes. We report the sequence of Mrg1 and MRG2 as well as their chromosomal locations in murine and human genomes. Both Mrgs share a high degree of sequence identity with the protein coding region of Meis1. We have also cloned the Xenopus laevis ortholog of (XMeis1). Sequence comparison of the murine and Xenopus clones reveals that Meis1 is highly conserved throughout its coding sequence as well as the 3' UTR. Finally, comparison of Meis1 and the closely related Mrgs to known homeoproteins suggests that Meis1 represents a new subfamily of TALE homeobox genes. PMID:9049632

  8. Relative stability of network states in Boolean network models of gene regulation in development.

    PubMed

    Zhou, Joseph Xu; Samal, Areejit; d'Hérouël, Aymeric Fouquier; Price, Nathan D; Huang, Sui

    2016-01-01

    Progress in cell type reprogramming has revived the interest in Waddington's concept of the epigenetic landscape. Recently researchers developed the quasi-potential theory to represent the Waddington's landscape. The Quasi-potential U(x), derived from interactions in the gene regulatory network (GRN) of a cell, quantifies the relative stability of network states, which determine the effort required for state transitions in a multi-stable dynamical system. However, quasi-potential landscapes, originally developed for continuous systems, are not suitable for discrete-valued networks which are important tools to study complex systems. In this paper, we provide a framework to quantify the landscape for discrete Boolean networks (BNs). We apply our framework to study pancreas cell differentiation where an ensemble of BN models is considered based on the structure of a minimal GRN for pancreas development. We impose biologically motivated structural constraints (corresponding to specific type of Boolean functions) and dynamical constraints (corresponding to stable attractor states) to limit the space of BN models for pancreas development. In addition, we enforce a novel functional constraint corresponding to the relative ordering of attractor states in BN models to restrict the space of BN models to the biological relevant class. We find that BNs with canalyzing/sign-compatible Boolean functions best capture the dynamics of pancreas cell differentiation. This framework can also determine the genes' influence on cell state transitions, and thus can facilitate the rational design of cell reprogramming protocols. PMID:26965665

  9. Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.

    PubMed

    Moskow, J J; Bullrich, F; Huebner, K; Daar, I O; Buchberg, A M

    1995-10-01

    Leukemia results from the accumulation of multiple genetic alterations that disrupt the control mechanisms of normal growth and differentiation. The use of inbred mouse strains that develop leukemia has greatly facilitated the identification of genes that contribute to the neoplastic transformation of hematopoietic cells. BXH-2 mice develop myeloid leukemia as a result of the expression of an ecotropic murine leukemia virus that acts as an insertional mutagen to alter the expression of cellular proto-oncogenes. We report the isolation of a new locus, Meis1, that serves as a site of viral integration in 15% of the tumors arising in BXH-2 mice. Meis1 was mapped to a distinct location on proximal mouse chromosome 11, suggesting that it represents a novel locus. Analysis of somatic cell hybrids segregating human chromosomes allowed localization of MEIS1 to human chromosome 2p23-p12, in a region known to contain translocations found in human leukemias. Northern (RNA) blot analysis demonstrated that a Meis1 probe detected a 3.8-kb mRNA present in all BXH-2 tumors, whereas tumors containing integrations at the Meis1 locus expressed an additional truncated transcript. A Meis1 cDNA clone that encoded a novel member of the homeobox gene family was identified. The homeodomain of Meis1 is most closely related to those of the PBX/exd family of homeobox protein-encoding genes, suggesting that Meis1 functions in a similar fashion by cooperative binding to a distinct subset of HOX proteins. Collectively, these results indicate that altered expression of the homeobox gene Meis1 may be one of the events that lead to tumor formation in BXH-2 mice. PMID:7565694

  10. Pathway-focused genetic evaluation of immune and inflammation related genes with chronic fatigue syndrome.

    PubMed

    Rajeevan, Mangalathu S; Dimulescu, Irina; Murray, Janna; Falkenberg, Virginia R; Unger, Elizabeth R

    2015-08-01

    Recent evidence suggests immune and inflammatory alterations are important in chronic fatigue syndrome (CFS). This study was done to explore the association of functionally important genetic variants in inflammation and immune pathways with CFS. Peripheral blood DNA was isolated from 50 CFS and 121 non-fatigued (NF) control participants in a population-based study. Genotyping was performed with the Affymetrix Immune and Inflammation Chip that covers 11K single nucleotide polymorphisms (SNPs) following the manufacturer's protocol. Genotyping accuracy for specific genes was validated by pyrosequencing. Golden Helix SVS software was used for genetic analysis. SNP functional annotation was done using SPOT and GenomePipe programs. CFS was associated with 32 functionally important SNPs: 11 missense variants, 4 synonymous variants, 11 untranslated regulatory region (UTR) variants and 6 intronic variants. Some of these SNPs were in genes within pathways related to complement cascade (SERPINA5, CFB, CFH, MASP1 and C6), chemokines (CXCL16, CCR4, CCL27), cytokine signaling (IL18, IL17B, IL2RB), and toll-like receptor signaling (TIRAP, IRAK4). Of particular interest is association of CFS with two missense variants in genes of complement activation, rs4151667 (L9H) in CFB and rs1061170 (Y402H) in CFH. A 5' UTR polymorphism (rs11214105) in IL18 also associated with physical fatigue, body pain and score for CFS case defining symptoms. This study identified new associations of CFS with genetic variants in pathways including complement activation providing additional support for altered innate immune response in CFS. Additional studies are needed to validate the findings of this exploratory study. PMID:26116897

  11. The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells.

    PubMed

    Rimmerman, Neta; Juknat, Ana; Kozela, Ewa; Levy, Rivka; Bradshaw, Heather B; Vogel, Zvi

    2011-08-01

    Cannabidiol (CBD) is a non-psychoactive plant cannabinoid that is clinically used in a 1:1 mixture with the psychoactive cannabinoid Δ(9)-tetrahydrocannabinol (THC) for the treatment of neuropathic pain and spasticity in multiple sclerosis. Our group previously reported that CBD exerts anti-inflammatory effects on microglial cells. In addition, we found that CBD treatment increases the accumulation of the endocannabinoid N-arachidonoyl ethanolamine (AEA), thus enhancing endocannabinoid signaling. Here we proceeded to investigate the effects of CBD on the modulation of lipid-related genes in microglial cells. Cell viability was tested using FACS analysis, AEA levels were measured using LC/MS/MS, gene array analysis was validated with real-time qPCR, and cytokine release was measured using ELISA. We report that CBD significantly upregulated the mRNAs of the enzymes sterol-O-acyl transferase (Soat2), which synthesizes cholesteryl esters, and of sterol 27-hydroxylase (Cyp27a1). In addition, CBD increased the mRNA of the lipid droplet-associated protein, perilipin2 (Plin2). Moreover, we found that pretreatment of the cells with the cholesterol chelating agent, methyl-β-cyclodextrin (MBCD), reversed the CBD-induced increase in Soat2 mRNA but not in Plin2 mRNA. Incubation with AEA increased the level of Plin2, but not of Soat2 mRNA. Furthermore, MBCD treatment did not affect the reduction by CBD of the LPS-induced release of the proinflammatory cytokine IL-1β. CBD treatment modulates cholesterol homeostasis in microglial cells, and pretreatment with MBCD reverses this effect without interfering with CBD's anti-inflammatory effects. The effects of the CBD-induced increase in AEA accumulation on lipid-gene expression are discussed. PMID:21533611

  12. Circadian rhythm-related genes: implication in autoimmunity and type 1 diabetes.

    PubMed

    Lebailly, B; Boitard, C; Rogner, U C

    2015-09-01

    Recent gene association and functional studies have proven the implication of several circadian rhythm-related genes in diabetes. Diabetes has been related to variation in central circadian regulation and peripheral oscillation. Different transcriptional regulators have been identified. Circadian genes are clearly implicated in metabolic pathways, pancreatic function and in type 2 diabetes. Much less evidence has been shown for the link between circadian regulation and type 1 diabetes. The hypothesis that circadian genes are involved in type 1 diabetes is reinforced by findings that the immune system undergoes circadian variation and that several autoimmune diseases are associated with circadian genes. Recent findings in the non-obese diabetic mouse model pinpoint to specific mechanisms controlling type 1 diabetes by the clock-related gene Arntl2 in the immune system. PMID:26332978

  13. Integrating Genetic and Network Analysis to Characterize Genes Related to Mouse Weight

    PubMed Central

    Zhang, Bin; Wang, Susanna; Plaisier, Christopher; Castellanos, Ruth; Brozell, Alec; Schadt, Eric E; Drake, Thomas A

    2006-01-01

    Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker data from an F2 mouse intercross to examine the large-scale organization of the gene co-expression network in liver, and annotate several gene modules in terms of 22 physiological traits. We identify chromosomal loci (referred to as module quantitative trait loci, mQTL) that perturb the modules and describe a novel approach that integrates network properties with genetic marker information to model gene/trait relationships. Specifically, using the mQTL and the intramodular connectivity of a body weight–related module, we describe which factors determine the relationship between gene expression profiles and weight. Our approach results in the identification of genetic targets that influence gene modules (pathways) that are related to the clinical phenotypes of interest. PMID:16934000

  14. Integrating genetic and network analysis to characterize genes related to mouse weight.

    PubMed

    Ghazalpour, Anatole; Doss, Sudheer; Zhang, Bin; Wang, Susanna; Plaisier, Christopher; Castellanos, Ruth; Brozell, Alec; Schadt, Eric E; Drake, Thomas A; Lusis, Aldons J; Horvath, Steve

    2006-08-18

    Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker data from an F2 mouse intercross to examine the large-scale organization of the gene co-expression network in liver, and annotate several gene modules in terms of 22 physiological traits. We identify chromosomal loci (referred to as module quantitative trait loci, mQTL) that perturb the modules and describe a novel approach that integrates network properties with genetic marker information to model gene/trait relationships. Specifically, using the mQTL and the intramodular connectivity of a body weight-related module, we describe which factors determine the relationship between gene expression profiles and weight. Our approach results in the identification of genetic targets that influence gene modules (pathways) that are related to the clinical phenotypes of interest. PMID:16934000

  15. Co-addition of manure increases the dissipation rates of tylosin A and the numbers of resistance genes in laboratory incubation experiments.

    PubMed

    Li, Qian; Wang, Yan; Zou, Yong-De; Liao, Xin-Di; Liang, Juan-Boo; Xin, Wen; Wu, Yin-Bao

    2015-09-15

    The behavior of veterinary antibiotics in the soil is commonly studied using the following methods to add antibiotics to the soil: (A) adding manure collected from animals fed a diet that includes antibiotics; (B) adding antibiotic-free animal manure spiked with antibiotics; and (C) the direct addition of antibiotics. However, most studies have only used methods (B) and (C) in their research, and few studies have simultaneously compared the different antibiotic addition methods. This study used tylosin A (TYLA) as a model antibiotic to compare the effects of these three commonly used antibiotic addition methods on the dissipation rates of TYLA and the numbers of resistance genes in laboratory incubation experiments. The results showed that the three treatment methods produced similar TYLA degradation trends; however, there were significant differences (P<0.05) in the TYLA degradation half-life (t1/2) among the three methods. The half-life of TYLA degradation in treatments A, B and C was 2.44 ± 0.04, 1.21 ± 0.03 and 5.13 ± 0.11 days, respectively. The presence of manure resulted in a higher electrical conductivity (EC), higher relative abundance of Citrobacter amalonaticus, higher macrolide resistant gene (ermB, ermF and ermT) count and lower ecological toxicity in the soil, which could partially explain the higher TYLA degradation rate in the treatments containing manure. The higher degradation rate of TYLA in treatment B when compared to treatment A could be due to the lower concentrations of tylosin B (TYLB) and tylosin D (TYLD). The main route for veterinary antibiotics to enter the soil is via the manure of animals that have been administered antibiotics. Therefore, the more appropriate method to study the degradation and ecotoxicity of antibiotic residues in the soil is by using manure from animals fed/administered the particular antibiotic rather than by adding the antibiotic directly to the soil. PMID:25958362

  16. Virus-induced gene silencing of fiber-related genes in cotton.

    PubMed

    Tuttle, John R; Haigler, Candace H; Robertson, Dominique Niki

    2015-01-01

    Virus-Induced Gene Silencing (VIGS) is a useful method for transient downregulation of gene expression in crop plants. The geminivirus Cotton leaf crumple virus (CLCrV) has been modified to serve as a VIGS vector for persistent gene silencing in cotton. Here the use of Green Fluorescent Protein (GFP) is described as a marker for identifying silenced tissues in reproductive tissues, a procedure that requires the use of transgenic plants. Suggestions are given for isolating and cloning combinations of target and marker sequences so that the total length of inserted foreign DNA is between 500 and 750 bp. Using this strategy, extensive silencing is achieved with only 200-400 bp of sequence homologous to an endogenous gene, reducing the possibility of off-target silencing. Cotyledons can be inoculated using either the gene gun or Agrobacterium and will continue to show silencing throughout fruit and fiber development. CLCrV is not transmitted through seed, and VIGS is limited to genes expressed in the maternally derived seed coat and fiber in the developing seed. This complicates the use of GFP as a marker for VIGS because cotton fibers must be separated from unsilenced tissue in the seed to determine if they are silenced. Nevertheless, fibers from a large number of seeds can be rapidly screened following placement into 96-well plates. Methods for quantifying the extent of silencing using semiquantitative RT-PCR are given. PMID:25740368

  17. Extraction of gene-disease relations from Medline using domain dictionaries and machine learning.

    PubMed

    Chun, Hong-Woo; Tsuruoka, Yoshimasa; Kim, Jin-Dong; Shiba, Rie; Nagata, Naoki; Hishiki, Teruyoshi; Tsujii, Jun'ichi

    2006-01-01

    We describe a system that extracts disease-gene relations from Medline. We constructed a dictionary for disease and gene names from six public databases and extracted relation candidates by dictionary matching. Since dictionary matching produces a large number of false positives, we developed a method of machine learning-based named entity recognition (NER) to filter out false recognitions of disease/gene names. We found that the performance of relation extraction is heavily dependent upon the performance of NER filtering and that the filtering improves the precision of relation extraction by 26.7% at the cost of a small reduction in recall. PMID:17094223

  18. Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling.

    PubMed

    Mariman, Edwin C M; Bouwman, Freek G; Aller, Erik E J G; van Baak, Marleen A; Wang, Ping

    2015-06-01

    The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rate<0.05). Six novel rare deleterious missense variants were found in the genes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling. PMID:25805767

  19. ‘Obesity’ is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism

    PubMed Central

    Wang, Zhengfei; Chen, Zhuo; Xu, Shixia; Ren, Wenhua; Zhou, Kaiya; Yang, Guang

    2015-01-01

    Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that ‘obesity’ might be an indicator of good health for cetaceans. PMID:26381091

  20. Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine-related genes in vitro and in vivo.

    PubMed

    Du, Guizhen; Hu, Jialei; Huang, Hongyu; Qin, Yufeng; Han, Xiumei; Wu, Di; Song, Ling; Xia, Yankai; Wang, Xinru

    2013-02-01

    Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500 µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo. PMID:23074026

  1. Identification of New Candidate Genes and Chemicals Related to Esophageal Cancer Using a Hybrid Interaction Network of Chemicals and Proteins

    PubMed Central

    Liu, Junbao; Li, Li-Peng; He, Yi-Chun; Gao, Ru-Jian; Cai, Yu-Dong; Jiang, Yang

    2015-01-01

    Cancer is a serious disease responsible for many deaths every year in both developed and developing countries. One reason is that the mechanisms underlying most types of cancer are still mysterious, creating a great block for the design of effective treatments. In this study, we attempted to clarify the mechanism underlying esophageal cancer by searching for novel genes and chemicals. To this end, we constructed a hybrid network containing both proteins and chemicals, and generalized an existing computational method previously used to identify disease genes to identify new candidate genes and chemicals simultaneously. Based on jackknife test, our generalized method outperforms or at least performs at the same level as those obtained by a widely used method - the Random Walk with Restart (RWR). The analysis results of the final obtained genes and chemicals demonstrated that they highly shared gene ontology (GO) terms and KEGG pathways with direct and indirect associations with esophageal cancer. In addition, we also discussed the likelihood of selected candidate genes and chemicals being novel genes and chemicals related to esophageal cancer. PMID:26058041

  2. Identification and characterization of T-cell antigen receptor-related genes in phylogenetically diverse vertebrate species.

    PubMed

    Rast, J P; Haire, R N; Litman, R T; Pross, S; Litman, G W

    1995-01-01

    Characterization of the structure, multiplicity, organization, and cell lineage-specific expression of T-cell receptor (TCR) genes of nonmammalian vertebrate species is central to the understanding of the evolutionary origins of rearranging genes of the vertebrate immune system. We recently described a polymerase chain reaction (PCR) strategy that relies on short sequence similarities shared by nearly all vertebrate TCR and immunoglobulin (Ig) variable (V) regions and have used this approach to isolate a TCR beta (TCRB) homolog from a cartilaginous fish. Using these short PCR products as probes in spleen cDNA and genomic libraries, we were able to isolate a variety of unique TCR and TCR-like genes. Here we report the identification and characterization of a chicken TCR gamma (TCRG) homolog, apparent Xenopus and pufferfish TCR alpha (TCRA) homologs, and two horned shark TCR delta (TCRD)-like genes. In addition, we have identified what could be a novel representative of the Ig gene superfamily in the pufferfish. This method of using short, minimally degenerate PCR primers should speed progress in the phylogenetic investigations of the TCR and related genes and lend important insights into both the origins and functions of these unique gene systems. PMID:7642232

  3. Hypospadias and variants in genes related to sex hormone biosynthesis and metabolism

    PubMed Central

    Carmichael, SL; Witte, JS; Ma, C; Lammer, EJ; Shaw, GM

    2013-01-01

    We examined whether variants in genes related to sex hormone biosynthesis and metabolism were associated with hypospadias in humans. We examined 332 relatively common tagSNPs in 20 genes. Analyses included 633 cases (84 mild, 322 moderate, 212 severe, 15 undetermined severity) and 855 population-based non-malformed male controls born in California from 1990–2003. We used logistic regression models to estimate odds ratios (OR) and 95 percent confidence intervals (CI) for each SNP. Several of the 332 studied SNPs had p<0.01: one in CYP3A4, four in HSD17B3, one in HSD3B1, 2 in STARD3 10 in SRD5A2 and seven in STS. In addition, haplotype analyses gave several associations with p<0.01. For HSD17B3, 14-SNP and 5-SNP blocks had ORs of 1.5 (95% CI 1.1, 2.0, p<0.001) and 2.8 (95% CI 1.6, 4.8, p<0.001), respectively. For SRD5A2, 9-SNP, 3-SNP and 8-SNP blocks had ORs of 1.7 (95% CI 1.3, 2.2, p<0.001), 1.4 (95% CI 1.1, 1.8, p=0.008) and 1.5 (95% CI 1.2, 1.9, p=0.002), respectively. Our study indicates that several genes that contribute to sex hormone biosynthesis and metabolism are associated with hypospadias risk. PMID:24281767

  4. Gene-related strain variation of Staphylococcus aureus for homologous resistance response to acid stress.

    PubMed

    Lee, Soomin; Ahn, Sooyeon; Lee, Heeyoung; Kim, Won-Il; Kim, Hwang-Yong; Ryu, Jae-Gee; Kim, Se-Ri; Choi, Kyoung-Hee; Yoon, Yohan

    2014-10-01

    This study investigated the effect of adaptation of Staphylococcus aureus strains to the acidic condition of tomato in response to environmental stresses, such as heat and acid. S. aureus ATCC 13565, ATCC 14458, ATCC 23235, ATCC 27664, and NCCP10826 habituated in tomato extract at 35°C for 24 h were inoculated in tryptic soy broth. The culture suspensions were then subjected to heat challenge or acid challenge at 60°C and pH 3.0, respectively, for 60 min. In addition, transcriptional analysis using quantitative real-time PCR was performed to evaluate the expression level of acid-shock genes, such as clpB, zwf, nuoF, and gnd, from five S. aureus strains after the acid habituation of strains in tomato at 35°C for 15 min and 60 min in comparison with that of the nonhabituated strains. In comparison with the nonhabituated strains, the five tomato-habituated S. aureus strains did not show cross protection to heat, but tomato-habituated S. aureus ATCC 23235 showed acid resistance. In quantitative real-time-PCR analysis, the relative expression levels of acid-shock genes (clpB, zwf, nuoF, and gnd) were increased the most in S. aureus ATCC 23235 after 60 min of tomato habituation, but there was little difference in the expression levels among the five S. aureus strains after 15 min of tomato habituation. These results indicate that the variation of acid resistance of S. aureus is related to the expression of acid-shock genes during acid habituation. PMID:25285500

  5. LIS1 Lissencephaly gene CNS expression: Relation to neuronal migration

    SciTech Connect

    Reiner, O. |; Gal-Gerber, O.; Sapir, T.

    1994-09-01

    Lis1 is the murine gene corresponding to human LIS1 gene involved in Miller-Dieker lissencephaly located on chromosome 17p13.3 as demonstrated by cDNA cloning, sequence analysis and genetic mapping. Lis1 expression was studied in developing mouse brain using in situ hybridization. At embryonic day 15, Lis1 expression was most prominently localized in the neuronal layer of the retina, the developing hippocampus, doral root ganglia, cranial ganglia and the thalamus. At postnatal day 5 a unique pattern of expression was detected in the developing cerebellum. Lis1 was expressed at high levels in the Purkinje cell layer when the granule cells were migrating through the Purkinje cell layer inwards. The expression of Lis1 in Purkinje cells in the adult is markedly reduced. Similarly, Lis1 was expressed in the ontogenetically older layers of the neocortex (layers 5 and 6) where younger neurons have to migrate through to settle in the superficial layers. Thus, at both sites a link between expression and neuronal migration was demonstrated. These studies on the expression pattern of Lis1 could be useful in understanding abnormalities in Miller-Dieker lissencephaly syndrome (MDS) patients.

  6. Isolation and expression analysis of proline metabolism-related genes in Chrysanthemum lavandulifolium.

    PubMed

    Zhang, Mi; Huang, He; Dai, Silan

    2014-03-10

    Proline plays a significant role in plant resistance to abiotic stresses, and its level is determined by a combination of synthesis, catabolism and transport. The primary proteins involved are Δ(1)-pyrroline-5-carboxylate synthetase (P5CS), proline dehydrogenase (PDH) and proline transporter (ProT). To utilise proline metabolism to improve the stress resistance of Chrysanthemum×morifolium, we isolated two P5CS-homologous genes (ClP5CS1 and ClP5CS2), one PDH gene (ClPDH) and four ProT-homologous genes (ClProT1-4) (GenBANK accession numbers: KF743136-KF743142) from Chrysanthemum lavandulifolium, which is closely related to chrysanthemums and exhibits strong resistance to stresses. Expression analysis of these genes in different organs and under various stresses indicated that ClP5CSs showed substantial constitutive expression, while ClPDH was only strongly expressed in the capitulum and was inhibited under most stresses. The expression patterns of four ClProT genes presented characteristics of organ specificity and disparity under stresses. Above all, the expression of ClProT2 was restricted to above-ground organs, especially strong in the capitulum and could be obviously induced by various stress conditions. Promoters of ClPDH and ClProTs contained many cis-acting regulatory elements involved in stress responses and plant growth and development. High levels of free proline were found in flower buds, the capitulum under the non-stress condition and later periods of stress conditions except cold treatment. Interestingly, organ specificity and disparity also exist in the level of free proline under different stress conditions. Our study indicates that ClProTs play significant roles in proline accumulation and stress responses, and that ClProT2 could be used to genetically modify the stress resistance of chrysanthemums. In addition, proline metabolism might be closely related to plant flowering and floral development. PMID:24434369

  7. A functional and phylogenetic comparison of quorum sensing related genes in Brucella melitensis 16M.

    PubMed

    Brambila-Tapia, Aniel Jessica Leticia; Pérez-Rueda, Ernesto

    2014-08-01

    A quorum-sensing (QS) system is involved in Brucella melitensis survival inside the host cell. Two transcriptional regulators identified in B. melitensis, BlxR and VjbR, regulate the expression of virB, an operon required for bacterial intracellular persistence. In this work, 628 genes affected by VjbR and 124 by BlxR were analyzed to gain insights into their functional and taxonomical distributions among the Bacteria and Archaea cellular domains. In this regard, the Cluster of Orthologous Groups (COG) genes and orthologous genes in 789 nonredundant bacterial and archaeal genomes were obtained and compared against a group of randomly selected genes. From these analyses, we found 71 coaffected genes between VjbR and BlxR. In the COG comparison, VjbR activated genes associated with intracellular trafficking, secretion and vesicular transport and defense mechanisms, while BlxR affected genes related to energy production and conversion (with an equal effect) and translation, ribosomal structure and biogenesis, posttranslational modifications and carbohydrate and amino acid metabolism (with a negative effect). When the taxonomical distribution of orthologous genes was evaluated, the VjbR- and BlxR-related genes presented more orthologous genes in Crenarchaeota (Archaea), Firmicutes, and Tenericutes and fewer genes in Proteobacteria than expected by chance. These findings suggest that QS system exert a fine-tuning modulation of gene expression, by which VjbR activates genes related to infection persistence and defense, while BlxR represses general bacterial metabolism for intracellular adaptations. Finally, these affected genes present a degree of presence among Bacteria and Archaea genomes that is different from that expected by chance. PMID:24994008

  8. Identification, Characterization, and Expression Analysis of Cell Wall Related Genes in Sorghum bicolor (L.) Moench, a Food, Fodder, and Biofuel Crop

    PubMed Central

    Rai, Krishan M.; Thu, Sandi W.; Balasubramanian, Vimal K.; Cobos, Christopher J.; Disasa, Tesfaye; Mendu, Venugopal

    2016-01-01

    Biomass based alternative fuels offer a solution to the world's ever-increasing energy demand. With the ability to produce high biomass in marginal lands with low inputs, sorghum has a great potential to meet second-generation biofuel needs. Despite the sorghum crop importance in biofuel and fodder industry, there is no comprehensive information available on the cell wall related genes and gene families (biosynthetic and modification). It is important to identify the cell wall related genes to understand the cell wall biosynthetic process as well as to facilitate biomass manipulation. Genome-wide analysis using gene family specific Hidden Markov Model of conserved domains identified 520 genes distributed among 20 gene families related to biosynthesis/modification of various cell wall polymers such as cellulose, hemicellulose, pectin, and lignin. Chromosomal localization analysis of these genes revealed that about 65% of cell wall related genes were confined to four chromosomes (Chr. 1–4). Further, 56 tandem duplication events involving 169 genes were identified in these gene families which could be associated with expansion of genes within families in sorghum. Additionally, we also identified 137 Simple Sequence Repeats related to 112 genes and target sites for 10 miRNAs in some important families such as cellulose synthase, cellulose synthase-like, and laccases, etc. To gain further insight into potential functional roles, expression analysis of these gene families was performed using publically available data sets in various tissues and under abiotic stress conditions. Expression analysis showed tissue specificity as well as differential expression under abiotic stress conditions. Overall, our study provides a comprehensive information on cell wall related genes families in sorghum which offers a valuable resource to develop strategies for altering biomass composition by plant breeding and genetic engineering approaches.

  9. Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs.

    PubMed

    Steegenga, Wilma T; Boekschoten, Mark V; Lute, Carolien; Hooiveld, Guido J; de Groot, Philip J; Morris, Tiffany J; Teschendorff, Andrew E; Butcher, Lee M; Beck, Stephan; Müller, Michael

    2014-06-01

    Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a causal relationship has yet to be shown. Using genome-wide assays, we analyzed age-induced changes in DNA methylation and their effect on gene expression with and without transient induction with the synthetic transcription modulating agent WY14,643. To demonstrate feasibility of the approach, we isolated peripheral blood mononucleated cells (PBMCs) from five young and five old healthy male volunteers and cultured them with or without WY14,643. Infinium 450K BeadChip and Affymetrix Human Gene 1.1 ST expression array analysis revealed significant differential methylation of at least 5 % (ΔYO > 5 %) at 10,625 CpG sites between young and old subjects, but only a subset of the associated genes were also differentially expressed. Age-related differential methylation of previously reported epigenetic biomarkers of aging including ELOVL2, FHL2, PENK, and KLF14 was confirmed in our study, but these genes did not display an age-related change in gene expression in PBMCs. Bioinformatic analysis revealed that differentially methylated genes that lack an age-related expression change predominantly represent genes involved in carcinogenesis and developmental processes, and expression of most of these genes were silenced in PBMCs. No changes in DNA methylation were found in genes displaying transiently induced changes in gene expression. In conclusion, aging-induced differential methylation often targets developmental genes and occurs mostly without change in gene expression. PMID:24789080

  10. An integrated database of wood-formation related genes in plants.

    PubMed

    Xu, Ting; Ma, Tao; Hu, Quanjun; Liu, Jianquan

    2015-01-01

    Wood, which consists mainly of plant cell walls, is an extremely important resource in daily lives. Genes whose products participate in the processes of cell wall and wood formation are therefore major subjects of plant science research. The Wood-Formation Related Genes database (WFRGdb, http://me.lzu.edu.cn/woodformation/) serves as a data resource center for genes involved in wood formation. To create this database, we collected plant genome data published in other online databases and predicted all cell wall and wood formation related genes using BLAST and HMMER. To date, 47 gene families and 33 transcription factors from 57 genomes (28 herbaceous, 22 woody and 7 non-vascular plants) have been covered and more than 122,000 genes have been checked and recorded. To provide easy access to these data, we have developed several search methods, which make it easy to download targeted genes or groups of genes free of charge in FASTA format. Sequence and phylogenetic analyses are also available online. WFRGdb brings together cell wall and wood formation related genes from all available plant genomes, and provides an integrative platform for gene inquiry, downloading and analysis. This database will therefore be extremely useful for those who focuses on cell wall and wood research. PMID:26078228

  11. Inhibition of Calcitonin Gene-Related Peptide Function: A Promising Strategy for Treating Migraine

    PubMed Central

    Durham, Paul L.

    2011-01-01

    The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine. Serum levels of CGRP, which are elevated during a migraine attack, have been reported to return to normal with alleviation of pain. In addition, CGRP administration has been shown to cause a migraine-like headache in susceptible individuals. Importantly, CGRP receptors are found on many cell types within the trigeminovascular system that are thought to play important roles in controlling inflammatory and nociceptive processes. Based on these findings, it was proposed that blockage of CGRP receptor function and, hence, the physiological effects of CGRP would be effective in aborting a migraine attack. This review will summarize key preclinical data that support the therapeutic potential of using CGRP receptor antagonists or molecules that bind CGRP within the context of current neurovascular theories on migraine pathology. PMID:18808507

  12. Identifying novel resistance genes in rice wild relatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice blast and sheath blight are major fungal diseases of cultivated rice (Oryza sativa L. ) that limit Arkansas rough rice yields and market potential. Resistance to these diseases has been found in rice wild relatives (Oryza spp.) A collection of these wild relatives originating from outside the U...

  13. Genome-Wide Comparative Analysis of Flowering-Related Genes in Arabidopsis, Wheat, and Barley

    PubMed Central

    Peng, Fred Y.; Hu, Zhiqiu; Yang, Rong-Cai

    2015-01-01

    Early flowering is an important trait influencing grain yield and quality in wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) in short-season cropping regions. However, due to large and complex genomes of these species, direct identification of flowering genes and their molecular characterization remain challenging. Here, we used a bioinformatic approach to predict flowering-related genes in wheat and barley from 190 known Arabidopsis (Arabidopsis thaliana (L.) Heynh.) flowering genes. We identified 900 and 275 putative orthologs in wheat and barley, respectively. The annotated flowering-related genes were clustered into 144 orthologous groups with one-to-one, one-to-many, many-to-one, and many-to-many orthology relationships. Our approach was further validated by domain and phylogenetic analyses of flowering-related proteins and comparative analysis of publicly available microarray data sets for in silico expression profiling of flowering-related genes in 13 different developmental stages of wheat and barley. These further analyses showed that orthologous gene pairs in three critical flowering gene families (PEBP, MADS, and BBX) exhibited similar expression patterns among 13 developmental stages in wheat and barley, suggesting similar functions among the orthologous genes with sequence and expression similarities. The predicted candidate flowering genes can be confirmed and incorporated into molecular breeding for early flowering wheat and barley in short-season cropping regions. PMID:26435710

  14. Recombination between elongation factor 1α genes from distantly related archaeal lineages

    PubMed Central

    Inagaki, Yuji; Susko, Edward; Roger, Andrew J.

    2006-01-01

    Homologous recombination (HR) and lateral gene transfer are major processes in genome evolution. The combination of the two processes, HR between genes in different species, has been documented but is thought to be restricted to very similar sequences in relatively closely related organisms. Here we report two cases of interspecific HR in the gene encoding the core translational protein translation elongation factor 1α (EF-1α) between distantly related archaeal groups. Maximum-likelihood sliding window analyses indicate that a fragment of the EF-1α gene from the archaeal lineage represented by Methanopyrus kandleri was recombined into the orthologous gene in a common ancestor of the Thermococcales. A second recombination event appears to have occurred between the EF-1α gene of the genus Methanothermobacter and its ortholog in a common ancestor of the Methanosarcinales, a distantly related euryarchaeal lineage. These findings suggest that HR occurs across a much larger evolutionary distance than generally accepted and affects highly conserved essential “informational” genes. Although difficult to detect by standard whole-gene phylogenetic analyses, interspecific HR in highly conserved genes may occur at an appreciable frequency, potentially confounding deep phylogenetic inference and hypothesis testing. PMID:16537397

  15. Genome-Wide Comparative Analysis of Flowering-Related Genes in Arabidopsis, Wheat, and Barley.

    PubMed

    Peng, Fred Y; Hu, Zhiqiu; Yang, Rong-Cai

    2015-01-01

    Early flowering is an important trait influencing grain yield and quality in wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) in short-season cropping regions. However, due to large and complex genomes of these species, direct identification of flowering genes and their molecular characterization remain challenging. Here, we used a bioinformatic approach to predict flowering-related genes in wheat and barley from 190 known Arabidopsis (Arabidopsis thaliana (L.) Heynh.) flowering genes. We identified 900 and 275 putative orthologs in wheat and barley, respectively. The annotated flowering-related genes were clustered into 144 orthologous groups with one-to-one, one-to-many, many-to-one, and many-to-many orthology relationships. Our approach was further validated by domain and phylogenetic analyses of flowering-related proteins and comparative analysis of publicly available microarray data sets for in silico expression profiling of flowering-related genes in 13 different developmental stages of wheat and barley. These further analyses showed that orthologous gene pairs in three critical flowering gene families (PEBP, MADS, and BBX) exhibited similar expression patterns among 13 developmental stages in wheat and barley, suggesting similar functions among the orthologous genes with sequence and expression similarities. The predicted candidate flowering genes can be confirmed and incorporated into molecular breeding for early flowering wheat and barley in short-season cropping regions. PMID:26435710

  16. Myelination-related genes are associated with decreased white matter integrity in schizophrenia.

    PubMed

    Chavarria-Siles, Ivan; White, Tonya; de Leeuw, Christiaan; Goudriaan, Andrea; Lips, Esther; Ehrlich, Stefan; Turner, Jessica A; Calhoun, Vince D; Gollub, Randy L; Magnotta, Vincent A; Ho, Beng-Choon; Smit, August B; Verheijen, Mark H G; Posthuma, Danielle

    2016-03-01

    Disruptions in white matter (WM) tract structures have been implicated consistently in the pathophysiology of schizophrenia. Global WM integrity--as measured by fractional anisotropy (FA)--is highly heritable and may provide a good endophenotype for genetic studies of schizophrenia. WM abnormalities in schizophrenia are not localized to one specific brain region but instead reflect global low-level decreases in FA coupled with focal abnormalities. In this study, we sought to investigate whether functional gene sets associated with schizophrenia are also associated with WM integrity. We analyzed FA and genetic data from the Mind Research Network Clinical Imaging Consortium to study the effect of multiple oligodendrocyte gene sets on schizophrenia and WM integrity using a functional gene set analysis in 77 subjects with schizophrenia and 104 healthy controls. We found that a gene set involved in myelination was significantly associated with schizophrenia and FA. This gene set includes 17 genes that are expressed in oligodendrocytes and one neuronal gene (NRG1) that is known to regulate myelination. None of the genes within the gene set were associated with schizophrenia or FA individually, suggesting that no single gene was driving the association of the gene set. Our findings support the hypothesis that multiple genetic variants in myelination-related genes contribute to the observed correlation between schizophrenia and decreased WM integrity as measured by FA. PMID:26014434

  17. Bovine gene polymorphisms related to fat deposition and meat tenderness.

    PubMed

    Fortes, Marina R S; Curi, Rogério A; Chardulo, Luis Artur L; Silveira, Antonio C; Assumpção, Mayra E O D; Visintin, José Antonio; de Oliveira, Henrique N

    2009-01-01

    Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP), thyroglobulin (TG) and diacylglycerol O-acyltransferase (DGAT1). A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus), Canchim (5/8 Bos taurus + 3/8 Bos indicus), Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus), Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus) and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus) breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM) procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus. PMID:21637649

  18. Antioxidant response and related gene expression in aged oat seed

    PubMed Central

    Kong, Lingqi; Huo, Heqiang; Mao, Peisheng

    2015-01-01

    To evaluate deterioration of oat seeds during storage, we analyzed oxygen radicals, antioxidant enzyme activity, proline content, and gene transcript levels in oat seeds with different moisture contents (MCs; 4, 16, and 28% w/w) during storage for 0, 6, and 12 months (CK, LT-6, and LT-12 treatments, respectively) at 4°C. The germination percentage decreased significantly with higher seed MCs and longer storage duration. The concentrations of superoxide radical and hydrogen peroxide increased with seed MC increasing. The activities of catalase (CAT), ascorbate peroxidase (APX), and superoxide dismutase (SOD) may have had a complementary or interacting role to scavenge reactive oxygen species. As the storage duration extended, the proline content decreased in seeds with 4 and 16% MC and increased in 28%. These findings suggest that proline played the main role in adaptation to oxidative stress in seeds with higher MC (28%), while antioxidant enzymes played the main role in seeds with lower MCs (4%, 16%). In the gene transcript analyses, SOD1 transcript levels were not consistent with total SOD activity. The transcript levels of APX1 and CAT1 showed similar trends to those of APX and CAT activity. The transcript levels of P5CS1, which encodes a proline biosynthetic enzyme, increased with seed MC increasing in CK. Compared with changing of proline content in seeds stored 12 months, PDH1 transcript levels showed the opposite trend and maintained the lower levels in seeds of 16 and 28% MCs. The transcript level of P5CS1 was significantly affected by MC, and PDH1 could improve stress resistance for seed aging and maintain seed vigor during long-term storage. PMID:25852711

  19. Bovine gene polymorphisms related to fat deposition and meat tenderness

    PubMed Central

    2009-01-01

    Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP), thyroglobulin (TG) and diacylglycerol O-acyltransferase (DGAT1). A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus), Canchim (5/8 Bos taurus + 3/8 Bos indicus), Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus), Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus) and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus) breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM) procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus. PMID:21637649

  20. Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA.

    PubMed

    Sarro, E C; Sullivan, R M; Barr, G

    2014-01-31

    Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpaired odor-shock conditioning for 5 days, which produces deficits in adult behavior and amygdala dysfunction. In adulthood, we used the Light/Dark box test to measure anxiety-related behaviors, measuring the latency to enter the lit area and quantified urination and defecation. The amygdala was then dissected and a microarray analysis was performed to examine changes in gene expression. Animals that had received early unpredictable trauma displayed significantly longer latencies to enter the lit area and more defecation and urination. The microarray analysis revealed over-represented genes related to learning and memory, synaptic transmission and trans-membrane transport. Gene ontology and pathway analysis identified highly represented disease states related to anxiety phenotypes, including social anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and bipolar disorder. Addiction-related genes were also overrepresented in this analysis. Unpredictable shock during early development increased anxiety-like behaviors in adulthood with concomitant changes in genes related to neurotransmission, resulting in gene expression patterns similar to anxiety-related psychiatric disorders. PMID:24240029

  1. Identification of Immunity Related Genes to Study the Physalis peruviana – Fusarium oxysporum Pathosystem

    PubMed Central

    Enciso-Rodríguez, Felix E.; González, Carolina; Rodríguez, Edwin A.; López, Camilo E.; Landsman, David; Barrero, Luz Stella; Mariño-Ramírez, Leonardo

    2013-01-01

    The Cape gooseberry (Physalisperuviana L) is an Andean exotic fruit with high nutritional value and appealing medicinal properties. However, its cultivation faces important phytosanitary problems mainly due to pathogens like Fusarium oxysporum, Cercosporaphysalidis and Alternaria spp. Here we used the Cape gooseberry foliar transcriptome to search for proteins that encode conserved domains related to plant immunity including: NBS (Nucleotide Binding Site), CC (Coiled-Coil), TIR (Toll/Interleukin-1 Receptor). We identified 74 immunity related gene candidates in P. peruviana which have the typical resistance gene (R-gene) architecture, 17 Receptor like kinase (RLKs) candidates related to PAMP-Triggered Immunity (PTI), eight (TIR-NBS-LRR, or TNL) and nine (CC–NBS-LRR, or CNL) candidates related to Effector-Triggered Immunity (ETI) genes among others. These candidate genes were categorized by molecular function (98%), biological process (85%) and cellular component (79%) using gene ontology. Some of the most interesting predicted roles were those associated with binding and transferase activity. We designed 94 primers pairs from the 74 immunity-related genes (IRGs) to amplify the corresponding genomic regions on six genotypes that included resistant and susceptible materials. From these, we selected 17 single band amplicons and sequenced them in 14 F. oxysporum resistant and susceptible genotypes. Sequence polymorphisms were analyzed through preliminary candidate gene association, which allowed the detection of one SNP at the PpIRG-63 marker revealing a nonsynonymous mutation in the predicted LRR domain suggesting functional roles for resistance. PMID:23844210

  2. Identification of immunity related genes to study the Physalis peruviana--Fusarium oxysporum pathosystem.

    PubMed

    Enciso-Rodríguez, Felix E; González, Carolina; Rodríguez, Edwin A; López, Camilo E; Landsman, David; Barrero, Luz Stella; Mariño-Ramírez, Leonardo

    2013-01-01

    The Cape gooseberry (Physalisperuviana L) is an Andean exotic fruit with high nutritional value and appealing medicinal properties. However, its cultivation faces important phytosanitary problems mainly due to pathogens like Fusarium oxysporum, Cercosporaphysalidis and Alternaria spp. Here we used the Cape gooseberry foliar transcriptome to search for proteins that encode conserved domains related to plant immunity including: NBS (Nucleotide Binding Site), CC (Coiled-Coil), TIR (Toll/Interleukin-1 Receptor). We identified 74 immunity related gene candidates in P. peruviana which have the typical resistance gene (R-gene) architecture, 17 Receptor like kinase (RLKs) candidates related to PAMP-Triggered Immunity (PTI), eight (TIR-NBS-LRR, or TNL) and nine (CC-NBS-LRR, or CNL) candidates related to Effector-Triggered Immunity (ETI) genes among others. These candidate genes were categorized by molecular function (98%), biological process (85%) and cellular component (79%) using gene ontology. Some of the most interesting predicted roles were those associated with binding and transferase activity. We designed 94 primers pairs from the 74 immunity-related genes (IRGs) to amplify the corresponding genomic regions on six genotypes that included resistant and susceptible materials. From these, we selected 17 single band amplicons and sequenced them in 14 F. oxysporum resistant and susceptible genotypes. Sequence polymorphisms were analyzed through preliminary candidate gene association, which allowed the detection of one SNP at the PpIRG-63 marker revealing a nonsynonymous mutation in the predicted LRR domain suggesting functional roles for resistance. PMID:23844210

  3. Phytate addition to soil induces changes in the abundance and expression of Bacillus β-propeller phytase genes in the rhizosphere.

    PubMed

    Jorquera, Milko A; Saavedra, Nicolás; Maruyama, Fumito; Richardson, Alan E; Crowley, David E; del C Catrilaf, Rosa; Henriquez, Evelyn J; de la Luz Mora, María

    2013-02-01

    Phytate-mineralizing rhizobacteria (PMR) perform an essential function for the mineralization of organic phosphorus but little is known about their ecology in soils and rhizosphere. In this study, PCR-based methods were developed for detection and quantification of the Bacillus β-propeller phytase (BPP) gene. Experiments were conducted to monitor the presence and persistence of a phytate-mineralizing strain, Bacillus sp. MQH19, after inoculation of soil microcosms and within the rhizosphere. The occurrence of the BPP gene in natural pasture soils from Chilean Andisols was also examined. The results showed that the Bacillus BPP gene was readily detected in sterile and nonsterile microcosms, and that the quantitative PCR (qPCR) methods could be used to monitor changes in the abundance of the BPP gene over time. Our results also show that the addition of phytate to nonsterile soils induced the expression of the BPP gene in the rhizosphere of ryegrass and the BPP gene was detected in all pasture soils sampled. This study shows that phytate addition soils induced changes in the abundance and expression of Bacillus BPP to genes in the rhizosphere and demonstrates that Bacillus BPP gene is cosmopolitan in pasture soils from Chilean Andisols. PMID:22928980

  4. 78 FR 39670 - World Trade Center Health Program; Addition of Prostate Cancer to the List of WTC-Related Health...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ...On May 2, 2013, the Administrator of the World Trade Center (WTC) Health Program received a petition (Petition 002) requesting the addition of prostate cancer to the List of WTC-Related Health Conditions (List) covered in the WTC Health Program. The Administrator has determined to publish a proposed rule adding malignant neoplasm of the prostate (prostate cancer) to the List in the WTC Health......

  5. Identification and characterization of stress resistance related genes of Brassica rapa.

    PubMed

    Ahmed, Nasar Uddin; Park, Jong-In; Jung, Hee-Jeong; Seo, Mi-Suk; Kumar, Thamilarasan Senthil; Lee, In-Ho; Nou, Ill-Sup

    2012-05-01

    Two biotic stress resistance related genes from the full-length cDNA library of Brassica rapa cv. Osome were identified from EST analysis and determined to be pathogenesis-related (PR) 12 Brassica defensin-like family protein (BrDLFP) and PR-10 Brassica Betv1 allergen family protein (BrBetv1AFP) after sequence analysis and homology study with other stress resistance related same family genes. In the expression analysis, both genes expressed in different organs and during all developmental growth stages in healthy plants. Expression of BrDLFP significantly increased and BrBetv1AFP gradually decreased after infection with Pectobacterium carotovorum subsp. carotovorum in Chinese cabbage. Expression of these two genes significantly changed after cold, salt, drought and ABA stress treatments. These two PR genes may therefore be involved in the plant resistance against biotic and abiotic stresses. PMID:22286206

  6. Folate-related gene variants in Irish families affected by neural tube defects

    PubMed Central

    Fisk Green, Ridgely; Byrne, Julianne; Crider, Krista S.; Gallagher, Margaret; Koontz, Deborah; Berry, Robert J.

    2013-01-01

    Periconceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural tube defects and birth defects overall occurred at a higher rate in the maternal lineage compared with the paternal lineage. The goal of this study was to look for evidence for genetic effects that could explain the discrepancy in the occurrence of these birth defects in the maternal vs. paternal lineage. We genotyped blood samples from 322 individuals from NTD-affected Irish families, identified through their membership in spina bifida associations. We looked for differences in distribution in maternal vs. paternal lineages of five genetic polymorphisms: the DHFR 19 bp deletion, MTHFD1 1958G>A, MTHFR 1298A>C, MTHFR 677C>T, and SLC19A1 80A>G. In addition to looking at genotypes individually, we determined the number of genotypes associated with decreased folate metabolism in each relative (“risk genotypes”) and compared the distribution of these genotypes in maternal vs. paternal relatives. Overall, maternal relatives had a higher number of genotypes associated with lower folate metabolism than paternal relatives (p = 0.017). We expected that relatives would share the same risk genotype as the individuals with NTDs and/or their mothers. However, we observed that maternal relatives had an over-abundance of any risk genotype, rather than one specific genotype. The observed genetic effects suggest an epigenetic mechanism in which decreased folate metabolism results in epigenetic alterations related to the increased rate of NTDs and other birth defects seen in the maternal lineage. Future studies on the etiology of NTDs and other birth defects could benefit from including multigenerational extended families, in order to explore potential epigenetic

  7. Immune-related genes associated with intestinal tissue in the sea cucumber Holothuria glaberrima.

    PubMed

    Ramírez-Gómez, Francisco; Ortíz-Pineda, Pablo A; Rojas-Cartagena, Carmencita; Suárez-Castillo, Edna C; García-Arrarás, José E; García-Ararrás, José E

    2008-01-01

    We have analyzed 5,173 expressed sequence tags (ESTs) from three cDNA libraries of normal and regenerating intestinal tissue of the sea cucumber Holothuria glaberrima and found 22 putative immune-related genes. These sequences showed similarities (e-value approx 10(-8)) to genes involved in immune processes or expressed by immune cells. Sequences were analyzed using bioinformatic tools to determine a putative identity. In addition, phylogenetic analyses were performed to find relationships with similar proteins in other organisms. The mRNAs for ten sequences were detected in coelomocytes by using reverse transcription-polymerase chain reaction (RT-PCR). Moreover, five of them showed a significant increase in expression after an LPS challenge, while the other five showed no significant changes. These results show the variety of immune molecules that may be found in holothurians and support the idea that the invertebrate immune system is more than a collection of simple innate responses. Our study also provides new data of importance in deciphering the evolution and development of the immune system. PMID:18092157

  8. Yeast-containing feed additive alters gene expression profiles associated with innate immunity in whole blood of a rodent model.

    PubMed

    Branson, Jennifer A; McLean, Derek J; Forsberg, Neil E; Bobe, Gerd

    2016-05-01

    Feeding a yeast-containing additive (YCA; OmniGen-AF) improves immune responses in ruminant livestock and reduces subsequent production losses. The objective was to identify molecular pathways by which dietary YCA may modify immune responses using a rodent model. Thirty-seven healthy, unchallenged CD rats received a diet containing 0 (control; n = 5, only 28 d), 0.5% (n = 15) or 1% (n = 17) YCA for 7 (n = 4/group), 14 (n = 3 or 4/group), 21 (n = 3 or 4/group) or 28 (n = 5/group) d. At the end of the feeding periods, whole blood was collected and the isolated RNA was analyzed for the expression of 84 genes involved in innate and cell-mediated adaptive immune responses. Three bacterial pattern recognition receptors TLR1 (0.5%: + 2.01; 1%: + 2.38), TLR6 (0.5%: + 2.11; 1%: + 2.34) and NOD2 (0.5%: + 2.32; 1%: + 2.23), two APC surface receptors CD1D1 (0.5%: + 1.75; 1%: + 2.33) and CD80 (0.5%: +2.45; 1%: +3.00), and the cell signaling molecule MAPK8 (0.5%: +1.87; 1%: +2.35) were significantly up-regulated by YCA at both inclusion rates. In conclusion, feeding YCA may potentially increase recognition and responses to bacterial pathogens and T-cell activation and differentiation and thereby maintain health and prevent production losses. PMID:27033362

  9. Physiological basis of tolerance to complete submergence in rice involves genetic factors in addition to the SUB1 gene.

    PubMed

    Singh, Sudhanshu; Mackill, David J; Ismail, Abdelbagi M

    2014-01-01

    Recurring floods in Asia cause poor crop establishment. Yields decline drastically when plants are completely submerged for a few days. Traditional rice cultivars predominate because they have acquired moderate tolerance to flooding but they carry the penalty of inherently lower grain yields. In contrast, modern high-yielding varieties are highly susceptible to flooding. Cultivars with tolerance to complete submergence were recently developed in the background of popular varieties by transferring the submergence tolerance gene SUBMERGENCE1 (SUB1) from the highly tolerant Indian landrace FR13A. The present study evaluated three pairs of Sub1 near-isogenic lines (NILs) together with FR13A and two of its submergence-tolerant derivatives under field conditions to assess the survival and growth processes occurring during submergence and recovery that are associated with SUB1. Under control conditions, the NILs showed similar growth and biomass accumulation, indicating that SUB1 had no apparent effects. Submergence substantially decreased biomass accumulation but with greater reduction in the genotypes lacking SUB1, particularly when submergence was prolonged for 17 days. When submerged, the lines lacking SUB1 showed greater elongation and lower or negative biomass accumulation. Sub1 lines maintained higher chlorophyll concentrations during submergence and lost less non-structural carbohydrates (NSC) after submergence. This indicates that the introgression of SUB1 resulted in better regulation of NSC during submergence and that high pre-submergence NSC is not essential for the submergence tolerance conferred by SUB1. During recovery, chlorophyll degradation was faster in genotypes lacking SUB1 and any surviving plants showed poorer and delayed emergence of tillers and leaves. Sub1 lines restored new leaf and tiller production faster. During submergence, FR13A showed not only slower leaf elongation but also accumulated extra biomass and was able to recover faster than Sub

  10. Physiological basis of tolerance to complete submergence in rice involves genetic factors in addition to the SUB1 gene

    PubMed Central

    Singh, Sudhanshu; Mackill, David J.; Ismail, Abdelbagi M.

    2014-01-01

    Recurring floods in Asia cause poor crop establishment. Yields decline drastically when plants are completely submerged for a few days. Traditional rice cultivars predominate because they have acquired moderate tolerance to flooding but they carry the penalty of inherently lower grain yields. In contrast, modern high-yielding varieties are highly susceptible to flooding. Cultivars with tolerance to complete submergence were recently developed in the background of popular varieties by transferring the submergence tolerance gene SUBMERGENCE1 (SUB1) from the highly tolerant Indian landrace FR13A. The present study evaluated three pairs of Sub1 near-isogenic lines (NILs) together with FR13A and two of its submergence-tolerant derivatives under field conditions to assess the survival and growth processes occurring during submergence and recovery that are associated with SUB1. Under control conditions, the NILs showed similar growth and biomass accumulation, indicating that SUB1 had no apparent effects. Submergence substantially decreased biomass accumulation but with greater reduction in the genotypes lacking SUB1, particularly when submergence was prolonged for 17 days. When submerged, the lines lacking SUB1 showed greater elongation and lower or negative biomass accumulation. Sub1 lines maintained higher chlorophyll concentrations during submergence and lost less non-structural carbohydrates (NSC) after submergence. This indicates that the introgression of SUB1 resulted in better regulation of NSC during submergence and that high pre-submergence NSC is not essential for the submergence tolerance conferred by SUB1. During recovery, chlorophyll degradation was faster in genotypes lacking SUB1 and any surviving plants showed poorer and delayed emergence of tillers and leaves. Sub1 lines restored new leaf and tiller production faster. During submergence, FR13A showed not only slower leaf elongation but also accumulated extra biomass and was able to recover faster than Sub

  11. SARS-CoV Regulates Immune Function-Related Gene Expression in Human Monocytic Cells

    PubMed Central

    Hu, Wanchung; Yen, Yu-Ting; Singh, Sher; Kao, Chuan-Liang

    2012-01-01

    Abstract Severe acute respiratory syndrome (SARS) is characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis, and monocytes/macrophages are the key players in the pathogenesis of SARS. In this study, we compared the transcriptional profiles of SARS coronavirus (SARS-CoV)-infected monocytic cells against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted from infected DC-SIGN-transfected monocytes (THP-1-DC-SIGN) at 6 and 24 h after infection, and the gene expression was profiled in oligonucleotide-based microarrays. Analysis of immune-related gene expression profiles showed that at 24 h after SARS-CoV infection: (1) IFN-α/β-inducible and cathepsin/proteasome genes were downregulated; (2) hypoxia/hyperoxia-related genes were upregulated; and (3) TLR/TLR-signaling, cytokine/cytokine receptor-related, chemokine/chemokine receptor-related, lysosome-related, MHC/chaperon-related, and fibrosis-related genes were differentially regulated. These results elucidate that SARS-CoV infection regulates immune-related genes in monocytes/macrophages, which may be important to the pathogenesis of SARS. PMID:22876772

  12. Utilization of digital differential display to identify differentially expressed genes related to rumen development.

    PubMed

    Kato, Daichi; Suzuki, Yutaka; Haga, Satoshi; So, KyoungHa; Yamauchi, Eri; Nakano, Miwa; Ishizaki, Hiroshi; Choi, Kichoon; Katoh, Kazuo; Roh, Sang-Gun

    2016-04-01

    This study aimed to identify the genes associated with the development of the rumen epithelium by screening for candidate genes by digital differential display (DDD) in silico. Using DDD in NCBI's UniGene database, expressed sequence tag (EST)-based gene expression profiles were analyzed in rumen, reticulum, omasum, abomasum and other tissues in cattle. One hundred and ten candidate genes with high expression in the rumen were derived from a library of all tissues. The expression levels of 11 genes in all candidate genes were analyzed in the rumen, reticulum, omasum and abomasum of nine Japanese Black male calves (5-week-old pre-weaning: n = 3; 15-week-old weaned calves: n = 6). Among the 11 genes, only 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), aldo-keto reductase family 1, member C1-like (AKR1C1), and fatty acid binding protein 3 (FABP3) showed significant changes in the levels of gene expression in the rumen between the pre- and post-weaning of calves. These results indicate that DDD analysis in silico can be useful for screening candidate genes related to rumen development, and that the changes in expression levels of three genes in the rumen may have been caused by weaning, aging or both. © 2015 Japanese Society of Animal Science. PMID:26388291

  13. Genetic Variation in Autophagy-Related Genes Influences the Risk and Phenotype of Buruli Ulcer

    PubMed Central

    Capela, Carlos; Dossou, Ange Dodji; Silva-Gomes, Rita; Sopoh, Ghislain Emmanuel; Makoutode, Michel; Menino, João Filipe; Fraga, Alexandra Gabriel; Cunha, Cristina; Carvalho, Agostinho; Rodrigues, Fernando; Pedrosa, Jorge

    2016-01-01

    Introduction Buruli ulcer (BU) is a severe necrotizing human skin disease caused by Mycobacterium ulcerans. Clinically, presentation is a sum of these diverse pathogenic hits subjected to critical immune-regulatory mechanisms. Among them, autophagy has been demonstrated as a cellular process of critical importance. Since microtubules and dynein are affected by mycolactone, the critical pathogenic exotoxin produced by M. ulcerans, cytoskeleton-related changes might potentially impair the autophagic process and impact the risk and progression of infection. Objective Genetic variants in the autophagy-related genes NOD2, PARK2 and ATG16L1 has been associated with susceptibility to mycobacterial diseases. Here, we investigated their association with BU risk, its severe phenotypes and its progression to an ulcerative form. Methods Genetic variants were genotyped using KASPar chemistry in 208 BU patients (70.2% with an ulcerative form and 28% in severe WHO category 3 phenotype) and 300 healthy endemic controls. Results The rs1333955 SNP in PARK2 was significantly associated with increased susceptibility to BU [odds ratio (OR), 1.43; P = 0.05]. In addition, both the rs9302752 and rs2066842 SNPs in NOD2 gee significantly increased the predisposition of patients to develop category 3 (OR, 2.23; P = 0.02; and OR 12.7; P = 0.03, respectively, whereas the rs2241880 SNP in ATG16L1 was found to significantly protect patients from presenting the ulcer phenotype (OR, 0.35; P = 0.02). Conclusion Our findings indicate that specific genetic variants in autophagy-related genes influence susceptibility to the development of BU and its progression to severe phenotypes. PMID:27128681

  14. CSCdb: a cancer stem cells portal for markers, related genes and functional information

    PubMed Central

    Shen, Yi; Yao, Heming; Wang, Minghui

    2016-01-01

    Cancer stem cells (CSCs), which have the ability to self-renew and differentiate into various tumor cell types, are a special class of tumor cells. Characterizing the genes involved in CSCs regulation is fundamental to understand the mechanisms underlying the biological process and develop treatment methods for tumor therapy. Recently, much effort has been expended in the study of CSCs and a large amount of data has been generated. However, to the best of our knowledge, database dedicated to CSCs is not available until now. We have thus developed a CSCs database (CSCdb), which includes marker genes, CSCs-related genes/microRNAs and functional annotations. The information in the CSCdb was manual collected from about 13 000 articles. The CSCdb provides detailed information of 1769 genes that have been reported to participate in the functional regulation of CSCs and 74 marker genes that can be used for identification or isolation of CSCs. The CSCdb also provides 9475 annotations about 13 CSCs-related functions, such as oncogenesis, radio resistance, tumorigenesis, differentiation, etc. Annotations of the identified genes, which include protein function description, post-transcription modification information, related literature, Gene Ontology (GO), protein-protein interaction (PPI) information and regulatory relationships, are integrated into the CSCdb to help users get information more easily. CSCdb provides a comprehensive resource for CSCs research work, which would assist in finding new CSCs-related genes and would be a useful tool for biologists. Database URL: http://bioinformatics.ustc.edu.cn/cscdb PMID:26989154

  15. Comparative sequence and expression analysis of tapetum specific male sterility related genes in Medicago truncatula.

    PubMed

    Shao, L H; Zheng, X W; Yi, D X; Li, C

    2016-01-01

    Heterosis, or enhancement through outbreeding, is one of the most promising approaches for increasing crop yield. Male sterility (MS), which promotes heterosis, has been widely applied in hybrid crop production. Medicago truncatula is a model legume species and is closely related to M. sativa, an important legume forage plant. Although the molecular mechanisms of MS in M. truncatula and M. sativa remain unclear, several studies of MS have been conducted in Arabidopsis thaliana. Previous research has shown that MS is associated with the destruction of tapetal cell layers. Disruption of tapetum developmental processes may result in pollen abortion. In an effort to identify genes useful for breeding in M. sativa, we identified MS related genes in M. truncatula using BLAST and homology to A. thaliana genes. In this study, we identified 63 tapetum specific male sterility (TSMS) related genes. The length of TSMS genes varied from 225 to 3747 bp. We identified 15 conserved domains and 8 cis-elements associated with TSMS related genes. Analysis of the phylogenetic relationships among these genes allowed them to be classified into three groups, MtTsms A, MtTsms B, and MtTsms C. Expression analyses revealed that these genes may be involved in developmental processes and response to abiotic stress. PMID:27421020

  16. CSCdb: a cancer stem cells portal for markers, related genes and functional information.

    PubMed

    Shen, Yi; Yao, Heming; Li, Ao; Wang, Minghui

    2016-01-01

    Cancer stem cells (CSCs), which have the ability to self-renew and differentiate into various tumor cell types, are a special class of tumor cells. Characterizing the genes involved in CSCs regulation is fundamental to understand the mechanisms underlying the biological process and develop treatment methods for tumor therapy. Recently, much effort has been expended in the study of CSCs and a large amount of data has been generated. However, to the best of our knowledge, database dedicated to CSCs is not available until now. We have thus developed a CSCs database (CSCdb), which includes marker genes, CSCs-related genes/microRNAs and functional annotations. The information in the CSCdb was manual collected from about 13 000 articles. The CSCdb provides detailed information of 1769 genes that have been reported to participate in the functional regulation of CSCs and 74 marker genes that can be used for identification or isolation of CSCs. The CSCdb also provides 9475 annotations about 13 CSCs-related functions, such as oncogenesis, radio resistance, tumorigenesis, differentiation, etc. Annotations of the identified genes, which include protein function description, post-transcription modification information, related literature, Gene Ontology (GO), protein-protein interaction (PPI) information and regulatory relationships, are integrated into the CSCdb to help users get information more easily. CSCdb provides a comprehensive resource for CSCs research work, which would assist in finding new CSCs-related genes and would be a useful tool for biologists.Database URL: http://bioinformatics.ustc.edu.cn/cscdb. PMID:26989154

  17. The human gene map for performance and health-related fitness phenotypes: the 2005 update

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The current review presents the 2005 update of the human gene map for physical performance and health-related fitness phenotypes. It is based on peer-reviewed papers published by the end of 2005. The genes and markers with evidence of association or linkage with a performance or fitness phenotype in...

  18. Measured Gene-by-Environment Interaction in Relation to Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Nigg, Joel; Nikolas, Molly; Burt, S. Alexandra

    2010-01-01

    Objective: To summarize and evaluate the state of knowledge regarding the role of measured gene-by-environment interactions in relation to attention-deficit/hyperactivity disorder. Method: A selective review of methodologic issues was followed by a systematic search for relevant articles on measured gene-by-environment interactions; the search…

  19. Multiple Thyrotropin β-Subunit and Thyrotropin Receptor-Related Genes Arose during Vertebrate Evolution

    PubMed Central

    Maugars, Gersende; Dufour, Sylvie; Cohen-Tannoudji, Joëlle; Quérat, Bruno

    2014-01-01

    Thyroid-stimulating hormone (TSH) is composed of a specific β subunit and an α subunit that is shared with the two pituitary gonadotropins. The three β subunits derive from a common ancestral gene through two genome duplications (1R and 2R) that took place before the radiation of vertebrates. Analysis of genomic data from phylogenetically relevant species allowed us to identify an additional Tshβ subunit-related gene that was generated through 2R. This gene, named Tshβ2, present in cartilaginous fish, little skate and elephant shark, and in early lobe-finned fish, coelacanth and lungfish, was lost in ray-finned fish and tetrapods. The absence of a second type of TSH receptor (Tshr) gene in these species suggests that both TSHs act through the same receptor. A novel Tshβ sister gene, named Tshβ3, was generated through the third genomic duplication (3R) that occurred early in the teleost lineage. Tshβ3 is present in most teleost groups but was lostin tedraodontiforms. The 3R also generated a second Tshr, named Tshrb. Interestingly, the new Tshrb was translocated from its original chromosomic position after the emergence of eels and was then maintained in its new position. Tshrb was lost in tetraodontiforms and in ostariophysians including zebrafish although the latter species have two TSHs, suggesting that TSHRb may be dispensable. The tissue distribution of duplicated Tshβs and Tshrs was studied in the European eel. The endocrine thyrotropic function in the eel would be essentially mediated by the classical Tshβ and Tshra, which are mainly expressed in the pituitary and thyroid, respectively. Tshβ3 and Tshrb showed a similar distribution pattern in the brain, pituitary, ovary and adipose tissue, suggesting a possible paracrine/autocrine mode of action in these non-thyroidal tissues. Further studies will be needed to determine the binding specificity of the two receptors and how these two TSH systems are interrelated. PMID:25386660

  20. Multiple thyrotropin β-subunit and thyrotropin receptor-related genes arose during vertebrate evolution.

    PubMed

    Maugars, Gersende; Dufour, Sylvie; Cohen-Tannoudji, Joëlle; Quérat, Bruno

    2014-01-01

    Thyroid-stimulating hormone (TSH) is composed of a specific β subunit and an α subunit that is shared with the two pituitary gonadotropins. The three β subunits derive from a common ancestral gene through two genome duplications (1R and 2R) that took place before the radiation of vertebrates. Analysis of genomic data from phylogenetically relevant species allowed us to identify an additional Tshβ subunit-related gene that was generated through 2R. This gene, named Tshβ2, present in cartilaginous fish, little skate and elephant shark, and in early lobe-finned fish, coelacanth and lungfish, was lost in ray-finned fish and tetrapods. The absence of a second type of TSH receptor (Tshr) gene in these species suggests that both TSHs act through the same receptor. A novel Tshβ sister gene, named Tshβ3, was generated through the third genomic duplication (3R) that occurred early in the teleost lineage. Tshβ3 is present in most teleost groups but was lostin tedraodontiforms. The 3R also generated a second Tshr, named Tshrb. Interestingly, the new Tshrb was translocated from its original chromosomic position after the emergence of eels and was then maintained in its new position. Tshrb was lost in tetraodontiforms and in ostariophysians including zebrafish although the latter species have two TSHs, suggesting that TSHRb may be dispensable. The tissue distribution of duplicated Tshβs and Tshrs was studied in the European eel. The endocrine thyrotropic function in the eel would be essentially mediated by the classical Tshβ and Tshra, which are mainly expressed in the pituitary and thyroid, respectively. Tshβ3 and Tshrb showed a similar distribution pattern in the brain, pituitary, ovary and adipose tissue, suggesting a possible paracrine/autocrine mode of action in these non-thyroidal tissues. Further studies will be needed to determine the binding specificity of the two receptors and how these two TSH systems are interrelated. PMID:25386660

  1. Screening of genes related to ovarian development in the swimming crab, Portunus trituberculatus, by suppression subtractive hybridization.

    PubMed

    Yu, Z B; Mu, C K; Song, W W; Li, R H; Chen, Y E; Wang, C L

    2015-01-01

    The swimming crab, Portunus trituberculatus, is an important marine animal and is widely cultured in China. In the present study, suppression subtractive hybridization was applied to identify the differentially expressed genes in the ovaries of mature and immature P. trituberculatus. One hundred and seventy six expressed sequence tag (ESTs) were identified, of which 100 were down-regulated, and 76 up-regulated. BLAST analysis identified 51 unigenes, of which 27 were down-regulated, and 24 up-regulated. Quantitative real-time reverse transcriptase polymerase chain reaction results indicated that the SSH technique is valuable in screening genes related to ovarian development. Genes identified in this study encoded proteins corresponding to a wide range of functions and included immune response protein, transcription initiation factor, metabolic proteins, chromosome, histone h3, ovarian development-related protein, and vitellogenin. In addition, 64 metabolic pathways were annotated in differentially expressed ESTs by using the Kyoto Encyclopedia of Genes and Genomes pathway. Four annotated pathways (oxidative phosphorylation, carbon metabolism, fatty acid degradation, and protein digestion and absorption) appeared to be involved in ovarian development. In ontology analysis, 5.83% of the cellular process genes in reverse subtraction cDNA library are involved in reproduction, and 5.88% involved in developmental process. In up-regulated genes, myosin II-expressed polehole-like protein; histone h3; ovigerous-hair stripping substance; peritrophin 48; and ovarian development-related protein appeared to be involved in ovarian development. Identification of differentially expressed genes in the mature and immature ovary of the swimming crab provides new insights for further studies on the mechanism underlying ovarian development in this species. PMID:26782517

  2. Transcriptome Analysis of Medicinal Plant Salvia miltiorrhiza and Identification of Genes Related to Tanshinone Biosynthesis

    PubMed Central

    Yang, Lei; Ding, Guohui; Lin, Haiyan; Cheng, Haining; Kong, Yu; Wei, Yukun; Fang, Xin; Liu, Renyi; Wang, Lingiian; Chen, Xiaoya; Yang, Changqing

    2013-01-01

    Salvia miltiorrhiza Bunge, a perennial plant of Lamiaceae, accumulates abietane-type diterpenoids of tanshinones in root, which have been used as traditional Chinese medicine to treat neuroasthenic insomnia and cardiovascular diseases. However, to date the biosynthetic pathway of tanshinones is only partially elucidated and the mechanism for their root-specific accumulation remains unknown. To identify enzymes and transcriptional regulators involved in the biosynthesis of tanshinones, we conducted transcriptome profiling of S. miltiorrhiza root and leaf tissues using the 454 GS-FLX pyrosequencing platform, which generated 550,546 and 525,292 reads, respectively. RNA sequencing reads were assembled and clustered into 64,139 unigenes (29,883 isotigs and 34,256 singletons). NCBI non-redundant protein databases (NR) and Swiss-Prot database searches anchored 32,096 unigenes (50%) with functional annotations based on sequence similarities. Further assignments with Gene Ontology (GO) terms and KEGG biochemical pathways identified 168 unigenes referring to the terpenoid backbone biosynthesis (including 144 MEP and MVA pathway genes and 24 terpene synthases). Comparative analysis of the transcriptomes identified 2,863 unigenes that were highly expressed in roots, including those encoding enzymes of early steps of tanshinone biosynthetic pathway, such as copalyl diphosphate synthase (SmCPS), kaurene synthase-like (SmKSL) and CYP76AH1. Other differentially expressed unigenes predicted to be related to tanshinone biosynthesis fall into cytochrome P450 monooxygenases, dehydrogenases and reductases, as well as regulatory factors. In addition, 21 P450 genes were selectively confirmed by real-time PCR. Thus we have generated a large unigene dataset which provides a valuable resource for further investigation of the radix development and biosynthesis of tanshinones. PMID:24260395

  3. Age-dependent expression of osteochondrosis-related genes in equine leukocytes

    PubMed Central

    Mendoza, L.; Piquemal, D.; Lejeune, J. P.; Vander Heyden, L.; Noguier, F.; Bruno, R.; Sandersen, C.; Serteyn, D.

    2015-01-01

    Introduction:  Osteochondrosis (OC) is a developmental disease in horses which has a significant impact on the horse's welfare and performance. The early disturbance in the process of endochondral ossification progresses to inflammatory and repair processes in older horses. Previously, differentially expressed genes in leukocytes of OC-affected horses have been identified. The aim of the present study is to detect age-related changes in these differentially expressed genes. Materials and Methods:  The expression of OC-related genes was analysed by real-time PCR and subsequent statistical analysis (ΔΔCT) in the leukocytes of 135 Belgian Warmblood horses divided into three different age groups: <12 months (n=47), 18–24 months (n=50) >30 months (n=38). Results:  Relative expression of genes of horses less than 12 months of age showed significant induction of the genes MGAT4A, PRKCG, MHCI, ApoB, ApoB3G, B4GALT6 and a significantly lower expression of the genes OAS3. Horses of 18–24 months of age, showed a significantly higher expression of the genes TBC1D9, MGAT4A, IFIH1, MHCIIa and MMP1. Horses of more than 30 months of age showed a significantly higher expression of the genes MGAT4A, HP, SECTM1 compared with their age-matched control groups. Conclusions:  The study demonstrates that OC-related genes are differentially expressed in horses of different ages compared with their age-matched controls. Some of the genes may be implicated in cell signalling and differentiation as well as carbohydrate and lipid metabolism and inflammation. However, the causal relationship between the differentially expressed genes and the development and progression of the OC lesions needs to be determined. PMID:26392886

  4. Expression profiles of DNA repair-related genes in rat target organs under subchronic cadmium exposure.

    PubMed

    Lei, Y X; Lu, Q; Shao, C; He, C C; Lei, Z N; Lian, Y Y

    2015-01-01

    We aimed to evaluate the toxicity of long-term exposure to different cadmium (Cd) doses in rats and expression profiles of DNA repair-related genes. The model rats were exposed to different concentrations of CdCl2 for 3 months, and 5 DNA repair-related genes - hMSH2, MLH1, XRCC1, hOGG1, ERCC1 - were cloned in different tissues, including the liver, kidney, heart, and lung. Accumulated amounts of Cd were detected in the tissues. Gene and protein detections were conducted via fluorescence quantitative real-time polymerase chain reaction and Western blotting, respectively. Methylated sequences of the 5 DNA repair-related gene promoters were used to investigate whether the low expression levels of the genes were related to methylation of the promoter. In the Cd-exposed group, 3 DNA repair genes (i.e., XRCC1, hOGG1, and ERCC1) significantly decreased in the rat liver, kidney, heart, and lung according to the β-actin internal standard (P < 0.01). Western blotting indicated the same trend for the different tissues. Each of the DNA repair genes had special characteristics; for example, hOGG1 gene expression decreased by 75% in the kidney, and XRCC1 gene expression decreased by 5% in the liver and heart when compared to the control group (P < 0.01). A negative correlation between the DNA repair gene expression levels and the cumulative levels of Cd was also suggested by malignancy pathology. The expression levels of 3 DNA repair genes (i.e., ERCC1, XRCC1, and hOGG1) played an important role in the rat response to Cd exposure but not DNA methylated protection. PMID:25729986

  5. Transcriptomics Analysis of Crassostrea hongkongensis for the Discovery of Reproduction-Related Genes

    PubMed Central

    Tong, Ying; Zhang, Yang; Huang, Jiaomei; Xiao, Shu; Zhang, Yuehuan; Li, Jun; Chen, Jinhui; Yu, Ziniu

    2015-01-01

    Background The reproductive mechanisms of mollusk species have been interesting targets in biological research because of the diverse reproductive strategies observed in this phylum. These species have also been studied for the development of fishery technologies in molluscan aquaculture. Although the molecular mechanisms underlying the reproductive process have been well studied in animal models, the relevant information from mollusks remains limited, particularly in species of great commercial interest. Crassostrea hongkongensis is the dominant oyster species that is distributed along the coast of the South China Sea and little genomic information on this species is available. Currently, high-throughput sequencing techniques have been widely used for investigating the basis of physiological processes and facilitating the establishment of adequate genetic selection programs. Results The C.hongkongensis transcriptome included a total of 1,595,855 reads, which were generated by 454 sequencing and were assembled into 41,472 contigs using de novo methods. Contigs were clustered into 33,920 isotigs and further grouped into 22,829 isogroups. Approximately 77.6% of the isogroups were successfully annotated by the Nr database. More than 1,910 genes were identified as being related to reproduction. Some key genes involved in germline development, sex determination and differentiation were identified for the first time in C.hongkongensis (nanos, piwi, ATRX, FoxL2, β-catenin, etc.). Gene expression analysis indicated that vasa, nanos, piwi, ATRX, FoxL2, β-catenin and SRD5A1 were highly or specifically expressed in C.hongkongensis gonads. Additionally, 94,056 single nucleotide polymorphisms (SNPs) and 1,699 simple sequence repeats (SSRs) were compiled. Conclusions Our study significantly increased C.hongkongensis genomic information based on transcriptomics analysis. The group of reproduction-related genes identified in the present study constitutes a new tool for research

  6. Centrin protein and genes in Trichomonas vaginalis and close relatives.

    PubMed

    Brugerolle, G; Bricheux, G; Coffe, G

    2000-01-01

    Anti-centrin monoclonal antibodies 20H5 and 11B2 produced against Clamydomononas centrin decorated the group of basal bodies as well as very closely attached structures in all trichomonads studied and in the devescovinids Foaina and Devescovina. Moreover, these antibodies decorated the undulating membrane in Trichomonas vaginalis, Trichomitus batrachorum, and Tritrichomonas foetus, and the cresta in Foaina. Centrin was not demonstrated in the dividing spindle and paradesmosis. Immunogold labeling, both in pre- and post-embedding, confirmed that centrin is associated with the basal body cylinder and is a component of the nine anchoring arms between the terminal plate of flagellar bases and the plasma-membrane. Centrin is also associated with the hook-shaped fibers attached to basal bodies (F1, F3), the X-fiber, and along sigmoid fibers (F2) at the pelta-axostyle junction, which is the microtubule organizing center for pelta-axostyle microtubules. There was no labeling on the striated costa and parabasal fibers nor on microtubular pelta-axostyle, but the fibrous structure inside the undulating membrane was labeled in T. vaginalis. Two proteins of 22-20 kDa corresponding to the centrin molecular mass were recognized by immunoblotting using these antibodies in the three trichomonad species examined. By screening a T. vaginalis cDNA library with 20H5 antibody, two genes encoding identical protein sequences were found. The sequence comprises the 4 typical EF-hand Ca++-binding domains present in every known centrin. Trichomonad centrin is closer to the green algal cluster (70% identity) than to the yeast Cdc31 cluster (55% identity) or the Alveolata cluster (46% identity). PMID:10750840

  7. Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies.

    PubMed

    Allikmets, R; Seddon, J M; Bernstein, P S; Hutchinson, A; Atkinson, A; Sharma, S; Gerrard, B; Li, W; Metzker, M L; Wadelius, C; Caskey, C T; Dean, M; Petrukhin, K

    1999-06-01

    Vitelliform macular dystrophy (VMD2, Best disease, MIM153700) is an early onset, autosomal, dominant macular degeneration characterized by the deposition of lipofuscin-like material within and below the retinal pigment epithelium (RPE); it is associated with degeneration of the RPE and overlying photoreceptors. Recently, we cloned the gene bestrophin, which is responsible for the disease, and identified a number of causative mutations in families with VMD2. Here, we report that the analysis of bestrophin in a collection of 259 age-related macular degeneration (AMD) patients provides evidence that mutations in the Best disease gene do not play a significant role in the predisposition of individuals to AMD. However, our results suggest that, in addition to Best disease, mutations within the bestrophin gene could be responsible for other forms of maculopathy with phenotypic characteristics similar to Best disease and for other diseases not included in the VMD category. PMID:10453731

  8. AGE-RELATED GENE EXPRESSION CHANGES IN HUMAN SKIN FIBROBLASTS INDUCED BY MMS

    EPA Science Inventory

    Age-Related Gene Expression Changes In Human Skin Fibroblasts Induced By methyl methanesulfonate. Geremy W. Knapp, Alan H. Tennant, and Russell D. Owen. Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U. S. Environmental Prote...

  9. Genes related to xylose fermentation and methods of using same for enhanced biofuel production

    DOEpatents

    Wohlbach, Dana J.; Gasch, Audrey P.

    2015-09-29

    The present invention provides isolated gene sequences involved in xylose fermentation and related recombinant yeast which are useful in methods of enhanced biofuel production, particularly ethanol production. Methods of bioengineering recombinant yeast useful for biofuel production are also provided.

  10. Genes related to xylose fermentation and methods of using same for enhanced biofuel production

    DOEpatents

    Wohlbach, Dana J.; Gasch, Audrey P.

    2014-08-05

    The present invention provides isolated gene sequences involved in xylose fermentation and related recombinant yeast which are useful in methods of enhanced biofuel production, particularly ethanol production. Methods of bioengineering recombinant yeast useful for biofuel production are also provided.

  11. Microarray Analysis of Gene Expression in Saccharomyces cerevisiae kap108Δ Mutants upon Addition of Oxidative Stress

    PubMed Central

    Belanger, Kenneth D.; Larson, Nathaniel; Kahn, Jonathan; Tkachev, Dmitry; Ay, Ahmet

    2016-01-01

    Protein transport between the nucleus and cytoplasm of eukaryotic cells is tightly regulated, providing a mechanism for controlling intracellular localization of proteins, and regulating gene expression. In this study, we have investigated the importance of nucleocytoplasmic transport mediated by the karyopherin Kap108 in regulating cellular responses to oxidative stress in Saccharomyces cerevisiae. We carried out microarray analyses on wild-type and kap108 mutant cells grown under normal conditions, shortly after introduction of oxidative stress, after 1 hr of oxidative stress, and 1 hr after oxidative stress was removed. We observe more than 500 genes that undergo a 40% or greater change in differential expression between wild-type and kap108Δ cells under at least one of these conditions. Genes undergoing changes in expression can be categorized in two general groups: 1) those that are differentially expressed between wild-type and kap108Δ cells, no matter the oxidative stress conditions; and 2) those that have patterns of response dependent upon both the absence of Kap108, and introduction or removal of oxidative stress. Gene ontology analysis reveals that, among the genes whose expression is reduced in the absence of Kap108 are those involved in stress response and intracellular transport, while those overexpressed are largely involved in mating and pheromone response. We also identified 25 clusters of genes that undergo similar patterns of change in gene expression when oxidative stresses are added and subsequently removed, including genes involved in stress response, oxidation–reduction processing, iron homeostasis, ascospore wall assembly, transmembrane transport, and cell fusion during mating. These data suggest that Kap108 is important for regulating expression of genes involved in a variety of specific cell functions. PMID:26888869

  12. Identification of mycoparasitism-related genes in Clonostachys rosea 67-1 active against Sclerotinia sclerotiorum

    PubMed Central

    Sun, Zhan-Bin; Sun, Man-Hong; Li, Shi-Dong

    2015-01-01

    Clonostachys rosea is a mycoparasite that has shown great potential in controlling various plant fungal pathogens. In order to find mycoparasitism-related genes in C. rosea, the transcriptome of the efficient isolate 67-1 in association with sclerotia of Sclerotinia sclerotiorum was sequenced and analysed. The results identified 26,351 unigenes with a mean length of 1,102 nucleotides, among which 18,525 were annotated in one or more databases of NR, KEGG, Swiss-Prot, GO and COG. Differentially expressed genes at 8 h, 24 h and 48 h after sclerotial induction were analysed, and 6,890 unigenes were upregulated compared with the control without sclerotia. 713, 1,008 and 1,929 genes were specifically upregulated expressed, while 1,646, 283 and 529 genes were specifically downregulated, respectively. Gene ontology terms analysis indicated that these genes were mainly involved in metabolism of biological process, catalysis of molecular function and cellular component. The expression levels of 12 genes that were upregulated after encountering with S. sclerotiorum were monitored using real-time PCR. The results indicated that the quantitative detection was consistent with the transcriptome analysis. The study provides transcriptional gene expression information on C. rosea parasitizing S. sclerotiorum and forms the basis for further investigation of mycoparasitism-related genes of C. rosea. PMID:26657839

  13. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

    PubMed Central

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Yan, Zuoqin; Qian, Ruizhe

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  14. Association Analysis of Dyslipidemia-Related Genes in Diabetic Nephropathy

    PubMed Central

    McKay, Gareth J.; Savage, David A.; Patterson, Christopher C.; Lewis, Gareth; McKnight, Amy Jayne; Maxwell, Alexander P.

    2013-01-01

    Type 1 diabetes (T1D) increases risk of the development of microvascular complications and cardiovascular disease (CVD). Dyslipidemia is a common risk factor in the pathogenesis of both CVD and diabetic nephropathy (DN), with CVD identified as the primary cause of death in patients with DN. In light of this commonality, we assessed single nucleotide polymorphisms (SNPs) in thirty-seven key genetic loci previously associated with dyslipidemia in a T1D cohort using a case-control design. SNPs (n = 53) were genotyped using Sequenom in 1467 individuals with T1D (718 cases with proteinuric nephropathy and 749 controls without nephropathy i.e. normal albumin excretion). Cases and controls were white and recruited from the UK and Ireland. Association analyses were performed using PLINK to compare allele frequencies in cases and controls. In a sensitivity analysis, samples from control individuals with reduced renal function (estimated glomerular filtration rate<60 ml/min/1.73 m2) were excluded. Correction for multiple testing was performed by permutation testing. A total of 1394 samples passed quality control filters. Following regression analysis adjusted by collection center, gender, duration of diabetes, and average HbA1c, two SNPs were significantly associated with DN. rs4420638 in the APOC1 region (odds ratio [OR]  = 1.51; confidence intervals [CI]: 1.19–1.91; P = 0.001) and rs1532624 in CETP (OR = 0.82; CI: 0.69–0.99; P = 0.034); rs4420638 was also significantly associated in a sensitivity analysis (P = 0.016) together with rs7679 (P = 0.027). However, no association was significant following correction for multiple testing. Subgroup analysis of end-stage renal disease status failed to reveal any association. Our results suggest common variants associated with dyslipidemia are not strongly associated with DN in T1D among white individuals. Our findings, cannot entirely exclude these key genes which are central to the process of

  15. A microbial TRP-like polycystic-kidney-disease-related ion channel gene

    PubMed Central

    Palmer, Christopher P.; Aydar, Ebru; Djamgoz, Mustafa B. A.

    2004-01-01

    Ion channel genes have been discovered in many microbial organisms. We have investigated a microbial TRP (transient receptor potential) ion channel gene which has most similarity to polycystic-kidney-disease-related ion channel genes. We have shown that this gene (pkd2) is essential for cellular viability, and is involved in cell growth and cell wall synthesis. Expression of this gene increases following damage to the cell wall. This fission yeast pkd2 gene, orthologues of which are found in all eukaryotic cells, appears to be a key signalling component in the regulation of cell shape and cell wall synthesis in yeast through an interaction with a Rho1-GTPase. A model for the mode of action of this Schizosaccharomyces pombe protein in a Ca2+ signalling pathway is hypothesized. PMID:15537393

  16. Differential Expression of Inflammation-Related Genes in Children with Down Syndrome

    PubMed Central

    Silva, Cláudia Regina Santos; Biselli-Périco, Joice Matos; Zampieri, Bruna Lancia; Silva, Wilson Araujo; de Souza, Jorge Estefano Santana; Bürger, Matheus Carvalho; Goloni-Bertollo, Eny Maria; Pavarino, Érika Cristina

    2016-01-01

    Objective. The aim of the study was to investigate the expression patterns of a specific set of genes involved in the inflammation process in children with Down Syndrome (DS) and children without the syndrome (control group) to identify differences that may be related to the immune abnormalities observed in DS individuals. Method. RNA samples were obtained from peripheral blood, and gene expression was quantified using the TaqMan® Array Plate Human Inflammation Kit, which facilitated the investigation into 92 inflammation-related genes and four reference genes using real-time polymerase chain reaction (qPCR). Results. Twenty genes showed differential expression in children with DS; 12 were overexpressed (PLA2G2D, CACNA1D, ALOX12, VCAM1, ICAM1, PLCD1, ADRB1, HTR3A, PDE4C, CASP1, PLA2G5, and PLCB4), and eight were underexpressed (LTA4H, BDKRB1, ADRB2, CD40LG, ITGAM, TNFRSF1B, ITGB1, and TBXAS1). After statistically correcting for the false discovery rate, only the genes BDKRB1 and LTA4H showed differential expression, and both were underexpressed within the DS group. Conclusion. DS children showed differential expression of inflammation-related genes that were not located on chromosome 21 compared with children without DS. The BDKRB1 and LTA4H genes may differentiate the case and control groups based on the inflammatory response, which plays an important role in DS pathogenesis. PMID:27293319

  17. Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens

    PubMed Central

    Zhao, Changjiu; Eisinger, Brian Earl; Driessen, Terri M.; Gammie, Stephen C.

    2014-01-01

    Motherhood involves a switch in natural rewards, whereby offspring become highly rewarding. Nucleus accumbens (NAC) is a key CNS region for natural rewards and addictions, but to date no study has evaluated on a large scale the events in NAC that underlie the maternal change in natural rewards. In this study we utilized microarray and bioinformatics approaches to evaluate postpartum NAC gene expression changes in mice. Modular Single-set Enrichment Test (MSET) indicated that postpartum (relative to virgin) NAC gene expression profile was significantly enriched for genes related to addiction and reward in five of five independently curated databases (e.g., Malacards, Phenopedia). Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, Gabrb3, Adra2a, Ntrk2, Cry1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis (WGCNA) identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder (BPD), and schizophrenia. Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions. PMID:25414651

  18. Response of key stress-related genes of the seagrass Posidonia oceanica in the vicinity of submarine volcanic vents

    NASA Astrophysics Data System (ADS)

    Lauritano, C.; Ruocco, M.; Dattolo, E.; Buia, M. C.; Silva, J.; Santos, R.; Olivé, I.; Costa, M. M.; Procaccini, G.

    2015-07-01

    Submarine volcanic vents are being used as natural laboratories to assess the effects of increased ocean acidity and carbon dioxide (CO2) concentration on marine organisms and communities. However, in the vicinity of volcanic vents other factors in addition to CO2, which is the main gaseous component of the emissions, may directly or indirectly confound the biota responses to high CO2. Here we used for the first time the expression of antioxidant and stress-related genes of the seagrass Posidonia oceanica to assess the stress levels of the species. Our hypothesis is that unknown factors are causing metabolic stress that may confound the putative effects attributed to CO2 enrichment only. We analyzed the expression of 35 antioxidant and stress-related genes of P. oceanica in the vicinity of submerged volcanic vents located in the islands of Ischia and Panarea, Italy, and compared them with those from control sites away from the influence of vents. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was used to characterize gene expression patterns. Fifty-one percent of genes analyzed showed significant expression changes. Metal detoxification genes were mostly down-regulated in relation to controls at both Ischia and Panarea, indicating that P. oceanica does not increase the synthesis of heavy metal detoxification proteins in response to the environmental conditions present at the two vents. The up-regulation of genes involved in the free radical detoxification response (e.g., CAPX, SODCP and GR) indicates that, in contrast with Ischia, P. oceanica at the Panarea site faces stressors that result in the production of reactive oxygen species, triggering antioxidant responses. In addition, heat shock proteins were also activated at Panarea and not at Ischia. These proteins are activated to adjust stress-accumulated misfolded proteins and prevent their aggregation as a response to some stressors, not necessarily high temperature. This is the first

  19. Systematic Analysis of Integrated Gene Functional Network of Four Chronic Stress-related Lifestyle Disorders

    PubMed Central

    Roy, Souvick; Chakraborty, Abhik; Ghosh, Chinmoy; Banerjee, Birendranath

    2015-01-01

    Background: Stress is a term used to define factors involved in changes in the physiological balances resulting in disease conditions. Chronic exposure to stress conditions in modern lifestyles has resulted in a group of disorders called lifestyle disorders. Genetic background and environmental factors are interrelated to lifestyle in determining the health status of individuals. Hence, identification of disease-associated genes is the primary step toward explanations of pathogenesis of these diseases. In functional genomics, large-scale molecular and physiological data are used for the identification of causative genes associated with a disease. Aim: The objective of our study was to find a common set of genes involved in chronic stress-related lifestyle diseases such as cardiovascular diseases (CVDs), type 2 diabetes (T2D), hypertension (HTN), and obesity. Materials and Methods: In our study, we have performed a systematic analysis of the functional gene network of four chronic stress-related lifestyle diseases by retrieving genes from published databases. We have tried to systematically construct a functional protein-protein interaction (PPI) network. The goals of establishing this network were the functional enrichment study of interacting partners as well as functional disease ontology annotation (FunDO) of the enriched genes. Results: This study enabled the identification of key genes involved in these stress-related lifestyle diseases by prioritizing candidate genes based on their degree of involvement. In this systematic analysis, we have found key genes for these diseases based on their involvement and association at the gene network level and PPI. Conclusion: We have deciphered a group of genes that in combination play a crucial role and may impact the function of the whole genome in the four lifestyle disorders mentioned. PMID:27330735

  20. Development of gene therapy for treatment of age-related macular degeneration.

    PubMed

    Askou, Anne Louise

    2014-07-01

    Intraocular neovascular diseases are the leading cause of blindness in the Western world in individuals over the age of 50. Age-related macular degeneration (AMD) is one of these diseases. Exudative AMD, the late-stage form, is characterized by abnormal neovessel development, sprouting from the choroid into the avascular subretinal space, where it can suddenly cause irreversible damage to the vulnerable photoreceptor (PR) cells essential for our high-resolution, central vision. The molecular basis of AMD is not well understood, but several growth factors have been implicated including vascular endothelial growth factor (VEGF), and the advent of anti-VEGF therapy has markedly changed the outcome of treatment. However, common to all current therapies for exudative AMD are the complications of repeated monthly intravitreal injections, which must be continued throughout one's lifetime to maintain visual benefits. Additionally, some patients do not benefit from established treatments. Strategies providing long-term suppression of inappropriate ocular angiogenesis are therefore needed, and gene therapy offers a potential powerful technique. This study aimed to develop a strategy based on RNA interference (RNAi) for the sustained attenuation of VEGF. We designed a panel of anti-VEGF short hairpin RNAs (shRNA), and based on the most potent shRNAs, microRNA (miRNA)-mimicked hairpins were developed. We demonstrated an additive VEGF silencing effect when we combined the miRNAs in a tricistronic miRNA cluster. To meet the requirements for development of medical treatments for AMD with long-term effects, the shRNA/miRNA is expressed from vectors based on adeno-associated virus (AAV) or lentivirus (LV). Both vector systems have been found superior in terms of transduction efficiency and persistence in gene expression in retinal cells. The capacity of AAV-encoded RNAi effector molecules to silence endogenous VEGF gene expression was evaluated in mouse models, including the model

  1. Starvation resistance and tissue-specific gene expression of stress-related genes in a naturally inbred ant population.

    PubMed

    Bos, Nick; Pulliainen, Unni; Sundström, Liselotte; Freitak, Dalial

    2016-04-01

    Starvation is one of the most common and severe stressors in nature. Not only does it lead to death if not alleviated, it also forces the starved individual to allocate resources only to the most essential processes. This creates energetic trade-offs which can lead to many secondary challenges for the individual. These energetic trade-offs could be exacerbated in inbred individuals, which have been suggested to have a less efficient metabolism. Here, we studied the effect of inbreeding on starvation resistance in a natural population of Formica exsecta ants, with a focus on survival and tissue-specific expression of stress, metabolism and immunity-related genes. Starvation led to large tissue-specific changes in gene expression, but inbreeding had little effect on most of the genes studied. Our results illustrate the importance of studying stress responses in different tissues instead of entire organisms. PMID:27152219

  2. Starvation resistance and tissue-specific gene expression of stress-related genes in a naturally inbred ant population

    PubMed Central

    Bos, Nick; Pulliainen, Unni; Sundström, Liselotte; Freitak, Dalial

    2016-01-01

    Starvation is one of the most common and severe stressors in nature. Not only does it lead to death if not alleviated, it also forces the starved individual to allocate resources only to the most essential processes. This creates energetic trade-offs which can lead to many secondary challenges for the individual. These energetic trade-offs could be exacerbated in inbred individuals, which have been suggested to have a less efficient metabolism. Here, we studied the effect of inbreeding on starvation resistance in a natural population of Formica exsecta ants, with a focus on survival and tissue-specific expression of stress, metabolism and immunity-related genes. Starvation led to large tissue-specific changes in gene expression, but inbreeding had little effect on most of the genes studied. Our results illustrate the importance of studying stress responses in different tissues instead of entire organisms. PMID:27152219

  3. Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

    PubMed Central

    Hokama, Masaaki; Oka, Sugako; Leon, Julio; Ninomiya, Toshiharu; Honda, Hiroyuki; Sasaki, Kensuke; Iwaki, Toru; Ohara, Tomoyuki; Sasaki, Tomio; LaFerla, Frank M.; Kiyohara, Yutaka; Nakabeppu, Yusaku

    2014-01-01

    Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM. PMID:23595620

  4. Mapping and annotating obesity-related genes in pig and human genomes.

    PubMed

    Martelli, Pier Luigi; Fontanesi, Luca; Piovesan, Damiano; Fariselli, Piero; Casadio, Rita

    2014-01-01

    Background. Obesity is a major health problem in both developed and emerging countries. Obesity is a complex disease whose etiology involves genetic factors in strong interplay with environmental determinants and lifestyle. The discovery of genetic factors and biological pathways underlying human obesity is hampered by the difficulty in controlling the genetic background of human cohorts. Animal models are then necessary to further dissect the genetics of obesity. Pig has emerged as one of the most attractive models, because of the similarity with humans in the mechanisms regulating the fat deposition. Results. We collected the genes related to obesity in humans and to fat deposition traits in pig. We localized them on both human and pig genomes, building a map useful to interpret comparative studies on obesity. We characterized the collected genes structurally and functionally with BAR+ and mapped them on KEGG pathways and on STRING protein interaction network. Conclusions. The collected set consists of 361 obesity related genes in human and pig genomes. All genes were mapped on the human genome, and 54 could not be localized on the pig genome (release 2012). Only for 3 human genes there is no counterpart in pig, confirming that this animal is a good model for human obesity studies. Obesity related genes are mostly involved in regulation and signaling processes/pathways and relevant connection emerges between obesity-related genes and diseases such as cancer and infectious diseases. PMID:23855670

  5. Predicting disease-related genes by topological similarity in human protein-protein interaction network

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Hu, Ke; Tang, Yi

    2010-08-01

    Predicting genes likely to be involved in human diseases is an important task in bioinformatics field. Nowadays, the accumulation of human protein-protein interactions (PPIs) data provides us an unprecedented opportunity to gain insight into human diseases. In this paper, we adopt the topological similarity in human protein-protein interaction network to predict disease-related genes. As a computational algorithm to speed up the identification of disease-related genes, the topological similarity has substantial advantages over previous topology-based algorithms. First of all, it provides a global measurement of similarity between two vertices. Secondly, quantity which can measure new topological feature has been integrated into the notion of topological similarity. Our method is specially designed for predicting disease-related genes of single disease-gene family. The proposed method is applied to human protein-protein interaction and hepatocellular carcinoma (HCC) data. The results show a significant enrichment of disease-related genes that are characterized by higher topological similarity than other genes.

  6. Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples.

    PubMed Central

    Kirchhamer, C V; Yuh, C H; Davidson, E H

    1996-01-01

    The cis-regulatory systems that control developmental expression of two sea urchin genes have been subjected to detailed functional analysis. Both systems are modular in organization: specific, separable fragments of the cis-regulatory DNA each containing multiple transcription factor target sites execute particular regulatory subfunctions when associated with reporter genes and introduced into the embryo. The studies summarized here were carried out on the CyIIIa gene, expressed in the embryonic aboral ectoderm and on the Endo16 gene, expressed in the embryonic vegetal plate, archenteron, and then midgut. The regulatory systems of both genes include modules that control particular aspects of temporal and spatial expression, and in both the territorial boundaries of expression depend on a combination of negative and positive functions. In both genes different regulatory modules control early and late embryonic expression. Modular cis-regulatory organization is widespread in developmentally regulated genes, and we present a tabular summary that includes many examples from mouse and Drosophila. We regard cis-regulatory modules as units of developmental transcription control, and also of evolution, in the assembly of transcription control systems. Images Fig. 2 PMID:8790328

  7. Nucleotide sequence and characterization of four additional genes of the hydrogenase structural operon from Rhizobium leguminosarum bv. viciae.

    PubMed Central

    Hidalgo, E; Palacios, J M; Murillo, J; Ruiz-Argüeso, T

    1992-01-01

    The nucleotide sequence of a 2.5-kbp region following the hydrogenase structural genes (hupSL) in the H2 uptake gene cluster from Rhizobium leguminosarum bv. viciae UPM791 was determined. Four closely linked genes encoding peptides of 27.9 (hupC), 22.1 (hupD), 19.0 (hupE), and 10.4 (hupF) kDa were identified immediately downstream of hupL. Proteins with comparable apparent molecular weights were detected by heterologous expression of these genes in Escherichia coli. The six genes, hupS to hupF, are arranged as an operon, and by mutant complementation analysis, it was shown that genes hupSLCD are cotranscribed. A transcription start site preceded by the -12 to -24 consensus sequence characteristic of NtrA-dependent promoters was identified upstream of hupS. On the basis of the lack of oxygen-dependent H2 uptake activity of a hupC::Tn5 mutant and on structural characteristics of the protein, we postulate that HupC is a b-type cytochrome involved in electron transfer from hydrogenase to oxygen. The product from hupE, which is needed for full hydrogenase activity, exhibited characteristics typical of a membrane protein. The features of HupC and HupE suggest that they form, together with the hydrogenase itself, a membrane-bound protein complex involved in hydrogen oxidation. Images PMID:1597428

  8. Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: The additive and subtractive effect of the three dopaminergic genes - DRD2, D{beta}H, and DAT1

    SciTech Connect

    Comings, D.E.; Wu, S.; Chiu, C.; Ring, R.H.; Gade, R.; Ahn, C.; Dietz, G.; Muhleman, D.

    1996-05-31

    Polymorphisms of three different dopaminergic genes, dopamine D{sub 2} receptor (DRD2), dopamine {beta}-hydroxylase (D{beta}H), and dopamine transporter (DAT1), were examined in Tourette syndrome (TS) probands, their relatives, and controls. Each gene individually showed a significant correlation with various behavioral variables in these subjects. The additive and subtractive effects of the three genes were examined by genotyping all three genes in the same set of subjects. For 9 of 20 TS associated comorbid behaviors there was a significant linear association between the degree of loading for markers of three genes and the mean behavior scores. The behavior variables showing the significant associations were, in order, attention deficit hyperactivity disorder (ADHD), stuttering, oppositional defiant, tics, conduct, obsessive-compulsive, mania, alcohol abuse, and general anxiety - behaviors that constitute the most overt clinical aspects of TS. For 16 of the 20 behavior scores there was a linear progressive decrease in the mean score with progressively lesser loading for the three gene markers. These results suggest that TS, ADHD, stuttering, oppositional defiant and conduct disorder, and other behaviors associated with TS, are polygenic, due in part to these three dopaminergic genes, and that the genetics of other polygenic psychiatric disorders may be deciphered using this technique. 144 refs., 2 figs., 13 tabs.

  9. Rapid turnover of antimicrobial-type cysteine-rich protein genes in closely related Oryza genomes.

    PubMed

    Shenton, Matthew R; Ohyanagi, Hajime; Wang, Zi-Xuan; Toyoda, Atsushi; Fujiyama, Asao; Nagata, Toshifumi; Feng, Qi; Han, Bin; Kurata, Nori

    2015-10-01

    Defensive and reproductive protein genes undergo rapid evolution. Small, cysteine-rich secreted peptides (CRPs) act as antimicrobial agents and function in plant intercellular signaling and are over-represented among reproductively expressed proteins. Because of their roles in defense, reproduction and development and their presence in multigene families, CRP variation can have major consequences for plant phenotypic and functional diversification. We surveyed the CRP genes of six closely related Oryza genomes comprising Oryza sativa ssp. japonica and ssp. indica, Oryza glaberrima and three accessions of Oryza rufipogon to observe patterns of evolution in these gene families and the effects of variation on their gene expression. These Oryza genomes, like other plant genomes, have accumulated large reservoirs of CRP sequences, comprising 26 groups totaling between 676 and 843 genes, in contrast to antimicrobial CRPs in animal genomes. Despite the close evolutionary relationships between the genomes, we observed rapid changes in number and structure among CRP gene families. Many CRP sequences are in gene clusters generated by local duplications, have undergone rapid turnover and are more likely to be silent or specifically expressed. By contrast, conserved CRP genes are more likely to be highly and broadly expressed. Variable CRP genes created by repeated duplication, gene modification and inactivation can gain new functions and expression patterns in newly evolved gene copies. For the CRP proteins, the process of gain/loss by deletion or duplication at gene clusters seems to be an important mechanism in evolution of the gene families, which also contributes to their expression evolution. PMID:25842177

  10. The study of the relation of DNA repair pathway genes SNPs and the sensitivity to radiotherapy and chemotherapy of NSCLC.

    PubMed

    Wang, Chunbo; Nie, Huan; Li, Yiqun; Liu, Guiyou; Wang, Xu; Xing, Shijie; Zhang, Liping; Chen, Xin; Chen, Yue; Li, Yu

    2016-01-01

    To analyze the relation between SNPs in DNA repair pathway-related genes and sensitivity of tumor radio-chemotherapy, 26 SNPs in 20 DNA repair genes were genotyped on 176 patients of NSCLC undertaking radio-chemotherapy treatment. In squamous cell carcinoma (SCC), as the rs2228000, rs2228001 (XPC), rs2273953 (TP73), rs2279744 (MDM2), rs2299939 (PTEN) and rs8178085, rs12334811 (DNA-PKcs) affected the sensitivity to chemotherapy, so did the rs8178085, rs12334811 to radiotherapy. Moreover rs344781, rs2273953 and rs12334811 were related with the survival time of SCC. In general, the "good" genotype GG (rs12334811) showed greater efficacy of radio-chemotherapy and MSF (24 months) on SCC. In adenocarcinoma, as the rs2699887 (PIK3), rs12334811 (DNA-PKcs) influenced the sensitivity to chemotherapy, so did the rs2299939, rs2735343 (PTEN) to radiotherapy. And rs402710, rs80270, rs2279744 and rs2909430 impacted the survival time of the adenocarcinoma patients. Both GG (rs2279744) and AG (rs2909430) showed a shorter survival time (MFS = 6). Additionally, some SNPs such as rs2228000, rs2228001 and rs344781 were found to regulate the expression of DNA repair pathway genes through eQTLs dataset analysis. These results indicate that SNPs in DNA repair pathway genes might regulate the expression and affect the DNA damage repair, and thereby impact the efficacy of radio-chemotherapy and the survival time of NSCLC. PMID:27246533

  11. The study of the relation of DNA repair pathway genes SNPs and the sensitivity to radiotherapy and chemotherapy of NSCLC

    PubMed Central

    Wang, Chunbo; Nie, Huan; Li, Yiqun; Liu, Guiyou; Wang, Xu; Xing, Shijie; Zhang, Liping; Chen, Xin; Chen, Yue; Li, Yu

    2016-01-01

    To analyze the relation between SNPs in DNA repair pathway-related genes and sensitivity of tumor radio-chemotherapy, 26 SNPs in 20 DNA repair genes were genotyped on 176 patients of NSCLC undertaking radio-chemotherapy treatment. In squamous cell carcinoma (SCC), as the rs2228000, rs2228001 (XPC), rs2273953 (TP73), rs2279744 (MDM2), rs2299939 (PTEN) and rs8178085, rs12334811 (DNA-PKcs) affected the sensitivity to chemotherapy, so did the rs8178085, rs12334811 to radiotherapy. Moreover rs344781, rs2273953 and rs12334811 were related with the survival time of SCC. In general, the “good” genotype GG (rs12334811) showed greater efficacy of radio-chemotherapy and MSF (24 months) on SCC. In adenocarcinoma, as the rs2699887 (PIK3), rs12334811 (DNA-PKcs) influenced the sensitivity to chemotherapy, so did the rs2299939, rs2735343 (PTEN) to radiotherapy. And rs402710, rs80270, rs2279744 and rs2909430 impacted the survival time of the adenocarcinoma patients. Both GG (rs2279744) and AG (rs2909430) showed a shorter survival time (MFS = 6). Additionally, some SNPs such as rs2228000, rs2228001 and rs344781 were found to regulate the expression of DNA repair pathway genes through eQTLs dataset analysis. These results indicate that SNPs in DNA repair pathway genes might regulate the expression and affect the DNA damage repair, and thereby impact the efficacy of radio-chemotherapy and the survival time of NSCLC. PMID:27246533

  12. SEPALLATA1/2-suppressed mature apples have low ethylene, high auxin and reduced transcription of ripening-related genes

    PubMed Central

    Schaffer, Robert J.; Ireland, Hilary S.; Ross, John J.; Ling, Toby J.; David, Karine M.

    2012-01-01

    Background and aims Fruit ripening is an important developmental trait in fleshy fruits, making the fruit palatable for seed dispersers. In some fruit species, there is a strong association between auxin concentrations and fruit ripening. We investigated the relationship between auxin concentrations and the onset of ethylene-related ripening in Malus × domestica (apples) at both the hormone and transcriptome levels. Methodology Transgenic apples suppressed for the SEPALLATA1/2 (SEP1/2) class of gene (MADS8/9) that showed severely reduced ripening were compared with untransformed control apples. In each apple type, free indole-3-acetic acid (IAA) concentrations were measured during early ripening. The changes observed in auxin were assessed in light of global changes in gene expression. Principal results It was found that mature MADS8/9-suppressed apples had a higher concentration of free IAA. This was associated with increased expression of the auxin biosynthetic genes in the indole-3-acetamide pathway. Additionally, in the MADS8/9-suppressed apples, there was less expression of the GH3 auxin-conjugating enzymes. A number of genes involved in the auxin-regulated transcription (AUX/IAA and ARF classes of genes) were also observed to change in expression, suggesting a mechanism for signal transduction at the start of ripening. Conclusions The delay in ripening observed in MADS8/9-suppressed apples may be partly due to high auxin concentrations. We propose that, to achieve low auxin associated with fruit maturation, the auxin homeostasis is controlled in a two-pronged manner: (i) by the reduction in biosynthesis and (ii) by an increase in auxin conjugation. This is associated with the change in expression of auxin-signalling genes and the up-regulation of ripening-related genes. PMID:23346344

  13. Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence

    PubMed Central

    Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

    2015-01-01

    Background: There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. Methods: All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. Results: The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. Conclusion: The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma. PMID:26131062

  14. Comprehensive Analysis of Genic Male Sterility-Related Genes in Brassica rapa Using a Newly Developed Br300K Oligomeric Chip

    PubMed Central

    Dong, Xiangshu; Feng, Hui; Xu, Ming; Lee, Jeongyeo; Kim, Yeon Ki; Lim, Yong Pyo; Piao, Zhongyun; Park, Young Doo; Ma, Hong; Hur, Yoonkang

    2013-01-01

    To identify genes associated with genic male sterility (GMS) that could be useful for hybrid breeding in Chinese cabbage (Brassicarapa ssp. pekinensis), floral bud transcriptome analysis was carried out using a B. rapa microarray with 300,000 probes (Br300K). Among 47,548 clones deposited on a Br300K microarray with seven probes of 60 nt length within the 3' 150 bp region, a total of 10,622 genes were differentially expressed between fertile and sterile floral buds; 4,774 and 5,848 genes were up-regulated over 2-fold in fertile and sterile buds, respectively. However, the expression of 1,413 and 199 genes showed fertile and sterile bud-specific features, respectively. Genes expressed specifically in fertile buds, possibly GMS-related genes, included homologs of several Arabidopsis male sterility-related genes, genes associated with the cell wall and synthesis of its surface proteins, pollen wall and coat components, signaling components, and nutrient supplies. However, most early genes for pollen development, genes for primexine and callose formation, and genes for pollen maturation and anther dehiscence showed no difference in expression between fertile and sterile buds. Some of the known genes associated with Arabidopsis pollen development showed similar expression patterns to those seen in this study, while others did not. BrbHLH89 and BrMYP99 are putative GMS genes. Additionally, 17 novel genes identified only in B. rapa were specifically and highly expressed only in fertile buds, implying the possible involvement in male fertility. All data suggest that Chinese cabbage GMS might be controlled by genes acting in post-meiotic tapetal development that are different from those known to be associated with Arabidopsis male sterility. PMID:24039743

  15. Evolution of hedgehog and hedgehog-related genes, their origin from Hog proteins in ancestral eukaryotes and discovery of a novel Hint motif

    PubMed Central

    Bürglin, Thomas R

    2008-01-01

    Background The Hedgehog (Hh) signaling pathway plays important roles in human and animal development as well as in carcinogenesis. Hh molecules have been found in both protostomes and deuterostomes, but curiously the nematode Caenorhabditis elegans lacks a bona-fide Hh. Instead a series of Hh-related proteins are found, which share the Hint/Hog domain with Hh, but have distinct N-termini. Results We performed extensive genome searches such as the cnidarian Nematostella vectensis and several nematodes to gain further insights into Hh evolution. We found six genes in N. vectensis with a relationship to Hh: two Hh genes, one gene with a Hh N-terminal domain fused to a Willebrand factor type A domain (VWA), and three genes containing Hint/Hog domains with distinct novel N-termini. In the nematode Brugia malayi we find the same types of hh-related genes as in C. elegans. In the more distantly related Enoplea nematodes Xiphinema and Trichinella spiralis we find a bona-fide Hh. In addition, T. spiralis also has a quahog gene like C. elegans, and there are several additional hh-related genes, some of which have secreted N-terminal domains of only 15 to 25 residues. Examination of other Hh pathway components revealed that T. spiralis - like C. elegans - lacks some of these components. Extending our search to all eukaryotes, we recovered genes containing a Hog domain similar to Hh from many different groups of protists. In addition, we identified a novel Hint gene family present in many eukaryote groups that encodes a VWA domain fused to a distinct Hint domain we call Vint. Further members of a poorly characterized Hint family were also retrieved from bacteria. Conclusion In Cnidaria and nematodes the evolution of hh genes occurred in parallel to the evolution of other genes that contain a Hog domain but have different N-termini. The fact that Hog genes comprising a secreted N-terminus and a Hog domain are found in many protists indicates that this gene family must have

  16. The Oxytocin Receptor Gene (OXTR) in Relation to State Levels of Loneliness in Adolescence: Evidence for Micro-Level Gene-Environment Interactions

    PubMed Central

    van Roekel, Eeske; Verhagen, Maaike; Scholte, Ron H. J.; Kleinjan, Marloes; Goossens, Luc; Engels, Rutger C. M. E.

    2013-01-01

    Previous research has shown that the rs53576 variant of the oxytocin receptor gene (OXTR) is associated with trait levels of loneliness, but results are inconsistent. The aim of the present study is to examine micro-level effects of the OXTR rs53576 variant on state levels of loneliness in early adolescents. In addition, gene-environment interactions are examined between this OXTR variant and positive and negative perceptions of company. Data were collected in 278 adolescents (58% girls), by means of the Experience Sampling Method (ESM). Sampling periods consisted of six days with nine assessments per day. A relation was found between the OXTR rs53576 variant and state loneliness, in girls only. Girls carrying an A allele had higher levels of state loneliness than girls carrying the GG genotype. In addition, adolescents with an A allele were more affected by negative perceptions of company than GG carriers, on weekend days only. No significant gene-environment interactions were found with positive company. Adolescents carrying an A allele were more susceptible to negative environments during weekend days than GG carriers. Our findings emphasize the importance of operationalizing the phenotype and the environment accurately. PMID:24223720

  17. miRTex: A Text Mining System for miRNA-Gene Relation Extraction

    PubMed Central

    Li, Gang; Ross, Karen E.; Arighi, Cecilia N.; Peng, Yifan; Wu, Cathy H.; Vijay-Shanker, K.

    2015-01-01

    MicroRNAs (miRNAs) regulate a wide range of cellular and developmental processes through gene expression suppression or mRNA degradation. Experimentally validated miRNA gene targets are often reported in the literature. In this paper, we describe miRTex, a text mining system that extracts miRNA-target relations, as well as miRNA-gene and gene-miRNA regulation relations. The system achieves good precision and recall when evaluated on a literature corpus of 150 abstracts with F-scores close to 0.90 on the three different types of relations. We conducted full-scale text mining using miRTex to process all the Medline abstracts and all the full-length articles in the PubMed Central Open Access Subset. The results for all the Medline abstracts are stored in a database for interactive query and file download via the website at http://proteininformationresource.org/mirtex. Using miRTex, we identified genes potentially regulated by miRNAs in Triple Negative Breast Cancer, as well as miRNA-gene relations that, in conjunction with kinase-substrate relations, regulate the response to abiotic stress in Arabidopsis thaliana. These two use cases demonstrate the usefulness of miRTex text mining in the analysis of miRNA-regulated biological processes. PMID:26407127

  18. Recognition- and defense-related gene expression at 3 resynthesis stages in lichen symbionts.

    PubMed

    Athukorala, Sarangi N P; Piercey-Normore, Michele D

    2015-01-01

    Recognition and defense responses are early events in plant-pathogen interactions and between lichen symbionts. The effect of elicitors on responses between lichen symbionts is not well understood. The objective of this study was to compare the difference in recognition- and defense-related gene expression as a result of culture extracts (containing secreted water-soluble elicitors) from compatible and incompatible interactions at each of 3 resynthesis stages in the symbionts of Cladonia rangiferina. This study investigated gene expression by quantitative PCR in cultures of C. rangiferina and its algal partner, Asterochloris glomerata/irregularis, after incubation with liquid extracts from cultures of compatible and incompatible interactions at 3 early resynthesis stages. Recognition-related genes were significantly upregulated only after physical contact, demonstrating symbiont recognition in later resynthesis stages than expected. One of 3 defense-related genes, chit, showed significant downregulation in early resynthesis stages and upregulation in the third resynthesis stage, demonstrating a need for the absence of chitinase early in thallus formation and a need for its presence in later stages as an algal defense reaction. This study revealed that recognition- and defense-related genes are triggered by components in culture extracts at 3 stages of resynthesis, and some defense-related genes may be induced throughout thallus growth. The parasitic nature of the interaction shows parallels between lichen symbionts and plant pathogenic systems. PMID:25485526

  19. NHR-23 dependent collagen and hedgehog-related genes required for molting

    SciTech Connect

    Kouns, Nathaniel A.; Nakielna, Johana; Behensky, Frantisek; Krause, Michael W.; Kostrouch, Zdenek; Kostrouchova, Marta

    2011-10-07

    Highlights: {yields} NHR-23 is a critical regulator of nematode development and molting. {yields} The manuscript characterizes the loss-of-function phenotype of an nhr-23 mutant. {yields} Whole genome expression analysis identifies new potential targets of NHR-23. {yields} Hedgehog-related genes are identified as NHR-23 dependent genes. {yields} New link between sterol mediated signaling and regulation by NHR-23 is found. -- Abstract: NHR-23, a conserved member of the nuclear receptor family of transcription factors, is required for normal development in Caenorhabditis elegans where it plays a critical role in growth and molting. In a search for NHR-23 dependent genes, we performed whole genome comparative expression microarrays on both control and nhr-23 inhibited synchronized larvae. Genes that decreased in response to nhr-23 RNAi included several collagen genes. Unexpectedly, several hedgehog-related genes were also down-regulated after nhr-23 RNAi. A homozygous nhr-23 deletion allele was used to confirm the RNAi knockdown phenotypes and the changes in gene expression. Our results indicate that NHR-23 is a critical co-regulator of functionally linked genes involved in growth and molting and reveal evolutionary parallels among the ecdysozoa.

  20. Identification of Genes Related to Paulownia Witches’ Broom by AFLP and MSAP

    PubMed Central

    Cao, Xibing; Fan, Guoqiang; Deng, Minjie; Zhao, Zhenli; Dong, Yanpeng

    2014-01-01

    DNA methylation is believed to play important roles in regulating gene expression in plant growth and development. Paulownia witches’ broom (PaWB) infection has been reported to be related to gene expression changes in paulownia plantlets. To determine whether DNA methylation is associated with gene expression changes in response to phytoplasma, we investigated variations in genomic DNA sequence and methylation in PaWB plantlets treated with methyl methane sulfonate (MMS) using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) techniques, respectively. The results indicated that PaWB seedings recovered a normal morphology after treatment with more than 15 mg·L−1 MMS. PaWB infection did not cause changes of the paulownia DNA sequence at the AFLP level; However, DNA methylation levels and patterns were altered. Quantitative real-time PCR (qRT-PCR) showed that three of the methylated genes were up-regulated and three were down-regulated in the MMS-treated PaWB plantlets that had regained healthy morphology. These six genes might be involved in transcriptional regulation, plant defense, signal transduction and energy. The possible roles of these genes in PaWB are discussed. The results showed that changes of DNA methylation altered gene expression levels, and that MSAP might help identify genes related to PaWB. PMID:25196603

  1. Steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation

    PubMed Central

    Lima, Gisele Negro; Maganhin, Carla Cristina; Simões, Ricardo Santos; Baracat, Maria Cândida Pinheiro; da Silva Sasso, Gisela Rodrigues; Fuchs, Luiz Fernando Portugal; de Jesus Simões, Manuel; Baracat, Edmund Chada; Júnior, José Maria Soares

    2015-01-01

    OBJECTIVE: To analyze steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation. METHODS: Thirty-two virgin adult female rats were randomized to two groups as follows: the control group GI received vehicle and the experimental group GII received melatonin supplementation (10 µg/night per animal) for 60 consecutive days. After the treatment, animals were anesthetized and the collected ovaries were immediately placed in liquid nitrogen for complementary deoxyribonucleic acid microarray analyses. A GeneChip® Kit Rat Genome 230 2.0 Affymetrix Array was used for gene analysis and the experiment was repeated three times for each group. The results were normalized with the GeneChip® Operating Software program and confirmed through analysis with the secondary deoxyribonucleic acid-Chip Analyzer (dChip) software. The data were confirmed by real-time reverse transcription polymerase chain reaction analysis. Genes related to ovarian function were further confirmed by immunohistochemistry. RESULTS: We found the upregulation of the type 9 adenylate cyclase and inhibin beta B genes and the downregulation of the cyclic adenosine monophosphate response element modulator and cytochrome P450 family 17a1 genes in the ovarian tissue of GII compared to those of the control group. CONCLUSION: Our data suggest that melatonin supplementation decreases gene expression of cyclic adenosine monophosphate, which changes ovarian steroidogenesis. PMID:25789524

  2. Identification of hepatocellular carcinoma-related genes with a machine learning and network analysis.

    PubMed

    Gui, Tuantuan; Dong, Xiao; Li, Rudong; Li, Yixue; Wang, Zhen

    2015-01-01

    Liver cancer is one of the leading causes of cancer mortality worldwide. Hepatocellular carcinoma (HCC) is the main type of liver cancer. We applied a machine learning approach with maximum-relevance-minimum-redundancy (mRMR) algorithm followed by incremental feature selection (IFS) to a set of microarray data generated from 43 tumor and 52 nontumor samples. With the machine learning approach, we identified 117 gene probes that could optimally separate tumor and nontumor samples. These genes not only include known HCC-relevant genes such as MT1X, BMI1, and CAP2, but also include cancer genes that were not found previously to be closely related to HCC, such as TACSTD2. Then, we constructed a molecular interaction network based on the protein-protein interaction (PPI) data from the STRING database and identified 187 genes on the shortest paths among the genes identified with the machine learning approach. Network analysis reveals new potential roles of ubiquitin C in the pathogenesis of HCC. Based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, we showed that the identified subnetwork is significantly enriched in biological processes related to cell death. These results bring new insights of understanding the process of HCC. PMID:25247452

  3. Differential expression of apoptosis-related genes in the cochlea of noise-exposed rats

    PubMed Central

    Hu, Bo Hua; Cai, Qunfeng; Manohar, Senthilvelan; Jiang, Haiyan; Ding, Dalian; Coling, Donald E.; Zheng, Guiliang; Salvi, Richard

    2009-01-01

    Exposure to intense noise induces apoptosis in hair cells in the cochlea. To identify the molecular changes associated with noise-induced apoptosis, we used quantitative real-time PCR to evaluate the changes in 84 apoptosis related genes in cochlear samples from the sensory epithelium and lateral wall. Sprague Dawley rats exposed to a continuous noise at 115 dB SPL for 2 h. The exposure caused a 40–60 dB threshold shift 4 h post-exposure that decreased to 20–30 dB 7 days post-exposure. These functional changes were associated with apoptotic markers including nuclear condensation and fragmentation and TUNEL staining. Immediately after the noise exposure, 12 genes were downregulated, whereas only one gene (Traf4) was upregulated. At 4 h post-exposure, 8 genes were upregulated; 3 (Tnrsf1a, Tnfrsf1b, Tnfrst5) belonged to the Tnfrsf family, 3 (Bir3, Mcl1 and Prok2) have anti-apoptotic properties and 1 (Gadd45a) is a target of p53. At 7 d post-exposure, all the upregulated genes returned to pre-noise levels. Interestingly, the normal control cochlea had high constitutive levels of several apoptosis-related genes. These constitutively expressed genes, together with the inducible genes, may participate in the induction of cochlear apoptotic activity. PMID:19348871

  4. Massive expansion of Ubiquitination-related gene families within the Chlamydiae.

    PubMed

    Domman, Daryl; Collingro, Astrid; Lagkouvardos, Ilias; Gehre, Lena; Weinmaier, Thomas; Rattei, Thomas; Subtil, Agathe; Horn, Matthias

    2014-11-01

    Gene loss, gain, and transfer play an important role in shaping the genomes of all organisms; however, the interplay of these processes in isolated populations, such as in obligate intracellular bacteria, is less understood. Despite a general trend towards genome reduction in these microbes, our phylogenomic analysis of the phylum Chlamydiae revealed that within the family Parachlamydiaceae, gene family expansions have had pronounced effects on gene content. We discovered that the largest gene families within the phylum are the result of rapid gene birth-and-death evolution. These large gene families are comprised of members harboring eukaryotic-like ubiquitination-related domains, such as F-box and BTB-box domains, marking the largest reservoir of these proteins found among bacteria. A heterologous type III secretion system assay suggests that these proteins function as effectors manipulating the host cell. The large disparity in copy number of members in these families between closely related organisms suggests that nonadaptive processes might contribute to the evolution of these gene families. Gene birth-and-death evolution in concert with genomic drift might represent a previously undescribed mechanism by which isolated bacterial populations diversify. PMID:25069652

  5. Massive Expansion of Ubiquitination-Related Gene Families within the Chlamydiae

    PubMed Central

    Domman, Daryl; Collingro, Astrid; Lagkouvardos, Ilias; Gehre, Lena; Weinmaier, Thomas; Rattei, Thomas; Subtil, Agathe; Horn, Matthias

    2014-01-01

    Gene loss, gain, and transfer play an important role in shaping the genomes of all organisms; however, the interplay of these processes in isolated populations, such as in obligate intracellular bacteria, is less understood. Despite a general trend towards genome reduction in these microbes, our phylogenomic analysis of the phylum Chlamydiae revealed that within the family Parachlamydiaceae, gene family expansions have had pronounced effects on gene content. We discovered that the largest gene families within the phylum are the result of rapid gene birth-and-death evolution. These large gene families are comprised of members harboring eukaryotic-like ubiquitination-related domains, such as F-box and BTB-box domains, marking the largest reservoir of these proteins found among bacteria. A heterologous type III secretion system assay suggests that these proteins function as effectors manipulating the host cell. The large disparity in copy number of members in these families between closely related organisms suggests that nonadaptive processes might contribute to the evolution of these gene families. Gene birth-and-death evolution in concert with genomic drift might represent a previously undescribed mechanism by which isolated bacterial populations diversify. PMID:25069652

  6. Glycosylation-related genes in NS0 cells are insensitive to moderately elevated ammonium concentrations

    PubMed Central

    Brodsky, Arthur Nathan; Caldwell, Mary; Bae, Sooneon; Harcum, Sarah W.

    2014-01-01

    NS0 and Chinese hamster ovary (CHO) cell lines are used to produce recombinant proteins for human therapeutics; however, ammonium accumulation can negatively impact cell growth, recombinant protein production, and protein glycosylation. To improve product quality and decrease costs, the relationship between ammonium and protein glycosylation needs to be elucidated. While ammonium has been shown to adversely affect glycosylation-related gene expression in CHO cells, NS0 studies have not been performed. Therefore, this study sought to determine if glycosylation in NS0 cells were ammonium-sensitive at the gene expression level. Using a DNA microarray that contained mouse glycosylation-related and housekeeping genes, the of these genes was analysed in response to various culture conditions – elevated ammonium, elevated salt, and elevated ammonium with proline. Surprisingly, no significant differences in gene expression levels were observed between the control and these conditions. Further, the elevated ammonium cultures were analysed using real-time quantitative reverse transcriptase PCR (qRT-PCR) for key glycosylation genes, and the qRT-PCR results corroborated the DNA microarray results, demonstrating that NS0 cells are ammonium-insensitive at the gene expression level. Since NS0 are known to have elevated nucleotide sugar pools under ammonium stress, and none of the genes directly responsible for these metabolic pools were changed, consequently cellular control at the translational or substrate-level must be responsible for the universally observed decreased glycosylation quality under elevated ammonium. PMID:25062658

  7. pdc1(0) mutants of Saccharomyces cerevisiae give evidence for an additional structural PDC gene: cloning of PDC5, a gene homologous to PDC1.

    PubMed Central

    Seeboth, P G; Bohnsack, K; Hollenberg, C P

    1990-01-01

    The PDC1 gene coding for a pyruvate decarboxylase (PDC; EC 4.1.1.1) was deleted from the Saccharomyces cerevisiae genome. The resulting pdc1(0) mutants were able to grow on glucose and still contained 60 to 70% of the wild-type PDC activity. Two DNA fragments with sequences homologous to that of the PDC1 gene were cloned from the yeast genome. One of the cloned genes (PDC5) was expressed at high rates predominantly in pdc1(0) strains and probably encodes the remaining PDC activity in these strains. Expression from the PDC1 promoter in PDC1 wild-type and pdc1(0) strains was examined by the use of two reporter genes. Deletion of PDC1 led to increased expression of the two reporter genes regardless of whether the fusions were integrated into the genome or present on autonomously replicating plasmids. The results suggested that this effect was due to feedback regulation of the PDC1 promoter-driven expression in S. cerevisiae pdc1(0) strains. The yeast PDC1 gene was expressed in Escherichia coli, leading to an active PDC. This result shows that the PDC1-encoded subunit alone can form an active tetramer without yeast-specific processing steps. Images FIG. 1 FIG. 4 FIG. 5 FIG. 6 PMID:2404950

  8. Comparative transcriptome analysis reveals defense-related genes and pathways against downy mildew in Vitis amurensis grapevine.

    PubMed

    Li, Xinlong; Wu, Jiao; Yin, Ling; Zhang, Yali; Qu, Junjie; Lu, Jiang

    2015-10-01

    Downy mildew (DM), caused by oomycete Plasmopara viticola (Pv), can lead to severe damage to Vitis vinifera grapevines. Vitis amurensis has generally been regarded as a DM resistant species. However, when V. amurensis 'Shuanghong' were inoculated with Pv strains 'ZJ-1-1' and 'JL-7-2', the former led to obvious DM symptoms (compatible), while the latter did not develop any DM symptoms but exhibited necrosis (incompatible). In order to underlie molecular mechanism in DM resistance, mRNA-seq based expression profiling of 'Shuanghong' was compared at 12, 24, 48 and 72 h post inoculation (hpi) with these two strains. Specific genes and their corresponding pathways responsible for incompatible interaction were extracted by comparing with compatible interaction. In the incompatible interaction, 37 resistance (R) genes were more expressed at the early stage of infection (12 hpi). Similarly, genes involved in defense signaling, including MAPK. ROS/NO, SA, JA, ET and ABA pathways, and genes associated with defense-related metabolites synthesis, such as pathogenesis-related genes and phenylpropanoids/stilbenoids/flavonoids biosynthesizing genes, were also activated mainly during the early stages of infection. On the other hand, Ca(2+) signaling and primary metabolism, such as photosynthesis and fatty acid synthesis, were more repressed after 'JL-7-2' challenge. Further quantification of some key defense-related factors, including phytohormones, phytoalexins and ROS, generally showed much more accumulation during the incompatible interaction, indicating their important roles in DM defense. In addition, a total of 43 and 52 RxLR effectors were detected during 'JL-7-2' and 'ZJ-1-1' infection processes, respectively. PMID:26151858

  9. Life spanning murine gene expression profiles in relation to chronological and pathological aging in multiple organs.

    PubMed

    Jonker, Martijs J; Melis, Joost P M; Kuiper, Raoul V; van der Hoeven, Tessa V; Wackers, Paul F K; Robinson, Joke; van der Horst, Gijsbertus T J; Dollé, Martijn E T; Vijg, Jan; Breit, Timo M; Hoeijmakers, Jan H J; van Steeg, Harry

    2013-10-01

    Aging and age-related pathology is a result of a still incompletely understood intricate web of molecular and cellular processes. We present a C57BL/6J female mice in vivo aging study of five organs (liver, kidney, spleen, lung, and brain), in which we compare genome-wide gene expression profiles during chronological aging with pathological changes throughout the entire murine life span (13, 26, 52, 78, 104, and 130 weeks). Relating gene expression changes to chronological aging revealed many differentially expressed genes (DEGs), and altered gene sets (AGSs) were found in most organs, indicative of intraorgan generic aging processes. However, only ≤ 1% of these DEGs are found in all organs. For each organ, at least one of 18 tested pathological parameters showed a good age-predictive value, albeit with much inter- and intraindividual (organ) variation. Relating gene expression changes to pathology-related aging revealed correlated genes and gene sets, which made it possible to characterize the difference between biological and chronological aging. In liver, kidney, and brain, a limited number of overlapping pathology-related AGSs were found. Immune responses appeared to be common, yet the changes were specific in most organs. Furthermore, changes were observed in energy homeostasis, reactive oxygen species, cell cycle, cell motility, and DNA damage. Comparison of chronological and pathology-related AGSs revealed substantial overlap and interesting differences. For example, the presence of immune processes in liver pathology-related AGSs that were not detected in chronological aging. The many cellular processes that are only found employing aging-related pathology could provide important new insights into the progress of aging. PMID:23795901

  10. Microevolution of Virulence-Related Genes in Helicobacter pylori Familial Infection

    PubMed Central

    Furuta, Yoshikazu; Konno, Mutsuko; Osaki, Takako; Yonezawa, Hideo; Ishige, Taichiro; Imai, Misaki; Shiwa, Yuh; Shibata-Hatta, Mari; Kanesaki, Yu; Yoshikawa, Hirofumi; Kamiya, Shigeru; Kobayashi, Ichizo

    2015-01-01

    Helicobacter pylori, a bacterial pathogen that can infect human stomach causing gastritis, ulcers and cancer, is known to have a high degree of genome/epigenome diversity as the result of mutation and recombination. The bacteria often infect in childhood and persist for the life of the host. One of the reasons of the rapid evolution of H. pylori is that it changes its genome drastically for adaptation to a new host. To investigate microevolution and adaptation of the H. pylori genome, we undertook whole genome sequencing of the same or very similar sequence type in multi-locus sequence typing (MLST) with seven genes in members of the same family consisting of parents and children in Japan. Detection of nucleotide substitutions revealed likely transmission pathways involving children. Nonsynonymous (amino acid changing) mutations were found in virulence-related genes (cag genes, vacA, hcpDX, tnfα, ggt, htrA and the collagenase gene), outer membrane protein (OMP) genes and other cell surface-related protein genes, signal transduction genes and restriction-modification genes. We reconstructed various pathways by which H. pylori can adapt to a new human host, and our results raised the possibility that the mutational changes in virulence-related genes have a role in adaptation to a child host. Changes in restriction-modification genes might remodel the methylome and transcriptome to help adaptation. This study has provided insights into H. pylori transmission and virulence and has implications for basic research as well as clinical practice. PMID:25978460

  11. Suppression of PCD-related genes affects salt tolerance in Arabidopsis.

    PubMed

    Bahieldin, Ahmed; Alqarni, Dhafer A M; Atef, Ahmed; Gadalla, Nour O; Al-Matary, Mohammed; Edris, Sherif; Al-Kordy, Magdy A; Makki, Rania M; Al-Doss, Abdullah A; Sabir, Jamal S M; Mutwakil, Mohammed H Z; El-Domyati, Fotouh M

    2016-01-01

    This work aims at examining a natural exciting phenomenon suggesting that suppression of genes inducing programmed cell death (PCD) might confer tolerance against abiotic stresses in plants. PCD-related genes were induced in tobacco under oxalic acid (OA) treatment (20mM), and plant cells were characterized to confirm the incidence of PCD. The results indicated that PCD was triggered 24h after the exposure to OA. Then, RNAs were extracted from tobacco cells 0, 2, 6, 12 and 24h after treatment for deep sequencing. RNA-Seq analyses were done with a special emphasis to clusters whose PCD-related genes were upregulated after 2h of OA exposure. Accordingly, 23 tobacco PCD-related genes were knocked down via virus-induced gene silencing (VIGS), whereas our results indicated the influence of five of them on inducing or suppressing PCD. Knockout T-DNA insertion mutants of these five genes in Arabidopsis were tested under salt stress (0, 100, 150, and 200mM NaCl), and the results indicated that a mutant of an antiapoptotic gene, namely Bax Inhibitor-1 (BI-1), whose VIGS induced PCD in tobacco, was salt sensitive, while a mutant of an apoptotic gene, namely mildew resistance locus O (Mlo), whose VIGS suppressed PCD, was salt tolerant as compared to the WT (Col) control. These data support our hypothesis that retarding PCD-inducing genes can result in higher levels of salt tolerance, while retarding PCD-suppressing genes can result in lower levels of salt tolerance in plants. PMID:27052474

  12. Superior Cervical Ganglia Neurons Induce Foxp3+ Regulatory T Cells via Calcitonin Gene-Related Peptide

    PubMed Central

    Szklany, Kirsten; Ruiter, Evelyn; Mian, Firoz; Kunze, Wolfgang; Bienenstock, John; Forsythe, Paul; Karimi, Khalil

    2016-01-01

    The nervous and immune systems communicate bidirectionally, utilizing diverse molecular signals including cytokines and neurotransmitters to provide an integrated response to changes in the body’s internal and external environment. Although, neuro-immune interactions are becoming better understood under inflammatory circumstances and it has been evidenced that interaction between neurons and T cells results in the conversion of encephalitogenic T cells to T regulatory cells, relatively little is known about the communication between neurons and naïve T cells. Here, we demonstrate that following co-culture of naïve CD4+ T cells with superior cervical ganglion neurons, the percentage of Foxp3 expressing CD4+CD25+ cells significantly increased. This was mediated in part by immune-regulatory cytokines TGF-β and IL-10, as well as the neuropeptide calcitonin gene-related peptide while vasoactive intestinal peptide was shown to play no role in generation of T regulatory cells. Additionally, T cells co-cultured with neurons showed a decrease in the levels of pro-inflammatory cytokine IFN-γ released upon in vitro stimulation. These findings suggest that the generation of Tregs may be promoted by naïve CD4+ T cell: neuron interaction through the release of neuropeptide CGRP. PMID:27022966

  13. Gene expression profiling of hormonal regulation related to the residual feed intake of Holstein cattle.

    PubMed

    Xi, Y M; Yang, Z; Wu, F; Han, Z Y; Wang, G L

    2015-09-11

    An accumulation of over a decade of research in cattle has shown that genetic selection for decreased residual feed intake (RFI), defined as the difference between an animal's actual feed intake and its expected feed intake, is a viable option for improving feed efficiency and reducing the feed requirements of herds, thereby improving the profitability of cattle producers. Hormonal regulation is one of the most important factors in feed intake. To determine the relationship between hormones and feed efficiency, we performed gene expression profiling of jugular vein serum on hormonal regulation of Chinese Holstein cattle with low and high RFI coefficients. 857 differential expression genes (from 24683 genes) were found. Among these, 415 genes were up-regulated and 442 genes were down-regulated in the low RFI group. The gene ontology (GO) search revealed 6 significant terms and 64 genes associated with hormonal regulation, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) selected the adipocytokine signaling pathway, insulin signaling pathway. In conclusion, the study indicated that the molecular expression of genes associated with hormonal regulation differs in dairy cows, depending on their RFI coefficients, and that these differences may be related to the molecular regulation of the leptin-NPY and insulin signaling pathways. PMID:26231801

  14. X-linked intellectual disability related genes disrupted by balanced X-autosome translocations.

    PubMed

    Moysés-Oliveira, Mariana; Guilherme, Roberta Santos; Meloni, Vera Ayres; Di Battista, Adriana; de Mello, Claudia Berlim; Bragagnolo, Silvia; Moretti-Ferreira, Danilo; Kosyakova, Nadezda; Liehr, Thomas; Carvalheira, Gianna Maria; Melaragno, Maria Isabel

    2015-12-01

    Detailed molecular characterization of chromosomal rearrangements involving X-chromosome has been a key strategy in identifying X-linked intellectual disability-causing genes. We fine-mapped the breakpoints in four women with balanced X-autosome translocations and variable phenotypes, in order to investigate the corresponding genetic contribution to intellectual disability. We addressed the impact of the gene interruptions in transcription and discussed the consequences of their functional impairment in neurodevelopment. Three patients presented with cognitive impairment, reinforcing the association between the disrupted genes (TSPAN7-MRX58, KIAA2022-MRX98, and IL1RAPL1-MRX21/34) and intellectual disability. While gene expression analysis showed absence of TSPAN7 and KIAA2022 expression in the patients, the unexpected expression of IL1RAPL1 suggested a fusion transcript ZNF611-IL1RAPL1 under the control of the ZNF611 promoter, gene disrupted at the autosomal breakpoint. The X-chromosomal breakpoint definition in the fourth patient, a woman with normal intellectual abilities, revealed disruption of the ZDHHC15 gene (MRX91). The expression assays did not detect ZDHHC15 gene expression in the patient, thus questioning its involvement in intellectual disability. Revealing the disruption of an X-linked intellectual disability-related gene in patients with balanced X-autosome translocation is a useful tool for a better characterization of critical genes in neurodevelopment. © 2015 Wiley Periodicals, Inc. PMID:26290131

  15. An integrative evolution theory of histo-blood group ABO and related genes.

    PubMed

    Yamamoto, Fumiichiro; Cid, Emili; Yamamoto, Miyako; Saitou, Naruya; Bertranpetit, Jaume; Blancher, Antoine

    2014-01-01

    The ABO system is one of the most important blood group systems in transfusion/transplantation medicine. However, the evolutionary significance of the ABO gene and its polymorphism remained unknown. We took an integrative approach to gain insights into the significance of the evolutionary process of ABO genes, including those related not only phylogenetically but also functionally. We experimentally created a code table correlating amino acid sequence motifs of the ABO gene-encoded glycosyltransferases with GalNAc (A)/galactose (B) specificity, and assigned A/B specificity to individual ABO genes from various species thus going beyond the simple sequence comparison. Together with genome information and phylogenetic analyses, this assignment revealed early appearance of A and B gene sequences in evolution and potentially non-allelic presence of both gene sequences in some animal species. We argue: Evolution may have suppressed the establishment of two independent, functional A and B genes in most vertebrates and promoted A/B conversion through amino acid substitutions and/or recombination; A/B allelism should have existed in common ancestors of primates; and bacterial ABO genes evolved through horizontal and vertical gene transmission into 2 separate groups encoding glycosyltransferases with distinct sugar specificities. PMID:25307962

  16. Predicting Gene Expression Level from Relative Codon Usage Bias: An Application to Escherichia coli Genome

    PubMed Central

    Roymondal, Uttam; Das, Shibsankar; Sahoo, Satyabrata

    2009-01-01

    We present an expression measure of a gene, devised to predict the level of gene expression from relative codon bias (RCB). There are a number of measures currently in use that quantify codon usage in genes. Based on the hypothesis that gene expressivity and codon composition is strongly correlated, RCB has been defined to provide an intuitively meaningful measure of an extent of the codon preference in a gene. We outline a simple approach to assess the strength of RCB (RCBS) in genes as a guide to their likely expression levels and illustrate this with an analysis of Escherichia coli (E. coli) genome. Our efforts to quantitatively predict gene expression levels in E. coli met with a high level of success. Surprisingly, we observe a strong correlation between RCBS and protein length indicating natural selection in favour of the shorter genes to be expressed at higher level. The agreement of our result with high protein abundances, microarray data and radioactive data demonstrates that the genomic expression profile available in our method can be applied in a meaningful way to the study of cell physiology and also for more detailed studies of particular genes of interest. PMID:19131380

  17. Alterations in replication timing of cancer-related genes in malignant human breast cancer cells.

    PubMed

    Fritz, Andrew; Sinha, Seema; Marella, Narasimharao; Berezney, Ronald

    2013-05-01

    The replication timing of nine genes commonly involved in cancer was investigated in the MCF10 cell lines for human breast cancer progression. Six of these nine genes are part of a constellation of tumor suppressor genes that play a major role in familial human breast cancer (TP53, ATM, PTEN, CHK2, BRCA1, and BRCA2). Three other genes are involved in a large number of human cancers including breast as either tumor suppressors (RB1 and RAD51) or as an oncogene (cMYC). Five of these nine genes (TP53, RAD51, ATM, PTEN, and cMYC) show significant differences (P < 0.05) in replication timing between MCF10A normal human breast cells and the corresponding malignant MCF10CA1a cells. These differences are specific to the malignant state of the MCF10CA1a cells since there were no significant differences in the replication timing of these genes between normal MCF10A cells and the non-malignant cancer MCF10AT1 cells. Microarray analysis further demonstrated that three of these five genes (TP53, RAD51, and cMYC) showed significant changes in gene expression (≥2-fold) between normal and malignant cells. Our findings demonstrate an alteration in the replication timing of a small subset of cancer-related genes in malignant breast cancer cells. These alterations partially correlate with the major transcriptional changes characteristic of the malignant state in these cells. PMID:23161755

  18. Evolutionary analysis of the APA genes in the Phaseolus genus: wild and cultivated bean species as sources of lectin-related resistance factors?

    PubMed

    Lioi, L; Galasso, I; Lanave, C; Daminati, M G; Bollini, R; Sparvoli, F

    2007-11-01

    The APA (Arcelin/Phytohemagglutinin/alpha-Amylase inhibitor) gene family is composed of various members, present in Phaseolus species and coding for lectin and lectin-related seed proteins having the double role of storage and defense proteins. Here members of the APA family have been identified by immunological, functional, and molecular analyses and representative genes were sequenced in nine wild species of Phaseolus. All taxa possessed at least one member of the true lectin gene. No arcelin type sequences have been isolated from the species examined. Among the wild species studied, only P. costaricensis contained an alpha-amylase inhibitor (alpha-AI). In addition P. augusti, P. maculatus, P. microcarpus, and P. oligospermus showed the presence of the lectin-related alpha-amylase inhibitor-like (AIL) genes and alpha-AI activity. Data from Southern blot analysis indicated the presence of only one lectin gene in P. parvulus and P. filiformis, while an extensive gene duplication of the APA locus was found in the other Phaseolus species. Phylogenetic analysis carried out on the nucleotide sequences showed the existence of two main clusters and clearly indicated that lectin-related genes originated from a paralogous duplication event preceding the development of the ancestor to the Phaseolus genus. The finding of detectable alpha-AI activity in species containing AIL genes suggests that exploiting APA genes variability in the Phaseolus genus may represent a valuable tool to find new members that may have acquired insecticidal activities. PMID:17701394

  19. Hormone therapy and maximal eccentric exercise alters myostatin-related gene expression in postmenopausal women.

    PubMed

    Dieli-Conwright, Christina M; Spektor, Tanya M; Rice, Judd C; Sattler, Fred R; Schroeder, E Todd

    2012-05-01

    We sought to evaluate baseline mRNA values and changes in gene expression of myostatin-related factors in postmenopausal women taking hormone therapy (HT) and not taking HT after eccentric exercise. Fourteen postmenopausal women participated including 6 controls not using HT (59 ± 4 years, 63 ± 17 kg) and 8 women using HT (59 ± 4 years, 89 ± 24 kg). The participants performed 10 sets of 10 maximal eccentric repetitions of single-leg extension on a dynamometer. Muscle biopsies from the vastus lateralis were obtained from the exercised leg at baseline and 4 hours after the exercise bout. Gene expression was determined using reverse transcriptase polymerase chain reaction for myostatin, activin receptor IIb (ActRIIb), follistatin, follistatin-related gene (FLRG), follistatin-like-3 (FSTL3), and GDF serum-associated protein-1 (GASP-1). In response to the exercise bout, myostatin and ActRIIb significantly decreased (p < 0.05), and follistatin, FLRG, FSTL3, and GASP-1 significantly increased in both groups (p < 0.05). Significantly greater changes in gene expression of all genes occurred in the HT group than in the control group after the acute eccentric exercise bout (p < 0.05). These data suggest that postmenopausal women using HT express greater myostatin-related gene expression, which may reflect a mechanism by which estrogen influences the preservation of muscle mass. Further, postmenopausal women using HT experienced a profoundly greater myostatin-related response to maximal eccentric exercise. PMID:22395277

  20. Ovarian steroids regulate gene expression related to DNA repair and neurodegenerative diseases in serotonin neurons of macaques

    PubMed Central

    Bethea, Cynthia L.; Reddy, Arubala P.

    2015-01-01

    Depression often accompanies the peri-menopausal transition and it often precedes overt symptomology in common neurodegenerative diseases (NDD; Alzheimer's, Parkinson's, Huntington, ALS). Serotonin dysfunction is frequently found in the different etiologies of depression. We have shown that ovariectomized (Ovx) monkeys treated with estradiol (E) for 28 days supplement with placebo or progesterone (P) on days 14-28 had reduced DNA fragmentation in serotonin neurons of the dorsal raphe nucleus; and long-term Ovx monkeys had fewer serotonin neurons than intact controls. We questioned the effect of E alone or E+P on gene expression related to DNA repair, protein folding (chaperones), the ubiquitin proteosome, axon transport, and NDD specific genes in serotonin neurons. Ovx macaques were treated with placebo, E or E+P (n=3/group) for 1 month. Serotonin neurons were laser captured and subjected to microarray analysis and qRT-PCR. Increases were confirmed with qRT-PCR in 5 genes that code for proteins involved in repair of strand breaks and nucleotide excision. NBN1, PCNA, GADD45A, RAD23A and GTF2H5 significantly increased with E or E+P treatment (all ANOVA p< 0.01). Chaperone genes HSP70, HSP60 and HSP27 significantly increased with E or E+P treatment (all ANOVA p<0.05). HSP90 showed a similar trend. Ubiquinase coding genes UBEA5, UBE2D3 and UBE3A (Parkin) increased with E or E+P (all ANOVA p<0.003). Transport related genes coding kinesin, dynein, and dynactin increased with E or E+P (all ANOVA p<0.03). SCNA (α synuclein) and ADAM10 (α secretase) increased (both ANOVA p<0.02), but PSEN1 (presenilin1) decreased (ANOVA p<0.02) with treatment. APP decreased 10-fold with E or E+P administration. Newman-Keuls posthoc comparisons indicated variation in the response to E alone versus E+P across the different genes. In summary, E or E+P increased gene expression for DNA repair mechanisms in serotonin neurons, thereby rendering them less vulnerable to stress-induced DNA

  1. Minimal genomes of mycoplasma-related endobacteria are plastic and contain host-derived genes for sustained life within Glomeromycota

    PubMed Central

    Naito, Mizue; Morton, Joseph B.; Pawlowska, Teresa E.

    2015-01-01

    Arbuscular mycorrhizal fungi (AMF, Glomeromycota) colonize roots of the majority of terrestrial plants. They provide essential minerals to their plant hosts and receive photosynthates in return. All major lineages of AMF harbor endobacteria classified as Mollicutes, and known as mycoplasma-related endobacteria (MRE). Except for their substantial intrahost genetic diversity and ability to transmit vertically, virtually nothing is known about the life history of these endobacteria. To understand MRE biology, we sequenced metagenomes of three MRE populations, each associated with divergent AMF hosts. We found that each AMF species harbored a genetically distinct group of MRE. Despite vertical transmission, all MRE populations showed extensive chromosomal rearrangements, which we attributed to genetic recombination, activity of mobile elements, and a history of plectroviral invasion. The MRE genomes are characterized by a highly reduced gene content, indicating metabolic dependence on the fungal host, with the mechanism of energy production remaining unclear. Several MRE genes encode proteins with domains involved in protein–protein interactions with eukaryotic hosts. In addition, the MRE genomes harbor genes horizontally acquired from AMF. Some of these genes encode small ubiquitin-like modifier (SUMO) proteases specific to the SUMOylation systems of eukaryotes, which MRE likely use to manipulate their fungal host. The extent of MRE genome plasticity and reduction, along with the large number of horizontally acquired host genes, suggests a high degree of adaptation to the fungal host. These features, together with the ubiquity of the MRE–Glomeromycota associations, emphasize the significance of MRE in the biology of Glomeromycota. PMID:25964324

  2. Bismerthiazol Inhibits Xanthomonas citri subsp. citri Growth and Induces Differential Expression of Citrus Defense-Related Genes.

    PubMed

    Yu, Xiaoyue; Armstrong, Cheryl M; Zhou, Mingguo; Duan, Yongping

    2016-07-01

    Citrus canker, caused by Xanthomonas citri ssp. citri, is a serious disease that causes substantial economic losses to the citrus industry worldwide. The bactericide bismerthiazol has been used to control rice bacterial blight (X. oryzae pv. oryzae). In this paper, we demonstrate that bismerthiazol can effectively control citrus canker by both inhibiting the growth of X. citri ssp. citri and triggering the plant's host defense response through the expression of several pathogenesis-related genes (PR1, PR2, CHI, and RpRd1) and the nonexpresser of PR genes (NPR1, NPR2, and NPR3) in 'Duncan' grapefruit, especially at early treatment times. In addition, we found that bismerthiazol induced the expression of the marker genes CitCHS and CitCHI in the flavonoid pathway and the PAL1 (phenylalanine ammonia lyase 1) gene in the salicylic acid (SA) biosynthesis pathway at different time points. Moreover, bismerthiazol also induced the expression of the priming defense-associated gene AZI1. Taken together, these results indicate that the induction of the defense response in 'Duncan' grapefruit by bismerthiazol may involve the SA signaling pathway and the priming defense and that bismerthiazol may serve as an alternative to copper bactericides for the control of citrus canker. PMID:26882850

  3. Environment effect on fruit ripening related gene to develop a new post harvest technology

    NASA Astrophysics Data System (ADS)

    Dwivany, Fenny; Esyanti, Rizkita Rahmi; Robertlee, Jekson; Paramaputra, Indra Chandra; Permatadewi, Rinda Kania; Tambun, Dina Hermawaty; Handayani, Resnanti Utami; Pratiwi, Aksarani'Sa; Zaskia, Herafi

    2014-03-01

    Ripening process of fruits is a very complex process, which involves ethylene production, causing alteration on molecular and physiology level. Environmental stress caused by biotic and abiotic stress conditions (such as pathogen, mechanical stress, physical and physiology stress) can stimulate ethylene production. High levels of ethylene in turn can also inhibit growth, cause premature ripening and induce the onset of senescence, which then potentially reduce plant productivity. The ACC Synthase (ACS) and ACC Oxidase (ACO) genes are genes that have role in the ethylene production. By regulating those genes, especially ethylene biosynthesis genes, we might improve the quality of fruit at post harvest condition. Therefore, in this research we studied fruit ripening related genes expression on banana such as MaACS family at different environment condition. The result of study can give contributions in developing of new plants with desired traits or new post harvest technologies.

  4. Transcriptome Analysis and Identification of Differentially Expressed Transcripts of Immune-Related Genes in Spleen of Gosling and Adult Goose

    PubMed Central

    Wang, Anqi; Liu, Fei; Chen, Shun; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Sun, Kunfeng; Wu, Ying; Chen, Xiaoyue; Cheng, Anchun

    2015-01-01

    The goose (Anser cygnoides), having high nutritional value, high-quality feathers and high economic benefit, is an economically important poultry species. However, the molecular mechanisms underlying the higher susceptibility to pathogens in goslings than in adult geese remains poorly understood. In this study, the histological sections of spleen tissue from a two-week-old gosling and an adult goose, respectively, were subjected to comparative analysis. The spleen of gosling was mainly composed of mesenchyma, accompanied by scattered lymphocytes, whereas the spleen parenchyma was well developed in the adult goose. To investigate goose immune-related genes, we performed deep transcriptome and gene expression analyses of the spleen samples using paired-end sequencing technology (Illumina). In total, 50,390 unigenes were assembled using Trinity software and TGICL software. Moreover, these assembled unigenes were annotated with gene descriptions and gene ontology (GO) analysis was performed. Through Kyoto encyclopedia of genes and genomes (KEGG) analysis, we investigated 558 important immune-relevant unigenes and 23 predicted cytokines. In addition, 22 immune-related genes with differential expression between gosling and adult goose were identified, among which the three genes showing largest differences in expression were immunoglobulin alpha heavy chain (IgH), mannan-binding lectin serine protease 1 isoform X1 (MASP1) and C–X–C chemokine receptor type 4 (CXCR4). Finally, of these 22 differentially expressed immune-related genes, seven genes, including tumor necrosis factor receptor superfamily member 13B (TNFRSF13B), C-C motif chemokine 4-like (CCL4), CXCR4, interleukin 2 receptor alpha (IL2RA), MHC class I heavy chain (MHCIα), transporter of antigen processing 2 (TAP2) IgH, were confirmed by quantitative real-time PCR (qRT-PCR). The expression levels of all the candidate unigenes were up-regulated in adult geese other than that of TNFRSF13B. The comparative

  5. Transcriptome Analysis and Identification of Differentially Expressed Transcripts of Immune-Related Genes in Spleen of Gosling and Adult Goose.

    PubMed

    Wang, Anqi; Liu, Fei; Chen, Shun; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Sun, Kunfeng; Wu, Ying; Chen, Xiaoyue; Cheng, Anchun

    2015-01-01

    The goose (Anser cygnoides), having high nutritional value, high-quality feathers and high economic benefit, is an economically important poultry species. However, the molecular mechanisms underlying the higher susceptibility to pathogens in goslings than in adult geese remains poorly understood. In this study, the histological sections of spleen tissue from a two-week-old gosling and an adult goose, respectively, were subjected to comparative analysis. The spleen of gosling was mainly composed of mesenchyma, accompanied by scattered lymphocytes, whereas the spleen parenchyma was well developed in the adult goose. To investigate goose immune-related genes, we performed deep transcriptome and gene expression analyses of the spleen samples using paired-end sequencing technology (Illumina). In total, 50,390 unigenes were assembled using Trinity software and TGICL software. Moreover, these assembled unigenes were annotated with gene descriptions and gene ontology (GO) analysis was performed. Through Kyoto encyclopedia of genes and genomes (KEGG) analysis, we investigated 558 important immune-relevant unigenes and 23 predicted cytokines. In addition, 22 immune-related genes with differential expression between gosling and adult goose were identified, among which the three genes showing largest differences in expression were immunoglobulin alpha heavy chain (IgH), mannan-binding lectin serine protease 1 isoform X1 (MASP1) and C-X-C chemokine receptor type 4 (CXCR4). Finally, of these 22 differentially expressed immune-related genes, seven genes, including tumor necrosis factor receptor superfamily member 13B (TNFRSF13B), C-C motif chemokine 4-like (CCL4), CXCR4, interleukin 2 receptor alpha (IL2RA), MHC class I heavy chain (MHCIα), transporter of antigen processing 2 (TAP2) IgH, were confirmed by quantitative real-time PCR (qRT-PCR). The expression levels of all the candidate unigenes were up-regulated in adult geese other than that of TNFRSF13B. The comparative

  6. Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other.

    PubMed Central

    Miyajima, N; Kadowaki, Y; Fukushige, S; Shimizu, S; Semba, K; Yamanashi, Y; Matsubara, K; Toyoshima, K; Yamamoto, T

    1988-01-01

    Two v-erbA-related genes, named ear-2 and ear-3, have been identified in the human genome and characterized by cDNA cloning. These genes are predicted to encode proteins that are very similar in primary structure to receptors for steroid hormones or thyroid hormone (T3). In addition, amino acid sequences of the ear-2 and ear-3 gene products are very similar each other especially at the DNA binding domain (86% homology) and at the putative ligand binding domain (76% homology). Northern hybridization with ear DNA probes of RNAs from various tissues of a human fetus reveals that the expression of ear-2 is high in the liver whereas the expression of ear-3 is relatively ubiquitous. Hybridization analysis of DNAs from sorted chromosomes shows that the ear-2 gene is located on chromosome 19 and ear-3 on chromosome 5, indicating that the two genes are clearly different from each other. Images PMID:2905047

  7. Biology-Driven Gene-Gene Interaction Analysis of Age-Related Cataract in the eMERGE Network.

    PubMed

    Hall, Molly A; Verma, Shefali S; Wallace, John; Lucas, Anastasia; Berg, Richard L; Connolly, John; Crawford, Dana C; Crosslin, David R; de Andrade, Mariza; Doheny, Kimberly F; Haines, Jonathan L; Harley, John B; Jarvik, Gail P; Kitchner, Terrie; Kuivaniemi, Helena; Larson, Eric B; Carrell, David S; Tromp, Gerard; Vrabec, Tamara R; Pendergrass, Sarah A; McCarty, Catherine A; Ritchie, Marylyn D

    2015-07-01

    Bioinformatics approaches to examine gene-gene models provide a means to discover interactions between multiple genes that underlie complex disease. Extensive computational demands and adjusting for multiple testing make uncovering genetic interactions a challenge. Here, we address these issues using our knowledge-driven filtering method, Biofilter, to identify putative single nucleotide polymorphism (SNP) interaction models for cataract susceptibility, thereby reducing the number of models for analysis. Models were evaluated in 3,377 European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a study site of the Electronic Medical Records and Genomics (eMERGE) Network, using logistic regression. All statistically significant models from the Marshfield Clinic were then evaluated in an independent dataset of 4,311 individuals (742 controls, 3,569 cases), using independent samples from additional study sites in the eMERGE Network: Mayo Clinic, Group Health/University of Washington, Vanderbilt University Medical Center, and Geisinger Health System. Eighty-three SNP-SNP models replicated in the independent dataset at likelihood ratio test P < 0.05. Among the most significant replicating models was rs12597188 (intron of CDH1)-rs11564445 (intron of CTNNB1). These genes are known to be involved in processes that include: cell-to-cell adhesion signaling, cell-cell junction organization, and cell-cell communication. Further Biofilter analysis of all replicating models revealed a number of common functions among the genes harboring the 83 replicating SNP-SNP models, which included signal transduction and PI3K-Akt signaling pathway. These findings demonstrate the utility of Biofilter as a biology-driven method, applicable for any genome-wide association study dataset. PMID:25982363

  8. Biology-Driven Gene-Gene Interaction Analysis of Age-Related Cataract in the eMERGE Network

    PubMed Central

    Hall, Molly A; Verma, Shefali S; Wallace, John; Lucas, Anastasia; Berg, Richard L; Connolly, John; Crawford, Dana C; Crosslin, David R; de Andrade, Mariza; Doheny, Kimberly F; Haines, Jonathan L; Harley, John B; Jarvik, Gail P; Kitchner, Terrie; Kuivaniemi, Helena; Larson, Eric B; Carrell, David S; Tromp, Gerard; Vrabec, Tamara R; Pendergrass, Sarah A; McCarty, Catherine A; Ritchie, Marylyn D

    2015-01-01

    Bioinformatics approaches to examine gene-gene models provide a means to discover interactions between multiple genes that underlie complex disease. Extensive computational demands and adjusting for multiple testing make uncovering genetic interactions a challenge. Here, we address these issues using our knowledge-driven filtering method, Biofilter, to identify putative single nucleotide polymorphism (SNP) interaction models for cataract susceptibility, thereby reducing the number of models for analysis. Models were evaluated in 3,377 European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a study site of the Electronic Medical Records and Genomics (eMERGE) Network, using logistic regression. All statistically significant models from the Marshfield Clinic were then evaluated in an independent dataset of 4,311 individuals (742 controls, 3,569 cases), using independent samples from additional study sites in the eMERGE Network: Mayo Clinic, Group Health/University of Washington, Vanderbilt University Medical Center, and Geisinger Health System. Eighty-three SNP-SNP models replicated in the independent dataset at likelihood ratio test P < 0.05. Among the most significant replicating models was rs12597188 (intron of CDH1)–rs11564445 (intron of CTNNB1). These genes are known to be involved in processes that include: cell-to-cell adhesion signaling, cell-cell junction organization, and cell-cell communication. Further Biofilter analysis of all replicating models revealed a number of common functions among the genes harboring the 83 replicating SNP-SNP models, which included signal transduction and PI3K-Akt signaling pathway. These findings demonstrate the utility of Biofilter as a biology-driven method, applicable for any genome-wide association study dataset. PMID:25982363

  9. Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees.

    PubMed

    Liu, Hui; Robinson, Gene E; Jakobsson, Eric

    2016-06-01

    The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization

  10. Conservation in Mammals of Genes Associated with Aggression-Related Behavioral Phenotypes in Honey Bees

    PubMed Central

    Robinson, Gene E.; Jakobsson, Eric

    2016-01-01

    The emerging field of sociogenomics explores the relations between social behavior and genome structure and function. An important question is the extent to which associations between social behavior and gene expression are conserved among the Metazoa. Prior experimental work in an invertebrate model of social behavior, the honey bee, revealed distinct brain gene expression patterns in African and European honey bees, and within European honey bees with different behavioral phenotypes. The present work is a computational study of these previous findings in which we analyze, by orthology determination, the extent to which genes that are socially regulated in honey bees are conserved across the Metazoa. We found that the differentially expressed gene sets associated with alarm pheromone response, the difference between old and young bees, and the colony influence on soldier bees, are enriched in widely conserved genes, indicating that these differences have genomic bases shared with many other metazoans. By contrast, the sets of differentially expressed genes associated with the differences between African and European forager and guard bees are depleted in widely conserved genes, indicating that the genomic basis for this social behavior is relatively specific to honey bees. For the alarm pheromone response gene set, we found a particularly high degree of conservation with mammals, even though the alarm pheromone itself is bee-specific. Gene Ontology identification of human orthologs to the strongly conserved honey bee genes associated with the alarm pheromone response shows overrepresentation of protein metabolism, regulation of protein complex formation, and protein folding, perhaps associated with remodeling of critical neural circuits in response to alarm pheromone. We hypothesize that such remodeling may be an adaptation of social animals to process and respond appropriately to the complex patterns of conspecific communication essential for social organization

  11. History of a prolific family: the Hes/Hey-related genes of the annelid Platynereis

    PubMed Central

    2014-01-01

    Background The Hes superfamily or Hes/Hey-related genes encompass a variety of metazoan-specific bHLH genes, with somewhat fuzzy phylogenetic relationships. Hes superfamily members are involved in a variety of major developmental mechanisms in metazoans, notably in neurogenesis and segmentation processes, in which they often act as direct effector genes of the Notch signaling pathway. Results We have investigated the molecular and functional evolution of the Hes superfamily in metazoans using the lophotrochozoan Platynereis dumerilii as model. Our phylogenetic analyses of more than 200 Metazoan Hes/Hey-related genes revealed the presence of five families, three of them (Hes, Hey and Helt) being pan-metazoan. Those families were likely composed of a unique representative in the last common metazoan ancestor. The evolution of the Hes family was shaped by many independent lineage specific tandem duplication events. The expression patterns of 13 of the 15 Hes/Hey-related genes in Platynereis indicate a broad functional diversification. Nevertheless, a majority of these genes are involved in two crucial developmental processes in annelids: neurogenesis and segmentation, resembling functions highlighted in other animal models. Conclusions Combining phylogenetic and expression data, our study suggests an unusual evolutionary history for the Hes superfamily. An ancestral multifunctional annelid Hes gene may have undergone multiples rounds of duplication-degeneration-complementation processes in the lineage leading to Platynereis, each gene copies ensuring their maintenance in the genome by subfunctionalisation. Similar but independent waves of duplications are at the origin of the multiplicity of Hes genes in other metazoan lineages. PMID:25250171

  12. THE HUMAN GENE MAP FOR PERFORMANCE AND HEALTH-RELATED FITNESS PHENOTYPES: THE 2004 UPDATE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We began this series in 2000 with the aim of making available in an easily accessible format all the advances on the genetic basis of a large family of exercise-related traits. The current review presents the 2004 update of the human gene map for physical performance and health-related fitness pheno...

  13. Cloning and phylogenetic analysis of polyphenol oxidase genes in common wheat and related species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cloning and phylogenetic analysis of polyphenol oxidase (PPO) genes in common wheat and its relatives would greatly advance the understanding of molecular mechanisms of grain PPO activity. In the present study, six wheat relative species, including T. urartu, T. boeoticum, T. monococcum, T. dicoccoi...

  14. A Drosophila muscle-specific gene related to the mouse quaking locus.

    PubMed

    Fyrberg, C; Becker, J; Barthmaier, P; Mahaffey, J; Fyrberg, E

    1997-09-15

    We have characterized a novel muscle-specific gene of Drosophila melanogaster, defined by enhancer trap strain 24B of Brand and Perrimon (1993). We show that transcripts of the gene accumulate within presumptive mesoderm and persist within developing muscles, strongly suggesting that the encoded protein is involved in muscle cell determination and differentiation. cDNA sequences reveal that the Drosophila protein is similar to quaking (64% identity over 210 amino acids), a protein essential for mouse embryogenesis, and gld-1 (53% identity over 162 amino acids) a germ-line-specific tumor suppressing protein of the nematode, Caenorhabditis elegans. We demonstrate that the Drosophila gene resides within the 93F chromosome subdivision, and describe its physical map. Finally, we have used the gene, which we have named quaking-related 93F (qkr93F), to identify a family of closely related KH domains. PMID:9332381

  15. Generation and Analysis of Expressed Sequence Tags (ESTs) from Halophyte Atriplex canescens to Explore Salt-Responsive Related Genes

    PubMed Central

    Li, Jingtao; Sun, Xinhua; Yu, Gang; Jia, Chengguo; Liu, Jinliang; Pan, Hongyu

    2014-01-01

    Little information is available on gene expression profiling of halophyte A. canescens. To elucidate the molecular mechanism for stress tolerance in A. canescens, a full-length complementary DNA library was generated from A. canescens exposed to 400 mM NaCl, and provided 343 high-quality ESTs. In an evaluation of 343 valid EST sequences in the cDNA library, 197 unigenes were assembled, among which 190 unigenes (83.1% ESTs) were identified according to their significant similarities with proteins of known functions. All the 343 EST sequences have been deposited in the dbEST GenBank under accession numbers JZ535802 to JZ536144. According to Arabidopsis MIPS functional category and GO classifications, we identified 193 unigenes of the 311 annotations EST, representing 72 non-redundant unigenes sharing similarities with genes related to the defense response. The sets of ESTs obtained provide a rich genetic resource and 17 up-regulated genes related to salt stress resistance were identified by qRT-PCR. Six of these genes may contribute crucially to earlier and later stage salt stress resistance. Additionally, among the 343 unigenes sequences, 22 simple sequence repeats (SSRs) were also identified contributing to the study of A. canescens resources. PMID:24960361

  16. De novo characterization of Larimichthys crocea transcriptome for growth-/immune-related gene identification and massive microsatellite (SSR) marker development

    NASA Astrophysics Data System (ADS)

    Han, Zhaofang; Xiao, Shijun; Liu, Xiande; Liu, Yang; Li, Jiakai; Xie, Yangjie; Wang, Zhi Yong

    2016-04-01

    The large yellow croaker, Larimichthys crocea is an important marine fish in China with a high economic value. In the last decade, the stock conservation and aquaculture industry of this species have been facing severe challenges because of wild population collapse and degeneration of important economic traits. However, genes contributing to growth and immunity in L. crocea have not been thoroughly analyzed, and available molecular markers are still not sufficient for genetic resource management and molecular selection. In this work, we sequenced the transcriptome in L. crocea liver tissue with a Roche 454 sequencing platform and assembled the transcriptome into 93 801 transcripts. Of them, 38 856 transcripts were successfully annotated in nt, nr, Swiss-Prot, InterPro, COG, GO and KEGG databases. Based on the annotation information, 3 165 unigenes related to growth and immunity were identified. Additionally, a total of 6 391 simple sequence repeats (SSRs) were identified from the transcriptome, among which 4 498 SSRs had enough flanking regions to design primers for polymerase chain reactions (PCR). To access the polymorphism of these markers, 30 primer pairs were randomly selected for PCR amplification and validation in 30 individuals, and 12 primer pairs (40.0%) exhibited obvious length polymorphisms. This work applied RNA-Seq to assemble and analyze a live transcriptome in L. crocea. With gene annotation and sequence information, genes related to growth and immunity were identified and massive SSR markers were developed, providing valuable genetic resources for future gene functional analysis and selective breeding of L. crocea.

  17. Antioxidative-related genes expression following perfluorooctane sulfonate (PFOS) exposure in the intertidal mud crab, Macrophthalmus japonicus

    NASA Astrophysics Data System (ADS)

    Park, Kiyun; Nikapitiya, Chamilani; Kwak, Tae-Soo; Kwak, Ihn-Sil

    2015-09-01

    Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant that is used as a surfactant in various industries and consumer products. The intertidal mud crab, Macrophthalmus japonicus, is one of the most abundant macrobenthic creatures. In this study, we have investigated the effect of PFOS on the molecular transcription of antioxidant and detoxification signaling in M. japonicus crab. The selected stress response genes were superoxide dismutases (CuZnSOD and MnSOD), catalase (CAT), glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (PHGPx), peroxiredoxin (Prx), and thioredoxin reductase (TrxR). Significant up-regulation of SODs and CAT was observed after 24 and 96 h exposure to PFOS at different concentrations. The gene expression levels of GPx, PHGPx, and TrXR were significantly up-regulated after exposure to PFOS for 96 h. The transcript levels of CAT and PHGPx were induced in dose- and time-dependent manners after PFOS treatments. However, Prx gene expression was significantly up-regulated in M. japonicus crabs exposed to 10 and 30 μg L-1 PFOS for 96 h. Additionally, PFOS toxicity in M. japonicus induced reduced survival rates at relatively high concentrations of PFOS exposure. Our findings support the contention that exposures to PFOS induced the response of genes related to oxidative stress and detoxification in M. japonicus crabs.

  18. No Association between Variation in Longevity Candidate Genes and Aging-related Phenotypes in Oldest-old Danes.

    PubMed

    Soerensen, Mette; Nygaard, Marianne; Debrabant, Birgit; Mengel-From, Jonas; Dato, Serena; Thinggaard, Mikael; Christensen, Kaare; Christiansen, Lene

    2016-06-01

    In this study we explored the association between aging-related phenotypes previously reported to predict survival in old age and variation in 77 genes from the DNA repair pathway, 32 genes from the growth hormone 1/ insulin-like growth factor 1/insulin (GH/IGF-1/INS) signalling pathway and 16 additional genes repeatedly considered as candidates for human longevity: APOE, APOA4, APOC3, ACE, CETP, HFE, IL6, IL6R, MTHFR, TGFB1, SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. Altogether, 1,049 single nucleotide polymorphisms (SNPs) were genotyped in 1,088 oldest-old (age 92-93 years) Danes and analysed with phenotype data on physical functioning (hand grip strength), cognitive functioning (mini mental state examination and a cognitive composite score), activity of daily living and self-rated health. Five SNPs showed association to one of the phenotypes; however, none of these SNPs were associated with a change in the relevant phenotype over time (7 years of follow-up) and none of the SNPs could be confirmed in a replication sample of 1,281 oldest-old Danes (age 94-100). Hence, our study does not support association between common variation in the investigated longevity candidate genes and aging-related phenotypes consistently shown to predict survival. It is possible that larger sample sizes are needed to robustly reveal associations with small effect sizes. PMID:26946122

  19. Subchronic effects of cadmium on the gonads, expressions of steroid hormones and sex-related genes in tilapia Oreochromis niloticus.

    PubMed

    Luo, Yongju; Shan, Dan; Zhong, Huan; Zhou, Yi; Chen, Wenzhi; Cao, Jinling; Guo, Zhongbao; Xiao, Jun; He, Fulin; Huang, Yifan; Li, Jian; Huang, Heming; Xu, Pao

    2015-12-01

    Cadmium (Cd) is one of the most toxic heavy metals in aquatic ecosystem which affects fish health and aquaculture. In the present study, we examined the bioaccumulation of Cd in the gonads of tilapia via dissolved and dietary routes. We evaluated the subchronic effects of Cd on the histology of gonads, steroid hormone levels and sex-related gene expressions in tilapia. In addition, we also studied maternal transfer of Cd. Our results indicated that Cd was accumulated significantly in both ovary and testis from both exposure routes. Histopathological analysis showed that Cd induced ovary and testis injuries. Estradiol levels were significantly increased in dissolved Cd exposed female fish. In addition, the Cd exposure displayed different effects on gene expressions in gonads. In females, the estrogen receptor (ERα) was stimulated in dissolved Cd-exposed fish at 70.32 and 143.78 μg/L for 30 days and in fish at 143.78 μg/L for 60 days. Vitellogenin expression was significantly down-regulated in the ovary of dissolved Cd-exposed fish. In testis, GR expression was elevated after 60 days of dissolved Cd and dietary exposure. Furthermore, Cd level was significantly higher in the eggs than that in the fry. Our results demonstrated that both dissolved and dietary Cd exposures affected gonad development by altering steroid hormone levels and sex-related gene expressions in tilapia. PMID:26471182

  20. Expression of epithelial cell iron-related genes upon infection by Neisseria meningitidis.

    PubMed

    Bonnah, Robert A; Muckenthaler, Martina U; Carlson, Hanqian; Minana, Belen; Enns, Caroline A; Hentze, Matthias W; So, Magdalene

    2004-05-01

    Infection by the obligate human pathogens Neisseria meningitidis (MC) and Neisseria gonorrhoeae (GC) reduces the expression of host epithelial cell transferrin receptor 1 (TfR-1) (Bonnah et al., 2000, Cellular Microbiology 2: 207-218). In addition, the rate and pattern of TfR-1 cycling is altered, leading to diminished uptake of Tf-iron by infected host cells. As Tf-iron is important for maintaining iron homeostasis in the eukaryotic cell, these findings raised the possibility that Neisseria infection might affect further pathways of epithelial cell iron metabolism. We used a specialized cDNA microarray platform, the 'IronChip', to investigate the expression of genes involved in iron transport, storage and regulation. We show that mRNA expression of several host genes involved in iron homeostasis is altered. Surprisingly, the general mRNA expression profile of infected cells closely resembled that of uninfected cells grown in an iron-limited environment. An important exception to this profile is TfR-1, the mRNA level of which is strongly reduced. Low TfR-1 expression may be explained in part by decreased activity of the iron-regulatory proteins (IRPs) in MC-infected cells, which may result in the destabilization of TfR-1 mRNA. Intriguingly, low IRP activity contrasts with the decrease in H-ferritin protein levels in infected cells. This finding suggests that low IRP activity may be responsible in part for the decrease in TfR-1 mRNA levels. A discussion of these novel findings in relation to MC infection and virulence is provided. PMID:15056217

  1. Effect of GA3 Treatment on Seed Development and Seed-Related Gene Expression in Grape

    PubMed Central

    Cheng, Chenxia; Xu, Xiaozhao; Singer, Stacy D.; Li, Jun; Zhang, Hongjing; Gao, Min; Wang, Li; Song, Junyang; Wang, Xiping

    2013-01-01

    Background The phytohormone gibberellic acid (GA3) is widely used in the table grape industry to induce seedlessness in seeded varieties. However, there is a paucity of information concerning the mechanisms by which GAs induce seedlessness in grapes. Methodology/Principal Findings In an effort to systematically analyze the cause of this GA3-induced seed abortion, we conducted an in depth characterization of two seeded grape cultivars (‘Kyoho’ and ‘Red Globe’), along with a seedless cultivar (‘Thompson Seedless’), following treatment with GA3. In a similar fashion to the seedless control, which exhibited GA3-induced abortion of the seeds 9 days after full bloom (DAF), both ‘Kyoho’ and ‘Red Globe’ seeded varieties exhibited complete abortion of the seeds 15 DAF when treated with GA3. Morphological analyses indicated that while fertilization appeared to occur normally following GA3 treatment, as well as in the untreated seedless control cultivar, seed growth eventually ceased. In addition, we found that GA3 application had an effect on redox homeostasis, which could potentially cause cell damage and subsequent seed abortion. Furthermore, we carried out an analysis of antioxidant enzyme activities, as well as transcript levels from various genes believed to be involved in seed development, and found several differences between GA3-treated and untreated controls. Conclusion Therefore, it seems that the mechanisms driving GA3-induced seedlessness are similar in both seeded and seedless cultivars, and that the observed abortion of seeds may result at least in part from a GA3-induced increase in cell damage caused by reactive oxygen species, a decrease in antioxidant enzymatic activities, and an alteration of the expression of genes related to seed development. PMID:24224035

  2. Transcriptome analysis of biomineralisation-related genes within the pearl sac: host and donor oyster contribution.

    PubMed

    McGinty, E L; Zenger, K R; Jones, D B; Jerry, D R

    2012-03-01

    Cultured pearl production is a complex biological process involving the implantation of a mantle graft from a donor pearl oyster along with a bead nucleus into the gonad of a second recipient host oyster. Therefore, pearl production potentially involves the genetic co-operation of two oyster genomes. Whilst many genes in the mantle tissue have been identified and linked to shell biomineralisation in pearl oysters, few studies have determined which of these biomineralisation genes are expressed in the pearl sac and potentially linked to pearl biomineralisation processes. It is also uncertain whether the host or donor oyster is primarily responsible for the expression of biomineralisation genes governing pearl formation, with only two shell matrix proteins previously identified as being expressed by the donor oyster in the pearl sac. To further our understanding of pearl formation, the pearl sac transcriptome of Pinctada maxima and Pinctada margaritifera was each sequenced to an equivalent 5× genome coverage with putative molluscan biomineralisation-related genes identified. Furthermore, the host and donor contribution of these expressed genes within the pearl sac were quantified using a novel approach whereby two pearl oyster species harbouring unique genomes, P. maxima or P. margaritifera, were used to produce xenografted pearl sacs. A total of 19 putative mollusc biomineralisation genes were identified and found to be expressed in the pearl sacs of P. maxima and P. margaritifera. From this list of expressed genes, species-diagnostic single nucleotide polymorphisms (SNP) were identified within seven of these genes; Linkine, N66, Perline, N44, MSI60, Calreticulin and PfCHS1. Based on the presence/absence of species diagnostic gene transcripts within xenografted pearl sacs, all seven genes were found to be expressed by the species used as the donor oyster. In one individual we also found that the host was expressing Linkine. These results convincingly show for the

  3. Pretransplant Immune- and Apoptosis-Related Gene Expression Is Associated with Kidney Allograft Function

    PubMed Central

    Kamińska, Dorota; Kościelska-Kasprzak, Katarzyna; Chudoba, Paweł; Mazanowska, Oktawia; Banasik, Mirosław; Żabinska, Marcelina; Boratyńska, Maria; Lepiesza, Agnieszka; Gomółkiewicz, Agnieszka; Dzięgiel, Piotr; Klinger, Marian

    2016-01-01

    Renal transplant candidates present immune dysregulation, caused by chronic uremia. The aim of the study was to investigate whether pretransplant peripheral blood gene expression of immune factors affects clinical outcome of renal allograft recipients. Methods. In a prospective study, we analyzed pretransplant peripheral blood gene expression in87 renal transplant candidates with real-time PCR on custom-designed low density arrays (TaqMan). Results. Immediate posttransplant graft function (14-day GFR) was influenced negatively by TGFB1 (P = 0.039) and positively by IL-2 gene expression (P = 0.040). Pretransplant blood mRNA expression of apoptosis-related genes (CASP3, FAS, and IL-18) and Th1-derived cytokine gene IFNG correlated positively with short- (6-month GFR CASP3: P = 0.027, FAS: P = 0.021, and IFNG: P = 0.029) and long-term graft function (24-month GFR CASP3: P = 0.003, FAS: P = 0.033, IL-18: P = 0.044, and IFNG: P = 0.04). Conclusion. Lowered pretransplant Th1-derived cytokine and apoptosis-related gene expressions were a hallmark of subsequent worse kidney function but not of acute rejection rate. The pretransplant IFNG and CASP3 and FAS and IL-18 genes' expression in the recipients' peripheral blood is the possible candidate for novel biomarker of short- and long-term allograft function. PMID:27382192

  4. Gene by Social-Environment Interaction for Youth Delinquency and Violence: Thirty-Nine Aggression-related Genes

    PubMed Central

    Liu, Hexuan; Li, Yi; Guo, Guang

    2014-01-01

    Complex human traits are likely to be affected by many environmental and genetic factors, and the interactions among them. However, previous gene-environment interaction (G×E) studies have typically focused on one or only a few genetic variants at a time. To provide a broader view of G×E, this study examines the relationship between 403 genetic variants from 39 genes and youth delinquency and violence. We find evidence that low social control is associated with greater genetic risk for delinquency and violence and high/moderate social control with smaller genetic risk for delinquency and violence. Our findings are consistent with prior G×E studies based on a small number of genetic variants, and, more importantly, we show that these findings still hold when a large number of genetic variants are considered simultaneously. A key implication of these findings is that the expression of multiple genes related to delinquency depends on the social environment: gene expression is likely to be amplified in low-social-control environments but, tends to be suppressed in high/moderate-social-control environments. This study not only deepens our understanding of how the social environment shapes individual behavior, but also provides important conceptual and methodological insights for future G×E research on complex human traits. PMID:25755300

  5. Expression of apoptosis-related genes in liver-specific growth hormone receptor gene-disrupted mice is sex dependent.

    PubMed

    Gesing, Adam; Wang, Feiya; List, Edward O; Berryman, Darlene E; Masternak, Michal M; Lewinski, Andrzej; Karbownik-Lewinska, Malgorzata; Kopchick, John J; Bartke, Andrzej

    2015-01-01

    Apoptosis is a process that affects life span and health. Mice with liver-specific disruption of the growth hormone receptor (GHR) gene (ie, Ghr gene) liver-specific growth hormone receptor knockout [LiGHRKO] mice), as opposed to mice with global deletion of the Ghr gene (GHRKO; Ghr-/-), are characterized by severe hepatic steatosis and lack of improved insulin sensitivity. We have previously shown that levels of proapoptotic factors are decreased in long-lived and insulin-sensitive GHRKO mice. In the current study, expression of specific apoptosis-related genes was assessed in brains, kidneys, and livers of male and female LiGHRKO and wild-type mice using real-time PCR. In the brain, expression of Caspase 3, Caspase 9, Smac/DIABLO, and p53 was decreased in females compared with males. Renal expression of Caspase 3 and Noxa also decreased in female mice. In the liver, no differences were seen between males and females. Also, no significant genotype effects were detected in the examined organs. Lack of significant genotype effect in kidneys contrasts with previous observations in GHRKO mice. Apparently, global GHR deletion induces beneficial changes in apoptotic factors, whereas liver-specific GHR disruption does not. Furthermore, sexual dimorphism may play an important role in regulating apoptosis during liver-specific suppression of the somatotrophic signaling. PMID:24550353

  6. Identification of differentially expressed genes related to aphid resistance in cucumber (Cucumis sativus L.)

    PubMed Central

    Liang, Danna; Liu, Min; Hu, Qijing; He, Min; Qi, Xiaohua; Xu, Qiang; Zhou, Fucai; Chen, Xuehao

    2015-01-01

    Cucumber, a very important vegetable crop worldwide, is easily damaged by pests. Aphids (Aphis gossypii Glover) are among the most serious pests in cucumber production and often cause severe loss of yield and make fruit quality get worse. Identifying genes that render cucumbers resistant to aphid-induced damage and breeding aphid-resistant cucumber varieties have become the most promising control strategies. In this study, a Illumina Genome Analyzer platform was applied to monitor changes in gene expression in the whole genome of the cucumber cultivar ‘EP6392’ which is resistant to aphids. Nine DGE libraries were constructed from infected and uninfected leaves. In total, 49 differentially expressed genes related to cucumber aphid resistance were screened during the treatment period. These genes are mainly associated with signal transduction, plant-pathogen interactions, flavonoid biosynthesis, amino acid metabolism and sugar metabolism pathways. Eight of the 49 genes may be associated with aphid resistance. Finally, expression of 9 randomly selected genes was evaluated by qRT-PCR to verify the results for the tag-mapped genes. With the exception of 1-aminocyclopropane-1-carboxylate oxidase homolog 6, the expression of the chosen genes was in agreement with the results of the tag-sequencing analysis patterns. PMID:25959296

  7. Identification of differentially expressed genes related to aphid resistance in cucumber (Cucumis sativus L.).

    PubMed

    Liang, Danna; Liu, Min; Hu, Qijing; He, Min; Qi, Xiaohua; Xu, Qiang; Zhou, Fucai; Chen, Xuehao

    2015-01-01

    Cucumber, a very important vegetable crop worldwide, is easily damaged by pests. Aphids (Aphis gossypii Glover) are among the most serious pests in cucumber production and often cause severe loss of yield and make fruit quality get worse. Identifying genes that render cucumbers resistant to aphid-induced damage and breeding aphid-resistant cucumber varieties have become the most promising control strategies. In this study, a Illumina Genome Analyzer platform was applied to monitor changes in gene expression in the whole genome of the cucumber cultivar 'EP6392' which is resistant to aphids. Nine DGE libraries were constructed from infected and uninfected leaves. In total, 49 differentially expressed genes related to cucumber aphid resistance were screened during the treatment period. These genes are mainly associated with signal transduction, plant-pathogen interactions, flavonoid biosynthesis, amino acid metabolism and sugar metabolism pathways. Eight of the 49 genes may be associated with aphid resistance. Finally, expression of 9 randomly selected genes was evaluated by qRT-PCR to verify the results for the tag-mapped genes. With the exception of 1-aminocyclopropane-1-carboxylate oxidase homolog 6, the expression of the chosen genes was in agreement with the results of the tag-sequencing analysis patterns. PMID:25959296

  8. Evidence for Related Functions of the RNA Genes of Saccharomyces cerevisiae

    PubMed Central

    Last, Robert L.; Maddock, Janine R.; Woolford, John L.

    1987-01-01

    The yeast genes RNA2-RNA11 are necessary for splicing of nuclear intron-containing pre-mRNAs. We investigated the relationships among these genes by asking whether increased expression of one RNA gene leads to suppression of the temperature-sensitive lethality of a mutation in any other RNA gene. The presence of extra plasmid-borne copies of the RNA3 gene relieves the lethality of temperature-sensitive rna4 mutations. A region of the yeast genome (SRN2) is described that suppresses temperature-sensitive rna2 mutations when it is present on either medium or high-copy number plasmids. Neither suppression occurs via a bypass of RNA gene function since null alleles of rna2 and rna4 are not suppressed by elevated dosage of SRN2 and RNA3, respectively. These results suggest that the SRN2 and RNA2 gene products have related functions, as do the RNA3 and RNA4 gene products. PMID:3322934

  9. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis.

    PubMed

    Wan, Lei; Tan, Hsueh-Li; Thomas-Ahner, Jennifer M; Pearl, Dennis K; Erdman, John W; Moran, Nancy E; Clinton, Steven K

    2014-12-01

    Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4 to 10 weeks of age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone repletion (2.5 mg/kg/d initiated 1 week after castration). Ten-week-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia. Of the 200 prostate cancer-related genes measured by quantitative NanoString, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P < 0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared with WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P < 0.0001) compared with intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways is reduced by lycopene feeding (Srd5a1) and by tomato feeding (Srd5a2, Pxn, and Srebf1). In addition, tomato feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, whereas lycopene feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. PMID:25315431

  10. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis

    PubMed Central

    Wan, Lei; Tan, Hsueh-Li; Thomas-Ahner, Jennifer M.; Pearl, Dennis K.; Erdman, John W.; Moran, Nancy E.; Clinton, Steven K.

    2014-01-01

    Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4-10 wk-of-age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone-repletion (2.5 mg/kg/d initiated 1 wk after castration). Ten-wk-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia (PIN). Of the 200 prostate cancer-related genes measured by quantitative NanoString®, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P<0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared to WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P<0.0001) compared to intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways are reduced by lycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. PMID:25315431

  11. Cardiac Energy Dependence on Glucose Increases Metabolites Related to Glutathione and Activates Metabolic Genes Controlled by Mechanistic Target of Rapamycin

    PubMed Central

    Schisler, Jonathan C.; Grevengoed, Trisha J.; Pascual, Florencia; Cooper, Daniel E.; Ellis, Jessica M.; Paul, David S.; Willis, Monte S.; Patterson, Cam; Jia, Wei; Coleman, Rosalind A.

    2015-01-01

    Background Long chain acyl‐CoA synthetases (ACSL) catalyze long‐chain fatty acids (FA) conversion to acyl‐CoAs. Temporal ACSL1 inactivation in mouse hearts (Acsl1H−/−) impaired FA oxidation and dramatically increased glucose uptake, glucose oxidation, and mTOR activation, resulting in cardiac hypertrophy. We used unbiased metabolomics and gene expression analyses to elucidate the cardiac cellular response to increased glucose use in a genetic model of inactivated FA oxidation. Methods and Results Metabolomics analysis identified 60 metabolites altered in Acsl1H−/− hearts, including 6 related to glucose metabolism and 11 to cysteine and glutathione pathways. Concurrently, global cardiac transcriptional analysis revealed differential expression of 568 genes in Acsl1H−/− hearts, a subset of which we hypothesized were targets of mTOR; subsequently, we measured the transcriptional response of several genes after chronic mTOR inhibition via rapamycin treatment during the period in which cardiac hypertrophy develops. Hearts from Acsl1H−/− mice increased expression of several Hif1α‐responsive glycolytic genes regulated by mTOR; additionally, expression of Scl7a5, Gsta1/2, Gdf15, and amino acid‐responsive genes, Fgf21, Asns, Trib3, Mthfd2, were strikingly increased by mTOR activation. Conclusions The switch from FA to glucose use causes mTOR‐dependent alterations in cardiac metabolism. We identified cardiac mTOR‐regulated genes not previously identified in other cellular models, suggesting heart‐specific mTOR signaling. Increased glucose use also changed glutathione‐related pathways and compensation by mTOR. The hypertrophy, oxidative stress, and metabolic changes that occur within the heart when glucose supplants FA as a major energy source suggest that substrate switching to glucose is not entirely benign. PMID:25713290

  12. Response of key stress-related genes of the seagrass Posidonia oceanica in the vicinity of submarine volcanic vents

    NASA Astrophysics Data System (ADS)

    Lauritano, C.; Ruocco, M.; Dattolo, E.; Buia, M. C.; Silva, J.; Santos, R.; Olivé, I.; Costa, M. M.; Procaccini, G.

    2015-03-01

    Submarine volcanic vents are being used as natural laboratories to assess the effects of CO2 on marine organisms and communities, as this gas is the main component of emissions. Seagrasses should positively react to increased dissolved carbon, but in vicinity of volcanic vents there may be toxic substances, that can have indirect effects on seagrasses. Here we analysed the expression of 35 stress-related genes in the Mediterranean keystone seagrass species P. oceanica in the vicinity of submerged volcanic vents located in the Islands of Ischia and Panarea, Italy, and compared them with those from control sites away from the influence of vents. Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR) was used to characterize the expression levels of genes. Fifty one per cent of genes analysed showed significant expression changes. Metal detoxification genes were mostly down-regulated in relation to controls both in Ischia and Panarea locations, indicating that P. oceanica does not increase the synthesis of heavy metal detoxification proteins in response to the environmental conditions present at the two vents. The expression levels of genes involved in free radical detoxification indicate that, in contrast with Ischia, P. oceanica at the Panarea vent face stressors that result in the production of reactive oxygen species triggering antioxidant responses. In addition, heat shock proteins were also activated at Panarea and not at Ischia. Overall, our study reveals that P. oceanica is generally under higher stress in the vicinity of the vents at Panarea than at Ischia, possibly resulting from environmental and evolutionary differences existing between the two volcanic sites. This is the first study analysing gene responses in marine plants living near natural CO2 vents and our results call for a careful consideration of factors, other than CO2 and acidification, that can cause stress to seagrasses and other organisms near volcanic vents.

  13. Expression profiling analysis of immune-related genes in channel catfish (Ictalurus punctatus) skin mucus following Flavobacterium columnare challenge.

    PubMed

    Ren, Yichao; Zhao, Honggang; Su, Baofeng; Peatman, Eric; Li, Chao

    2015-10-01

    Fish are covered by a watery gel-mucus, mainly secreted by the goblet cells, serving as the physical and biochemical barrier between the external environment and the interior milieu, playing more important roles in fish that without scale. Despite the important roles of mucus in fish immunity, the knowledge of detailed molecular events happened during infection process is still limited. While most studies were focused on characterizing the protein and enzyme activities in the mucus following challenge, no studies have examined the gene expression profiles in fish mucus. In this regard, herein we carried out the first gene profiling analysis in catfish mucus using real-time PCR. Ten important immune-related genes were selected according to our previous studies. Their expression levels were examined in the early timepoints (namely, 1 h, 2 h, 4 h, 8 h, and 24 h) following Flavobacterium columnare challenge. Notably, expression levels of most of the selected genes were rapidly altered by the challenge. Seven genes were down-regulated, while only three genes were up-regulated. In addition, the gene expression patterns in mucus were very different from the mucosal surfaces (skin, gill and intestine) and the classical immune organs (liver, spleen and kidney). The unique expression patterns obtained here may be resulted from the great advantage of the large amount of attached bacteria in the mucus than the internal tissues, and resulted from the bacteria virulent actors to suppress the host immune response. Taken together, our results can expand our knowledge of fish mucosal immunity, and the un-lethal mucus sampling can provide early insight for developing the strategies for selection of disease resistant families and strains in catfish as well as other fish species. PMID:26220643

  14. A Genome-Wide Association Study of the Maize Hypersensitive Defense Response Identifies Genes That Cluster in Related Pathways

    PubMed Central

    Venkata, Bala P.; Marla, Sandeep; Ji, Jiabing; Gachomo, Emma; Chu, Kevin; Negeri, Adisu; Benson, Jacqueline; Nelson, Rebecca; Bradbury, Peter; Nielsen, Dahlia; Holland, James B.; Balint-Kurti, Peter J.; Johal, Gurmukh

    2014-01-01

    Much remains unknown of molecular events controlling the plant hypersensitive defense response (HR), a rapid localized cell death that limits pathogen spread and is mediated by resistance (R-) genes. Genetic control of the HR is hard to quantify due to its microscopic and rapid nature. Natural modifiers of the ectopic HR phenotype induced by an aberrant auto-active R-gene (Rp1-D21), were mapped in a population of 3,381 recombinant inbred lines from the maize nested association mapping population. Joint linkage analysis was conducted to identify 32 additive but no epistatic quantitative trait loci (QTL) using a linkage map based on more than 7000 single nucleotide polymorphisms (SNPs). Genome-wide association (GWA) analysis of 26.5 million SNPs was conducted after adjusting for background QTL. GWA identified associated SNPs that colocalized with 44 candidate genes. Thirty-six of these genes colocalized within 23 of the 32 QTL identified by joint linkage analysis. The candidate genes included genes predicted to be in involved programmed cell death, defense response, ubiquitination, redox homeostasis, autophagy, calcium signalling, lignin biosynthesis and cell wall modification. Twelve of the candidate genes showed significant differential expression between isogenic lines differing for the presence of Rp1-D21. Low but significant correlations between HR-related traits and several previously-measured disease resistance traits suggested that the genetic control of these traits was substantially, though not entirely, independent. This study provides the first system-wide analysis of natural variation that modulates the HR response in plants. PMID:25166276

  15. Cyclic stretch promotes osteogenesis-related gene expression in osteoblast-like cells through a cofilin-associated mechanism

    PubMed Central

    GAO, JIE; FU, SHANMIN; ZENG, ZHAOBIN; LI, FEIFEI; NIU, QIANNAN; JING, DA; FENG, XUE

    2016-01-01

    Osteoblasts have the capacity to perceive and transduce mechanical signals, and thus, regulate the mRNA and protein expression of a variety of genes associated with osteogenesis. Cytoskeletal reconstruction, as one of the earliest perception events for external mechanical stimulation, has previously been demonstrated to be essential for mechanotransduction in bone cells. However, the mechanism by which mechanical signals induce cytoskeletal deformation remains poorly understood. The actin-binding protein, cofilin, promotes the depolymerization of actin and is understood to be important in the regulation of activities in various cell types, including endothelial, neuronal and muscle cells. However, to the best of our knowledge, the importance of cofilin in osteoblastic mechanotransduction has not been previously investigated. In the present study, osteoblast-like MG-63 cells were subjected to physiological cyclic stretch stimulation (12% elongation) for 1, 4, 8, 12 and 24 h, and the expression levels of cofilin and osteogenesis-associated genes were quantified with reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining and western blotting analyses. Additionally, knockdown of cofilin using RNA interference was conducted, and the mRNA levels of osteogenesis-associated genes were compared between osteoblast-like cells in the presence and absence of cofilin gene knockdown. The results of the present study demonstrated that cyclic stretch stimulates the expression of genes associated with osteoblastic activities in MG-63 cells, including alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (Runx2) and collagen-1 (COL-1). Cyclic stretch also regulates the mRNA and protein expression of cofilin in MG-63 cells. Furthermore, stretch-induced increases in the levels of osteogenesis-associated genes, including ALP, OCN, Runx2 and COL-1, were reduced following cofilin gene knockdown. Together, these results

  16. Seasonal Patterns of Soil Respiration and Related Soil Biochemical Properties under Nitrogen Addition in Winter Wheat Field

    PubMed Central

    Liang, Guopeng; Houssou, Albert A.; Wu, Huijun; Cai, Dianxiong; Wu, Xueping; Gao, Lili; Li, Jing; Wang, Bisheng; Li, Shengping

    2015-01-01

    Understanding the changes of soil respiration under increasing N fertilizer in cropland ecosystems is crucial to accurately predicting global warming. This study explored seasonal variations of soil respiration and its controlling biochemical properties under a gradient of Nitrogen addition during two consecutive winter wheat growing seasons (2013–2015). N was applied at four different levels: 0, 120, 180 and 240 kg N ha-1 year-1 (denoted as N0, N12, N18 and N24, respectively). Soil respiration exhibited significant seasonal variation and was significantly affected by soil temperature with Q10 ranging from 2.04 to 2.46 and from 1.49 to 1.53 during 2013–2014 and 2014–2015 winter wheat growing season, respectively. Soil moisture had no significant effect on soil respiration during 2013–2014 winter wheat growing season but showed a significant and negative correlation with soil respiration during 2014–2015 winter wheat growing season. Soil respiration under N24 treatment was significantly higher than N0 treatment. Averaged over the two growing seasons, N12, N18 and N24 significantly increased soil respiration by 13.4, 16.4 and 25.4% compared with N0, respectively. N addition also significantly increased easily extractable glomalin-related soil protein (EEG), soil organic carbon (SOC), total N, ammonium N and nitrate N contents. In addition, soil respiration was significantly and positively correlated with β-glucosidase activity, EEG, SOC, total N, ammonium N and nitrate N contents. The results indicated that high N fertilization improved soil chemical properties, but significantly increased soil respiration. PMID:26629695

  17. Breeding site selection by coho salmon (Oncorhynchus kisutch) in relation to large wood additions and factors that influence reproductive success

    USGS Publications Warehouse

    Clark, Steven M.; Dunham, Jason B.; McEnroe, Jeffery R.; Lightcap, Scott W.

    2014-01-01

    The fitness of female Pacific salmon (Oncorhynchus spp.) with respect to breeding behavior can be partitioned into at least four fitness components: survival to reproduction, competition for breeding sites, success of egg incubation, and suitability of the local environment near breeding sites for early rearing of juveniles. We evaluated the relative influences of habitat features linked to these fitness components with respect to selection of breeding sites by coho salmon (Oncorhynchus kisutch). We also evaluated associations between breeding site selection and additions of large wood, as the latter were introduced into the study system as a means of restoring habitat conditions to benefit coho salmon. We used a model selection approach to organize specific habitat features into groupings reflecting fitness components and influences of large wood. Results of this work suggest that female coho salmon likely select breeding sites based on a wide range of habitat features linked to all four hypothesized fitness components. More specifically, model parameter estimates indicated that breeding site selection was most strongly influenced by proximity to pool-tail crests and deeper water (mean and maximum depths). Linkages between large wood and breeding site selection were less clear. Overall, our findings suggest that breeding site selection by coho salmon is influenced by a suite of fitness components in addition to the egg incubation environment, which has been the emphasis of much work in the past.

  18. Androgen Regulated Genes in Human Prostate Xenografts in Mice: Relation to BPH and Prostate Cancer

    PubMed Central

    Love, Harold D.; Booton, S. Erin; Boone, Braden E.; Breyer, Joan P.; Koyama, Tatsuki; Revelo, Monica P.; Shappell, Scott B.; Smith, Jeffrey R.; Hayward, Simon W.

    2009-01-01

    Benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP) are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ) human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1) highly expressed in prostate, 2) had significant expression changes in response to androgens, and, 3) encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues. PMID:20027305

  19. COMT but not serotonin-related genes modulates the influence of childhood abuse on anger traits

    PubMed Central

    Perroud, Nader; Jaussent, Isabelle; Guillaume, Sébastien; Bellivier, Frank; Baud, Patrick; Jollant, Fabrice; Leboyer, Marion; Lewis, Cathryn; Malafosse, Alain; Courtet, Philippe

    2010-01-01

    Anger-related traits are regulated by genes as well as early environmental factors. Both childhood maltreatment and genes underlie vulnerability to suicidal behaviors, possibly by affecting the constitution of intermediate phenotypes such as anger traits. The aim of this study was to test the interaction between nine candidate genes and childhood maltreatment in modulating anger-related traits in 875 adult suicide attempters. The State-Trait Anger Expression Inventory and the Childhood Trauma Questionnaire were used to examine anger traits and traumatic childhood experiences respectively. The functional polymorphism of the catecholamine-O-methyl-transferase (COMT) gene Val158Met significantly modulated the association between sexual abuse and anger-trait level (p=0.001). In the presence of sexual abuse, individuals carrying the Val high-activity allele displayed greater disposition towards anger than individuals homozygous for the Met allele (p=0.0003). Notably, none of the serotonin-related genes influenced the effect of childhood abuse on anger traits. The results of the present study suggest that anger-trait level is influenced by the interaction between childhood abuse and functional polymorphism in the COMT gene. This study was carried out in a population with a high frequency of childhood abuse and a high disposition towards anger, and replication in healthy subjects is needed. PMID:20002200

  20. Oxyphilic and non-oxyphilic thyroid carcinoma cell lines differ in expressing apoptosis-related genes.

    PubMed

    Allìa, E; Cassoni, P; Marrocco, T; Volante, M; Bussolati, B; Wong, M; Clark, O H; Papotti, M

    2003-07-01

    Oxyphilic tumors of the thyroid are characterized by mitochondrion-rich cells and extensive DNA fragmentation. In order to clarify if a different expression of apoptosis-related genes could be responsible for DNA fragmentation in oxyphilic cell tumors, two thyroid follicular carcinoma-derived cell lines, having oxyphilic (XTC.UC1) and non-oxyphilic (WRO) features, were compared applying a gene array technique. Under basal culture conditions, several pro-apoptotic genes [caspases 3 and 10, Fas and the tumor necrosis factor-related apoptosis-inducing ligand (trail) genes] were switched on in oxyphilic, but not in non-oxyphilic cells. No difference in the mitochondrial apoptosis-related genes (bax, bad, bcl family etc.) was observed. Using the ISEL technique, the extent of DNA fragmentation did not differ under basal conditions in the two cell lines. Conversely, following an oxidative pro-apoptotic stress (6-h methylene blue treatment and light exposure), XTC.UC1 cells showed an extensive DNA fragmentation (up to 70% of cells), dramatically exceeding that observed in WRO cells (up to 20% of cells). In contrast, the oxidative stimulus induced a remarkable apoptosis gene activation in non-oxyphilic WRO cells only. These results suggest that oxyphilic cells may have a unique silent activation of a pro-apoptotic phenotype, which could be responsible for DNA instability and lead to cell death as the consequence of an increased sensitivity to ischemic stresses, as frequently observed in vivo. PMID:14594119

  1. Mutation analysis of TMC1 identifies four new mutations and suggests an additional deafness gene at locus DFNA36-DFNB7/11

    PubMed Central

    Hilgert, Nele; Alasti, Fatemeh; Dieltjens, Nele; Pawlik, Barbara; Wollnik, Bernd; Uyguner, Oya; Delmaghani, Sedigheh; Weil, Dominique; Petit, Christine; Danis, Evi; Yang, Tao; Pandelia, Efthimia; Petersen, Michael B.; Goossens, Dirk; Favero, Jurgen Del; Sanati, Mohammad Hossein; Smith, Richard JH; Van Camp, Guy

    2016-01-01

    Hearing loss is the most frequent sensorineural disorder, affecting 1 in 1000 newborns. In more than half of these babies, the hearing loss is inherited. Hereditary hearing loss is a very heterogeneous trait, with about 100 gene localizations and 44 gene identifications for nonsyndromic hearing loss. TMC1 has been identified as the disease-causing gene for autosomal dominant and autosomal recessive nonsyndromic hearing loss at the DFNA36 and DFNB7/11 loci, respectively. To date, two dominant and 18 recessive TMC1 mutations have been reported as the cause of hearing loss in 34 families. In this report, we describe linkage to DFNA36 and DFNB7/11 in one family with dominant and 10 families with recessive nonsyndromic sensorineural hearing loss. In addition, mutation analysis of TMC1 was performed in 51 familial Turkish patients with autosomal recessive hearing loss. TMC1 mutations were identified in seven of the families segregating recessive hearing loss. The pathogenic variants we found included two known mutations, c.100C>T and c.1165C>T, and four new mutations, c.2350C>T, c.776+1G>A, c.767_768del and c.1166G>A. The absence of TMC1 mutations in the remaining six linked families implies the presence of mutations outside the coding region of this gene, or alternatively, at least one additional deafness-causing gene in this region. The analysis of copy number variations in TMC1 as well as DNA sequencing of 15 additional candidate genes did not reveal any proven pathogenic changes, leaving both hypotheses open. PMID:18616530

  2. The mouse protein synthesis initiation factor 4A gene family includes two related functional genes which are differentially expressed.

    PubMed Central

    Nielsen, P J; Trachsel, H

    1988-01-01

    We have cloned and characterized a family of mouse genomic sequences hybridizing to mouse cDNA probes coding for eIF-4A, one of the protein synthesis initiation factors involved in the binding of mRNA to the ribosome. We estimate that there is a total of approximately 9-13 eIF-4A pseudogenes. We also found an eIF-4A intronless retroposon which, when compared to the cDNA, contains a single nucleotide difference. This possibly functional gene contains a mouse repetitive B1 element integrated in the promoter region. Furthermore, we have cloned two intron-containing eIF-4A genes (termed eIF-4AI and eIF-4AII). The eIF-4AII gene codes for a previously unknown form of eIF-4A. Northern blot hybridization with RNA from several mouse organs shows a variation in eIF-4AI expression within a factor of 7. In contrast, relative to liver, eIF-4AII expression is 20- to 30-times higher in brain and kidney, 10- to 17-fold higher in lung and heart, and is about equally abundant in liver, spleen and thymus. These data suggest that the relative efficiency of protein synthesis initiation for different mRNAs, as reflected by discrimination in messenger 5'-terminal cap recognition and binding to ribosomes, varies in different tissues. Images PMID:3046931

  3. Addition of Escherichia coli K-12 Growth Observation and Gene Essentiality Data to the EcoCyc Database

    PubMed Central

    Mackie, Amanda; Paley, Suzanne; Keseler, Ingrid M.; Shearer, Alexander; Paulsen, Ian T.

    2014-01-01

    The sets of compounds that can support growth of an organism are defined by the presence of transporters and metabolic pathways that convert nutrient sources into cellular components and energy for growth. A collection of known nutrient sources can therefore serve both as an impetus for investigating new metabolic pathways and transporters and as a reference for computational modeling of known metabolic pathways. To establish such a collection for Escherichia coli K-12, we have integrated data on the growth or nongrowth of E. coli K-12 obtained from published observations using a variety of individual media and from high-throughput phenotype microarrays into the EcoCyc database. The assembled collection revealed a substantial number of discrepancies between the high-throughput data sets, which we investigated where possible using low-throughput growth assays on soft agar and in liquid culture. We also integrated six data sets describing 16,119 observations of the growth of single-gene knockout mutants of E. coli K-12 into EcoCyc, which are relevant to antimicrobial drug design, provide clues regarding the roles of genes of unknown function, and are useful for validating metabolic models. To make this information easily accessible to EcoCyc users, we developed software for capturing, querying, and visualizing cellular growth assays and gene essentiality data. PMID:24363340

  4. Further investigations of the relation between polymorphisms in sex steroid related genes and autistic-like traits.

    PubMed

    Zettergren, Anna; Karlsson, Sara; Hovey, Daniel; Jonsson, Lina; Melke, Jonas; Anckarsäter, Henrik; Lichtenstein, Paul; Lundström, Sebastian; Westberg, Lars

    2016-06-01

    Autism spectrum disorders (ASDs) are more prevalent in boys than in girls, indicating that high levels of testosterone during early development may be a risk factor. Evidence for this hypothesis comes from studies showing associations between fetal testosterone levels, as well as indirect measures of prenatal androgenization, and ASDs and autistic-like traits (ALTs). In a recent study we reported associations between ALTs and single nucleotide polymorphisms (SNPs) in the genes encoding estrogen receptor 1 (ESR1), steroid-5-alpha-reductase, type 2 (SRD5A2) and sex hormone-binding globulin (SHBG) in a subset (n=1771) from the Child and Adolescent Twin Study in Sweden (CATSS). The aim of the present study was to try to replicate these findings in an additional, larger, sample of individuals from the CATSS (n=10,654), as well as to analyze additional SNPs of functional importance in SHBG and SRD5A2. No associations between the previously associated SNPs in the genes ESR1 and SRD5A2 and ALTs could be seen in the large replication sample. Still, our results show that two non-linked SNPs (rs6259 and rs9901675) at the SHBG gene locus might be of importance for language impairment problems in boys. The results of the present study do not point toward a major role for the investigated SNPs in the genes ESR1 and SRD5A2 in ALTs, but a possible influence of genetic variation in SHBG, especially for language impairment problems in boys, cannot be ruled out. PMID:26930261

  5. Cloning the Gravity and Shear Stress Related Genes from MG-63 Cells by Subtracting Hybridization

    NASA Astrophysics Data System (ADS)

    Zhang, Shu; Dai, Zhong-quan; Wang, Bing; Cao, Xin-sheng; Li, Ying-hui; Sun, Xi-qing

    2008-06-01

    Background The purpose of the present study was to clone the gravity and shear stress related genes from osteoblast-like human osteosarcoma MG-63 cells by subtractive hybridization. Method MG-63 cells were divided into two groups (1G group and simulated microgravity group). After cultured for 60 h in two different gravitational environments, two groups of MG-63 cells were treated with 1.5Pa fluid shear stress (FSS) for 60 min, respectively. The total RNA in cells was isolated. The gravity and shear stress related genes were cloned by subtractive hybridization. Result 200 clones were gained. 30 positive clones were selected using PCR method based on the primers of vector and sequenced. The obtained sequences were analyzed by blast. changes of 17 sequences were confirmed by RT-PCR and these genes are related to cell proliferation, cell differentiation, protein synthesis, signal transduction and apoptosis. 5 unknown genes related to gravity and shear stress were found. Conclusion In this part of our study, our result indicates that simulated microgravity may change the activities of MG-63 cells by inducing the functional alterations of specific genes.

  6. Regulation of some salt defense-related genes in relation to physiological and biochemical changes in three sugarcane genotypes subjected to salt stress.

    PubMed

    Poonsawat, Wasinee; Theerawitaya, Cattarin; Suwan, Therapatt; Mongkolsiriwatana, Chareerat; Samphumphuang, Thapanee; Cha-um, Suriyan; Kirdmanee, Chalermpol

    2015-01-01

    Sugarcane (Saccharum officinale L.; Poaceae) is a sugar-producing plant widely grown in tropic. Being a glycophytic species, it is very sensitive to salt stress, and salinity severely reduces growth rate and cane yield. The studies investigating the regulation of salt defense metabolite-related genes in relation to final biochemical products in both susceptible and tolerant genotypes of sugarcane are largely lacking. We therefore investigated the expression levels of sugarcane shaggy-like kinase (SuSK), sucrose transporter (SUT), proline biosynthesis (pyrolline-5-carboxylate synthetase; P5CS), ion homeostasis (NHX1), and catalase (CAT2) mRNAs, and contents of Na(+), soluble sugar, and free proline in three sugarcane genotypes (A19 mutant, K88-92, and K92-80) when subjected to salt stress (200 mM NaCl). The relative expression levels of salt defense-related genes in salt-stressed plantlets of sugarcane cv. K88-92 were upregulated in relation to salt exposure times when compared with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as housekeeping gene. In addition, final biochemical products, i.e., low Na(+), sucrose enrichment, and free proline accumulation, were evidently demonstrated in salt-stressed plantlets. Chlorophyll b, total chlorophyll, total carotenoid concentrations, and maximum quantum yield of PSII (F v/F m) in positive check (K88-92) were maintained under salt stress, leading to high net photosynthetic rate (P n) and growth retention (root length, fresh weight, and leaf area). In contrast, photosynthetic abilities in negative check, K92-80, and A19 mutant lines grown under salt stress declined significantly in comparison to control, leading to a reduction in P n and an inhibition of overall growth characters. The study concludes that the genetic background of sugarcane cv. K88-92 may further be exploited to play a key role as parental clone for sugarcane breeding program for salt-tolerant purposes. PMID:25012031

  7. Identification of Candidate Genes in Scleroderma-Related Pulmonary Arterial Hypertension

    PubMed Central

    Grigoryev, DN; Mathai, SC; Fisher, MR; Girgis, RE; Zaiman, AL; Housten-Harris, T; Cheadle, C; Gao, L; Hummers, LK; Champion, HC; Garcia, JGN; Wigley, FM; Tuder, RM; Barnes, KC; Hassoun, PM

    2008-01-01

    We hypothesize that pulmonary arterial hypertension (PAH)-associated genes identified by expression profiling of peripheral blood mononuclear cells (PBMCs) from patients with idiopathic pulmonary arterial hypertension (IPAH) can also be identified in PBMCs from scleroderma patients with PAH (PAH-SSc). Gene expression profiles of PBMCs collected from IPAH (n=9), PAH-SSc (n=10) patients and healthy controls (n=5) were generated using HG_U133A_2.0 GeneChips and processed by RMA/GCOS_1.4/SAM_1.21 data analysis pipeline. Disease severity in consecutive patients was assessed by functional status and hemodynamic measurements. The expression profiles were analyzed using PAH severity-stratification, and identified candidate genes were validated with real time PCR (rtPCR). Transcriptomics of PBMCs from IPAH patients was highly comparable with that of PMBCs from PAH-SSc patients. The PBMC gene expression patterns significantly correlate with right atrium pressure (RA) and cardiac index (CI), known predictors of survival in PAH. Array stratification by RA and CI identified 364 PAH-associated candidate genes. Gene ontology analysis revealed significant (Zscore > 1.96) alterations in angiogenesis genes according to PAH severity: MMP9 and VEGF were significantly upregulated in mild as compared to severe PAH and healthy controls, as confirmed by rtPCR. These data demonstrate that PBMCs from patients with PAH-SSc carry distinct transcriptional expression. Furthermore, our findings suggest an association between angiogenesis-related gene expression and severity of PAH in PAH-SSc patients. Deciphering the role of genes involved in vascular remodeling and PAH development may reveal new treatment targets for this devastating disorder. PMID:18355767

  8. High frequency of additional gene mutations in acute myeloid leukemia with MLL partial tandem duplication: DNMT3A mutation is associated with poor prognosis

    PubMed Central

    Kao, Hsiao-Wen; Liang, Der-Cherng; Kuo, Ming-Chung; Wu, Jin-Hou; Dunn, Po; Wang, Po-Nan; Lin, Tung-Liang; Shih, Yu-Shu; Liang, Sung-Tzu; Lin, Tung-Huei; Lai, Chen-Yu; Lin, Chun-Hui; Shih, Lee-Yung

    2015-01-01

    The mutational profiles of acute myeloid leukemia (AML) with partial tandem duplication of mixed-lineage leukemia gene (MLL-PTD) have not been comprehensively studied. We studied 19 gene mutations for 98 patients with MLL-PTD AML to determine the mutation frequency and clinical correlations. MLL-PTD was screened by reverse-transcriptase PCR and confirmed by real-time quantitative PCR. The mutational analyses were performed with PCR-based assays followed by direct sequencing. Gene mutations of signaling pathways occurred in 63.3% of patients, with FLT3-ITD (44.9%) and FLT3-TKD (13.3%) being the most frequent. 66% of patients had gene mutations involving epigenetic regulation, and DNMT3A (32.7%), IDH2 (18.4%), TET2 (18.4%), and IDH1 (10.2%) mutations were most common. Genes of transcription pathways and tumor suppressors accounted for 23.5% and 10.2% of patients. RUNX1 mutation occurred in 23.5% of patients, while none had NPM1 or double CEBPA mutation. 90.8% of MLL-PTD AML patients had at least one additional gene mutation. Of 55 MLL-PTD AML patients who received standard chemotherapy, age older than 50 years and DNMT3A mutation were associated with inferior outcome. In conclusion, gene mutations involving DNA methylation and activated signaling pathway were common co-existed gene mutations. DNMT3A mutation was a poor prognostic factor in MLL-PTD AML. PMID:26375248

  9. Spatiotemporal patterns of the Huntingtin-interacting protein 1-related gene in the mouse head.

    PubMed

    Masuda, Tomoyuki; Sakuma, Chie; Ueno, Takayuki; Yamada, Yuriko; Ohmomo, Hideki; Ueda, Shuichi; Yamagishi, Toshiyuki; Yaginuma, Hiroyuki

    2013-12-01

    Huntingtin-interacting protein 1-related (Hip1r) was originally identified due to its homology to Huntingtin-interacting protein 1, which contributes to the development of Huntington's disease (HD). We studied the expression of the mouse Hip1r (mHip1r) gene in the mouse head by in situ hybridization. In early embryogenesis at embryonic day (E) 13, mHip1r expression was especially prominent in the olfactory epithelium, cerebral cortex layer 1, cortical plate, and dentate gyrus. During later development from E15 to E17, strong expression of mHip1r transcripts continued to be observed in the olfactory epithelium, cortical plate, and dentate gyrus. Furthermore, not only the subplate and subventricular zone of the cortex, but also secretory glands, such as the nasal gland and the submandibular gland, were mHip1r-positive. Other positive tissues included the retinal ganglion cells, vomeronasal organ, trigeminal ganglion, and the developing molar tooth. In the adult mouse brain, similar expression patterns were observed in the cerebral cortex layers and other brain regions except the cerebellum. Additionally, by using an antibody against mHip1r, we confirmed these expression patterns at the protein level. Specific expression of mHip1r in the embryonic brain and secretory glands suggests a possible role for Hip1r in normal development and in the pathology of HD. PMID:24712472

  10. Neuroprotective changes of striatal degeneration-related gene expression by acupuncture in an MPTP mouse model of Parkinsonism: microarray analysis.

    PubMed

    Choi, Yeong-Gon; Yeo, Sujung; Hong, Yeon-Mi; Lim, Sabina

    2011-04-01

    Acupuncture at acupoints GB34 and LR3 has been reported to inhibit nigrostriatal degeneration in Parkinsonism models, yet the genes related to this preventive effect of acupuncture on the nigrostriatal dopaminergic system remain elusive. This study investigated gene expression profile changes in the striatal region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism models after acupuncture at the acupoints GB34 and LR3 using a whole transcript genechip microarray (Affymetrix genechip mouse gene 1.0 ST array). It was confirmed that acupuncture at these acupoints could inhibit the decrease of tyrosine hydroxylase and dopamine transporter in the nigrostriatal region of the MPTP model while acupuncture at the non-acupoints could not counteract this decrease. Genechip gene array analysis (fold change cutoff 1.3 and P < 0.05) showed that 12 of the 69 probes up-regulated in MPTP when compared to the control were down-regulated by acupuncture at the acupoints. Of these 12 probes, 11 probes (nine annotated genes) were exclusively down-regulated by acupuncture only at the acupoints; the Gfral gene was excluded because it was commonly down-regulated by acupuncture at both the acupoints and the non-acupoints. In addition, 28 of the 189 probes down-regulated in MPTP when compared to the control were up-regulated by acupuncture at the acupoints. Of these 28 probes, 19 probes (seven annotated genes) were exclusively up-regulated by acupuncture only at the acupoints while nine probes were commonly up-regulated by acupuncture at both the acupoints and the non-acupoints. The regulation patterns of representative genes in real-time RT-PCR correlated with those of the genes in the microarray. These results suggest that the 30 probes (16 annotated genes), which are affected by MPTP and acupuncture only at the acupoints, are responsible for exerting in the striatal regions the inhibitory effect of acupuncture at the acupoints on MPTP-induced striatal

  11. Regulation of iron transport related genes by boron in the marine bacterium Marinobacter algicola DG893.

    PubMed

    Romano, Ariel; Trimble, Lyndsay; Hobusch, Ashtian R; Schroeder, Kristine J; Amin, Shady A; Hartnett, Andrej D; Barker, Ryan A; Crumbliss, Alvin L; Carrano, Carl J

    2013-08-01

    While there has been extensive interest in the use of boron isotope ratios as a surrogate of pH in paleoclimate studies in the context of climate change-related questions, the high (0.4 mM) concentration and the depth-independent (conservative or non-nutrient-like) concentration profile of this element have led to boron being neglected as a potentially biologically relevant element in the modern ocean. Here we report that boron affects the expression of a number of protein and genes in the "algal-associated" Gram-negative marine bacterium Marinobacter algicola DG893. Most intriguingly, a number of these proteins and genes are related to iron uptake. In a recent separate publication we have shown that boron regulates one such iron transport related protein, i.e. the periplasmic iron binding protein FbpA via a direct interaction of the metalloid with this protein. Here we show that a number of other iron uptake related genes are also affected by boron but in the opposite way i.e. they are up-regulated. We propose that the differential effect of boron on FbpA expression relative to other iron transport related genes is a result of an interaction between boron and the global iron regulatory protein Fur. PMID:23775459

  12. Chromosome assignment of four photosynthesis-related genes and their variability in wheat species.

    PubMed

    Ogihara, Y; Shimizu, H; Hasegawa, K; Tsujimoto, H; Sasakuma, T

    1994-06-01

    Copy numbers of four photosynthesis-related genes, PhyA, Ppc, RbcS and Lhcb1 (*)1, in wheat genomes were estimated by slot-blot analysis, and these genes were assigned to the chromosome arms of common wheat by Southern hybridization of DNA from an aneuploid series of the cultivar Chinese Spring. The copy number of PhyA was estimated to be one locus per haploid genome, and this gene was assigned to chromosomes 4AL, 4BS and 4DS. The Ppc gene showed a low copy number of small multigenes, and was located on the short arm of homoeologous group 3 chromosomes and the long arm of chromosomes of homoeologous group 7. RbcS consisted of a multigene family, with approximately 100 copies in the common wheat genome, and was located on the short arm of group 2 chromosomes and the long arm of group 5 chromosomes. Lhcb1 (*)1 also consisted of a multigene family with about 50 copies in common wheat. Only a limited number of restriction fragments (approximately 15%) were used to determine the locations of members of this family on the long arm of group 1 chromosomes owing to the multiplicity of DNA bands. The variability of hybridized bands with the four genes was less in polyploids, but was more in the case of multigene families. RFLP analysis of polyploid wheats and their presumed ancestors was carried out with probes of the oat PhyA gene, the maize Ppc gene, the wheat RbcS gene and the wheat Lhcb1 (*)1 gene. The RFLP patterns of common wheat most closely resembled those of T. Dicoccum (Emmer wheat), T. urartu (A genome), Ae. speltoides (S genome) and Ae. squarrosa (D genome). Diversification of genes in the wheat complex appear to have occurred