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  1. GATA factors in endocrine neoplasia.

    Science.gov (United States)

    Pihlajoki, Marjut; Färkkilä, Anniina; Soini, Tea; Heikinheimo, Markku; Wilson, David B

    2016-02-01

    GATA transcription factors are structurally-related zinc finger proteins that recognize the consensus DNA sequence WGATAA (the GATA motif), an essential cis-acting element in the promoters and enhancers of many genes. These transcription factors regulate cell fate specification and differentiation in a wide array of tissues. As demonstrated by genetic analyses of mice and humans, GATA factors play pivotal roles in the development, homeostasis, and function of several endocrine organs including the adrenal cortex, ovary, pancreas, parathyroid, pituitary, and testis. Additionally, GATA factors have been shown to be mutated, overexpressed, or underexpressed in a variety of endocrine tumors (e.g., adrenocortical neoplasms, parathyroid tumors, pituitary adenomas, and sex cord stromal tumors). Emerging evidence suggests that GATA factors play a direct role in the initiation, proliferation, or propagation of certain endocrine tumors via modulation of key developmental signaling pathways implicated in oncogenesis, such as the WNT/β-catenin and TGFβ pathways. Altered expression or function of GATA factors can also affect the metabolism, ploidy, and invasiveness of tumor cells. This article provides an overview of the role of GATA factors in endocrine neoplasms. Relevant animal models are highlighted. PMID:26027919

  2. GATA2 regulates dendritic cell differentiation.

    Science.gov (United States)

    Onodera, Koichi; Fujiwara, Tohru; Onishi, Yasushi; Itoh-Nakadai, Ari; Okitsu, Yoko; Fukuhara, Noriko; Ishizawa, Kenichi; Shimizu, Ritsuko; Yamamoto, Masayuki; Harigae, Hideo

    2016-07-28

    Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Lin(-)Sca-1(+)Kit(+) cells, common myeloid-restricted progenitors, and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 +190. These results suggest that GATA2 plays an important role in cell-fate specification toward the myeloid vs T-lymphocyte lineage by regulating lineage-specific transcription factors in DC progenitors, thereby contributing to DC differentiation. PMID:27259979

  3. GATA2 regulates GATA1 expression through LSD1-mediated histone modification.

    Science.gov (United States)

    Guo, Yidi; Fu, Xueqi; Huo, Bo; Wang, Yongsen; Sun, Jing; Meng, Lingyuan; Hao, Tian; Zhao, Zhizhuang Joe; Hu, Xin

    2016-01-01

    The dynamic and reversed expression of GATA1 and GATA2 are essential for proper erythroid differentiation. Our previous work demonstrates that LSD1, a histone H3K4 demethylase, represses GATA2 expression at late stage of erythroid differentiation. K562 and MEL cells were used and cultured in Roswell Park Memorial Institute-1640 medium (RPMI) and Dulbecco's modified Eagle's medium (DMEM), respectively. Western blot assay was used to examine the GATA1, GATA2, TAL1, HDAC1, HDAC2, CoREST and β-actin protein. The immunoprecipitation assay and GST pull-down assay were employed to detect the precipitated protein complexes and investigate the interaction between the proteins. The small interfering RNA (siRNA) and nonspecific control siRNA were synthesized to silence the target genes. Double fluorescence immunostaining was used to observe the association of LSD1 with GATA2 in K562 cells. The results indicated that knockdown of LSD1 in K562 cell causes increased H3K4 di-methylation at GATA1 locus and activates GATA1 expression, demonstrating that LSD1 represses GATA1 expression through LSD1-mediated histone demethylation. Upon induced erythroid differentiation of K562 cells, the interaction between GATA2 and LSD1 is decreased, consistent with a de-repression of GATA1 expression. Meanwhile, the interaction between TAL1 and LSD1 is increased, which forms a complex that efficiently suppresses GATA2 expression. In conclusion, these observations reveal an elegant mechanism to modulate GATA1 and GATA2 expression during erythroid differentiation. While LSD1 mainly forms complex with GATA2 to repress GATA1 expression in hematopoietic progenitor cells, it mostly forms complex with TAL1 to repress GATA2 expression in differentiated cells. PMID:27347333

  4. Friend of GATA-1 Represses GATA-3–dependent Activity in CD4+ T Cells

    OpenAIRE

    Zhou, Meixia; Ouyang, Wenjun; Gong, Qian; Katz, Samuel G.; White, J. Michael; Orkin, Stuart H.; Murphy, Kenneth M.

    2001-01-01

    The development of naive CD4+ T cells into a T helper (Th) 2 subset capable of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal transducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in several stages of hematopoietic development including erythrocyte and megakaryocyte differentiation, but whether FOG-1 regulat...

  5. Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa

    Directory of Open Access Journals (Sweden)

    Mäki Markku

    2008-04-01

    Full Text Available Abstract Background Human gastrointestinal mucosa regenerates vigorously throughout life, but the factors controlling cell fate in mature mucosa are poorly understood. GATA transcription factors direct cell proliferation and differentiation in many organs, and are implicated in tumorigenesis. GATA-4 and GATA-6 are considered crucial for the formation of murine gastrointestinal mucosa, but their role in human gastrointestinal tract remains unexplored. We studied in detail the expression patterns of these two GATA factors and a GATA-6 down-stream target, Indian hedgehog (Ihh, in normal human gastrointestinal mucosa. Since these factors are considered important for proliferation and differentiation, we also explored the possible alterations in their expression in gastrointestinal neoplasias. The expression of the carcinogenesis-related protein Indian hedgehog was also investigated in comparison to GATA factors. Methods Samples of normal and neoplastic gastrointestinal tract from children and adults were subjected to RNA in situ hybridization with 33P labelled probes and immunohistochemistry, using an avidin-biotin immunoperoxidase system. The pathological tissues examined included samples of chronic and atrophic gastritis as well as adenomas and adenocarcinomas of the colon and rectum. Results GATA-4 was abundant in the differentiated epithelial cells of the proximal parts of the gastrointestinal tract but was absent from the distal parts. In contrast, GATA-6 was expressed throughout the gastrointestinal epithelium, and in the distal gut its expression was most intense at the bottom of the crypts, i.e. cells with proliferative capacity. Both factors were also present in Barrett's esophagus and metaplasia of the stomach. GATA-6 expression was reduced in colon carcinoma. Ihh expression overlapped with that of GATA-6 especially in benign gastrointestinal neoplasias. Conclusion The results suggest differential but overlapping functions for GATA-4 and

  6. GATA3: A master of many trades in immune regulation

    OpenAIRE

    Wan, Yisong Y.

    2014-01-01

    GATA3 has conventionally been regarded as a transcription factor that drives the differentiation of T helper (Th) 2 cells. Increasing evidence points to function for GATA3 beyond controlling Th2 differentiation. GATA3 regulates T cell development, proliferation and maintenance. Furthermore, recent studies have demonstrated important roles for GATA3 in innate lymphoid cells. Thus GATA3 emerges as a factor with diverse functions in immune regulation, which are in some cases cell-type specific a...

  7. Shift in GATA3 functions, and GATA3 mutations, control progression and clinical presentation in breast cancer

    OpenAIRE

    Cohen, Helit; Ben-Hamo, Rotem; Gidoni, Moriah; Yitzhaki, Ilana; Kozol, Renana; Zilberberg, Alona; Efroni, Sol

    2014-01-01

    Introduction GATA binding protein 3 (GATA3) is a regulator of mammary luminal cell differentiation, and an estrogen receptor (ER) associated marker in breast cancer. Tumor suppressor functions of GATA3 have been demonstrated primarily in basal-like breast cancers. Here, we focused on its function in luminal breast cancer, where GATA3 is frequently mutated, and its levels are significantly elevated. Methods GATA3 target genes were identified in normal- and luminal cancer- mammary cells by ChIP...

  8. GATA-2 and GATA-3 regulate trophoblast-specific gene expression in vivo.

    NARCIS (Netherlands)

    G.T. Ma (Grace); M.E. Roth (Matthew); J.C. Groskopf (John); F.G. Grosveld (Frank); J.D. Engel (Douglas); D.I.H. Linzer (Daniel); F.Y. Tsai (Fong-Ying); S.H. Orkin (Stuart)

    1997-01-01

    textabstractWe previously demonstrated that the zinc finger transcription factors GATA-2 and GATA-3 are expressed in trophoblast giant cells and that they regulate transcription from the mouse placental lactogen I gene promoter in a transfected trophoblast cell line. We present evidence here that bo

  9. GATA3 in breast cancer: tumor suppressor or oncogene?

    OpenAIRE

    Takaku, Motoki; Grimm, Sara A; Wade, Paul A.

    2015-01-01

    GATA3 is a highly conserved, essential transcription factor expressed in a number of tissues, including the mammary gland. GATA3 expression is required for normal development of the mammary gland where it is estimated to be the most abundant transcription factor in luminal epithelial cells. In breast cancer, GATA3 expression is highly correlated with the luminal transcriptional program. Recent genomic analysis of human breast cancers has revealed high frequency mutation in GATA3 in luminal tu...

  10. Structure and Specificity of GATA Proteins in Th2 Development

    OpenAIRE

    Ranganath, Sheila; Murphy, Kenneth M.

    2001-01-01

    Development of Th2 subset of CD4+ T cells involves the interleukin-4 (IL-4)- and Stat6-dependent increase in GATA-3 expression during primary activation. Recently we reported that the phenotypic stability and factor independence of Th2 cells involves acquisition of an intracellular pathway that maintains GATA-3 expression. Evidence from retroviral expression studies implied that this pathway involved an autoactivation of GATA-3 expression, since Stat6-deficient T cells induced endogenous GATA...

  11. Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis

    OpenAIRE

    Xuan, Shouhong; Borok, Matthew J.; Decker, Kimberly J.; Battle, Michele A.; Duncan, Stephen A.; Hale, Michael A.; MacDonald, Raymond J.; Sussel, Lori

    2012-01-01

    Pancreatic agenesis is a human disorder caused by defects in pancreas development. To date, only a few genes have been linked to pancreatic agenesis in humans, with mutations in pancreatic and duodenal homeobox 1 (PDX1) and pancreas-specific transcription factor 1a (PTF1A) reported in only 5 families with described cases. Recently, mutations in GATA6 have been identified in a large percentage of human cases, and a GATA4 mutant allele has been implicated in a single case. In the mouse, Gata4 a...

  12. Transcriptome and phenotypic analysis reveals Gata3-dependent signalling pathways in murine hair follicles

    OpenAIRE

    Kurek, Dorota; Garinis, George; Doorninck, Hikke; Van Der Wees, Jacqueline; Grosveld, Frank

    2007-01-01

    textabstractAbstract The transcription factor Gata3 is crucially involved in epidermis and hair follicle differentiation. Yet, little is known about how Gata3 co-ordinates stem cell lineage determination in skin, what pathways are involved and how Gata3 differentially regulates distinct cell populations within the hair follicle. Here, we describe a conditional Gata3-/- mouse (K14-Gata3-/-) in which Gata3 is specifically deleted in epidermis and hair follicles. K14-Gata3-/- mice show aberrant ...

  13. GATA Factor-G-Protein-Coupled Receptor Circuit Suppresses Hematopoiesis.

    Science.gov (United States)

    Gao, Xin; Wu, Tongyu; Johnson, Kirby D; Lahvic, Jamie L; Ranheim, Erik A; Zon, Leonard I; Bresnick, Emery H

    2016-03-01

    Hematopoietic stem cells (HSCs) originate from hemogenic endothelium within the aorta-gonad-mesonephros (AGM) region of the mammalian embryo. The relationship between genetic circuits controlling stem cell genesis and multi-potency is not understood. A Gata2 cis element (+9.5) enhances Gata2 expression in the AGM and induces the endothelial to HSC transition. We demonstrated that GATA-2 rescued hematopoiesis in +9.5(-/-) AGMs. As G-protein-coupled receptors (GPCRs) are the most common targets for FDA-approved drugs, we analyzed the GPCR gene ensemble to identify GATA-2-regulated GPCRs. Of the 20 GATA-2-activated GPCR genes, four were GATA-1-activated, and only Gpr65 expression resembled Gata2. Contrasting with the paradigm in which GATA-2-activated genes promote hematopoietic stem and progenitor cell genesis/function, our mouse and zebrafish studies indicated that GPR65 suppressed hematopoiesis. GPR65 established repressive chromatin at the +9.5 site, restricted occupancy by the activator Scl/TAL1, and repressed Gata2 transcription. Thus, a Gata2 cis element creates a GATA-2-GPCR circuit that limits positive regulators that promote hematopoiesis. PMID:26905203

  14. GATA Factor-G-Protein-Coupled Receptor Circuit Suppresses Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Xin Gao

    2016-03-01

    Full Text Available Hematopoietic stem cells (HSCs originate from hemogenic endothelium within the aorta-gonad-mesonephros (AGM region of the mammalian embryo. The relationship between genetic circuits controlling stem cell genesis and multi-potency is not understood. A Gata2 cis element (+9.5 enhances Gata2 expression in the AGM and induces the endothelial to HSC transition. We demonstrated that GATA-2 rescued hematopoiesis in +9.5−/− AGMs. As G-protein-coupled receptors (GPCRs are the most common targets for FDA-approved drugs, we analyzed the GPCR gene ensemble to identify GATA-2-regulated GPCRs. Of the 20 GATA-2-activated GPCR genes, four were GATA-1-activated, and only Gpr65 expression resembled Gata2. Contrasting with the paradigm in which GATA-2-activated genes promote hematopoietic stem and progenitor cell genesis/function, our mouse and zebrafish studies indicated that GPR65 suppressed hematopoiesis. GPR65 established repressive chromatin at the +9.5 site, restricted occupancy by the activator Scl/TAL1, and repressed Gata2 transcription. Thus, a Gata2 cis element creates a GATA-2-GPCR circuit that limits positive regulators that promote hematopoiesis.

  15. GATA-1 directly regulates Nanog in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter activity can be significantly repressed by ectopic expression of GATA-1 evidenced by a promoter reporter assay. Mutation studies reveal that one of the four putative binding sites counts for GATA-1 repressing Nanog promoter activity. Direct binding of GATA-1 on Nanog proximal promoter is confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data provide new insights into the expanded regulatory circuitry that coordinates Nanog expression. - Highlights: • The Nanog proximal promoter conceives functional element for GATA-1. • GATA-1 occupies the Nanog proximal promoter in vitro and in vivo. • GATA-1 transcriptionally suppresses Nanog

  16. GATA-1 directly regulates Nanog in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wen-Zhong; Ai, Zhi-Ying [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Wang, Zhi-Wei [School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027 (China); Chen, Lin-Lin [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Guo, Ze-Kun, E-mail: gzknwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Zhang, Yong, E-mail: zylabnwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China)

    2015-09-25

    Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter activity can be significantly repressed by ectopic expression of GATA-1 evidenced by a promoter reporter assay. Mutation studies reveal that one of the four putative binding sites counts for GATA-1 repressing Nanog promoter activity. Direct binding of GATA-1 on Nanog proximal promoter is confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data provide new insights into the expanded regulatory circuitry that coordinates Nanog expression. - Highlights: • The Nanog proximal promoter conceives functional element for GATA-1. • GATA-1 occupies the Nanog proximal promoter in vitro and in vivo. • GATA-1 transcriptionally suppresses Nanog.

  17. Analysis list: Gata2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Gata2 Blood,Uterus + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gata...2.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gata2.5.tsv http://dbarchive.biosciencedbc.jp/...kyushu-u/mm9/target/Gata2.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gata2.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Gata2.Uterus.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Uterus.gml ...

  18. Embryonic expression and cloning of the murine GATA-3 gene.

    OpenAIRE

    K. M. George; Leonard, M W; Roth, M. E.; Lieuw, Ken; Kioussis, D; Grosveld, Frank; Engel, Douglas

    1994-01-01

    textabstractWe describe the embryonic expression pattern as well as the cloning and initial transcriptional regulatory analysis of the murine (m) GATA-3 gene. In situ hybridization shows that mGATA-3 mRNA accumulation is temporally and spatially regulated during early development: although found most abundantly in the placenta prior to 10 days of embryogenesis, mGATA-3 expression becomes restricted to specific cells within the embryonic central nervous system (in the mesencephalon, diencephal...

  19. PKG-1α mediates GATA4 transcriptional activity.

    Science.gov (United States)

    Ma, Yanlin; Wang, Jun; Yu, Yanhong; Schwartz, Robert J

    2016-06-01

    GATA4, a zinc-finger transcription factor, is central for cardiac development and diseases. Here we show that GATA4 transcriptional activity is mediated by cell signaling via cGMP dependent PKG-1α activity. Protein kinase G (PKG), a serine/tyrosine specific kinase is the major effector of cGMP signaling. We observed enhanced transcriptional activity elicited by co-expressed GATA4 and PKG-1α. Phosphorylation of GATA4 by PKG-1α was detected on serine 261 (S261), while the C-terminal activation domain of GATA4 associated with PKG-1α. GATA4's DNA binding activity was enhanced by PKG-1α via by both phosphorylation and physical association. More importantly, a number of human disease-linked GATA4 mutants exhibited impaired S261 phosphorylation, pointing to defective S261 phosphorylation in the elaboration of human heart diseases. We showed S261 phosphorylation was favored by PKG-1α but not by PKA, and several other kinase signaling pathways such as MAPK and PKC. Our observations demonstrate that cGMP-PKG signaling mediates transcriptional activity of GATA4 and links defective GATA4 and PKG-1α mutations to the development of human heart disease. PMID:26946174

  20. Expression of GATA-3 during lymphocyte differentiation and mouse embryogenesis

    OpenAIRE

    Oosterwegel, Mariëtte; Timmerman, Janneke; Leiden, Jeffrey; Clevers, Hans

    1992-01-01

    The GATA family of C4 zinc-finger transcription factors has been implicated in tissuespecific gene regulation in birds and mammals. One of the members of this family, GATA-3, is reportedly expressed specifically in the T-cell lineage, where it interacts with GATA motifs in the TCR-α α, TCR-β/, and TCR-δ enhancers, thereby controlling the T-cell phenotype. To evaluate the differentiation control properties of GATA-3, we have now documented its expression pattern during lymphoid differentiation...

  1. Structure and expression of the humic GATA3 gene

    Energy Technology Data Exchange (ETDEWEB)

    Labastie, M.C.; Bories, D.; Chabret, C.; Gregoire, J.M.; Romeo, P.H. (INSERM, Creteil (France)); Chretien, S. (INSERM, Paris (France))

    1994-05-01

    GATA3, a member of the GATA family that is abundantly expressed in the T-lymphocyte lineage, is thought to participate in T-cell receptor gene activation through binding to enhancers. To understand GATA3 gene regulation, the authors cloned the human gene and the 5[prime] end of the mouse GATA3 gene. They show that the human GATA3 gene contains six exons distributed over 17 kb of DNA. The two human GATA3 zinc fingers are encoded by two separate exons highly conserved with those of GATA1, but no other structural homologies between these two genes can be found. The human and mouse GATA3 transcription units start at a major initiation site. The promoter sequence analysis of these two genes revealed that they are embedded within a CpG island and share structural features often found in the promoters of housekeeping genes. Finally, they show that a DNA fragment containing the human GATA3 transcription unit, 3 kb upstream from the initiation site and 4 kb downstream from the polyadenylation site, displays T-cell specificity. 34 refs., 4 figs.

  2. The role of GATA3 in breast carcinomas: a review.

    Science.gov (United States)

    Asch-Kendrick, Rebecca; Cimino-Mathews, Ashley

    2016-02-01

    GATA3 is a zinc-binding transcription factor that regulates the differentiation of many human tissue types, including the mammary gland. In surgical pathology, immunohistochemistry for GATA3 is largely used to support urothelial or breast origin in a carcinoma of unknown origin. GATA3 is sensitive but not entirely specific in this setting. Although GATA3 labeling is highest in estrogen receptor-positive carcinomas, it also labels estrogen receptor-negative carcinomas and thus has particular diagnostic utility in the setting of triple-negative breast carcinomas, which are typically negative for other mammary-specific markers. PMID:26772397

  3. GATA-3 in Human T Cell Helper Type 2 Development

    OpenAIRE

    Skapenko, Alla; Leipe, Jan; Niesner, Uwe; Devriendt, Koen; Beetz, Rolf; Radbruch, Andreas; Kalden, Joachim R.; Lipsky, Peter E; Schulze-Koops, Hendrik

    2004-01-01

    The delineation of the in vivo role of GATA-3 in human T cell differentiation is a critical step in the understanding of molecular mechanisms directing human immune responses. We examined T cell differentiation and T cell–mediated effector functions in individuals lacking one functional GATA-3 allele. CD4 T cells from GATA-3+/− individuals expressed significantly reduced levels of GATA-3, associated with markedly decreased T helper cell (Th)2 frequencies in vivo and in vitro. Moreover, Th2 ce...

  4. Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis.

    OpenAIRE

    Labbaye, C; Valtieri, M; Barberi, T; Meccia, E; Masella, B; Pelosi, E; Condorelli, G L; Testa, U; Peschle, C

    1995-01-01

    We have explored the expression of the transcription factors GATA-1, GATA-2, and NF-E2 in purified early hematopoietic progenitor cells (HPCs) induced to gradual unilineage erythroid or granulocytic differentiation by growth factor stimulus. GATA-2 mRNA and protein, already expressed in quiescent HPCs, is rapidly induced as early as 3 h after growth factor stimulus, but then declines in advanced erythroid and granulocytic differentiation and maturation. NF-E2 and GATA-1 mRNAs and proteins, th...

  5. GATA3 inhibits GCM1 activity and trophoblast cell invasion.

    Science.gov (United States)

    Chiu, Yueh Ho; Chen, Hungwen

    2016-01-01

    Development of human placenta involves the invasion of trophoblast cells from anchoring villi into the maternal decidua. Placental transcription factor GCM1 regulates trophoblast cell invasion via transcriptional activation of HtrA4 gene, which encodes a serine protease enzyme. The GATA3 transcription factor regulates trophoblast cell differentiation and is highly expressed in invasive murine trophoblast giant cells. The regulation of trophoblastic invasion by GCM1 may involve novel cellular factors. Here we show that GATA3 interacts with GCM1 and inhibits its activity to suppress trophoblastic invasion. Immunohistochemistry demonstrates that GATA3 and GCM1 are coexpressed in villous cytotrophoblast cells, syncytiotrophoblast layer, and extravillous trophoblast cells of human placenta. Interestingly, GATA3 interacts with GCM1, but not the GCM2 homologue, through the DNA-binding domain and first transcriptional activation domain in GCM1 and the transcriptional activation domains and zinc finger 1 domain in GATA3. While GATA3 did not affect DNA-binding activity of GCM1, it suppressed transcriptional activity of GCM1 and therefore HtrA4 promoter activity. Correspondingly, GATA3 knockdown elevated HtrA4 expression in BeWo and JEG-3 trophoblast cell lines and enhanced the invasion activities of both lines. This study uncovered a new GATA3 function in placenta as a negative regulator of GCM1 activity and trophoblastic invasion. PMID:26899996

  6. Origin and evolution of GATA2a and GATA2b in teleosts: insights from tongue sole, Cynoglossus semilaevis.

    Science.gov (United States)

    Liu, Jinxiang; Jiang, Jiajun; Wang, Zhongkai; He, Yan; Zhang, Quanqi

    2016-01-01

    Background. Following the two rounds of whole-genome duplication that occurred during deuterostome evolution, a third genome duplication occurred in the lineage of teleost fish and is considered to be responsible for much of the biological diversification within the lineage. GATA2, a member of GATA family of transcription factors, is an important regulator of gene expression in hematopoietic cell in mammals, yet the role of this gene or its putative paralogs in ray-finned fishes remains relatively unknown. Methods. In this study, we attempted to identify GATA2 sequences from the transcriptomes and genomes of multiple teleosts using the bioinformatic tools MrBayes, MEME, and PAML. Following identification, comparative analysis of genome structure, molecular evolution rate, and expression by real-time qPCR were used to predict functional divergence of GATA2 paralogs and their relative transcription in organs of female and male tongue soles (Cynoglossus semilaevis). Results. Two teleost GATA2 genes were identified in the transcriptomes of tongue sole and Japanese flounder (Paralichthysolivaceus). Synteny and phylogenetic analysis confirmed that the two genes likely originated from the teleost-specific genome duplication . Additionally, selection pressure analysis predicted these gene duplicates to have undergone purifying selection and possible divergent new functions. This was supported by differential expression pattern of GATA2a and GATA2b observed in organs of female and male tongue soles. Discussion. Our results indicate that two GATA2 genes originating from the first teleost-specific genome duplication have remained transcriptionally active in some fish species and have likely undergone neofunctionalization. This knowledge provides novel insights into the evolution of the teleost GATA2 genes and constituted important groundwork for further research on the GATA gene family. PMID:27019782

  7. GATA-4 transcription factor regulates hepatic hepcidin expression.

    Science.gov (United States)

    Island, Marie-Laure; Fatih, Nadia; Leroyer, Patricia; Brissot, Pierre; Loreal, Olivier

    2011-08-01

    Hepcidin, a hormone mainly synthesized by hepatocytes and secreted in plasma, controls iron bioavailability. Thus, by inducing the internalization of the iron exporter ferroportin, it regulates iron release from macrophages, enterocytes and hepatocytes towards plasma. Abnormal levels of hepcidin expression alter plasma iron parameters and lead to iron metabolism disorders. Understanding the mechanisms controlling hepcidin (HAMP encodes hepcidin) gene expression is therefore an important goal. We identified a potential GATA-binding site within the human hepcidin promoter. Indeed, in hepatic HepG2 cells, luciferase experiments demonstrated that mutation of this GATA-binding site impaired the hepcidin promoter transcriptional activity in basal conditions. Gel-retardation experiments showed that GATA-4 could bind to this site. Co-transfection of a GATA-4 expression vector with a hepcidin promoter reporter construct enhanced hepcidin promoter transcriptional activity. Furthermore, modulation of GATA4 mRNA expression using specific siRNAs (small interfering RNAs) down-regulated endogenous hepcidin gene expression. Finally, we found that mutation of the GATA-binding site impaired the interleukin-6 induction of hepcidin gene expression, but did not prevent the bone morphogenetic protein-6 response. In conclusion, the findings of the present study (i) indicate that GATA-4 may participate in the control of hepcidin expression, and (ii) suggest that alteration of its expression could contribute to the development of iron-related disorders. PMID:21609320

  8. Higher Levels of GATA3 Predict Better Survival in Women with Breast Cancer

    OpenAIRE

    Yoon, Nam K.; Maresh, Erin L.; Shen, Dejun; Elshimali, Yahya; Apple, Sophia; Horvath, Steve; Mah, Vei; Bose, Shikha; Chia, David; Chang, Helena R.; Goodglick, Lee

    2010-01-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. GATA3 in particular is necessary for mammary gland maturation, and its loss has been implicated in breast cancer development. Our goal was to validate the ability of GATA3 expression to predict survival in breast cancer patients. Protein expression of GATA3 was analyzed on a high density tissue microarray consisting of 242 cases of breast cancer. We associated GATA3 expression wit...

  9. GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells

    OpenAIRE

    Abba, Martín C; Nunez, María I.; Colussi, Andrea G; Croce, María V; Segal-Eiras, Amada; Aldaz, C. Marcelo

    2006-01-01

    Introduction Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be involved in the growth control and differentiation of breast epithelial cells. In SAGE (serial analysis of gene expression) studies we observed an intriguing significant correlation...

  10. GATA Factor-G-Protein-Coupled Receptor Circuit Suppresses Hematopoiesis

    OpenAIRE

    Xin Gao; Tongyu Wu; Kirby D. Johnson; Jamie L. Lahvic; Erik A. Ranheim; Leonard I. Zon; Emery H. Bresnick

    2016-01-01

    Summary Hematopoietic stem cells (HSCs) originate from hemogenic endothelium within the aorta-gonad-mesonephros (AGM) region of the mammalian embryo. The relationship between genetic circuits controlling stem cell genesis and multi-potency is not understood. A Gata2 cis element (+9.5) enhances Gata2 expression in the AGM and induces the endothelial to HSC transition. We demonstrated that GATA-2 rescued hematopoiesis in +9.5−/− AGMs. As G-protein-coupled receptors (GPCRs) are the most common t...

  11. GATA Factor-G-Protein-Coupled Receptor Circuit Suppresses Hematopoiesis

    OpenAIRE

    Gao, Xin; Wu, Tongyu; Johnson, Kirby D.; Lahvic, Jamie L.; Ranheim, Erik A.; Zon, Leonard I.; Bresnick, Emery H.

    2016-01-01

    Summary Hematopoietic stem cells (HSCs) originate from hemogenic endothelium within the aorta-gonad-mesonephros (AGM) region of the mammalian embryo. The relationship between genetic circuits controlling stem cell genesis and multi-potency is not understood. A Gata2 cis element (+9.5) enhances Gata2 expression in the AGM and induces the endothelial to HSC transition. We demonstrated that GATA-2 rescued hematopoiesis in +9.5−/− AGMs. As G-protein-coupled receptors (GPCRs) are the most common t...

  12. GATA-3 Function in Innate and Adaptive Immunity.

    OpenAIRE

    Tindemans, Irma; Serafini, Nicolas; Di Santo, James P.; Hendriks, Rudi W

    2014-01-01

    : The zinc-finger transcription factor GATA-3 has received much attention as a master regulator of T helper 2 (Th2) cell differentiation, during which it controls interleukin-4 (IL-4), IL-5, and IL-13 expression. More recently, GATA-3 was shown to contribute to type 2 immunity through regulation of group 2 innate lymphoid cell (ILC2) development and function. Furthermore, during thymopoiesis, GATA-3 represses B cell potential in early T cell precursors, activates TCR signaling in pre-T cells,...

  13. GATA3 in Development and Cancer Differentiation: Cells GATA Have It!

    OpenAIRE

    Chou, Jonathan; Provot, Sylvain; Werb, Zena

    2010-01-01

    There is increasing evidence that the numerous mechanisms that regulate cell differentiation during normal development are also involved in tumorigenesis. In breast cancer, differentiation markers expressed by the primary tumor are routinely profiled to guide clinical decisions. Indeed, numerous studies have shown that the differentiation profile correlates with the metastatic potential of tumors. The transcription factor GATA3 has emerged recently as a strong predictor of clinical outcome in...

  14. Altered translation of GATA1 in Diamond-Blackfan anemia

    OpenAIRE

    Ludwig, Leif S.; Gazda, Hanna T.; Eng, Jennifer C.; Eichhorn, Stephen W.; Thiru, Prathapan; Ghazvinian, Roxanne; George, Tracy I.; Gotlib, Jason R.; Beggs, Alan H.; Sieff, Colin A.; Lodish, Harvey F.; Lander, Eric S.; Sankaran, Vijay G

    2014-01-01

    Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA)[superscript 1, 2], congenital asplenia[superscript 3] and T cell leukemia[superscript 4]. Yet, how mutations in genes encoding ubiquitously expressed proteins such as these result in cell-type– and tissue-specific defects remains unknown[superscript 5]. Here, we identify mutations in GATA1, encoding the critical hematopoietic transcription factor GATA-binding protein-1, that reduce le...

  15. GATA3 abnormalities and the phenotypic spectrum of HDR syndrome

    OpenAIRE

    Muroya, K.; Hasegawa, T; Ito, Y.; Nagai, T.; Isotani, H.; Iwata, Y.; K. Yamamoto; Fujimoto, S.; Seishu, S.; Fukushima, Y.; Hasegawa, Y.; Ogata, T.

    2001-01-01

    We report on GATA3 analysis and the phenotypic spectrum in nine Japanese families with the HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) (MIM 146255). Fluorescence in situ hybridisation and microsatellite analyses showed heterozygous gross deletions including GATA3 in four families. Sequence analysis showed heterozygous novel mutations in three families: a missense mutation within the first zinc finger domain at exon 4 (T823A, W275R), an unusual mutation at ex...

  16. GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas

    Science.gov (United States)

    Haraguchi, Toshiaki; Miyoshi, Hiroaki; Hiraoka, Koji; Yokoyama, Shintaro; Ishibashi, Yukinao; Hashiguchi, Toshihiro; Matsuda, Koutaro; Hamada, Tetsuya; Okawa, Takahiro; Shiba, Naoto; Ohshima, Koichi

    2016-01-01

    Objective Recent studies have investigated the significance of GATA3 expression in patients with various malignant tumors. However, no previous studies have evaluated the clinicopathological importance of GATA3 expression in soft tissue sarcomas (STS) patients. Methods We evaluated GATA3 expression in 76 STS cases using immunohistochemical analysis, and statistically compared clinicopathological characteristics between GATA3-positive and GATA3-negative cases. Result GATA3-positive expression was significantly associated with a higher mitotic count (P < 0.0001). Disease-free survival (DFS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0104). Overall survival (OS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0006). GATA3-positive expression was significantly associated with shorter DFS in both univariate analysis (hazard ratio [HR], 2.719; P = 0.012) and multivariate analysis (HR, 2.711; P = 0.014). GATA3-positive expression was also significantly associated with worse OS in both univariate analysis (HR, 5.730; P = 0.0007) and multivariate analysis (HR, 5.789; P = 0.0008). Conclusion These results indicate that GATA3 is an independent prognostic factor and suggest that evaluation of GATA3 expression might enable more effective clinical follow-up using prognostic stratification of STS patients. PMID:27249072

  17. Whole genome duplications and expansion of the vertebrate GATA transcription factor gene family

    Directory of Open Access Journals (Sweden)

    Bowerman Bruce

    2009-08-01

    Full Text Available Abstract Background GATA transcription factors influence many developmental processes, including the specification of embryonic germ layers. The GATA gene family has significantly expanded in many animal lineages: whereas diverse cnidarians have only one GATA transcription factor, six GATA genes have been identified in many vertebrates, five in many insects, and eleven to thirteen in Caenorhabditis nematodes. All bilaterian animal genomes have at least one member each of two classes, GATA123 and GATA456. Results We have identified one GATA123 gene and one GATA456 gene from the genomic sequence of two invertebrate deuterostomes, a cephalochordate (Branchiostoma floridae and a hemichordate (Saccoglossus kowalevskii. We also have confirmed the presence of six GATA genes in all vertebrate genomes, as well as additional GATA genes in teleost fish. Analyses of conserved sequence motifs and of changes to the exon-intron structure, and molecular phylogenetic analyses of these deuterostome GATA genes support their origin from two ancestral deuterostome genes, one GATA 123 and one GATA456. Comparison of the conserved genomic organization across vertebrates identified eighteen paralogous gene families linked to multiple vertebrate GATA genes (GATA paralogons, providing the strongest evidence yet for expansion of vertebrate GATA gene families via genome duplication events. Conclusion From our analysis, we infer the evolutionary birth order and relationships among vertebrate GATA transcription factors, and define their expansion via multiple rounds of whole genome duplication events. As the genomes of four independent invertebrate deuterostome lineages contain single copy GATA123 and GATA456 genes, we infer that the 0R (pre-genome duplication invertebrate deuterostome ancestor also had two GATA genes, one of each class. Synteny analyses identify duplications of paralogous chromosomal regions (paralogons, from single ancestral vertebrate GATA123 and GATA456

  18. Functionally distinct Gata3/Chd4 complexes coordinately establish T helper 2 (Th2) cell identity

    OpenAIRE

    Hosokawa, Hiroyuki; Tanaka, Tomoaki; Suzuki, Yutaka; Iwamura, Chiaki; Ohkubo, Shuichi; Endoh, Kanji; Kato, Miki; Endo, Yusuke; Onodera, Atsushi; Tumes, Damon John; Kanai, Akinori; Sugano, Sumio; Nakayama, Toshinori

    2013-01-01

    GATA binding protein 3 (Gata3) is a GATA family transcription factor that controls differentiation of naïve CD4 T cells into T helper 2 (Th2) cells. However, it is unknown how Gata3 simultaneously activates Th2-specific genes while repressing those of other Th lineages. Here we show that chromodomain helicase DNA-binding protein 4 (Chd4) forms a complex with Gata3 in Th2 cells that both activates Th2 cytokine transcription and represses the Th1 cytokine IFN-γ. We define a Gata3/Chd4/p300 tran...

  19. A GATA Box in the GATA-1 Gene Hematopoietic Enhancer Is a Critical Element in the Network of GATA Factors and Sites That Regulate This Gene

    OpenAIRE

    Nishimura, Shigeko; Takahashi, Satoru; Kuroha, Takashi; Suwabe, Naruyoshi; Nagasawa, Toshiro; Trainor, Cecelia; Yamamoto, Masayuki

    2000-01-01

    A region located at kbp −3.9 to −2.6 5′ to the first hematopoietic exon of the GATA-1 gene is necessary to recapitulate gene expression in both the primitive and definitive erythroid lineages. In transfection analyses, this region activated reporter gene expression from an artificial promoter in a position- and orientation-independent manner, indicating that the region functions as the GATA-1 gene hematopoietic enhancer (G1HE). However, when analyzed in transgenic embryos in vivo, G1HE activi...

  20. Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis.

    Science.gov (United States)

    Labbaye, C; Valtieri, M; Barberi, T; Meccia, E; Masella, B; Pelosi, E; Condorelli, G L; Testa, U; Peschle, C

    1995-01-01

    We have explored the expression of the transcription factors GATA-1, GATA-2, and NF-E2 in purified early hematopoietic progenitor cells (HPCs) induced to gradual unilineage erythroid or granulocytic differentiation by growth factor stimulus. GATA-2 mRNA and protein, already expressed in quiescent HPCs, is rapidly induced as early as 3 h after growth factor stimulus, but then declines in advanced erythroid and granulocytic differentiation and maturation. NF-E2 and GATA-1 mRNAs and proteins, though not detected in quiescent HPCs, are gradually induced at 24-48 h in both erythroid and granulocytic culture. Beginning at late differentiation/early maturation stage, both transcription factors are further accumulated in the erythroid pathway, whereas they are suppressed in the granulopoietic series. Similarly, the erythropoietin receptor (EpR) is induced and sustainedly expressed during erythroid differentiation, although beginning at later times (i.e., day 5), whereas it is barely expressed in the granulopoietic pathway. In the first series of functional studies, HPCs were treated with antisense oligomers targeted to transcription factor mRNA: inhibition of GATA-2 expression caused a decreased number of both erythroid and granulocyte-monocytic clones, whereas inhibition of NF-E2 or GATA-1 expression induced a selective impairment of erythroid colony formation. In a second series of functional studies, HPCs treated with retinoic acid were induced to shift from erythroid to granulocytic differentiation (Labbaye et al. 1994. Blood. 83:651-656); this was coupled with abrogation of GATA-1, NF-E2, and EpR expression and conversely enhanced GATA-2 levels. These results indicate the expression and key role of GATA-2 in the early stages of HPC proliferation/differentiation. Conversely, NF-E2 and GATA-1 expression and function are apparently restricted to erythroid differentiation and maturation: their expression precedes that of the EpR, and their function may be in part mediated

  1. Accentuated response to phenylhydrazine and erythropoietin in mice genetically impaired for their GATA-1 expression (GATA-1(low) mice).

    Science.gov (United States)

    Vannucchi, A M; Bianchi, L; Cellai, C; Paoletti, F; Carrai, V; Calzolari, A; Centurione, L; Lorenzini, R; Carta, C; Alfani, E; Sanchez, M; Migliaccio, G; Migliaccio, A R

    2001-05-15

    The response of mice genetically unable to up-regulate GATA-1 expression (GATA-1(low) mice) to acute (phenylhydrazine [PHZ]-induced anemia) and chronic (in vivo treatment for 5 days with 10 U erythropoietin [EPO] per mouse) erythroid stimuli was investigated. Adult GATA-1(low) mice are profoundly thrombocytopenic (platelet counts [x 10(9)/L] 82.0 +/- 28.0 vs 840 +/- 170.0 of their control littermates, P Hct) (approximately.47 proportion of 1.0 [47%]). The spleens of these mutants are 2.5-fold larger than normal and contain 5-fold more megakaryocytic (4A5(+)), erythroid (TER-119(+)), and bipotent (erythroid/megakaryocytic, TER-119(+)/4A5(+)) precursor cells. Both the marrow and the spleen of these animals contain higher frequencies of burst-forming units-erythroid (BFU-E)- and colony-forming units-erythroid (CFU-E)-derived colonies (2-fold and 6-fold, respectively) than their normal littermates. The GATA-1(low) mice recover 2 days faster from the PHZ-induced anemia than their normal littermates (P Hct of the GATA-1(low) mice raised to.68 proportion of 1.0 (68%) vs the.55 proportion of 1.0 (55%) reached by the controls (P <.01). Both the GATA-1(low) and the normal mice respond to PHZ and EPO with similar (2- to 3-fold) increases in size and cellularity of the spleen (increases are limited mostly to cells, both progenitor and precursor, of the erythroid lineage). However, in spite of the similar relative cellular increases, the increases of all these cell populations are significantly higher, in absolute cell numbers, in the mutant than in the wild-type mice. In conclusion, the GATA-1(low) mutation increases the magnitude of the response to erythroid stimuli as a consequence of the expansion of the erythroid progenitor cells in their spleen. PMID:11342429

  2. Differential Contribution of the Gata1 Gene Hematopoietic Enhancer to Erythroid Differentiation▿ †

    OpenAIRE

    Suzuki, Mikiko; Moriguchi, Takashi; Ohneda, Kinuko; Yamamoto, Masayuki

    2008-01-01

    GATA1 is a key regulator of erythroid cell differentiation. To examine how Gata1 gene expression is regulated in a stage-specific manner, transgenic mouse lines expressing green fluorescent protein (GFP) reporter from the Gata1 locus in a bacterial artificial chromosome (G1BAC-GFP) were prepared. We found that the GFP reporter expression faithfully recapitulated Gata1 gene expression. Using GFP fluorescence in combination with hematopoietic surface markers, we established a purification proto...

  3. Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning

    OpenAIRE

    Lim, Kim-Chew; Hosoya, Tomonori; Brandt, William; Ku, Chia-Jui; Hosoya-Ohmura, Sakie; Camper, Sally A.; Yamamoto, Masayuki; Engel, James Douglas

    2012-01-01

    The transcription factor GATA-2 plays vital roles in quite diverse developmental programs, including hematopoietic stem cell (HSC) survival and proliferation. We previously identified a vascular endothelial (VE) enhancer that regulates GATA-2 activity in pan-endothelial cells. To more thoroughly define the in vivo regulatory properties of this enhancer, we generated a tamoxifen-inducible Cre transgenic mouse line using the Gata2 VE enhancer (Gata2 VECre) and utilized it to temporally direct t...

  4. GATA transcription factors as tissue-specific master regulators for induced responses

    OpenAIRE

    Block, Dena Hs; Shapira, Michael

    2015-01-01

    GATA transcription factors play important roles in directing developmental genetic programs and cell differentiation, and are conserved in animals, plants and fungi. C. elegans has 11 GATA-type transcription factors that orchestrate development of the gut, epidermis and vulva. However, the expression of certain GATA proteins persists into adulthood, where their function is less understood. Accumulating evidence demonstrates contributions of 2 terminal differentiation GATA transcription factor...

  5. GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland

    OpenAIRE

    Kouros-Mehr, Hosein; Slorach, Euan M.; Sternlicht, Mark D.; Werb, Zena

    2006-01-01

    The GATA family of transcription factors plays fundamental roles in cell-fate specification. However, it is unclear if these genes are necessary for the maintenance of cellular differentiation after development. We identified GATA-3 as the most highly enriched transcription factor in the mammary epithelium of pubertal mice. GATA-3 was found in the luminal cells of mammary ducts and the body cells of terminal end buds (TEBs). Upon conditional deletion of GATA-3, mice exhibited severe defects i...

  6. Impairment of Host Defense against Disseminated Candidiasis in Mice Overexpressing GATA-3▿

    OpenAIRE

    Haraguchi, Norihiro; Ishii, Yukio; Morishima, Yuko; Yoh, Keigyou; Matsuno, Yosuke; Kikuchi, Norihiro; Sakamoto, Tohru; Takahashi, Satoru; HIZAWA, NOBUYUKI

    2010-01-01

    Candida species are the most common source of nosocomial invasive fungal infections. Previous studies have indicated that T-helper immune response is the critical host factor for susceptibility to Candida infection. The transcription factor GATA-3 is known as the master regulator for T-helper type 2 (Th2) differentiation. We therefore investigated the role of GATA-3 in the host defense against systemic Candida infection using GATA-3-overexpressing transgenic mice. The survival of GATA-3-overe...

  7. Decreased Expression of the GATA3 Gene Is Associated with Poor Prognosis in Primary Gastric Adenocarcinoma

    OpenAIRE

    Keshari, Rajiv Prasad; Wang, Wei; Zhang, Yu; Wang, Dan-dan; Li, Yuan-Fang; YUAN, SHU-QIANG; Qiu, Hai-Bo; Huang, Chun-yu; Chen, Yong-ming; Xia, Jian-chuan; Zhou, Zhi-Wei

    2014-01-01

    Background GATA binding protein 3 (GATA3) was recently proposed to function as a tumor suppressor gene in some types of human cancer. This study aims to investigate GATA3 expression and its prognostic significance in primary gastric adenocarcinoma. Methodology/Principal Findings Using real-time quantitative PCR (RT-qPCR) and immunohistochemical staining methods, GATA3 expression was analyzed in tissue samples from a consecutive series of 402 gastric adenocarcinoma patients who underwent resec...

  8. The Gata3 transcription factor is required for the survival of embryonic and adult sympathetic neurons

    OpenAIRE

    Tsarovina, Konstantina; Reiff, Tobias; Stubbusch, Jutta; Kurek, Dorota; Grosveld, Frank; Parlato, Rosanna; Schütz, Günther; Rohrer, Hermann

    2010-01-01

    textabstractThe transcription factor Gata3 is essential for the development of sympathetic neurons and adrenal chromaffin cells. As Gata3 expression is maintained up to the adult stage, we addressed its function in differentiated sympathoadrenal cells at embryonic and adult stages by conditional Gata3 elimination. Inactivation of Gata3 in embryonic DBH-expressing neurons elicits a strong reduction in neuron numbers due to apoptotic cell death and reduced proliferation. No selective effect on ...

  9. Loss of GATA3 in bladder cancer promotes cell migration and invasion

    OpenAIRE

    Li, Yi; Ishiguro, Hitoshi; Kawahara, Takashi; Kashiwagi, Eiji; Izumi, Koji; Miyamoto, Hiroshi

    2014-01-01

    The transcription factor GATA3 is known as a breast tumor suppressor as well as a urothelial marker, and its loss is often seen in high-grade invasive bladder cancer. Nonetheless, GATA3 functions in bladder cancer cells remain largely unknown. In this study, we assessed the effects of GATA3 silencing via RNA interference on cell migration, invasion, and proliferation of bladder cancer. GATA3 expression was downregulated in all four bladder cancer lines examined, compared with a non-neoplastic...

  10. GATA Factor-Dependent Positive-Feedback Circuit in Acute Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Koichi R. Katsumura

    2016-08-01

    Full Text Available The master regulatory transcription factor GATA-2 triggers hematopoietic stem and progenitor cell generation. GATA2 haploinsufficiency is implicated in myelodysplastic syndrome (MDS and acute myeloid leukemia (AML, and GATA2 overexpression portends a poor prognosis for AML. However, the constituents of the GATA-2-dependent genetic network mediating pathogenesis are unknown. We described a p38-dependent mechanism that phosphorylates GATA-2 and increases GATA-2 target gene activation. We demonstrate that this mechanism establishes a growth-promoting chemokine/cytokine circuit in AML cells. p38/ERK-dependent GATA-2 phosphorylation facilitated positive autoregulation of GATA2 transcription and expression of target genes, including IL1B and CXCL2. IL-1β and CXCL2 enhanced GATA-2 phosphorylation, which increased GATA-2-mediated transcriptional activation. p38/ERK-GATA-2 stimulated AML cell proliferation via CXCL2 induction. As GATA2 mRNA correlated with IL1B and CXCL2 mRNAs in AML-M5 and high expression of these genes predicted poor prognosis of cytogenetically normal AML, we propose that the circuit is functionally important in specific AML contexts.

  11. A monoallelic-to-biallelic T-cell transcriptional switch regulates GATA3 abundance

    OpenAIRE

    Ku, Chia-Jui; Lim, Kim-Chew; Kalantry, Sundeep; Maillard, Ivan; Engel, James Douglas; Hosoya, Tomonori

    2015-01-01

    Ku et al. show that loss of one Gata3 allele leads to diminished expansion of immature T cells as well as aberrant induction of myeloid transcription factor PU.1. Gata3 is monoallelically expressed in hematopoietic stem cells and early T-cell progenitors. Half of the developing cells switch to biallelic Gata3 transcription abruptly at midthymopoiesis.

  12. Post-transcriptional protein modification of Gata4%Gata4转录后蛋白共价修饰

    Institute of Scientific and Technical Information of China (English)

    俞立玮

    2012-01-01

    Gata4是心脏发育重要的转录因子,其转录活性和DNA亲和力受转录后蛋白共价修饰的调节,并影响下游目的基因和相关转录因子表达,胚胎干细胞分化,心肌细胞生长和心脏发育.该文总结Gata4转录后蛋白共价修饰对其转录活性的影响,寻找其与心脏发育和先天性心脏病( congenital heart disease,CHD)的关系.结果发现乙酰化、磷酸化、SUMO化使其转录活性和DNA亲和力升高,下游基因表达上升,促进胚胎干细胞分化等呈正性调节;去乙酰化和甲基化下调Gata4转录活性,呈负性调节.因此,Gata4蛋白共价修饰对研究先天性心脏病及其他一些心脏疾病有重要的临床意义.%Gata4 is an important transcription factor in heart development. Gata4 post-transcriptional protein modification regulates transcriptional activity and DNA binding, which in turn affects expression of downstream genes and transcription factors, differentiation of embryonic stem cells and cardiogenesis. This article summarizes the effect of post-transcriptional protein modification on transcriptional activity of Gata4 and the relationship between this effect and congenital heart disease. It was shown that acetylation, phosphorylation and SUMOylation upregulate transcriptiona) activity, DNA binding, downstream gene expression and embryonic stem cell differentiation. On the other hand, methylation and deacetylation downregulate Gata4 transcriptional activity. Post-transcriptional protein modification of Gata4 is very important in clinical research on congenital and other heart diseases.

  13. Report on FS survey for project of introduction of highly energy-efficient trolley buses into the Mexico Metropolitan Area in FY 1997; 1997 nendo chosa hokokusho (Mexico city eno sho energy gata trolley bus donyu project FS chosa)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    Traffic jam and air pollution by automobiles are currently getting severe in the Mexico Metropolitan Area. Trolley buses were introduced for improving the environment more than ten years ago. Vehicles become too old for use, and their energy efficiency is low. In this project, 200 highly energy-efficient trolley buses are introduced to replace old inefficient trolley buses, which results in the improved traffic convenience in the City and enhanced energy efficiency. The new energy-efficient trolley buses are made of energy-efficient control VVVF inverters produced and exported by MELCO (Mitsubishi Electric Corporation), energy-efficient motors by MELMEX (Mitsubishi Electric Corporation, Mexico), and bodies by MASA which is a major manufacturer of bus bodies. The objective of this research is to analyze the background of introduction of new energy-efficient trolley buses and the effects of the present project. The results of analysis are going to be utilized for future promotion of the Joint Implementation and Clean Development Mechanism. 30 refs., 30 figs., 24 tabs.

  14. GATA-3 is required for early T lineage progenitor development

    OpenAIRE

    Hosoya, Tomonori; Kuroha, Takashi; Moriguchi, Takashi; Cummings, Dustin; Maillard, Ivan; Lim, Kim-Chew; Engel, James Douglas

    2009-01-01

    Most T lymphocytes appear to arise from very rare early T lineage progenitors (ETPs) in the thymus, but the transcriptional programs that specify ETP generation are not completely known. The transcription factor GATA-3 is required for the development of T lymphocytes at multiple late differentiation steps as well as for the development of thymic natural killer cells. However, a role for GATA-3 before the double-negative (DN) 3 stage of T cell development has to date been obscured both by the ...

  15. Involvement of GATA transcription factors in the regulation of endogenous bovine interferon-tau gene transcription.

    Science.gov (United States)

    Bai, Hanako; Sakurai, Toshihiro; Kim, Min-Su; Muroi, Yoshikage; Ideta, Atsushi; Aoyagi, Yoshito; Nakajima, Hiromi; Takahashi, Masashi; Nagaoka, Kentaro; Imakawa, Kazuhiko

    2009-12-01

    Expression of interferon-tau (IFNT), necessary for pregnancy establishment in ruminant ungulates, is regulated in a temporal and spatial manner. However, molecular mechanisms by which IFNT gene transcription is regulated in this manner have not been firmly established. In this study, DNA microarray/RT-PCR analysis between bovine trophoblast CT-1 and Mardin-Darby bovine kidney (MDBK) cells was initially performed, finding that transcription factors GATA2, GATA3, and GATA6 mRNAs were specific to CT-1 cells. These mRNAs were also found in Days 17, 20, and 22 (Day 0 = day of estrus) bovine conceptuses. In examining other bovine cell lines, ovary cumulus granulosa (oCG) and ear fibroblast (EF) cells, GATA2 and GATA3, but not GATA6, were found specific to the bovine trophoblast cells. In transient transfection analyses using the upstream region (-631 to +59 bp) of bovine IFNT gene (bIFNT, IFN-tau-c1), over-expression of GATA2/GATA3 did not affect the transcription of bIFNT-reporter construct in human choriocarcinoma JEG3 cells. Transfection of GATA2, GATA3, ETS2, and/or CDX2, however, was effective in the up-regulation of the bIFNT construct transfected into bovine oCG and EF cells. One Point mutation studies revealed that among six potential GATA binding sites located on the upstream region of the bIFNT gene, the one next to ETS2 site exhibited reduced luciferase activity. In CT-1 cells, endogenous bIFNT gene transcription was up-regulated by over-expression of GATA2 or GATA3, but down-regulated by siRNA specific to GATA2 mRNA. These data suggest that GATA2/3 is involved in trophoblast-specific regulation of bIFNT gene transcription. PMID:19598245

  16. Intestinal GATA4 deficiency protects from diet-induced hepatic steatosis

    OpenAIRE

    Patankar, Jay V.; Obrowsky, Sascha; Doddapattar, Prakash; Hoefler, Gerald; Battle, Michele; Levak-Frank, Sanja; Kratky, Dagmar

    2012-01-01

    Background & Aims GATA4, a zinc finger domain transcription factor, is critical for jejunal identity. Mice with an intestine-specific GATA4 deficiency (GATA4iKO) are resistant to diet-induced obesity and insulin resistance. Although they have decreased intestinal lipid absorption, hepatic de novo lipogenesis is inhibited. Here, we investigated dietary lipid-dependent and independent effects on the development of steatosis and fibrosis in GATA4iKO mice. Methods GATA4iKO and control mice were f...

  17. GATA-3 controls T cell maintenance and proliferation downstream of TCR and cytokine signals

    OpenAIRE

    Wang, Yunqi; Misumi, Ichiro; Gu, Ai-Di; Curtis, T. Anthony; Su, Lishan; Whitmire, Jason K.; Wan, Yisong Y.

    2013-01-01

    GATA-3 is a master regulator for TH2 differentiation. It is however poorly understood if GATA-3 controls mature T cell function beyond TH2 determination. We show that TCR signals and cytokine stimulation promoted GATA-3 expression in CD8 T cells, which controlled cell proliferation. While GATA-3-deficient CD8 T cells were generated, their peripheral maintenance was impaired with reduced IL-7R expression. GATA-3-deficient T cells had defective responses to viral infection and alloantigen. c-My...

  18. T cell receptor-dependent translational control of GATA-3 enhances Th2 differentiation1

    OpenAIRE

    Kevin D. Cook; Miller, Jim

    2010-01-01

    The differentiation of CD4+ T cells into the Th2 subset is controlled by the transcription factor, GATA-3. GATA-3 is both necessary and sufficient for Th2 differentiation and works through the induction of chromatin remodeling at the Th2 effector cytokine loci. We show here that IL-4 stimulation induces GATA-3 mRNA upregulation, but the level of GATA-3 protein induced is insufficient for Th2 differentiation. The levels of GATA-3 protein and Th2 differentiation are enhanced by concomitant TCR ...

  19. Molecular characterization and expression profiles of GATA6 in tongue sole (Cynoglossus semilaevis).

    Science.gov (United States)

    Liu, Jinxiang; Zhang, Wei; Sun, Yan; Wang, Zhigang; Zhang, Quanqi; Wang, Xubo

    2016-08-01

    GATA-binding protein 6 (GATA6), a transcription factor of the GATA family, plays an important role in gonadal cell proliferation, differentiation, and endoderm development. In this study, the full-length coding sequence of tongue sole (Cynoglossus semilaevis) GATA6 was identified. The sequence consisted of 1494 nucleotides encoding a peptide of 497 amino acids, which included two conserved zinc finger domains. Phylogenetic, gene structure, and synteny analysis showed that C. semilaevis GATA6 was homologous to teleost and tetrapod GATA6. C. semilaevis GATA6 mRNA exhibited high expression in heart, intestine, liver, kidney, and gonad. Embryonic development expression profiles revealed that GATA6 is involved in morphogenesis because its expression increased at the blastula stage. The in situ hybridization results showed strong GATA6 signals in spermatogonia, spermatocytes, and Sertoli cells of the testis. The signals were also detected in the oogonia and oocytes of the ovary. The expression of C. semilaevis GATA6 was sexually dimorphic, and the methylation pattern in the promoter region varied among males, females, and pseudomales. These results suggested that GATA6 might influence the gonad development and reproduction of C. semilaevis. This study provides the groundwork for further development of breeding techniques in C. semilaevis. PMID:27040526

  20. An NK and T Cell Enhancer Lies 280 Kilobase Pairs 3′ to the Gata3 Structural Gene ▿

    OpenAIRE

    Hosoya-Ohmura, Sakie; Lin, Yu-Hsuan; Herrmann, Mary; Kuroha, Takashi; Rao, Arvind; Moriguchi, Takashi; Lim, Kim-Chew; Hosoya, Tomonori; Engel, James Douglas

    2011-01-01

    Transcription factor GATA-3 is vital for multiple stages of T cell and natural killer (NK) cell development, and yet the factors that directly regulate Gata3 transcription during hematopoiesis are only marginally defined. Here, we show that neither of the Gata3 promoters, previously implicated in its tissue-specific regulation, is alone capable of directing Gata3 transcription in T lymphocytes. In contrast, by surveying large swaths of DNA surrounding the Gata3 locus, we located a cis element...

  1. Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway

    OpenAIRE

    Giguère Vincent; Wilson Brian J

    2008-01-01

    Abstract Background The transcription factor GATA3 has recently been shown to be necessary for mammary gland morphogenesis and luminal cell differentiation. There is also an increasing body of data linking GATA3 to the estrogen receptor α (ERα) pathway. Among these it was shown that GATA3 associates with the promoter of the ERα gene and ERα can reciprocally associate with the GATA3 gene. GATA3 has also been directly implicated in a differentiated phenotype in mouse models of mammary tumourige...

  2. THE TRANSCRIPTION FACTOR GATA2 REGULATES DIFFERENTIATION OF BROWN ADIPOCYTES

    Science.gov (United States)

    Brown fat tissue is functionally different than the white fat, since brown fat burns lipid to generate heat for body temperature maintenance. However, brown fat cells share with white fat cells a similar molecular mechanism for fat cell formation. We have demonstrated previously that the GATA family...

  3. Development of the mammalian liver and ventral pancreas is dependent on GATA4

    Directory of Open Access Journals (Sweden)

    Li Jixuan

    2007-04-01

    Full Text Available Abstract Background In the mouse, the parenchyma of both the liver and ventral pancreas is specified from adjacent domains of the ventral foregut endoderm. GATA4, a zinc finger transcription factor, is strongly expressed in these endodermal domains and molecular analyses have implicated GATA4 in potentiating liver gene expression during the onset of hepatogenesis. We therefore hypothesized that GATA4 has an integral role in controlling the early stages of pancreatic and liver development. Results To determine whether GATA4 contributes to development of either the pancreas or liver we characterized the formation of pancreatic and hepatic tissues in embryos derived from Gata4-/- ES cells by tetraploid embryo complementation. In the absence of GATA4, development of the liver and ventral pancreas was disrupted. At embryonic day (E 9.5, the liver bud failed to expand although, contrary to expectations, the hepatic endoderm was able to form a pseudo-stratified epithelial liver bud that expressed hepatic genes. Moreover, as we had shown previously, the embryos lacked septum transversum mesenchyme suggesting that liver defects may be cell non-autonomous. Analyses of pancreatic development revealed a complete absence of the ventral but not the dorsal pancreas in Gata4-/- embryos. Moreover, Gata6-/- embryos displayed a similar, although less dramatic phenotype, suggesting a critical role for multiple GATA factors at the earliest stages of ventral pancreas development. Conclusion This study defines integral roles for GATA factors in controlling early development of the mammalian liver and pancreas.

  4. GATA family of transcription factors of vertebrates: phylogenetics and chromosomal synteny

    Indian Academy of Sciences (India)

    Chunjiang He; Hanhua Cheng; Rongjia Zhou

    2007-12-01

    GATA genes are an evolutionarily conserved family, which encode a group of important transcription factors involved in the regulation of diverse processes including the development of the heart, haematopoietic system and sex gonads. However, the evolutionary history of the GATA family has not been completely understood. We constructed a complete phylogenetic tree with functional domain information of the GATA genes of both vertebrates and several invertebrates, and mapped the GATA genes onto relevant chromosomes. Conserved synteny was observed around the GATA loci on the chromosomes. GATAs have a tendency to segregate onto different chromosomes during evolution. The phylogenetic tree is consistent with the relevant functions of GATA members. Analysis of the zinc finger domain showed that the domain tends to be duplicated during evolution from invertebrates to vertebrates. We propose that the balance between duplications of zinc finger domains and GATA members should be maintained to exert their physiological roles in each evolutionary stage. Therefore, evolutionary pressure on the GATAs must exist to maintain the balance during evolution from invertebrates to vertebrates. These results reveal the evolutionary characteristics of the GATA family and contribute to a better understanding of the relationship between evolution and biological functions of the gene family, which will help to uncover the GATAs’ biological roles, evolution and their relationship with associated diseases.

  5. GATA3 mutation in a family with hypoparathyroidism, deafness and renal dysplasia syndrome

    Institute of Scientific and Technical Information of China (English)

    Zi-Yang Zhu; Qiao-Li Zhou; Shi-Ning Ni; Wei Gu

    2014-01-01

    Background: The hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by GATA3 gene mutation. We report here a case that both of a Chinese boy and his father had HDR syndrome which caused by a novel mutation of GATA3. Methods: Polymerase chain reaction and DNA sequencing was performed to detect the exons of the GATA3 gene for mutation analysis. Results: Sequence analysis of GATA3 revealed a heterozygous nonsense mutation in this family: a mutation of GATA3 at exon 2 (c.515C >A) that resulted in a premature stop at codon 172 (p.S172X) with a loss of two zinc fi nger domains. Conclusion: We identifi ed a novel nonsense mutation which will expand the spectrum of HDR-associated GATA3 mutations.

  6. Characterization of a Functional ZBP-89 Binding Site That Mediates Gata1 Gene Expression during Hematopoietic Development*

    OpenAIRE

    Ohneda, Kinuko; Ohmori, Shin'ya; Ishijima, Yasushi; Nakano, Mayu; Yamamoto, Masayuki

    2009-01-01

    GATA-1 is a lineage-restricted transcription factor that plays essential roles in hematopoietic development. The Gata1 gene hematopoietic enhancer allowed Gata1 reporter expression in erythroid cells and megakaryocytes of transgenic mice. The Gata1 hematopoietic enhancer activity is strictly dependent on a GATA site located in the 5′ region of the enhancer. However, the importance of the GC-rich region adjacent to the 3′-end of this GATA site has been also suggested. In this study, we show th...

  7. Gata3-deficient mice develop parathyroid abnormalities due to dysregulation of the parathyroid-specific transcription factor Gcm2

    OpenAIRE

    Irina V. Grigorieva; Mirczuk, Samantha; Gaynor, Katherine U.; Nesbit, M. Andrew; Grigorieva, Elena F; Wei, Qiaozhi; Ali, Asif; Fairclough, Rebecca J.; Stacey, Joanna M; Stechman, Michael J.; Mihai, Radu; Kurek, Dorota; Fraser, William D.; Hough, Tertius; Condie, Brian G.

    2010-01-01

    Heterozygous mutations of GATA3, which encodes a dual zinc-finger transcription factor, cause hypoparathyroidism with sensorineural deafness and renal dysplasia. Here, we have investigated the role of GATA3 in parathyroid function by challenging Gata3+/– mice with a diet low in calcium and vitamin D so as to expose any defects in parathyroid function. This led to a higher mortality among Gata3+/– mice compared with Gata3+/+ mice. Compared with their wild-type littermates, Gata3+/– mice had lo...

  8. Breast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover

    OpenAIRE

    Adomas, Aleksandra B; Grimm, Sara A.; Malone, Christine; Takaku, Motoki; Sims, Jennifer K.; Wade, Paul A.

    2014-01-01

    Background The transcription factor GATA3 is a favorable prognostic indicator in estrogen receptor-α (ERα)-positive breast tumors in which it participates with ERα and FOXA1 in a complex transcriptional regulatory program driving tumor growth. GATA3 mutations are frequent in breast cancer and have been classified as driver mutations. To elucidate the contribution(s) of GATA3 alterations to cancer, we studied two breast cancer cell lines, MCF7, which carries a heterozygous frameshift mutation ...

  9. Similarity of GATA-3 Expression between Rat and Human Mammary Glands

    OpenAIRE

    KINOSHITA, YUICHI; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; SHIKATA, NOBUAKI; Tsubura, Airo

    2014-01-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whol...

  10. A highly conserved regulatory element controls hematopoietic expression of GATA-2 in zebrafish

    OpenAIRE

    Zhang Michael Q; Sakamoto Kathleen M; Shankar Deepa B; Zhao Fang; Jiang Hong; Yang Zhongan; Lin Shuo

    2007-01-01

    Abstract Background GATA-2 is a transcription factor required for hematopoietic stem cell survival as well as for neuronal development in vertebrates. It has been shown that specific expression of GATA-2 in blood progenitor cells requires distal cis-acting regulatory elements. Identification and characterization of these elements should help elucidating transcription regulatory mechanisms of GATA-2 expression in hematopoietic lineage. Results By pair-wise alignments of the zebrafish genomic s...

  11. REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis

    OpenAIRE

    Yoshihiro Kawasaki; Kosuke Matsumura; Masaya Miyamoto; Shinnosuke Tsuji; Masumi Okuno; Sakiko Suda; Masaya Hiyoshi; Joji Kitayama; Tetsu Akiyama

    2015-01-01

    The transcription factor GATA6 is a critical regulator of cell proliferation and development in the gastrointestinal tract. We have recently reported that GATA6 induces the expression of the intestinal stem cell marker LGR5 and enhances the clonogenicity and tumorigenicity of colon cancer cells, but not the growth of these cells cultured under adherent conditions. Here we show that REG4, a member of the regenerating islet-derived (REG) family, is also a target of GATA6. We further demonstrate...

  12. Repercussion of Megakaryocyte-Specific Gata1 Loss on Megakaryopoiesis and the Hematopoietic Precursor Compartment

    Science.gov (United States)

    Meinders, Marjolein; Hoogenboezem, Mark; Scheenstra, Maaike R.; De Cuyper, Iris M.; Papadopoulos, Petros; Németh, Tamás; Mócsai, Attila; van den Berg, Timo K.; Kuijpers, Taco W.

    2016-01-01

    During hematopoiesis, transcriptional programs are essential for the commitment and differentiation of progenitors into the different blood lineages. GATA1 is a transcription factor expressed in several hematopoietic lineages and essential for proper erythropoiesis and megakaryopoiesis. Megakaryocyte-specific genes, such as GP1BA, are known to be directly regulated by GATA1. Mutations in GATA1 can lead to dyserythropoietic anemia and pseudo gray-platelet syndrome. Selective loss of Gata1 expression in adult mice results in macrothrombocytopenia with platelet dysfunction, characterized by an excess of immature megakaryocytes. To specifically analyze the impact of Gata1 loss in mature committed megakaryocytes, we generated Gata1-Lox|Pf4-Cre mice (Gata1cKOMK). Consistent with previous findings, Gata1cKOMK mice are macrothrombocytopenic with platelet dysfunction. Supporting this notion we demonstrate that Gata1 regulates directly the transcription of Syk, a tyrosine kinase that functions downstream of Clec2 and GPVI receptors in megakaryocytes and platelets. Furthermore, we show that Gata1cKOMK mice display an additional aberrant megakaryocyte differentiation stage. Interestingly, these mice present a misbalance of the multipotent progenitor compartment and the erythroid lineage, which translates into compensatory stress erythropoiesis and splenomegaly. Despite the severe thrombocytopenia, Gata1cKOMK mice display a mild reduction of TPO plasma levels, and Gata1cKOMK megakaryocytes show a mild increase in Pf4 mRNA levels; such a misbalance might be behind the general hematopoietic defects observed, affecting locally normal TPO and Pf4 levels at hematopoietic stem cell niches. PMID:27152938

  13. GATA3 Inhibits Breast Cancer Metastasis through the Reversal of Epithelial-Mesenchymal Transition*

    OpenAIRE

    Yan, Wei; Cao, Qing Jackie; Arenas, Richard B.; Bentley, Brooke; SHAO, RONG

    2010-01-01

    GATA3, a transcription factor that regulates T lymphocyte differentiation and maturation, is exclusively expressed in early stage well differentiated breast cancers but not in advanced invasive cancers. However, little is understood regarding its activity and the mechanisms underlying this differential expression in cancers. Here, we employed GATA3-positive, non-invasive (MCF-7) and GATA3-negative, invasive (MDA-MB-231) breast cancer cells to define its role in the transformation between thes...

  14. Downstream Targets of GATA3 in the Vestibular Sensory Organs of the Inner Ear

    OpenAIRE

    Alvarado, David M; Veile, Rose; Speck, Judith; Warchol, Mark; Lovett, Michael

    2009-01-01

    Haploinsufficiency for the transcription factor GATA3 leads to hearing loss in humans. It is expressed throughout the auditory sensory epithelium (SE). In the vestibular organs, GATA3 is limited to the striola reversal zone of the utricle. Stereocilia orientation shifts 180° at this region which contains morphologically-distinct type I hair cells. The striola is conserved in all amniotes, its function is unknown and GATA3 is the only known marker of the reversal zone. To identify downstream t...

  15. Dosage-dependent rescue of definitive nephrogenesis by a distant Gata3 enhancer

    OpenAIRE

    Hasegawa, Susan L.; Moriguchi, Takashi; Rao, Arvind; Kuroha, Takashi; Engel, James Douglas; Lim, Kim-Chew

    2006-01-01

    Human GATA3 haploinsufficiency leads to HDR (hypoparathyroidism, deafness and renal dysplasia) syndrome, demonstrating that the development of a specific subset of organs in which this transcription factor is expressed is exquisitely sensitive to gene dosage. We previously showed that murine GATA-3 is essential for definitive kidney development, and that a large YAC transgene faithfully recapitulated GATA-3 expression in the urogenital system. Here we describe the localization and activity of...

  16. GATA3 controls the specification of prosensory domain and neuronal survival in the mouse cochlea

    OpenAIRE

    Luo, Xiong-jian; Deng, Min; Xie, Xiaoling; Huang, Liang; Wang, Hui; Jiang, Lichun; Liang, Guoqing; Hu, Fang; Tieu, Roger; Chen, Rui; Gan, Lin

    2013-01-01

    HDR syndrome (also known as Barakat syndrome) is a developmental disorder characterized by hypoparathyroidism, sensorineural deafness and renal disease. Although genetic mapping and subsequent functional studies indicate that GATA3 haplo-insufficiency causes human HDR syndrome, the role of Gata3 in sensorineural deafness and auditory system development is largely unknown. In this study, we show that Gata3 is continuously expressed in the developing mouse inner ear. Conditional knockout of Gat...

  17. Altered translation of GATA1 in Diamond-Blackfan anemia

    OpenAIRE

    Ludwig, Leif S.; Gazda, Hanna T.; Eng, Jennifer C.; Eichhorn, Stephen W.; Thiru, Prathapan; Ghazvinian, Roxanne; George, Tracy I.; Gotlib, Jason R.; Beggs, Alan H.; Sieff, Colin A.; Lodish, Harvey F.; Lander, Eric S.; Sankaran, Vijay G

    2014-01-01

    Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA),1,2 congenital asplenia,3 and T-cell leukemia.4 Yet how mutations in such ubiquitously expressed proteins result in cell-type and tissue specific defects remains a mystery.5 Here, we show that GATA1 mutations that reduce full-length protein levels of this critical hematopoietic transcription factor can cause DBA in rare instances. We show that ribosomal protein haploinsufficiency, the...

  18. Transactivation of human osteoprotegerin promoter by GATA-3

    OpenAIRE

    Shyan-Yuan Kao; Stankovic, Konstantina M.

    2015-01-01

    Osteoprotegerin (OPG) is a key regulator of bone remodeling. Mutations in OPG are involved in a variety of human diseases. We have shown that cochlear spiral ganglion cells secrete OPG at high levels and lack of OPG causes sensorineural hearing loss in addition to the previously described conductive hearing loss. In order to study the regulation of OPG expression, we conducted a database search on regulatory elements in the promoter region of the OPG gene, and identified two potential GATA-3 ...

  19. GATA3 inhibits GCM1 activity and trophoblast cell invasion

    OpenAIRE

    Yueh Ho Chiu; Hungwen Chen

    2016-01-01

    Development of human placenta involves the invasion of trophoblast cells from anchoring villi into the maternal decidua. Placental transcription factor GCM1 regulates trophoblast cell invasion via transcriptional activation of HtrA4 gene, which encodes a serine protease enzyme. The GATA3 transcription factor regulates trophoblast cell differentiation and is highly expressed in invasive murine trophoblast giant cells. The regulation of trophoblastic invasion by GCM1 may involve novel cellular ...

  20. Breast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover

    International Nuclear Information System (INIS)

    The transcription factor GATA3 is a favorable prognostic indicator in estrogen receptor-α (ERα)-positive breast tumors in which it participates with ERα and FOXA1 in a complex transcriptional regulatory program driving tumor growth. GATA3 mutations are frequent in breast cancer and have been classified as driver mutations. To elucidate the contribution(s) of GATA3 alterations to cancer, we studied two breast cancer cell lines, MCF7, which carries a heterozygous frameshift mutation in the second zinc finger of GATA3, and T47D, wild-type at this locus. Immunofluorescence staining and subcellular fractionation were employed to verify cellular localization of GATA3 in T47D and MCF7 cells. To test protein stability, cells were treated with translation inhibitor, cycloheximide or proteasome inhibitor, MG132, and GATA3 abundance was measured over time using immunoblot. GATA3 turn-over in response to hormone was determined by treating the cells with estradiol or ERα agonist, ICI 182,780. DNA binding ability of recombinant GATA3 was evaluated using electrophoretic mobility shift assay and heparin chromatography. Genomic location of GATA3 in MCF7 and T47D cells was assessed by chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq). GATA3 localized in the nucleus in T47D and MCF7 cells, regardless of the mutation status. The truncated protein in MCF7 had impaired interaction with chromatin and was easily released from the nucleus. Recombinant mutant GATA3 was able to bind DNA to a lesser degree than the wild-type protein. Heterozygosity for the truncating mutation conferred protection from regulated turnover of GATA3, ERα and FOXA1 following estrogen stimulation in MCF7 cells. Thus, mutant GATA3 uncoupled protein-level regulation of master regulatory transcription factors from hormone action. Consistent with increased protein stability, ChIP-seq profiling identified greater genome-wide accumulation of GATA3 in MCF7 cells bearing the mutation

  1. A highly conserved regulatory element controls hematopoietic expression of GATA-2 in zebrafish

    Directory of Open Access Journals (Sweden)

    Zhang Michael Q

    2007-08-01

    Full Text Available Abstract Background GATA-2 is a transcription factor required for hematopoietic stem cell survival as well as for neuronal development in vertebrates. It has been shown that specific expression of GATA-2 in blood progenitor cells requires distal cis-acting regulatory elements. Identification and characterization of these elements should help elucidating transcription regulatory mechanisms of GATA-2 expression in hematopoietic lineage. Results By pair-wise alignments of the zebrafish genomic sequences flanking GATA-2 to orthologous regions of fugu, mouse, rat and human genomes, we identified three highly conserved non-coding sequences in the genomic region flanking GATA-2, two upstream of GATA-2 and another downstream. Using both transposon and bacterial artificial chromosome mediated germline transgenic zebrafish analyses, one of the sequences was established as necessary and sufficient to direct hematopoietic GFP expression in a manner that recapitulates that of GATA-2. In addition, we demonstrated that this element has enhancer activity in mammalian myeloid leukemia cell lines, thus validating its functional conservation among vertebrate species. Further analysis of potential transcription factor binding sites suggested that integrity of the putative HOXA3 and LMO2 sites is required for regulating GATA-2/GFP hematopoietic expression. Conclusion Regulation of GATA-2 expression in hematopoietic cells is likely conserved among vertebrate animals. The integrated approach described here, drawing on embryological, transgenesis and computational methods, should be generally applicable to analyze tissue-specific gene regulation involving distal DNA cis-acting elements.

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

    Directory of Open Access Journals (Sweden)

    Duncan Stephen A

    2006-04-01

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

  3. Novel and Functional DNA Sequence Variants within the GATA6 Gene Promoter in Ventricular Septal Defects

    Directory of Open Access Journals (Sweden)

    Chunyu Li

    2014-07-01

    Full Text Available Congenital heart disease (CHD is the most common birth defect in humans. Genetic causes and underlying molecular mechanisms for isolated CHD remain largely unknown. Studies have demonstrated that GATA transcription factor 6 (GATA6 plays an essential role in the heart development. Mutations in GATA6 gene have been associated with diverse types of CHD. As GATA6 functions in a dosage-dependent manner, we speculated that changed GATA6 levels, resulting from DNA sequence variants (DSVs within the gene regulatory regions, may mediate the CHD development. In the present study, GATA6 gene promoter was genetically and functionally analyzed in large groups of patients with ventricular septal defect (VSD (n = 359 and ethnic-matched healthy controls (n = 365. In total, 11 DSVs, including four SNPs, were identified in VSD patients and controls. Two novel and heterozygous DSVs, g.22169190A>T and g.22169311C>G, were identified in two VSD patients, but in none of controls. In cultured cardiomyocytes, the activities of the GATA6 gene promoter were significantly reduced by the DSVs g.22169190A>T and g.22169311C>G. Therefore, our findings suggested that the DSVs within the GATA6 gene promoter identified in VSD patients may change GATA6 levels, contributing to the VSD development as a risk factor.

  4. Acetylation of GATA-3 affects T-cell survival and homing to secondary lymphoid organs

    OpenAIRE

    Yamagata, Tetsuya; Mitani, Kinuko; Oda, Hideaki; Suzuki, Takahiro; Honda, Hiroaki; Asai, Takashi; Maki, Kazuhiro; Nakamoto, Tetsuya; Hirai, Hisamaru

    2000-01-01

    Acetylation of a transcription factor has recently been shown to play a significant role in gene regulation. Here we show that GATA-3 is acetylated in T cells and that a mutation introduced into amino acids 305–307 (KRR-GATA3) creates local hypoacetylation in GATA-3. Remarkably, KRR-GATA3 possesses the most potent suppressive effect when compared with other mutants that are disrupted in putative acetylation targets. Expressing this mutant in peripheral T cells results in defective T-cell homi...

  5. Group 3 innate lymphoid cells continuously require the transcription factor GATA3 after commitment

    OpenAIRE

    Zhong, Chao; Cui, Kairong; Wilhelm, Christoph; Hu, Gangqing; Mao, Kairui; Belkaid, Yasmine; Zhao, Keji; Zhu, Jinfang

    2015-01-01

    The transcription factor GATA3 is indispensable for the development of all interleukin-7 receptor α (IL-7Rα)-expressing innate lymphoid cells (ILCs). However, the functional role of low GATA3 expression in committed ILC3s has not been identified. We report that GATA3 regulates homeostasis of ILC3s by controlling IL-7Rα expression. In addition, GATA3 is critical for the development of the NKp46+ ILC3 subset by regulating the balance between the transcription factors T-bet and RORγt. Alhough GA...

  6. From the cradle to the grave: activities of GATA-3 throughout T cell development and differentiation

    OpenAIRE

    Hosoya, Tomonori; Maillard, Ivan; Engel, James Douglas

    2010-01-01

    GATA family transcription factors play multiple vital roles in hematopoiesis in many cell lineages, and in particular, T cells require GATA-3 for execution of several developmental steps. Transcriptional activation of the Gata3 gene is observed throughout T-cell development and differentiation in stage-specific fashion. GATA-3 has been described as a master regulator of T-helper 2 (Th2) cell differentiation in mature CD4+ T cells. During T-cell development in the thymus, its roles in the CD4 ...

  7. Dissecting the Relation between a nuclear receptor and GATA: binding affinity studies of thyroid hormone receptor and GATA2 on TSHβ promoter.

    Directory of Open Access Journals (Sweden)

    Ana Carolina Migliorini Figueira

    Full Text Available BACKGROUND: Much is known about how genes regulated by nuclear receptors (NRs are switched on in the presence of a ligand. However, the molecular mechanism for gene down-regulation by liganded NRs remains a conundrum. The interaction between two zinc-finger transcription factors, Nuclear Receptor and GATA, was described almost a decade ago as a strategy adopted by the cell to up- or down-regulate gene expression. More recently, cell-based assays have shown that the Zn-finger region of GATA2 (GATA2-Zf has an important role in down-regulation of the thyrotropin gene (TSHβ by liganded thyroid hormone receptor (TR. METHODOLOGY/PRINCIPAL FINDINGS: In an effort to better understand the mechanism that drives TSHβ down-regulation by a liganded TR and GATA2, we have carried out equilibrium binding assays using fluorescence anisotropy to study the interaction of recombinant TR and GATA2-Zf with regulatory elements present in the TSHβ promoter. Surprisingly, we observed that ligand (T3 weakens TR binding to a negative regulatory element (NRE present in the TSHβ promoter. We also show that TR may interact with GATA2-Zf in the absence of ligand, but T3 is crucial for increasing the affinity of this complex for different GATA response elements (GATA-REs. Importantly, these results indicate that TR complex formation enhances DNA binding of the TR-GATA2 in a ligand-dependent manner. CONCLUSIONS: Our findings extend previous results obtained in vivo, further improving our understanding of how liganded nuclear receptors down-regulate gene transcription, with the cooperative binding of transcription factors to DNA forming the core of this process.

  8. Continued expression of GATA3 is necessary for cochlear neurosensory development.

    Directory of Open Access Journals (Sweden)

    Jeremy S Duncan

    Full Text Available Hair cells of the developing mammalian inner ear are progressively defined through cell fate restriction. This process culminates in the expression of the bHLH transcription factor Atoh1, which is necessary for differentiation of hair cells, but not for their specification. Loss of several genes will disrupt ear morphogenesis or arrest of neurosensory epithelia development. We previously showed in null mutants that the loss of the transcription factor, Gata3, results specifically in the loss of all cochlear neurosensory development. Temporal expression of Gata3 is broad from the otic placode stage through the postnatal ear. It therefore remains unclear at which stage in development Gata3 exerts its effect. To better understand the stage specific effects of Gata3, we investigated the role of Gata3 in cochlear neurosensory specification and differentiation utilizing a LoxP targeted Gata3 line and two Cre lines. Foxg1(Cre∶Gata3(f/f mice show recombination of Gata3 around E8.5 but continue to develop a cochlear duct without differentiated hair cells and spiral ganglion neurons. qRT-PCR data show that Atoh1 was down-regulated but not absent in the duct whereas other hair cell specific genes such as Pou4f3 were completely absent. In addition, while Sox2 levels were lower in the Foxg1(Cre:Gata3(f/f cochlea, Eya1 levels remained normal. We conclude that Eya1 is unable to fully upregulate Atoh1 or Pou4f3, and drive differentiation of hair cells without Gata3. Pax2-Cre∶Gata3(f/f mice show a delayed recombination of Gata3 in the ear relative to Foxg1(Cre:Gata3(f/f . These mice exhibited a cochlear duct containing patches of partially differentiated hair cells and developed only few and incorrectly projecting spiral ganglion neurons. Our conditional deletion studies reveal a major role of Gata3 in the signaling of prosensory genes and in the differentiation of cochlear neurosenory cells. We suggest that Gata3 may act in combination with Eya1, Six1, and

  9. PU.1 Suppresses Th2 Cytokine Expression via Silencing of GATA3 Transcription in Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Takuya Yashiro

    Full Text Available The transcription factor PU.1 is predominantly expressed in dendritic cells (DCs and is essential for DC differentiation. Although there are several reports that PU.1 positively regulates the expression of DC-specific genes, whether PU.1 also has a suppressive effect on DCs is largely unknown. Here we demonstrate that PU.1 suppresses the expression of Th2 cytokines including IL-13 and IL-5 in bone marrow-derived DCs (BMDCs, through repression of the expression of GATA3, which is a master regulator of Th2 differentiations. When PU.1 siRNA was introduced into BMDCs, LPS-induced expression of IL-13 and IL-5 was increased along with upregulation of the constitutive expression of GATA2 and GATA3. The additional introduction of GATA3 siRNA but not of GATA2 siRNA abrogated PU.1 siRNA-mediated upregulation of IL-13 and IL-5. A chromatin immunoprecipitation assay showed that PU.1 bound to Gata3 proximal promoter region, which is more dominant than the distal promoter in driving GATA3 transcription in DCs. The degree of histone acetylation at the Gata3 promoter was decreased in PU.1 siRNA-introduced DCs, suggesting the involvement of PU.1 in chromatin modification of the Gata3 promoter. Treatment with a histone deacetylase (HDAC inhibitor, trichostatin A, increased the degree of histone H3 acetylation at the Gata3 promoter and induced the subsequent expression of GATA3. Experiments using HDAC inhibitors and siRNAs showed that HDAC3 suppressed GATA3 expression. The recruitment of HDAC3 to the Gata3 promoter was decreased by PU.1 knockdown. LPS-induced IL-13 expression was dramatically reduced in BMDCs generated from mice lacking the conserved GATA3 response element, termed CGRE, which is an essential site for the binding of GATA3 on the Il-13 promoter. The degree of H3K4me3 at CGRE was significantly increased in PU.1 siRNA-transfected stimulated DCs. Our results indicate that PU.1 plays pivotal roles in DC development and function, serving not only as a

  10. cAMP-dependent proteolysis of GATA-6 is linked to JNK-signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ushijima, Hironori [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan); Maeda, Masatomo, E-mail: mmaeda@iwate-med.ac.jp [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6. Black-Right-Pointing-Pointer Effect of a JNK activator anisomycin on the proteolysis was examined. Black-Right-Pointing-Pointer Anisomycin stimulated the export of nuclear GATA-6 into the cytoplasm. Black-Right-Pointing-Pointer JNK activated the CRM1 mediated nuclear export of GATA-6. Black-Right-Pointing-Pointer JNK further stimulated slowly the degradation of GATA-6 by cytoplasmic proteasomes. -- Abstract: A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6 by proteasomes around its IC50. We further examined the effects of SP600125 on the degradation of GATA-6 in detail, since an activator of JNK (anisomycin) is available. Interestingly, anisomycin immediately stimulated the export of nuclear GATA-6 into the cytoplasm, and then the cytoplasmic content of GATA-6 decreased slowly through degradation by proteasomes. Such an effect of anisomycin was inhibited by SP600125, indicating that the observed phenomenon might be linked to the JNK signaling pathway. The inhibitory effect of SP600125 could not be ascribed to the inhibition of PKA, since phosphorylation of CREB occurred in the presence of dbcAMP and SP600125. The nuclear export of GATA-6 was inhibited by leptomycin B, suggesting that CRM1-mediated export could be activated by anisomycin. Furthermore, it seems likely that the JNK activated by anisomycin may stimulate not only the nuclear export of GATA-6 through CRM1 but also the degradation of GATA-6 by cytoplasmic proteasomes. In contrast, A-kinase might activate only the latter process through JNK.

  11. GATA3 expression in breast carcinoma: utility in triple-negative, sarcomatoid, and metastatic carcinomas☆, ☆☆

    OpenAIRE

    Cimino-Mathews, Ashley; Subhawong, Andrea P.; Illei, Peter B.; Sharma, Rajni; Halushka, Marc K.; Vang, Russell; Fetting, John H.; Park, Ben Ho; Argani, Pedram

    2013-01-01

    GATA3 plays an integral role in breast luminal cell differentiation and is implicated in breast cancer progression. GATA3 immunohistochemistry is a useful marker of breast cancer; however, its use in specific subtypes is unclear. Here, we evaluate GATA3 expression in 86 invasive ductal carcinomas including triple-negative, Her-2, and luminal subtypes, in addition to 13 metaplastic carcinomas and in 34 fibroepithelial neoplasms. In addition, we report GATA3 expression in matched primary and me...

  12. Progesterone receptor activation downregulates GATA3 by transcriptional repression and increased protein turnover promoting breast tumor growth

    OpenAIRE

    Izzo, Franco; Mercogliano, Florencia; Venturutti, Leandro; Tkach, Mercedes; Inurrigarro, Gloria; Schillaci, Roxana; Cerchietti, Leandro; Elizalde, Patricia V.; Proietti, Cecilia J.

    2014-01-01

    Introduction The transcription factor GATA3 is involved in mammary gland development and is crucial for the maintenance of the differentiated status of luminal epithelial cells. The role of GATA3 in breast cancer as a tumor suppressor has been established, although insights into the mechanism of GATA3 expression loss are still required. Methods Chromatin immunoprecipitation assays were conducted to study progestin modulation of recruitment of transcription factors to GATA3 promoter. We perfor...

  13. Negative association between GATA3 and fascin could predict relapse-free and overall survival in patients with breast cancer.

    Science.gov (United States)

    Min, Kyueng-Whan; Kim, Dong-Hoon; Do, Sung-Im; Chae, Seoung Wan; Kim, Kyungeun; Sohn, Jin Hee; Pyo, Jung-Soo; Lee, Hyun Joo; Kim, Dong Hyun; Oh, Sukjoong; Choi, Seon Hyeong; Park, Yong Lai; Park, Chan Heun; Kim, Eun-Kyung; Kwon, Mi Jung; Seo, Jinwon; Moon, Kyoung Min

    2016-04-01

    GATA3 and fascin proteins are known prognostic markers in several cancers. GATA3 is a key regulator of mammary gland morphogenesis and luminal cell differentiation, whereas fascin is a pro-metastatic actin-bundling protein. In this study, we analyzed and compared the predictive abilities of GATA3 and fascin for clinical outcomes of patients with breast cancer. The combined expression pattern based on GATA3-/+ and fascin-/+ was evaluated by immunostaining using a tissue microarray, and relationships between protein expression and several clinicopathological parameters were analyzed. GATA3 expression was associated with good prognostic parameters, but fascin was correlated with poor prognostic parameters. On comparing GATA3 and fascin, we found an inverse relationship between fascin and GATA3 expressions. On analysis of combined markers, GATA3+/fascin- was correlated with improved clinical outcomes compared to GATA3-/fascin+. Univariate and multivariate analyses revealed significant differences in relapse-free and overall survival between GATA3+/fascin- and GATA3-/fascin+. Combined marker analysis of GATA3/fascin showed an inverse association and improved prognostic information for patients with breast cancer. PMID:26719157

  14. Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators

    Science.gov (United States)

    Belaguli, N. S.; Sepulveda, J. L.; Nigam, V.; Charron, F.; Nemer, M.; Schwartz, R. J.

    2000-01-01

    Combinatorial interaction among cardiac tissue-restricted enriched transcription factors may facilitate the expression of cardiac tissue-restricted genes. Here we show that the MADS box factor serum response factor (SRF) cooperates with the zinc finger protein GATA-4 to synergistically activate numerous myogenic and nonmyogenic serum response element (SRE)-dependent promoters in CV1 fibroblasts. In the absence of GATA binding sites, synergistic activation depends on binding of SRF to the proximal CArG box sequence in the cardiac and skeletal alpha-actin promoter. GATA-4's C-terminal activation domain is obligatory for synergistic coactivation with SRF, and its N-terminal domain and first zinc finger are inhibitory. SRF and GATA-4 physically associate both in vivo and in vitro through their MADS box and the second zinc finger domains as determined by protein A pullout assays and by in vivo one-hybrid transfection assays using Gal4 fusion proteins. Other cardiovascular tissue-restricted GATA factors, such as GATA-5 and GATA-6, were equivalent to GATA-4 in coactivating SRE-dependent targets. Thus, interaction between the MADS box and C4 zinc finger proteins, a novel regulatory paradigm, mediates activation of SRF-dependent gene expression.

  15. The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms.

    Science.gov (United States)

    Hewitt, K J; Johnson, K D; Gao, X; Keles, S; Bresnick, E H

    2016-01-01

    Transcriptional regulators mediate the genesis and function of the hematopoietic system by binding complex ensembles of cis-regulatory elements to establish genetic networks. While thousands to millions of any given cis-element resides in a genome, how transcriptional regulators select these sites and how site attributes dictate functional output is not well understood. An instructive system to address this problem involves the GATA family of transcription factors that control vital developmental and physiological processes and are linked to multiple human pathologies. Although GATA factors bind DNA motifs harboring the sequence GATA, only a very small subset of these abundant motifs are occupied in genomes. Mechanistic studies revealed a unique configuration of a GATA factor-regulated cis-element consisting of an E-box and a downstream GATA motif separated by a short DNA spacer. GATA-1- or GATA-2-containing multiprotein complexes at these composite elements control transcription of genes critical for hematopoietic stem cell emergence in the mammalian embryo, hematopoietic progenitor cell regulation, and erythroid cell maturation. Other constituents of the complex include the basic helix-loop-loop transcription factor Scl/TAL1, its heterodimeric partner E2A, and the Lim domain proteins LMO2 and LDB1. This chapter reviews the structure/function of E-box-GATA composite cis-elements, which collectively constitute an important sector of the hematopoietic stem and progenitor cell cistrome. PMID:27137654

  16. The Gata3 transcription factor is required for the survival of embryonic and adult sympathetic neurons

    NARCIS (Netherlands)

    K. Tsarovina (Konstantina); T. Reiff (Tobias); J. Stubbusch (Jutta); D. Kurek (Dorota); F.G. Grosveld (Frank); R. Parlato (Rosanna); G. Schütz (Günther); H. Rohrer (Hermann)

    2010-01-01

    textabstractThe transcription factor Gata3 is essential for the development of sympathetic neurons and adrenal chromaffin cells. As Gata3 expression is maintained up to the adult stage, we addressed its function in differentiated sympathoadrenal cells at embryonic and adult stages by conditional Gat

  17. Kzp Regulates the Transcription of gata2 and pu.1 during Primitive Hematopoiesis in Zebrafish Embryos

    Institute of Scientific and Technical Information of China (English)

    Fang Liu; Shaohua Yao; Ting Zhang; Chun Xiao; Yanna Shang; Jin Liu; Xianming Mo

    2012-01-01

    Kaiso zinc finger-containing protein (Kzp),a maternally-derived transcription factor,controls dorsoventral patterning during zebrafish gastrulation.Here,we uncovered a new function for Kzp in zebrafish embryonic primitive hematopoiesis.The depletion of kzp led to defects in primitive hematopoiesis including the development of the erythroid and myeloid lineages.On the other hand,overexpression of kzp caused the ectopic expression of gatal,gata2,and pu.1.Chromosome immunoprecipitation assays revealed that Kzp protein directly binds to gatal,gata2,and pu.1 promoters.Interestingly,the ectopic expression of gata2 was able to rescue the erythroid,but not the myeloid lineage in kzp-depleted zebrafish embryos.gatal expression controlled by Kzp was dependent on gata2 during primitive erythropoiesis.Our results indicate that Kzp is a critical transcriptional factor for the expression of gata2 and pu.1 to modulate primitive hematopoiesis.

  18. GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway.

    Science.gov (United States)

    Bergeron, Francis; Nadeau, Gabriel; Viger, Robert S

    2015-03-01

    GATA4 is an essential transcription factor required for the initiation of genital ridge formation, for normal testicular and ovarian differentiation at the time of sex determination, and for male and female fertility in adulthood. In spite of its crucial roles, the genes and/or gene networks that are ultimately regulated by GATA4 in gonadal tissues remain to be fully understood. This is particularly true for the steroidogenic lineages such as Leydig cells of the testis where many in vitro (promoter) studies have provided good circumstantial evidence that GATA4 is a key regulator of Leydig cell gene expression and steroidogenesis, but formal proof is still lacking. We therefore performed a microarray screening analysis of MA-10 Leydig cells in which Gata4 expression was knocked down using an siRNA strategy. Analysis identified several GATA4-regulated pathways including cholesterol synthesis, cholesterol transport, and especially steroidogenesis. A decrease in GATA4 protein was associated with decreased expression of steroidogenic genes previously suspected to be GATA4 targets such as Cyp11a1 and Star. Gata4 knockdown also led to an important decrease in other novel steroidogenic targets including Srd5a1, Gsta3, Hsd3b1, and Hsd3b6, as well as genes known to participate in cholesterol metabolism such as Scarb1, Ldlr, Soat1, Scap, and Cyp51. Consistent with the decreased expression of these genes, a reduction in GATA4 protein compromised the ability of MA-10 cells to produce steroids both basally and under hormone stimulation. These data therefore provide strong evidence that GATA4 is an essential transcription factor that sits atop of the Leydig cell steroidogenic program. PMID:25504870

  19. An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation

    OpenAIRE

    Yagi, Ryoji; Zhu, Jinfang; Paul, William E.

    2011-01-01

    CD4 Th are critical for orchestrating adaptive immune responses. The expression of the transcription factor GATA3 (GATA-binding protein 3) is up-regulated or down-regulated during Th2 or Th1 cell differentiation, respectively. Furthermore, GATA3 is responsible for induction of Th2 differentiation and represses Th1 differentiation. In this review, we present an updated view on the molecular mechanisms through which GATA3 regulates Th1/Th2 differentiation. During Th2 cell differentiation, GATA3...

  20. Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types

    OpenAIRE

    Wei, Gang; Abraham, Brian J.; Yagi, Ryoji; Jothi, Raja; Cui, Kairong; Sharma, Suveena; Narlikar, Leelavati; Northrup, Daniel L.; Tang, Qingsong; Paul, William E.; Zhu, Jinfang; Zhao, Keji

    2011-01-01

    The transcription factor GATA3 plays an essential role during T cell development and T helper 2 (Th2) cell differentiation. To understand GATA3-mediated gene regulation, we identified genome-wide GATA3 binding sites in ten well-defined developmental and effector T lymphocyte lineages. In the thymus, GATA3 directly regulated many critical factors, including Th-POK, Notch1 and T cell receptor subunits. In the periphery, GATA3 induced a large number of Th2 cell-specific as well as Th2 cell non-s...

  1. Genetic variant rs1058240 at the microRNA-binding site in the GATA3 gene may regulate its mRNA expression

    OpenAIRE

    Yang, Fang; CHEN, FENXIA; Gu, Jun; Zhang, Wenwen; Luo, Jiayan; Guan, Xiaoxiang

    2014-01-01

    The GATA binding protein 3 (GATA3) is a member of a family of 6 GATA dual zinc finger transcription factors (GATA1-6), which are required for the development and morphogenesis of the mammary gland. GATA3 is considered to play a dual role in oncogenesis and cancer development, whereas somatic GATA3 mutations have been reported in breast cancer. Variants of the GATA3 genetic 3′ untranslated region (3′UTR) microRNA (miRNA) binding sites have been associated with breast cancer risk. However, the ...

  2. Lineage-affiliated transcription factors bind the Gata3 Tce1 enhancer to mediate lineage-specific programs

    Science.gov (United States)

    Ohmura, Sakie; Mizuno, Seiya; Oishi, Hisashi; Ku, Chia-Jui; Hermann, Mary; Hosoya, Tomonori; Takahashi, Satoru; Engel, James Douglas

    2016-01-01

    The transcription factor GATA3 is essential for the genesis and maturation of the T cell lineage, and GATA3 dysregulation has pathological consequences. Previous studies have shown that GATA3 function in T cell development is regulated by multiple signaling pathways and that the Notch nuclear effector, RBP-J, binds specifically to the Gata3 promoter. We previously identified a T cell–specific Gata3 enhancer (Tce1) lying 280 kb downstream from the structural gene and demonstrated in transgenic mice that Tce1 promoted T lymphocyte–specific transcription of reporter genes throughout T cell development; however, it was not clear if Tce1 is required for Gata3 transcription in vivo. Here, we determined that the canonical Gata3 promoter is insufficient for Gata3 transcriptional activation in T cells in vivo, precluding the possibility that promoter binding by a host of previously implicated transcription factors alone is responsible for Gata3 expression in T cells. Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte–specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell–regulatory element. Together, our data show that Tce1 is both necessary and sufficient for critical aspects of Gata3 T cell–specific transcriptional activity. PMID:26808502

  3. Lineage-affiliated transcription factors bind the Gata3 Tce1 enhancer to mediate lineage-specific programs.

    Science.gov (United States)

    Ohmura, Sakie; Mizuno, Seiya; Oishi, Hisashi; Ku, Chia-Jui; Hermann, Mary; Hosoya, Tomonori; Takahashi, Satoru; Engel, James Douglas

    2016-03-01

    The transcription factor GATA3 is essential for the genesis and maturation of the T cell lineage, and GATA3 dysregulation has pathological consequences. Previous studies have shown that GATA3 function in T cell development is regulated by multiple signaling pathways and that the Notch nuclear effector, RBP-J, binds specifically to the Gata3 promoter. We previously identified a T cell-specific Gata3 enhancer (Tce1) lying 280 kb downstream from the structural gene and demonstrated in transgenic mice that Tce1 promoted T lymphocyte-specific transcription of reporter genes throughout T cell development; however, it was not clear if Tce1 is required for Gata3 transcription in vivo. Here, we determined that the canonical Gata3 promoter is insufficient for Gata3 transcriptional activation in T cells in vivo, precluding the possibility that promoter binding by a host of previously implicated transcription factors alone is responsible for Gata3 expression in T cells. Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte-specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell-regulatory element. Together, our data show that Tce1 is both necessary and sufficient for critical aspects of Gata3 T cell-specific transcriptional activity. PMID:26808502

  4. GATA-3 EXPRESSION IN PERIPHERAL BLOOD LYMPHOCYTES OF PATIENTS WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    V. N. Mineev

    2010-01-01

    Full Text Available The aim of the study is to establish the features of expression of GATA-3 in peripheral lymphocytes from bronchial asthma patients (BA. Material and methods. 10 healthy controls, 15 patients with allergic (atopic and 15 persons with non-allergic BA were examined. A transcription factor GATA-3 expressed in peripheral lymphocytes was analyzed by Western blot after the lymphocytes were lysed. Preparation of cell lysates, and Western blotting were performed by means of a standard procedure (Amersham. An antibody against GATA-3 (Abcam, UK was used. Levels of the protein were analyzed versus β-actin levels using anti-actin antibody (Sigma Aldrich, USA. Results. Expression of GATA-3 was significantly increased in lymphocytes of patients with allergic BA as compared to healthy persons and non-allergic BA patients. The level of GATA-3 negatively correlated with the degree of airflow obstruction and positively correlated with dosage of parenteral steroids administered. Conclusion. GATA-3 may play a key role in the pathophysiology of BA. One may suggest that increased expression of GATA-3 transcription factor in atopic BA underlie high levels of Th2-cytokines production in allergic disease

  5. GATA-3 expression in the development of anterior chamber associated immune deviation

    Institute of Scientific and Technical Information of China (English)

    FU Tao; YANG Pei-zeng; HUANG Xiang-kun; HUANG Qiang; ZHOU Hong-yan; LI Bing; ZHONG Hua-hong; CHEN Xuan

    2005-01-01

    Background Anterior chamber associated immune deviation (ACAID) is characterized by a Th2 cell response. GATA-3 has been shown to be necessary for the activation of Th2 cells. This study was designed to examine the expression of GATA-3 in the development of ACAID. Methods ACAID was induced by injection of 50 μg interphotoreceptor retinoid binding protein (IRBP) into the anterior chamber (AC) of Wistar rats. Delayed-type hypersensitivity (DTH) was evaluated on day 3, 7, 14, 21, 28 after IRBP inoculation. GATA-3 expression was detected using immunohistochemical staining. The expression of GATA-3 mRNA at different time points after AC injection of IRBP was assayed by reverse transcriptase polymerase chain reaction (RT-PCR). Results A significant DTH reaction was observed in Wistar rats on day 3 and 5 after IRBP inoculation. The DTH reaction was decreased 7 days after IRBP inoculation. GATA-3 expression was weak at both mRNA and protein levels in the normal spleen, but was significantly increased on day 5, 7, 14, and 21 after AC injection of IRBP. Conclusion The expression of GATA-3 is increased during ACAID, suggesting that GATA-3 may be involved in the development of ACAID.

  6. Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects

    Institute of Scientific and Technical Information of China (English)

    Ji-Ping Shan; Xiao-Li Wang; Yuan-Gang Qiao; Hong-Xin Wan Yan; Wen-Hui Huang; Shu-Chao Pang; Bo Yan

    2014-01-01

    Background: Congenital heart disease (CHD) is the most common human birth defect. Genetic causes for CHD remain largely unknown. GATA transcription factor 5 (GATA 5) is an essential regulator for the heart development. Mutations in the GATA5 gene have been reported in patients with a variety of CHD. Since misregulation of gene expression have been associated with human diseases, we speculated that changed levels of cardiac transcription factors, GATA5, may mediate the development of CHD. Methods: In this study, GATA5 gene promoter was genetically and functionally analyzed in large cohorts of patients with ventricular septal defect (VSD) (n=343) and ethnic-matched healthy controls (n=348). Results: Two novel and heterozygous DNA sequence variants (DSVs), g.61051165A>G and g.61051463delC, were identified in three VSD patients, but not in the controls. In cultured cardiomyocytes, GATA5 gene promoter activities were significantly decreased by DSV g.61051165A>G and increased by DSV g.61051463delC. Moreover, fathers of the VSD patients carrying the same DSVs had reduced diastolic function of left ventricles. Three SNPs, g.61051279C>T (rs77067995), g.61051327A>C (rs145936691) and g.61051373G>A (rs80197101), and one novel heterozygous DSV, g.61051227C>T, were found in both VSD patients and controls with similar frequencies. Conclusion: Our data suggested that the DSVs in the GATA5 gene promoter may increase the susceptibility to the development of VSD as a risk factor.

  7. REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis.

    Science.gov (United States)

    Kawasaki, Yoshihiro; Matsumura, Kosuke; Miyamoto, Masaya; Tsuji, Shinnosuke; Okuno, Masumi; Suda, Sakiko; Hiyoshi, Masaya; Kitayama, Joji; Akiyama, Tetsu

    2015-01-01

    The transcription factor GATA6 is a critical regulator of cell proliferation and development in the gastrointestinal tract. We have recently reported that GATA6 induces the expression of the intestinal stem cell marker LGR5 and enhances the clonogenicity and tumorigenicity of colon cancer cells, but not the growth of these cells cultured under adherent conditions. Here we show that REG4, a member of the regenerating islet-derived (REG) family, is also a target of GATA6. We further demonstrate that REG4 is downregulated by overexpression of miR-363, which suppresses GATA6 expression. Moreover, we show that GATA6-mediated activation of REG4 enhances the growth of colon cancer cells under adherent conditions and is required for their tumorigenicity. Taken together, our findings demonstrate that GATA6 simultaneously induces the expression of genes essential for the growth of colon cancer cells under adherent conditions (REG4) and genes required for their clonogenicity (LGR5), and that the miR-363-GATA6-REG4/LGR5 signaling cascade promotes the tumorigenicity of colon cancer cells. PMID:26387746

  8. SUMOylation regulates the transcriptional repression activity of FOG-2 and its association with GATA-4.

    Directory of Open Access Journals (Sweden)

    José Perdomo

    Full Text Available Friend of GATA 2 (FOG-2, a co-factor of several GATA transcription factors (GATA-4, -5 and 6, is a critical regulator of coronary vessel formation and heart morphogenesis. Here we demonstrate that FOG-2 is SUMOylated and that this modification modulates its transcriptional activity. FOG-2 SUMOylation occurs at four lysine residues (K324, 471, 915, 955 [corrected]. Three of these residues are part of the characteristic SUMO consensus site (ψKXE, while K955 is found in the less frequent TKXE motif. Absence of SUMOylation did not affect FOG-2's nuclear localization. However, mutation of the FOG-2 SUMOylation sites, or de-SUMOylation, with SENP-1 or SENP-8 resulted in stronger transcriptional repression activity in both heterologous cells and cardiomyocytes. Conversely, increased FOG-2 SUMOylation by overexpression of SUMO-1 or expression of a SUMO-1-FOG-2 fusion protein rendered FOG-2 incapable of repressing GATA-4-mediated activation of the B-type natriuretic peptide (BNP promoter. Moreover, we demonstrate both increased interaction between a FOG-2 SUMO mutant and GATA-4 and enhanced SUMOylation of wild-type FOG-2 by co-expression of GATA-4. These data suggest a new dynamics in which GATA-4 may alter the activity of FOG-2 by influencing its SUMOylation status.

  9. Regulation of an Autoimmune Model for Multiple Sclerosis in Th2-Biased GATA3 Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Viromi Fernando

    2014-01-01

    Full Text Available T helper (Th2 cells have been proposed to play a neuroprotective role in multiple sclerosis (MS. This is mainly based on “loss-of-function” studies in an animal model for MS, experimental autoimmune encephalomyelitis (EAE, using blocking antibodies against Th2 related cytokines, and knockout mice lacking Th2-related molecules. We tested whether an increase of Th2 responses (“gain-of-function” approach could alter EAE, the approach of novel GATA binding protein 3 (GATA3-transgenic (tg mice that overexpress GATA3, a transcription factor required for Th2 differentiation. In EAE induced with myelin oligodendrocyte glycoprotein (MOG35−55 peptide, GATA3-tg mice had a significantly delayed onset of disease and a less severe maximum clinical score, compared with wild-type C57BL/6 mice. Histologically, GATA3-tg mice had decreased levels of meningitis and demyelination in the spinal cord, and anti-inflammatory cytokine profiles immunologically, however both groups developed similar levels of MOG-specific lymphoproliferative responses. During the early stage, we detected higher levels of interleukin (IL-4 and IL-10, with MOG and mitogen stimulation of regional lymph node cells in GATA3-tg mice. During the late stage, only mitogen stimulation induced higher IL-4 and lower interferon-γ and IL-17 production in GATA3-tg mice. These results suggest that a preexisting bias toward a Th2 immune response may reduce the severity of inflammatory demyelinating diseases, including MS.

  10. Identification of functional mutations in GATA4 in patients with congenital heart disease.

    Directory of Open Access Journals (Sweden)

    Erli Wang

    Full Text Available Congenital heart disease (CHD is one of the most prevalent developmental anomalies and the leading cause of noninfectious morbidity and mortality in newborns. Despite its prevalence and clinical significance, the etiology of CHD remains largely unknown. GATA4 is a highly conserved transcription factor that regulates a variety of physiological processes and has been extensively studied, particularly on its role in heart development. With the combination of TBX5 and MEF2C, GATA4 can reprogram postnatal fibroblasts into functional cardiomyocytes directly. In the past decade, a variety of GATA4 mutations were identified and these findings originally came from familial CHD pedigree studies. Given that familial and sporadic CHD cases allegedly share a basic genetic basis, we explore the GATA4 mutations in different types of CHD. In this study, via direct sequencing of the GATA4 coding region and exon-intron boundaries in 384 sporadic Chinese CHD patients, we identified 12 heterozygous non-synonymous mutations, among which 8 mutations were only found in CHD patients when compared with 957 controls. Six of these non-synonymous mutations have not been previously reported. Subsequent functional analyses revealed that the transcriptional activity, subcellular localization and DNA binding affinity of some mutant GATA4 proteins were significantly altered. Our results expand the spectrum of GATA4 mutations linked to cardiac defects. Together with the newly reported mutations, approximately 110 non-synonymous mutations have currently been identified in GATA4. Our future analysis will explore why the evolutionarily conserved GATA4 appears to be hypermutable.

  11. 海门山羊GATA-4转录因子的表达%Expressionof GATA-4 transcription factor in Haimen goats

    Institute of Scientific and Technical Information of China (English)

    何远清; 潘晔; 殷黎静

    2012-01-01

    本试验选用2个山羊品种(海门山羊和安徽白山羊),采用实时定量PCR技术,检测了GATA-4转录因子在2个山羊品种下丘脑、肌肉、心脏、垂体、卵巢、肝、子宫、脾、肾和脑组织中的表达情况.结果显示:GATA-4转录因子在海门山羊各组织中都有表达,且在海门山羊下丘脑和垂体组织中GATA-4转录因子的表达量高于安徽白山羊.表明GATA-4在海门山羊下丘脑和垂体组织中的表达水平可能影响海门山羊的繁殖能力.%The expression level of GATA-4 transcription factor in hypothalamus, muscle, heart, pituitary gland, ovary, liver, uterus, spleen, kidney and brain of Haimen goats and Anhui white goats were detected by realtime quantitative PCR. The results indicated that GATA-4 transcription factor was expressed in all detected tissues of Haimen goats. The expression levels of GATA-4 in hypothalamus and pituitary gland of Haimen goats were higher than those in Anhui white goats. All results revealed that the GATA-4 expression levels in hypothalamus and pituitary gland might have effect on reproduction capability of Haimen goats.

  12. Optical conductivity measurements of GaTa4Se8 under high pressure: evidence of a bandwidth-controlled insulator-to-metal Mott transition

    International Nuclear Information System (INIS)

    The optical properties of a GaTa4Se8 single crystal are investigated under high pressure. At ambient pressure, the optical conductivity exhibits a charge gap of 0.12 eV and a broad mid infrared band at ∼0.55 eV. As pressure is increased, the low energy spectral weight is strongly enhanced and the optical gap is rapidly filled, pointing to an insulator to metal transition around 6 GPa. The overall evolution of the optical conductivity demonstrates that GaTa4Se8 is a Mott insulator which undergoes a bandwidth controlled Mott metal-insulator transition under pressure, in remarkably good agreement with theory. With the use of our optical data and ab initio band structure calculations, our results were successfully compared to the (U/D, T/D) phase diagram predicted by dynamical mean field theory for strongly correlated systems. (authors)

  13. Optical conductivity measurements of GaTa4Se8 under high pressure: evidence of a bandwidth-controlled insulator-to-metal Mott transition.

    Science.gov (United States)

    Ta Phuoc, V; Vaju, C; Corraze, B; Sopracase, R; Perucchi, A; Marini, C; Postorino, P; Chligui, M; Lupi, S; Janod, E; Cario, L

    2013-01-18

    The optical properties of a GaTa(4)Se(8) single crystal are investigated under high pressure. At ambient pressure, the optical conductivity exhibits a charge gap of ≈0.12 eV and a broad midinfrared band at ≈0.55 eV. As pressure is increased, the low energy spectral weight is strongly enhanced and the optical gap is rapidly filled, pointing to an insulator to metal transition around 6 GPa. The overall evolution of the optical conductivity demonstrates that GaTa(4)Se(8) is a Mott insulator which undergoes a bandwidth-controlled Mott metal-insulator transition under pressure, in remarkably good agreement with theory. With the use of our optical data and ab initio band structure calculations, our results were successfully compared to the (U/D, T/D) phase diagram predicted by dynamical mean field theory for strongly correlated systems. PMID:23373949

  14. Molecular analysis of the interaction between the hematopoietic master transcription factors GATA-1 and PU.1

    DEFF Research Database (Denmark)

    Liew, Chu Wai; Rand, Kasper Dyrberg; Simpson, Raina J Y; Yung, Wendy W; Mansfield, Robyn E; Crossley, Merlin; Proetorius-Ibba, Mette; Nerlov, Claus; Poulsen, Flemming M; Mackay, Joel P

    2006-01-01

    GATA-1 and PU.1 are transcription factors that control erythroid and myeloid development, respectively. The two proteins have been shown to function in an antagonistic fashion, with GATA-1 repressing PU.1 activity during erythropoiesis and PU.1 repressing GATA-1 function during myelopoiesis. It has...... also become clear that this functional antagonism involves direct interactions between the two proteins. However, the molecular basis for these interactions is not known, and a number of inconsistencies exist in the literature. We have used a range of biophysical methods to define the molecular details...

  15. Dynamic expression of T-bet and GATA3 by regulatory T cells maintains immune tolerance

    OpenAIRE

    Yu, Fang; Sharma, Suveena; Edwards, Julie; Feigenbaum, Lionel; Zhu, Jinfang

    2014-01-01

    Regulatory T (Treg) cells can express the transcription factors T-bet and GATA3 but the function of this expression and whether such cells represent stable subsets is still unknown. By using multiple reporter tools, we show that the expression of T-bet and GATA3 in Treg cells is dynamically influenced by the cytokine environment. Treg cell-specific deletion of either Tbx21 or Gata3 genes singly did not result in loss of Treg cell functions; however, mice with combined deficiency of both genes...

  16. GATA-3 dose-dependent checkpoints in early T cell commitment1

    OpenAIRE

    Scripture-Adams, Deirdre D.; Damle, Sagar S.; Li, Long; Elihu, Koorosh J.; Qin, Shuyang; Arias, Alexandra M.; Butler, Robert R.; Champhekar, Ameya; Zhang, Jingli A.; Rothenberg, Ellen V.

    2014-01-01

    GATA-3 expression is crucial for T cell development and peaks during commitment to the T-cell lineage, midway through the CD4−CD8− (DN) 1-3 stages. We used RNA interference and conditional deletion to reduce GATA-3 protein acutely at specific points during T-cell differentiation in vitro. Even moderate GATA-3 reduction killed DN1 cells, delayed progression to DN2 stage, skewed DN2 gene regulation, and blocked appearance of DN3 phenotype. Although a Bcl-2 transgene rescued DN1 survival and imp...

  17. GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells

    OpenAIRE

    Pai, Sung-Yun; Truitt, Morgan L.; Ho, I-Cheng

    2004-01-01

    T helper type 2 (Th2) cells secrete IL-4, IL-5, IL-10, and IL-13 and mediate allergic and asthmatic disease. GATA-3 is a Th2-specific transcription factor that appears in overexpression studies and transgenic systems to function as a Th2 lineage determinant. Because GATA-3 is also crucial for development of the T lineage and throughout thymic development, direct demonstration that GATA-3 is required for Th2 development by targeted deletion has been lacking. Using a conditional knockout approa...

  18. GATA-3 regulates the homeostasis and activation of CD8+ T cells1

    OpenAIRE

    Tai, Tzong-Shyuan; Pai, Sung-Yun; Ho, I-Cheng

    2012-01-01

    GATA-3, a C2C2 type zinc finger transcription factor, regulates many steps of T cell development and differentiation. It is also required for optimal production of type 2 cytokines by CD8+ T cells. However, its role in the development and function of this subset of T cells is still poorly characterized. Here we report that GATA-3 is required for MHC-mediated positive selection and final maturation of CD8 single positive thymocytes. Deficiency of GATA-3 mediated by a CD4cre transgene led to ag...

  19. GATA4 gene mutation in congenital heart disease%先天性心脏病GATA4基因突变研究进展

    Institute of Scientific and Technical Information of China (English)

    张艳丽

    2015-01-01

    GATA4 gene mutations are common in children with congenital heart disease.More than 120 mutations have been found in ventricular septal defect,atrial septal defects and the tetralogy of fallot.But the relationship between genotype and clinical phenotype has not yet been elucidated.This article summarizes the published germline and somatic mutations of GATA4 gene in human congenital heart disease,and provides insight into the phenotypic spectrum of GATA4 gene mutation.%GATA4基因突变在先天性心脏病患儿中较为常见.目前为止,已发现超过120个突变位点,其中在室间隔缺损、房室间隔缺损或法洛四联症患者中多见,但突变基因型与临床表型间的关系至今仍未阐明.该文总结了在人类先天性心脏病中已发表的GATA4基因突变位点,并绘制出功能性改变的基因突变图谱.

  20. Tyrosine phosphorylation of RACK1 triggers cardiomyocyte hypertrophy by regulating the interaction between p300 and GATA4.

    Science.gov (United States)

    Suzuki, Hidetoshi; Katanasaka, Yasufumi; Sunagawa, Yoichi; Miyazaki, Yusuke; Funamoto, Masafumi; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

    2016-09-01

    The zinc finger protein GATA4 is a transcription factor involved in cardiomyocyte hypertrophy. It forms a functional complex with the intrinsic histone acetyltransferase (HAT) p300. The HAT activity of p300 is required for the acetylation and transcriptional activity of GATA4, as well as for cardiomyocyte hypertrophy and the development of heart failure. In the present study, we have identified Receptor for Activated Protein Kinase C1 (RACK1) as a novel GATA4-binding protein using tandem affinity purification and mass spectrometry analyses. We found that exogenous RACK1 repressed phenylephrine (PE)-induced hypertrophic responses, such as myofibrillar organization, increased cell size, and hypertrophy-associated gene transcription, in cultured cardiomyocytes. RACK1 physically interacted with GATA4 and the overexpression of RACK1 reduced PE-induced formation of the p300/GATA4 complex and the acetylation and DNA binding activity of GATA4. In response to hypertrophic stimulation in cultured cardiomyocytes and in the hearts of hypertensive heart disease model rats, the tyrosine phosphorylation of RACK1 was increased, and the binding between GATA4 and RACK1 was reduced. In addition, the tyrosine phosphorylation of RACK1 was required for the disruption of the RACK1/GATA4 complex and for the formation of the p300/GATA4 complex. These findings demonstrate that RACK1 is involved in p300/GATA4-dependent hypertrophic responses in cardiomyocytes and is a promising therapeutic target for heart failure. PMID:27208796

  1. Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway

    Directory of Open Access Journals (Sweden)

    Giguère Vincent

    2008-06-01

    Full Text Available Abstract Background The transcription factor GATA3 has recently been shown to be necessary for mammary gland morphogenesis and luminal cell differentiation. There is also an increasing body of data linking GATA3 to the estrogen receptor α (ERα pathway. Among these it was shown that GATA3 associates with the promoter of the ERα gene and ERα can reciprocally associate with the GATA3 gene. GATA3 has also been directly implicated in a differentiated phenotype in mouse models of mammary tumourigenesis. The purpose of our study was to compare coexpressed genes, by meta-analysis, of GATA3 and relate these to a similar analysis for ERα to determine the depth of overlap. Results We have used a newly described method of meta-analysis of multiple cancer studies within the Oncomine database, focusing here predominantly upon breast cancer studies. We demonstrate that ERα and GATA3 reciprocally have the highest overlap with one another. Furthermore, we show that when both coexpression meta-analysis lists for ERα and GATA3 are compared there is a significant overlap between both and, like ERα, GATA3 coexpresses with ERα pathway partners such as pS2 (TFF1, TFF3, FOXA1, BCL2, ERBB4, XBP1, NRIP1, IL6ST, keratin 18(KRT18 and cyclin D1 (CCND1. Moreover, as these data are derived from human tumour samples this adds credence to previous cell-culture or murine based studies. Conclusion GATA3 is hypothesized to be integral to the ERα pathway given the following: (1 The large overlap of coexpressed genes as seen by meta-analysis, between GATA3 and ERα, (2 The highest coexpressing gene for GATA3 was ERα and vice-versa, (3 GATA3, like ERα, coexpresses with many well-known ERα pathway partners such as pS2.

  2. Analysis of disease-causing GATA1 mutations in murine gene complementation systems

    OpenAIRE

    Campbell, Amy E.; Wilkinson-White, Lorna; Mackay, Joel P.; Matthews, Jacqueline M.; Blobel, Gerd A.

    2013-01-01

    Disease-causing mutations in GATA1 impair binding to the cofactors FOG1 or TAL1 but not DNA.Different substitutions at the same residue selectively disrupt FOG1 or TAL1 binding leading to distinct disease phenotypes.

  3. GATA-3 REGULATES THE SELF-RENEWAL OF LONG-TERM HEMATOPOIETIC STEM CELLS

    Science.gov (United States)

    Frelin, Catherine; Herrington, Robert; Janmohamed, Salima; Barbara, Mary; Tran, Gary; Paige, Christopher J.; Benveniste, Patricia; Zuñiga-Pflücker, Juan-Carlos; Souabni, Abdallah; Busslinger, Meinrad; Iscove, Norman N

    2016-01-01

    Gata3 is expressed and required for differentiation and function throughout the T lymphocyte lineage. Despite evidence it may also be expressed in multipotent hematopoietic stem cells (HSC), any role in these cells has remained unclear. Here we show GATA3 was cytoplasmic in quiescent long-term stem cells from steady state bone marrow, but relocated to the nucleus when HSC cycle. Relocation depended on p38-MAPK signaling and was associated with diminished capacity for long-term reconstitution upon transfer to irradiated mice. Deletion of Gata3 enhanced repopulating capacity and augmented self-renewal of long term HSC in cell-autonomous fashion, without affecting cell cycle. These observations position Gata3 as a regulator of the balance between self-renewal and differentiation in HSC acting downstream of the p38 signaling pathway. PMID:23974957

  4. Histone demethylase LSD1-mediated repression of GATA-2 is critical for erythroid differentiation

    Directory of Open Access Journals (Sweden)

    Guo Y

    2015-06-01

    Full Text Available Yidi Guo,1 Xueqi Fu,1,2 Yue Jin,1 Jing Sun,1 Ye Liu,1 Bo Huo,1 Xiang Li,1 Xin Hu1–31School of Life Sciences, Jilin University, 2Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University, 3National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of ChinaBackground: The transcription factor GATA-2 is predominantly expressed in hematopoietic stem and progenitor cells and counteracts the erythroid-specific transcription factor GATA-1, to modulate the proliferation and differentiation of hematopoietic cells. During hematopoietic cell differentiation, GATA-2 exhibits dynamic expression patterns, which are regulated by multiple transcription factors.Methods: Stable LSD1-knockdown cell lines were established by growing murine erythroleukemia (MEL or mouse embryonic stem cells together with virus particles, in the presence of Polybrene® at 4 µg/mL, for 24–48 hours followed by puromycin selection (1 µg/mL for 2 weeks. Real-time polymerase chain reaction (PCR-based quantitative chromatin immunoprecipitation (ChIP analysis was used to test whether the TAL1 transcription factor is bound to 1S promoter in the GATA-2 locus or whether LSD1 colocalizes with TAL1 at the 1S promoter. The sequential ChIP assay was utilized to confirm the role of LSD1 in the regulation of H3K4me2 at the GATA-2 locus during erythroid differentiation. Western blot analysis was employed to detect the protein expression. The alamarBlue® assay was used to examine the proliferation of the cells, and the absorbance was monitored at optical density (OD 570 nm and OD 600 nm.Results: In this study, we showed that LSD1 regulates the expression of GATA-2 during erythroid differentiation. Knockdown of LSD1 results in increased GATA-2 expression and inhibits the differentiation of MEL and embryonic stem cells. Furthermore, we demonstrated that LSD1 binds to the 1S promoter of the

  5. GATA-3 EXPRESSION IN PERIPHERAL BLOOD LYMPHOCYTES OF PATIENTS WITH BRONCHIAL ASTHMA

    OpenAIRE

    Mineev, V.N.; L. N. Sorokina; M. A. Nyoma; V. I. Trofimov

    2014-01-01

    The aim of the study is to establish the features of expression of GATA-3 in peripheral lymphocytes from bronchial asthma patients (BA). Material and methods. 10 healthy controls, 15 patients with allergic (atopic) and 15 persons with non-allergic BA were examined. A transcription factor GATA-3 expressed in peripheral lymphocytes was analyzed by Western blot after the lymphocytes were lysed. Preparation of cell lysates, and Western blotting were performed by means of a standard procedure (Ame...

  6. Genome-Wide Organization of GATA1 and TAL1 Determined at High Resolution.

    Science.gov (United States)

    Han, G Celine; Vinayachandran, Vinesh; Bataille, Alain R; Park, Bongsoo; Chan-Salis, Ka Yim; Keller, Cheryl A; Long, Maria; Mahony, Shaun; Hardison, Ross C; Pugh, B Franklin

    2016-01-01

    Erythroid development and differentiation from multiprogenitor cells into red blood cells requires precise transcriptional regulation. Key erythroid transcription factors, GATA1 and TAL1, cooperate, along with other proteins, to regulate many aspects of this process. How GATA1 and TAL1 are juxtaposed along the DNA and their cognate DNA binding site across the mouse genome remains unclear. We applied high-resolution ChIP-exo (chromatin immunoprecipitation followed by 5'-to-3' exonuclease treatment and then massively parallel DNA sequencing) to GATA1 and TAL1 to study their positional organization across the mouse genome during GATA1-dependent maturation. Two complementary methods, MultiGPS and peak pairing, were used to determine high-confidence binding locations by ChIP-exo. We identified ∼10,000 GATA1 and ∼15,000 TAL1 locations, which were essentially confirmed by ChIP-seq (chromatin immunoprecipitation followed by massively parallel DNA sequencing). Of these, ∼4,000 locations were bound by both GATA1 and TAL1. About three-quarters of them were tightly linked to a partial E-box located 7 or 8 bp upstream of a WGATAA motif. Both TAL1 and GATA1 generated distinct characteristic ChIP-exo peaks around WGATAA motifs that reflect their positional arrangement within a complex. We show that TAL1 and GATA1 form a precisely organized complex at a compound motif consisting of a TG 7 or 8 bp upstream of a WGATAA motif across thousands of genomic locations. PMID:26503782

  7. Genome-Wide Organization of GATA1 and TAL1 Determined at High Resolution

    OpenAIRE

    Han, G. Celine; Vinayachandran, Vinesh; Bataille, Alain R.; Park, Bongsoo; Chan-Salis, Ka Yim; Keller, Cheryl A.; Long, Maria; Mahony, Shaun; Hardison, Ross C.; Pugh, B. Franklin

    2015-01-01

    Erythroid development and differentiation from multiprogenitor cells into red blood cells requires precise transcriptional regulation. Key erythroid transcription factors, GATA1 and TAL1, cooperate, along with other proteins, to regulate many aspects of this process. How GATA1 and TAL1 are juxtaposed along the DNA and their cognate DNA binding site across the mouse genome remains unclear. We applied high-resolution ChIP-exo (chromatin immunoprecipitation followed by 5′-to-3′ exonuclease treat...

  8. GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model

    OpenAIRE

    Kouros-Mehr, Hosein; Bechis, Seth K.; Slorach, Euan M.; Littlepage, Laurie E.; Egeblad, Mikala; Ewald, Andrew J.; Pai, Sung-Yun; Ho, I-Cheng; Werb, Zena

    2008-01-01

    How breast cancers are able to disseminate and metastasize is poorly understood. Using hyperplasia transplant system, we show that tumor dissemination and metastasis occur in discrete steps during tumor progression. Bioinformatic analysis revealed that loss of the transcription factor GATA-3 marked progression from adenoma to early carcinoma and onset of tumor dissemination. Restoration of GATA-3 in late carcinomas induced tumor differentiation suppressed tumor dissemination. Targeted deletio...

  9. Cyclic Regulation of T-Bet and GATA-3 in Human Endometrium

    OpenAIRE

    Inman, Danielle; Kawana, Kei; Schust, Danny; Lininger, Ruth; Young, Steven

    2008-01-01

    Endometrial cytokine expression is poorly understood. T-Bet and GATA-3 regulate cytokine expression in T-lymphocytes. Previous work has demonstrated expression of T-Bet in human endometrium. Changes in human endometrial T-Bet and GATA-3 mRNA and protein expression during the normal menstrual cycle were characterized. Human endometrium from each phase of the menstrual cycle underwent real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry to examine expression and lo...

  10. GATA-3 transcriptional imprinting in Th2 lymphocytes: A mathematical model

    OpenAIRE

    Höfer, Thomas; Nathansen, Holger; Löhning, Max; Radbruch, Andreas; Heinrich, Reinhart

    2002-01-01

    Immunological memory involves the fast recall of cytokine expression by T helper (Th) lymphocytes. Two distinct profiles of cytokine expression, Th1 and Th2, can be induced by antigen and polarizing signals during activation of naive Th cells and can subsequently be reexpressed on stimulation by antigen alone. The transcription factor GATA-3 induces Th2 development. GATA-3 is activated by the Th2-polarizing stimulus, IL-4, and has recently been observed to autoactivate it...

  11. An Essential Role of the Transcription Factor GATA-3 for the Function of Regulatory T Cells

    OpenAIRE

    Wang, Yunqi; Su, Maureen A.; Wan, Yisong Y.

    2011-01-01

    Forkhead Box P3 (Foxp3)-expressing regulatory T (Treg) cells are central to maintaining self-tolerance and immune homeostasis. How Treg cell function and Foxp3 expression are regulated is an important question under intensive investigation. Here, we have demonstrated an essential role for the transcription factor GATA-3, a previously recognized Th2 cell master regulator, in controlling Treg cell function. Treg cell-specific GATA-3 deletion led to a spontaneous inflammatory disorder in mice. G...

  12. GATA3 in the urinary bladder: suppression of neoplastic transformation and down-regulation by androgens

    OpenAIRE

    Li, Yi; Ishiguro, Hitoshi; Kawahara, Takashi; Miyamoto, Yurina; Izumi, Koji; Miyamoto, Hiroshi

    2014-01-01

    Recent evidence suggests the involvement of sex hormone receptors in bladder cancer initiation, while precise functions of androgens and estrogens in the carcinogenesis step remain poorly understood. We recently found down-regulation of GATA3, a zinc-finger transcription factor and a new urothelial marker, in bladder cancer, which also correlated with expression status of androgen receptor (AR) and estrogen receptors (ERs). We here assessed whether GATA3 acted as a suppressor of bladder tumor...

  13. Overexpression of the Transcription Factor GATA-3 Enhances the Development of Pulmonary Fibrosis

    OpenAIRE

    Kimura, Toru; Ishii, Yukio; Yoh, Keigyou; Morishima, Yuko; Iizuka, Takashi; Kiwamoto, Takumi; Matsuno, Yosuke; HOMMA, SHINSUKE; Nomura, Akihiro; Sakamoto, Tohru; Takahashi, Satoru; Sekizawa, Kiyohisa

    2006-01-01

    Recent studies have demonstrated that Th2 cytokines, such as interleukin-4 and interleukin-13, enhance fibrotic processes by activating fibroblast proliferation and collagen production, whereas interferon-γ, a Th1 cytokine, inhibits these processes. Th1 and Th2 cells both differentiate from common T precursor cells, with transcription factor GATA-3 a key regulator of Th2 differentiation. In the present study, therefore, we examined the effects of GATA-3 overexpression on the development of pu...

  14. Function of GATA transcription factors in hydroxyurea-induced HEL cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    HEL cells, a human erythroleukemia cell line, mainly express the fetal (γ)globin gene and trace amount of the embryonic (ε)globin gene, but not adult (β) globin gene. Here we show that hydroxyurea (HU) can induce HEL cells to express adult (β) globin gene and lead these cells to terminal differentiation. Results showed in Gel mobility shift assays that GATA factors could specifically bind to the regulatory elements of humanβ- globin gene, including the proximal regulatory element (theβ- promoter) and the distal regulatory elements (the DNase I hypersensitive sites in the LCR, HS2-HS4 core sequences). However, the DNA binding patterns of GATA factors were quite different between HU-induced and uninduced HEL cells. Western-blot analysis of nuclear extracts from both the uninduced and HU- induced HEL cells revealed that the level of GATA-2 transcription factor decreased, whereas the level of GATA-1 transcription factor increased following the time of hydroxyurea induction. Furthermore, using RT-PCR analysis the expression of human β-globin gene in HU-induced HEL cells could be blocked again when HEL cells were incubated in the presence of antisense oligonucleotides for hGATA-1, suggesting that the upregulation of hGATA-1 transcription factor might be critical for the expression of humanβ- globin gene in HU-induced HEL cells.

  15. Dissecting the Relation between a Nuclear Receptor and GATA: Binding Affinity Studies of Thyroid Hormone Receptor and GATA2 on TSHβ Promoter

    OpenAIRE

    Ana Carolina Migliorini Figueira; Igor Polikarpov; Dmitry Veprintsev; Guilherme Martins Santos

    2010-01-01

    BACKGROUND: Much is known about how genes regulated by nuclear receptors (NRs) are switched on in the presence of a ligand. However, the molecular mechanism for gene down-regulation by liganded NRs remains a conundrum. The interaction between two zinc-finger transcription factors, Nuclear Receptor and GATA, was described almost a decade ago as a strategy adopted by the cell to up- or down-regulate gene expression. More recently, cell-based assays have shown that the Zn-finger region of GATA2 ...

  16. Expression of GATA3 in breast tumor and its clinical significance%乳腺肿瘤组织中GATA3的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    程凯; 周晓蝶; 余波; 王海; 周晓军; 石群立

    2015-01-01

    目的:探讨乳腺肿瘤组织中转录因子GATA3的表达及其与临床病理特征的相关性。方法应用免疫组化EnVision两步法检测132例乳腺恶性肿瘤组织、29例乳腺良性肿瘤组织及35例乳腺癌旁组织中GATA3蛋白的表达,并将GATA3的表达与临床病理特征进行对比分析。结果(1)GATA3在正常人乳腺腺腔细胞中表达,乳腺癌组织中GATA3的阳性率为77%;(2)乳腺弥漫性大B细胞淋巴瘤和梭形细胞恶性肿瘤中GATA3不表达;(3) GATA3在三阴型乳腺癌中的阳性率低于其他分子类型乳腺癌(χ2=29.354,P<0.001)。结论 GATA3表达与乳腺肿瘤的病理类型和病理分级相关,可作为乳腺癌鉴别诊断和预后的标志物。%Purpose To investigate the expression of GATA3 in breast tumors and its clinical significance. Methods Immunohisto-chemistry EnVision method was used to detect the expression of GATA3 protein in 132 cases of breast malignant tumor tissue, 29 cases of breast benign tumor tissue, 35 cases of breast carcinoma adjacent tissue. Besides, the GATA3 expression level was compared with several clinicopathological parameters. Result (1) All the breast normal tissues expressed GATA3, while 77% of the breast cancer tissue were found to be GATA3 positive. (2) GATA3 did not expressed in diffuse large B cell lymphoma and spindle cell malignant tumor of breast. (3) In the triple negative breast cancer, the expression of GATA3 was lower than that of any other subtypes of breast carcinoma (χ2 =29. 354, P<0. 001). Conclusion The positive expression of GATA3 is correlated to classification and grade in breast tumor. Detection of the expression of this biological maker may provide a valuable marker for the differential diagnosis and prog-nostic of breast carcinoma.

  17. Multilocus DNA-fingerprinting using oligonucleotide probes (GATA)4 and (GGAT)4 in rainbow trout (Oncorhynchus mykiss)

    OpenAIRE

    Vergara N.; Iturra P.; Aguirre

    1998-01-01

    Oligonucleotide probes (GATA)4 and (GGAT)4 for minisatellite loci produced DNA fingerprinting patterns which are unique in individual rainbow trout. These patterns can be used to monitor the efficiency of manipulation of production characters in gynogenetic individuals. The (GATA)4 probe produced highly individual patterns that differentiated individuals among gynogenetic offspring, and could be easily scored.Probes de oligonucleotídeos (GATA)4 e (GGAT)4 para locos mini-satélites produziram p...

  18. High-Throughput siRNA Screening to Reveal GATA-2 Upstream Transcriptional Mechanisms in Hematopoietic Cells

    OpenAIRE

    Saito, Yo; Fujiwara, Tohru; Ohashi, Keiichi; Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Harigae, Hideo

    2015-01-01

    Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in both hematopoietic stem and progenitor cells and is essential for cell proliferation, survival, and differentiation. Recently, evidence from studies of aplastic anemia, MonoMAC syndrome, and lung cancer has demonstrated a mechanistic link between GATA-2 and human pathophysiology. GATA-2-dependent disease processes have been extensively analyzed; however, the tra...

  19. A loss-of-function and H2B-Venus transcriptional reporter allele for Gata6 in mice

    OpenAIRE

    Freyer, Laina; Schröter, Christian; Saiz, Néstor; Schrode, Nadine; Nowotschin, Sonja; Martinez-Arias, Alfonso; Hadjantonakis, Anna-Katerina

    2015-01-01

    Background The GATA-binding factor 6 (Gata6) gene encodes a zinc finger transcription factor that often functions as a key regulator of lineage specification during development. It is the earliest known marker of the primitive endoderm lineage in the mammalian blastocyst. During gastrulation, GATA6 is expressed in early cardiac mesoderm and definitive endoderm progenitors, and is necessary for development of specific mesoderm and endoderm-derived organs including the heart, liver, and pancrea...

  20. Critical Role for GATA3 in Mediating Tie2 Expression and Function in Large Vessel Endothelial Cells*

    OpenAIRE

    Song, Haihua; Suehiro, Jun-ichi; Kanki, Yasuharu; Kawai, Yoshiko; Inoue, Kenji; Daida, Hiroyuki; Yano, Kiichiro; Ohhashi, Toshio; Oettgen, Peter; Aird, William C; Kodama, Tatsuhiko; Minami, Takashi

    2009-01-01

    Endothelial phenotypes are highly regulated in space and time by both transcriptional and post-transcriptional mechanisms. There is increasing evidence that the GATA family of transcription factors function as signal transducers, coupling changes in the extracellular environment to changes in downstream target gene expression. Here we show that human primary endothelial cells derived from large blood vessels express GATA2, -3, and -6. Of these factors, GATA3 was expressed at the highest level...

  1. Localization of Distant Urogenital System-, Central Nervous System-, and Endocardium-Specific Transcriptional Regulatory Elements in the GATA-3 Locus

    OpenAIRE

    Lakshmanan, Ganesh; Lieuw, Ken H.; Lim, Kim-Chew; Gu, Yi; Grosveld, Frank; Engel, James Douglas; Karis, Alar

    1999-01-01

    We found previously that neither a 6-kbp promoter fragment nor even a 120-kbp yeast artificial chromosome (YAC) containing the whole GATA-3 gene was sufficient to recapitulate its full transcription pattern during embryonic development in transgenic mice. In an attempt to further identify tissue-specific regulatory elements modulating the dynamic embryonic pattern of the GATA-3 gene, we have examined the expression of two much larger (540- and 625-kbp) GATA-3 YACs in transgenic animals. A lac...

  2. Treatment of Allergic Airway Inflammation and Hyperresponsiveness by Antisense-Induced Local Blockade of Gata-3 Expression

    OpenAIRE

    Finotto, Susetta; De Sanctis, George T.; Lehr, Hans A.; Herz, Udo; Buerke, Michael; Schipp, Mechthild; Bartsch, Brigitte; Atreya, Raja; Schmitt, Edgar; Peter R. Galle; Renz, Harald; Neurath, Markus F

    2001-01-01

    Recent studies in transgenic mice have revealed that expression of a dominant negative form of the transcription factor GATA-3 in T cells can prevent T helper cell type 2 (Th2)-mediated allergic airway inflammation in mice. However, it remains unclear whether GATA-3 plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of GATA-3 can be used for the therapy of allergic airway inflammation and hyperresponsiveness. Here, we ana...

  3. Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development

    OpenAIRE

    Pimanda, John E; Ottersbach, Katrin; Knezevic, Kathy; Kinston, Sarah; Chan, Wan Y.I.; Wilson, Nicola K; Landry, Josette-Renée; Wood, Andrew D.; Kolb-Kokocinski, Anja; Green, Anthony R.; Tannahill, David; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold

    2007-01-01

    Conservation of the vertebrate body plan has been attributed to the evolutionary stability of gene-regulatory networks (GRNs). We describe a regulatory circuit made up of Gata2, Fli1, and Scl/Tal1 and their enhancers, Gata2-3, Fli1+12, and Scl+19, that operates during specification of hematopoiesis in the mouse embryo. We show that the Fli1+12 enhancer, like the Gata2-3 and Scl+19 enhancers, targets hematopoietic stem cells (HSCs) and relies on a combination of Ets, Gata, and E-Box motifs. We...

  4. The Diagnostic Value of Transcription Factors T-bet/GATA3 Ratio in Predicting Antibody-Mediated Rejection

    OpenAIRE

    Xue Li; Qiquan Sun; Mingchao Zhang; Jinsong Chen; Zhihong Liu

    2013-01-01

    Background. Previous data showed that the predominance of intraglomerular T-bet or GATA3 is correlated with different mechanisms of rejection, suggesting that the ratio of T-bet/GATA3 might be used to distinguish antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR). Methods. We compared the intraglomerular T-bet/GATA3 ratio in ABMR and TCMR. The intragraft expression of T-bet and GATA3 was studied via immunohistochemistry. The correlation of the diagnosis of AMR with the ra...

  5. GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation

    OpenAIRE

    Ho, I-Cheng; Tai, Tzong-Shyuan; Pai, Sung-Yun

    2009-01-01

    Many advances in our understanding of the molecules that regulate the development, differentiation and function of T cells have been made over the past few years. One important regulator of T-cell differentiation is the transcription factor GATA3 (GATA-binding protein 3). Although the main function of GATA3 is to act as a master transcription factor for the differentiation of T helper 2 (TH2) cells, new research has helped to uncover crucial functions of GATA3 in T cells that go beyond TH2-ce...

  6. Mast cell diversion of T-lineage precursor cells by the essential T-lineage transcription factor GATA-3

    OpenAIRE

    Taghon, Tom; Yui, Mary A.; Rothenberg, Ellen V.

    2007-01-01

    GATA-3 is essential for T cell development from the earliest stages. However, highly abundant GATA-3 can drive T-lineage precursors to a non-T fate, depending on Notch signaling and developmental stage. GATA-3 overexpression blocked pro-T cell survival when Notch-Delta signals were present, but enhanced viability in their absence. In double-negative (DN1) and DN2 but not DN3 fetal thymocytes, GATA-3 overexpression rapidly induced mast cell lineage respecification with high frequency by direct...

  7. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents.

    Science.gov (United States)

    Wlodarski, Marcin W; Hirabayashi, Shinsuke; Pastor, Victor; Starý, Jan; Hasle, Henrik; Masetti, Riccardo; Dworzak, Michael; Schmugge, Markus; van den Heuvel-Eibrink, Marry; Ussowicz, Marek; De Moerloose, Barbara; Catala, Albert; Smith, Owen P; Sedlacek, Petr; Lankester, Arjan C; Zecca, Marco; Bordon, Victoria; Matthes-Martin, Susanne; Abrahamsson, Jonas; Kühl, Jörn Sven; Sykora, Karl-Walter; Albert, Michael H; Przychodzien, Bartlomiej; Maciejewski, Jaroslaw P; Schwarz, Stephan; Göhring, Gudrun; Schlegelberger, Brigitte; Cseh, Annámaria; Noellke, Peter; Yoshimi, Ayami; Locatelli, Franco; Baumann, Irith; Strahm, Brigitte; Niemeyer, Charlotte M

    2016-03-17

    Germline GATA2 mutations cause cellular deficiencies with high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia. Mutation carriers were older at diagnosis and more likely to present with monosomy 7 and advanced disease compared with wild-type cases. For stratified analysis according to karyotype, 108 additional primary MDS patients registered with EWOG-MDS were studied. Overall, we identified 57 MDS patients with germline GATA2 mutations. GATA2 mutations were highly prevalent among patients with monosomy 7 (37%, all ages) reaching its peak in adolescence (72% of adolescents with monosomy 7). Unexpectedly, monocytosis was more frequent in GATA2-mutated patients. However, when adjusted for the selection bias from monosomy 7, mutational status had no effect on the hematologic phenotype. Finally, overall survival and outcome of hematopoietic stem cell transplantation (HSCT) were not influenced by mutational status. This study identifies GATA2 mutations as the most common germline defect predisposing to pediatric MDS with a very high prevalence in adolescents with monosomy 7. GATA2 mutations do not confer poor prognosis in childhood MDS. However, the high risk for progression to advanced disease must guide decision-making toward timely HSCT. PMID:26702063

  8. GATA-1 and c-myb crosstalk during red blood cell differentiation through GATA-1 binding sites in the c-myb promoter

    Czech Academy of Sciences Publication Activity Database

    Bartůněk, Petr; Králová, Jarmila; Blendiger, G.; Dvořák, Michal; Zenke, M.

    2003-01-01

    Roč. 22, č. 13 (2003), s. 1927-1935. ISSN 0950-9232 R&D Projects: GA ČR GV301/98/K042 Institutional research plan: CEZ:AV0Z5052915 Keywords : GATA-1 * c-myb * erythropoiesis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.495, year: 2003

  9. Disruption of a GATA4/Ankrd1 signaling axis in cardiomyocytes leads to sarcomere disarray: implications for anthracycline cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Billy Chen

    Full Text Available Doxorubicin (Adriamycin is an effective anti-cancer drug, but its clinical usage is limited by a dose-dependent cardiotoxicity characterized by widespread sarcomere disarray and loss of myofilaments. Cardiac ankyrin repeat protein (CARP, ANKRD1 is a transcriptional regulatory protein that is extremely susceptible to doxorubicin; however, the mechanism(s of doxorubicin-induced CARP depletion and its specific role in cardiomyocytes have not been completely defined. We report that doxorubicin treatment in cardiomyocytes resulted in inhibition of CARP transcription, depletion of CARP protein levels, inhibition of myofilament gene transcription, and marked sarcomere disarray. Knockdown of CARP with small interfering RNA (siRNA similarly inhibited myofilament gene transcription and disrupted cardiomyocyte sarcomere structure. Adenoviral overexpression of CARP, however, was unable to rescue the doxorubicin-induced sarcomere disarray phenotype. Doxorubicin also induced depletion of the cardiac transcription factor GATA4 in cardiomyocytes. CARP expression is regulated in part by GATA4, prompting us to examine the relationship between GATA4 and CARP in cardiomyocytes. We show in co-transfection experiments that GATA4 operates upstream of CARP by activating the proximal CARP promoter. GATA4-siRNA knockdown in cardiomyocytes inhibited CARP expression and myofilament gene transcription, and induced extensive sarcomere disarray. Adenoviral overexpression of GATA4 (AdV-GATA4 in cardiomyocytes prior to doxorubicin exposure maintained GATA4 levels, modestly restored CARP levels, and attenuated sarcomere disarray. Interestingly, siRNA-mediated depletion of CARP completely abolished the Adv-GATA4 rescue of the doxorubicin-induced sarcomere phenotype. These data demonstrate co-dependent roles for GATA4 and CARP in regulating sarcomere gene expression and maintaining sarcomeric organization in cardiomyocytes in culture. The data further suggests that concurrent

  10. KLF1 stabilizes GATA-1 and TAL1 occupancy in the human β-globin locus.

    Science.gov (United States)

    Kang, Yujin; Kim, Yea Woon; Yun, Jangmi; Shin, Jongo; Kim, AeRi

    2015-03-01

    KLF1 is an erythroid specific transcription factor that binds to regulatory regions of erythroid genes. Binding sites of KLF1 are often found near binding sites of GATA-1 and TAL1. In the β-globin locus, KLF1 is required for forming active chromatin structure, although its role is unclear. To explore the role of KLF1 in transcribing the human γ-globin genes, we stably reduced the expression of KLF1 in erythroid K562 cells, compromising its association in the β-globin locus. The γ-globin transcription was reduced with disappearance of active chromatin structure of the locus in the KLF1 knockdown cells. Interestingly, GATA-1 and TAL1 binding was reduced in the β-globin locus, even though their expressions were not affected by KLF1 knockdown. The KLF1-dependent GATA-1 and TAL1 binding was observed in the adult locus transcribing the β-globin gene and in several erythroid genes, where GATA-1 occupancy is independent from TAL1. These results indicate that KLF1 plays a role in facilitating and/or stabilizing GATA-1 and TAL1 occupancy in the erythroid genes, contributing to the generation of active chromatin structure such as histone acetylation and chromatin looping. PMID:25528728

  11. Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders.

    Science.gov (United States)

    Wakabayashi, Aoi; Ulirsch, Jacob C; Ludwig, Leif S; Fiorini, Claudia; Yasuda, Makiko; Choudhuri, Avik; McDonel, Patrick; Zon, Leonard I; Sankaran, Vijay G

    2016-04-19

    Whole-exome sequencing has been incredibly successful in identifying causal genetic variants and has revealed a number of novel genes associated with blood and other diseases. One limitation of this approach is that it overlooks mutations in noncoding regulatory elements. Furthermore, the mechanisms by which mutations in transcriptionalcis-regulatory elements result in disease remain poorly understood. Here we used CRISPR/Cas9 genome editing to interrogate three such elements harboring mutations in human erythroid disorders, which in all cases are predicted to disrupt a canonical binding motif for the hematopoietic transcription factor GATA1. Deletions of as few as two to four nucleotides resulted in a substantial decrease (>80%) in target gene expression. Isolated deletions of the canonical GATA1 binding motif completely abrogated binding of the cofactor TAL1, which binds to a separate motif. Having verified the functionality of these three GATA1 motifs, we demonstrate strong evolutionary conservation of GATA1 motifs in regulatory elements proximal to other genes implicated in erythroid disorders, and show that targeted disruption of such elements results in altered gene expression. By modeling transcription factor binding patterns, we show that multiple transcription factors are associated with erythroid gene expression, and have created predictive maps modeling putative disruptions of their binding sites at key regulatory elements. Our study provides insight into GATA1 transcriptional activity and may prove a useful resource for investigating the pathogenicity of noncoding variants in human erythroid disorders. PMID:27044088

  12. Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell.

    Science.gov (United States)

    Ushijima, Hironori; Horyozaki, Akiko; Maeda, Masatomo

    2016-09-01

    Transcription factor GATA-6 plays a key role in normal cell differentiation of the mesoderm and endoderm. On the other hand, GATA-6 is abnormally overexpressed in many clinical gastrointestinal cancer tissue samples, and accelerates cell proliferation or an anti-apoptotic response in cancerous tissues. We previously showed that activation of the JNK signaling cascade causes proteolysis of GATA-6. In this study, we demonstrated that anisomycin, a JNK activator, stimulates nuclear export of GATA-6 in a colorectal cancer cell line, DLD-1. Concomitantly, anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest in a plate culture. However, it did not induce apoptosis under growth arrest conditions. Furthermore, the growth of DLD-1 cells in a spheroid culture was suppressed by anisomycin. Although 5-FU showed only a slight inhibitory effect on 3D spheroid cultures, the same concentration of 5-FU together with a low concentration of anisomycin exhibited strong growth inhibition. These results suggest that the induction of GATA-6 dysfunction may be more effective for chemotherapy for colorectal cancer, although the mechanism underlying the synergistic effect of 5-FU and anisomycin remains unknown. PMID:27404124

  13. Gata3 Hypomorphic Mutant Mice Rescued with a Yeast Artificial Chromosome Transgene Suffer a Glomerular Mesangial Cell Defect.

    Science.gov (United States)

    Moriguchi, Takashi; Yu, Lei; Otsuki, Akihito; Ainoya, Keiko; Lim, Kim-Chew; Yamamoto, Masayuki; Engel, James Douglas

    2016-09-01

    GATA3 is a zinc finger transcription factor that plays a crucial role in embryonic kidney development, while its precise functions in the adult kidney remain largely unexplored. Here, we demonstrate that GATA3 is specifically expressed in glomerular mesangial cells and plays a critical role in the maintenance of renal glomerular function. Newly generated Gata3 hypomorphic mutant mice exhibited neonatal lethality associated with severe renal hypoplasia. Normal kidney size was restored by breeding the hypomorphic mutant with a rescuing transgenic mouse line bearing a 662-kb Gata3 yeast artificial chromosome (YAC), and these animals (termed G3YR mice) survived to adulthood. However, most of the G3YR mice showed degenerative changes in glomerular mesangial cells, which deteriorated progressively during postnatal development. Consequently, the G3YR adult mice suffered severe renal failure. We found that the 662-kb Gata3 YAC transgene recapitulated Gata3 expression in the renal tubules but failed to direct sufficient GATA3 activity to mesangial cells. Renal glomeruli of the G3YR mice had significantly reduced amounts of platelet-derived growth factor receptor (PDGFR), which is known to participate in the development and maintenance of glomerular mesangial cells. These results demonstrate a critical role for GATA3 in the maintenance of mesangial cells and its absolute requirement for prevention of glomerular disease. PMID:27296697

  14. High-Throughput siRNA Screening to Reveal GATA-2 Upstream Transcriptional Mechanisms in Hematopoietic Cells.

    Directory of Open Access Journals (Sweden)

    Yo Saito

    Full Text Available Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in both hematopoietic stem and progenitor cells and is essential for cell proliferation, survival, and differentiation. Recently, evidence from studies of aplastic anemia, MonoMAC syndrome, and lung cancer has demonstrated a mechanistic link between GATA-2 and human pathophysiology. GATA-2-dependent disease processes have been extensively analyzed; however, the transcriptional mechanisms upstream of GATA-2 remain less understood. Here, we conducted high-throughput small-interfering-RNA (siRNA library screening and showed that YN-1, a human erythroleukemia cell line, expressed high levels of GATA-2 following the activation of the hematopoietic-specific 1S promoter. As transient luciferase reporter assay in YN-1 cells revealed the highest promoter activity in the 1S promoter fused with GATA-2 intronic enhancer (+9.9 kb/1S; therefore, we established a cell line capable of stably expressing +9.9 kb/1S-Luciferase. Subsequently, we screened 995 transcription factor genes and revealed that CITED2 acts as a GATA-2 activator in human hematopoietic cells. These results provide novel insights into and further identify the regulatory mechanism of GATA-2.

  15. The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma

    Science.gov (United States)

    The transcription factor GATA3 is crucial for the differentiation of naive CD4+ T cells into T helper 2 (Th2) cells. Here, we show that deletion of Gata3 allowed the appearance of interferon-g (IFN-g)-producing cells in the absence of interleukin-12 (IL-12) and IFN-g. Such IFN-g production was tra...

  16. The GATA3 gene is involved in leprosy susceptibility in Brazilian patients.

    Science.gov (United States)

    Medeiros, Priscila; da Silva, Weber Laurentino; de Oliveira Gimenez, Bruna Beatriz; Vallezi, Keren Bastos; Moraes, Milton Ozório; de Souza, Vânia Niéto Brito; Latini, Ana Carla Pereira

    2016-04-01

    Leprosy outcome is a complex trait and the host-pathogen-environment interaction defines the emergence of the disease. Host genetic risk factors have been successfully associated to leprosy. The 10p13 chromosomal region was linked to leprosy in familial studies and GATA3 gene is a strong candidate to be part of this association. Here, we tested tag single nucleotide polymorphisms at GATA3 in two case-control samples from Brazil comprising a total of 1633 individuals using stepwise strategy. The A allele of rs10905284 marker was associated with leprosy resistance. Then, a functional analysis was conducted and showed that individuals carrying AA genotype express higher levels of GATA-3 protein in lymphocytes. So, we confirmed that the rs10905284 is a locus associated to leprosy and influences the levels of this transcription factor in the Brazilian population. PMID:26807920

  17. Expression patterns of GATA3 and the androgen receptor are strongly correlated in patients with triple-negative breast cancer.

    Science.gov (United States)

    Kim, Sewha; Moon, Byung-In; Lim, Woosung; Park, Sanghui; Cho, Min Sun; Sung, Sun Hee

    2016-09-01

    GATA-binding protein 3 (GATA3) is a diagnostically useful immunohistochemical marker of breast cancer. Because of its strong association with estrogen receptor expression, GATA3 has markedly reduced sensitivity in triple-negative breast cancer (TNBC). We constructed a tissue microarray using a large series of TNBCs and evaluated GATA3 expression by TNBC subtype as defined by surrogate immunohistochemical markers. A total of 205 TNBCs were classified into cancers of the molecular apocrine type (n=23, 11.2%), claudin-low type (n=21, 10.2%), basal-like type (n=91, 44.4%), mixed type (n=62, 30.2%), and null type (n=8, 3.9%). The GATA3 scores (staining intensity × proportion) were categorized as negative (0), focally positive (1-10), or positive (11-300). GATA3 staining was negative in 153 cancers (74.6%), focally positive in 11 (5.4%), and positive in 41 (20.0%). The rate of focal positivity or positivity for GATA3 was significantly higher in the molecular apocrine type (73.9%, 17/23) than in other types of TNBCs (P=.001). The mean GATA3 score of molecular apocrine-type TNBC was significantly higher than that of the other types (P=.001) and differed significantly between androgen receptor (AR)-positive and AR-negative TNBCs (P<.001). In conclusion, GATA3 expression was correlated strongly with AR-positive, molecular apocrine-type TNBCs. Co-expression of AR and GATA3 is a specific feature of molecular apocrine-type TNBC, which may serve as a diagnostic aid for cancer of unknown primary. PMID:27184484

  18. GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes

    Directory of Open Access Journals (Sweden)

    Lamartine Jérôme

    2009-09-01

    Full Text Available Abstract Background The general population is constantly exposed to low levels of radiation through natural, occupational or medical irradiation. Even if the biological effects of low-level radiation have been intensely debated and investigated, the molecular mechanisms underlying the cellular response to low doses remain largely unknown. Results The present study investigated the role of GATA3 protein in the control of the cellular and molecular response of human keratinocytes exposed to a 1 cGy dose of X-rays. Chromatin immunoprecipitation showed GATA3 to be able to bind the promoter of 4 genes responding to a 1 cGy exposure. To go further into the role of GATA3 after ionizing radiation exposure, we studied the cellular and molecular consequences of radiation in GATA3 knock-down cells. Knock-down was obtained by lentiviral-mediated expression of an shRNA targeting the GATA3 transcript in differentiated keratinocytes. First, radiosensitivity was assessed: the toxicity, in terms of immediate survival (with XTT test, associated with 1 cGy radiation was found to be increased in GATA3 knock-down cells. The impact of GATA3 knock-down on the transcriptome of X-ray irradiated cells was also investigated, using oligonucleotide microarrays to assess changes between 3 h and 72 h post-irradiation in normal vs GATA3 knock-down backgrounds; transcriptome response was found to be completely altered in GATA3 knock-down cells, with a strong induction/repression peak 48 h after irradiation. Functional annotation revealed enrichment in genes known to be involved in chaperone activity, TGFβ signalling and stress response. Conclusion Taken together, these data indicate that GATA3 is an important regulator of the cellular and molecular response of epidermal cells to very low doses of radiation.

  19. GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes

    International Nuclear Information System (INIS)

    Background: The general population is constantly exposed to low levels of radiation through natural, occupational or medical irradiation. Even if the biological effects of low-level radiation have been intensely debated and investigated, the molecular mechanisms underlying the cellular response to low doses remain largely unknown. Results: The present study investigated the role of GATA3 protein in the control of the cellular and molecular response of human keratinocytes exposed to a 1 cGy dose of X-rays. Chromatin immunoprecipitation showed GATA3 to be able to bind the promoter of 4 genes responding to a 1 cGy exposure. To go further into the role of GATA3 after ionizing radiation exposure, we studied the cellular and molecular consequences of radiation in GATA3 knock-down cells. Knockdown was obtained by lentiviral-mediated expression of an shRNA targeting the GATA3 transcript in differentiated keratinocytes. First, radiosensitivity was assessed: the toxicity, in terms of immediate survival (with XTT test), associated with 1 cGy radiation was found to be increased in GATA3 knock-down cells. The impact of GATA3 knock-down on the transcriptome of X-ray irradiated cells was also investigated, using oligonucleotide micro-arrays to assess changes between 3 h and 72 h post-irradiation in normal vs GATA3 knock-down backgrounds; transcriptome response was found to be completely altered in GATA3 knock-down cells, with a strong induction/repression peak 48 h after irradiation. Functional annotation revealed enrichment in genes known to be involved in chaperone activity, TGFβ signalling and stress response. Conclusion: Taken together, these data indicate that GATA3 is an important regulator of the cellular and molecular response of epidermal cells to very low doses of radiation. (authors)

  20. GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bonin, F.; Molina, M.; Berthier-Vergnes, O.; Lamartine, J. [Universite de Lyon, Lyon, F-69003 (France); Universite Lyon 1, Lyon, F-69003 (France); CNRS, UMR5534, Centre de Genetique Moleculaire et Cellulaire, Villeurbanne, F-69622 (France); Malet, C.; Ginestet, C. [Centre Leon Berard, Service de Radiotherapie, Lyon F-69008 (France); Martin, M.T. [Laboratoire de Genomique et Radiobiologie de la Keratinopoiese, CEA, IRCM, Evry F-91000 (France)

    2009-07-01

    Background: The general population is constantly exposed to low levels of radiation through natural, occupational or medical irradiation. Even if the biological effects of low-level radiation have been intensely debated and investigated, the molecular mechanisms underlying the cellular response to low doses remain largely unknown. Results: The present study investigated the role of GATA3 protein in the control of the cellular and molecular response of human keratinocytes exposed to a 1 cGy dose of X-rays. Chromatin immunoprecipitation showed GATA3 to be able to bind the promoter of 4 genes responding to a 1 cGy exposure. To go further into the role of GATA3 after ionizing radiation exposure, we studied the cellular and molecular consequences of radiation in GATA3 knock-down cells. Knockdown was obtained by lentiviral-mediated expression of an shRNA targeting the GATA3 transcript in differentiated keratinocytes. First, radiosensitivity was assessed: the toxicity, in terms of immediate survival (with XTT test), associated with 1 cGy radiation was found to be increased in GATA3 knock-down cells. The impact of GATA3 knock-down on the transcriptome of X-ray irradiated cells was also investigated, using oligonucleotide micro-arrays to assess changes between 3 h and 72 h post-irradiation in normal vs GATA3 knock-down backgrounds; transcriptome response was found to be completely altered in GATA3 knock-down cells, with a strong induction/repression peak 48 h after irradiation. Functional annotation revealed enrichment in genes known to be involved in chaperone activity, TGF{beta} signalling and stress response. Conclusion: Taken together, these data indicate that GATA3 is an important regulator of the cellular and molecular response of epidermal cells to very low doses of radiation. (authors)

  1. NK Cell-Specific Gata3 Ablation Identifies the Maturation Program Required for Bone Marrow Exit and Control of Proliferation.

    Science.gov (United States)

    Ali, Alaa Kassim; Oh, Jun Seok; Vivier, Eric; Busslinger, Meinrad; Lee, Seung-Hwan

    2016-02-15

    NK cells are innate lymphocytes capable of eliciting an innate immune response to pathogens. NK cells develop and become mature in the bone marrow (BM) before they migrate out to peripheral organs. Although the developmental program leading to mature NK cells has been studied in the context of several transcription factors, the stage-specific role of GATA3 in NK cell development has been incompletely understood. Using NKp46-Cre-Gata3(fl/fl) mice in which Gata3 deficiency was induced as early as the immature stage of NK cell differentiation, we demonstrated that GATA3 is required for the NK cell maturation beyond the CD27 single-positive stage and is indispensable for the maintenance of liver-resident NK cells. The frequencies of NK cells from NKp46-Cre-Gata3(fl/fl) mice were found higher in the BM but lower in peripheral organs compared with control littermates, indicating that GATA3 controls the maturation program required for BM egress. Despite the defect in maturation, upon murine CMV infection, NK cells from NKp46-Cre-Gata3(fl/fl) mice expanded vigorously, achieving NK cell frequencies surpassing those in controls and therefore provided comparable protection. The heightened proliferation of NK cells from NKp46-Cre-Gata3(fl/fl) mice was cell intrinsic and associated with enhanced upregulation of CD25 expression. Taken together, our results demonstrate that GATA3 is a critical regulator for NK cell terminal maturation and egress out of the BM and that immature NK cells present in the periphery of NKp46-Cre-Gata3(fl/fl) mice can rapidly expand and provide a reservoir of NK cells capable of mounting an efficient cytotoxic response upon virus infection. PMID:26773150

  2. Characterization of transcription factors binding to-120 GATA motif of rat βbminy-globin promoter

    OpenAIRE

    Pavlović Sonja T.; Mitrović Tatjana; Karan-Đurašević Teodora; Nikčević Gordana T.

    2005-01-01

    The aim of this study was to elucidate the regulation of rat adult βbminy-globin gene transcription. We used DNasel foot printing, gel mobility shift and super shift assays to characterize transcription factors involved in this regulation. In this study we analyzed GATA motif at-120 bp in the distal promoter of βbminy-globin gene. Footprint analysis revealed the binding of nuclear factors from MEL cells to the GATA motif. By using gel mobility shift assay two protein complexes were detected. ...

  3. Displasia cística mamária em uma gata

    OpenAIRE

    Cartagna Lúcia Maria; Irigoyen Luiz Francisco; Fighera Rafael Almeida; Souza Tatiana Mello de

    2005-01-01

    Displasia cística mamária ou mastose é uma rara condição que afeta gatas adultas ou idosas. O presente relato descreve um caso de displasia cística mamária diagnosticado em uma gata sem raça definida de sete anos de idade, com histórico clínico de aumento de volume mamário generalizado por mais de um ano. O diagnóstico foi realizado com base nos achados clínicos, citopatológicos e histopatológicos.

  4. Critical role of p38 and GATA3 in natural helper cell function1

    OpenAIRE

    Furusawa, Jun-Ichi; Moro, Kazuyo; Motomura, Yasutaka; Okamoto, Kazuo; Zhu, Jinfang; Takayanagi, Hiroshi; Kubo, Masato; Koyasu, Shigeo

    2013-01-01

    Natural helper (NH) cells, a member of Lin−IL-2R+IL-7R+IL-25R+IL-33R+GATA3+ group 2 innate lymphoid cell subset, are characterized by the expression of transcription factors GATA3 and RORα and production of large amounts of Th2 cytokines such as IL-5, IL-6 and IL-13 upon IL-33 stimulation or a combination of IL-2 and IL-25. We studied in this paper the signal transduction pathway(s) critical for the cytokine expression and development of NH cell. Either stimulation with IL-33 or a combination...

  5. Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    GATA-5, a zinc-finger transcription factor and member of the GATA family proteins 1–6, is known to be involved in cellular differentiation. We recently found that tumor-specific hypermethylation of the GATA5 CpG island (CGI) occurs in renal cell carcinoma (RCC) and is associated with an adverse clinical outcome. In this study, we investigated whether epigenetic GATA5 alterations may result in changes in GATA5 mRNA expression levels and correlate with the observed prognostic impact of epigenetic changes in GATA5 in RCC. Quantitative real-time reverse-transcribed polymerase chain reaction was applied to measure relative GATA5 mRNA expression levels in 135 kidney tissue samples, including 77 clear cell RCC (ccRCC) tissues and 58 paired adjacent normal renal tissue samples. Relative GATA5 expression levels were determined using the ΔΔCt method and detection of three endogenous control genes then compared to previously measured values of relative methylation. The mean relative GATA5 mRNA expression level exhibited an approximately 31-fold reduction in tumor specimens compared with corresponding normal tissues (p < 0.001, paired t-test). Decreased GATA5 mRNA expression was inversely correlated with increased GATA5 CGI methylation (p < 0.001) and was associated with shortened recurrence-free survival in ccRCC patients (p = 0.023, hazard ratio = 0.25). GATA5 mRNA expression is decreased in ccRCC, likely due to gene silencing by methylation of the GATA5 CGI. Moreover, reduced GATA5 mRNA levels were associated with a poor clinical outcome, indicating a possible role of GATA5 for the development of aggressive ccRCC phenotypes

  6. Structural basis of simultaneous recruitment of the transcriptional regulators LMO2 and FOG1/ZFPM1 by the transcription factor GATA1

    OpenAIRE

    Wilkinson-White, Lorna; Gamsjaeger, Roland; Dastmalchi, Siavoush; Wienert, Beeke; Stokes, Philippa H.; Crossley, Merlin; Mackay, Joel P.; Matthews, Jacqueline M.

    2011-01-01

    The control of red blood cell and megakaryocyte development by the regulatory protein GATA1 is a paradigm for transcriptional regulation of gene expression in cell lineage differentiation and maturation. Most GATA1-regulated events require GATA1 to bind FOG1, and essentially all GATA1-activated genes are cooccupied by a TAL1/E2A/LMO2/LDB1 complex; however, it is not known whether FOG1 and TAL1/E2A/LMO2/LDB1 are simultaneously recruited by GATA1. Our structural data reveal that the FOG1-bindin...

  7. c-Myb and GATA-3 cooperatively regulate IL-13 expression via CGRE and recruit MLL for histone modification of the IL-13 locus

    OpenAIRE

    Kozuka, Teruhiko; Sugita, Mayumi; Shetzline, Susan; Gewirtz, Alan M.; Nakata, Yuji

    2011-01-01

    The c-Myb and GATA-3 transcription factors play important roles in T-cell development. We recently reported that c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression and ultimately Th2 cell development in human peripheral blood T-cells. However, c-Myb roles for Th2 cytokine expression were not demonstrated. Here, we report that c-Myb and GATA-3 cooperatively play an essential role in IL-13 expression though direct binding to a conserved GATA-3 response e...

  8. Gata1 expression driven by the alternative HS2 enhancer in the spleen rescues the hematopoietic failure induced by the hypomorphic Gata1low mutation

    OpenAIRE

    Migliaccio, Anna Rita; Martelli, Fabrizio; Verrucci, Maria; Sanchez, Massimo; Valeri, Mauro; Migliaccio, Giovanni; Vannucchi, Alessandro Maria; Zingariello, Maria; Di Baldassarre, Angela; Ghinassi, Barbara; Rana, Rosa Alba; van Hensbergen, Yvette; Fibbe, Willem E.

    2009-01-01

    Rigorously defined reconstitution assays developed in recent years have allowed recognition of the delicate relationship that exists between hematopoietic stem cells and their niches. This balance ensures that hematopoiesis occurs in the marrow under steady-state conditions. However, during development, recovery from hematopoietic stress and in myeloproliferative disorders, hematopoiesis occurs in extramedullary sites whose microenvironments are still poorly defined. The hypomorphic Gata1low ...

  9. Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome.

    Science.gov (United States)

    Nováková, Michaela; Žaliová, Markéta; Suková, Martina; Wlodarski, Marcin; Janda, Aleš; Froňková, Eva; Campr, Vít; Lejhancová, Kateřina; Zapletal, Ondřej; Pospíšilová, Dagmar; Černá, Zdeňka; Kuhn, Tomáš; Švec, Peter; Pelková, Vendula; Zemanová, Zuzana; Kerndrup, Gitte; van den Heuvel-Eibrink, Marry; van der Velden, Vincent; Niemeyer, Charlotte; Kalina, Tomáš; Trka, Jan; Starý, Jan; Hrušák, Ondřej; Mejstříková, Ester

    2016-06-01

    GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. In GATA-2-deficient cases, we found the most profound B-cell lymphopenia, including its progenitors in blood and bone marrow, which correlated with significantly diminished intronRSS-Kde recombination excision circles in comparison to other myelodysplastic syndrome/aplastic anemia cases. The other typical features of GATA-2 deficiency (monocytopenia and natural killer cell lymphopenia) were less discriminative. In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B-cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naïve cells). PMID:27013649

  10. Prevalence, clinical characteristics and prognosis of GATA2-related myelodysplastic syndromes (MDS) in children and adolescents

    DEFF Research Database (Denmark)

    Wlodarski, Marcin W; Hirabayashi, Shinsuke; Pastor, Victor; Starý, Jan; Hasle, Henrik; Masetti, Riccardo; Dworzak, Michael; Schmugge, Markus; van den Heuvel-Eibrink, Marry; Ussowicz, Marek; De Moerloose, Barbara; Catala, Albert; Smith, Owen P; Sedlacek, Petr; Lankester, Arjan C; Zecca, Marco; Bordon, Victoria; Matthes-Martin, Susanne; Abrahamsson, Jonas; Kühl, Jörn Sven; Sykora, Karl-Walter; Albert, Michael H; Przychodzien, Bartlomiej; Maciejewski, Jaroslaw; Schwarz, Stephan; Göhring, Gudrun; Schlegelberger, Brigitte; Cseh, Annámaria; Noellke, Peter; Yoshimi, Ayami; Locatelli, Franco; Baumann, Irith; Strahm, Brigitte; Niemeyer, Charlotte M

    2015-01-01

    MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia. Mutation carriers were older at diagnosis and more...

  11. Screening of 99 Danish patients with congenital heart disease for GATA4 mutations

    DEFF Research Database (Denmark)

    Zhang, Litu; Tümer, Zeynep; Jacobsen, Joes Ramsøe;

    2006-01-01

    Congenital heart disease (CHD) affects nearly 1% of the population, but only few genes involved in human CHD are presently known. Germ-line mutations in the zinc finger transcription factor GATA4 have been associated with familial cases of atrial and ventricular septal defects and pulmonary...

  12. Striking Similarity: GATA-3 Regulates ILC2 and Th2 Cells

    OpenAIRE

    Liang ZHOU

    2012-01-01

    Innate lymphoid cells (ILCs) and T helper (Th) cells share similar effector functions. In this issue of Immunity, Hoyler et al. (2012) and Mjosberg et al. (2012) demonstrate that GATA-3, a Th2 regulator, controls ILC2 differentiation, maintenance, and function.

  13. Gata3 drives development of RORγt+ group 3 innate lymphoid cells

    NARCIS (Netherlands)

    N. Serafini (Nicolas); R.G.J. Klein Wolterink (Roel); N. Satoh-Takayama (Naoko); W. Xu (Weiwei); C.A. Vosshenrich (Christian); R.W. Hendriks (Rudi); J.P. di Santo (James)

    2014-01-01

    textabstractGroup 3 innate lymphoid cells (ILC3) include IL-22-producing NKp46+ cells and IL-17A/IL-22-producing CD4+ lymphoid tissue inducerlike cells that express RORγt and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and

  14. Activation of GATA4 gene expression at the early stage of cardiac specification

    Science.gov (United States)

    Yilbas, Ayse; Hamilton, Alison; Wang, Yingjian; Mach, Hymn; Lacroix, Natascha; Davis, Darryl; Chen, Jihong; LI, Qiao

    2014-03-01

    Currently, there are no effective treatments to directly repair damaged heart tissue after cardiac injury since existing therapies focus on rescuing or preserving reversibly damaged tissue. Cell-based therapies using cardiomyocytes generated from stem cells present a promising therapeutic approach to directly replace damaged myocardium with new healthy tissue. However, the molecular mechanisms underlying the commitment of stem cells into cardiomyocytes are not fully understood and will be critical to guide this new technology into the clinic. Since GATA4 is a critical regulator of cardiac differentiation, we examined the molecular basis underlying the early activation of GATA4 gene expression during cardiac differentiation of pluripotent stem cells. Our studies demonstrate the direct involvement of histone acetylation and transcriptional coactivator p300 in the regulation of GATA4 gene expression. More importantly, we show that histone acetyltransferase (HAT) activity is important for GATA4 gene expression with the use of curcumin, a HAT inhibitor. In addition, the widely used histone deacetylase inhibitor valproic acid enhances both histone acetylation and cardiac specification.

  15. Gata4 is required for formation of the genital ridge in mice.

    Directory of Open Access Journals (Sweden)

    Yueh-Chiang Hu

    Full Text Available In mammals, both testis and ovary arise from a sexually undifferentiated precursor, the genital ridge, which first appears during mid-gestation as a thickening of the coelomic epithelium on the ventromedial surface of the mesonephros. At least four genes (Lhx9, Sf1, Wt1, and Emx2 have been demonstrated to be required for subsequent growth and maintenance of the genital ridge. However, no gene has been shown to be required for the initial thickening of the coelomic epithelium during genital ridge formation. We report that the transcription factor GATA4 is expressed in the coelomic epithelium of the genital ridge, progressing in an anterior-to-posterior (A-P direction, immediately preceding an A-P wave of epithelial thickening. Mouse embryos conditionally deficient in Gata4 show no signs of gonadal initiation, as their coelomic epithelium remains a morphologically undifferentiated monolayer. The failure of genital ridge formation in Gata4-deficient embryos is corroborated by the absence of the early gonadal markers LHX9 and SF1. Our data indicate that GATA4 is required to initiate formation of the genital ridge in both XX and XY fetuses, prior to its previously reported role in testicular differentiation of the XY gonad.

  16. Statins activate GATA-6 and induce differentiated vascular smooth muscle cells

    International Nuclear Information System (INIS)

    The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) beyond cholesterol lowering involve their direct actions on vascular smooth muscle cells (VSMCs). However, the effects of statins on phenotypic modulation of VSMCs are unknown. We herein show that simvastatin (Sm) and atorvastatin (At) inhibited DNA synthesis in human aortic VSMCs dose-dependently, while cell toxicity was not observed below the concentration of 1 μM of Sm or 100 nM of At. Stimulating proliferative VSMCs with Sm or At induced the expression of SM-α-actin and SM-MHC, highly specific markers of differentiated phenotype. Sm up-regulated the binding activity of GATA-6 to SM-MHC GATA site and activated the transfected SM-MHC promoter in proliferative VSMCs, while mutating the GATA-6 binding site abolished this activation. Geranylgeranylpyrophosphate (10 μM), an inhibitor of Rho family proteins, abolished the statin-mediated induction of the differentiated phenotype in VSMCs. These findings suggest that statins activate GATA-6 and induce differentiated VSMCs

  17. Assessment of the role of transcript for GATA-4 as a marker of unfavorable outcome in human adrenocortical neoplasms

    Directory of Open Access Journals (Sweden)

    Martin Regina M

    2004-07-01

    Full Text Available Abstract Background Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis. When adrenocortical neoplasms are diagnosed in the early stages, distinction between carcinoma and adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict tumor recurrence or dissemination. GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal of the present study was to assess whether this reciprocal change in the expression of GATA factors might be relevant for predicting the prognosis of human adrenocortical neoplasms. Since human adrenal cortices express luteinizing hormone (LH/hCG receptor and the gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor. Methods We conducted a study on 13 non-metastasizing (NM and 10 metastasizing/recurrent (MR tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR in normal and tumoral human adrenal cortices was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR complemented by dot blot hybridization. Results Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, was detected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10 MR tumors, with larger amounts of mRNA found among those presenting aggressive clinical behavior. Transcripts for LH receptor were observed both in normal tissue and neoplasms. A more intense LHR transcript accumulation was observed on those tumors with better clinical outcome. Conclusion Our data suggest that the expression of GATA-6 in

  18. The human enhancer-binding protein Gata3 binds to several T-cell receptor regulatory elements.

    OpenAIRE

    Marine, J; Winoto, A

    1991-01-01

    The tissue-specific developmental regulation of the alpha, beta, gamma and delta T-cell antigen receptor (TCR) genes is controlled by the corresponding distinct enhancers and their enhancer-binding proteins. To find a common TCR regulatory element, we have studied the ability of the newly described enhancer-binding protein Gata3 to bind to the sequence motif (A/T)GATA(G/A) shared between enhancer elements of all four TCR genes. Gata3 was shown in the chicken to be an enhancer-binding protein ...

  19. Impaired proteasome function activates GATA3 in T-cells and upregulates CTLA-4: relevance for Sezary syndrome

    OpenAIRE

    Gibson, Heather M; Mishra, Anjali; Chan, Derek V.; Hake, Timothy S.; Porcu, Pierluigi; Wong, Henry K.

    2012-01-01

    Highly regulated expression of the negative co-stimulatory molecule CTLA-4 on T-cells modulates T-cell activation and proliferation. CTLA-4 is preferentially expressed in Th2 T-cells, whose differentiation depends on the transcriptional regulator GATA3. Sezary syndrome (SS) is a T-cell malignancy characterized by Th2 cytokine skewing, impaired T-cell responses, and over-expression of GATA3 and CTLA-4. GATA3 is regulated by phosphorylation and ubiquitination. In SS cells, we detected increased...

  20. Distinct functions of the transcription factors Gata3 and ThPOK during intrathymic CD4 T cell differentiation*

    OpenAIRE

    Wang, Lie; Wildt, Kathryn F.; Zhu, Jinfang; Zhang, Xianyu; Feigenbaum, Lionel; Tessarollo, Lino; Paul, William E.; Fowlkes, B.J.; Bosselut, Rémy

    2008-01-01

    The transcription factors Gata3 and Zbtb7b are required for intrathymic CD4 T cell differentiation, but their precise roles in this process remain unclear. Here we show that, contrary to previous findings, Gata3 disruption blocked CD4 T cell lineage differentiation before CD4 lineage commitment, and in some contexts permitted ‘redirection’ of MHC class II-restricted thymocytes into the CD8 lineage. We found that Gata3 promotes Zbtb7b expression, and binds within a region of the Zbtb7b locus e...

  1. The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma

    OpenAIRE

    Yagi, Ryoji; Junttila, Ilkka S.; Wei, Gang; Urban, Joseph F.; Zhao, Keji; Paul, William E.; Zhu, Jinfang

    2010-01-01

    The transcription factor GATA3 is crucial for the differentiation of naïve CD4+ T cells into T helper 2 (Th2) cells. Here we show that deletion of Gata3 allowed the appearance of interferon γ (IFNγ)-producing cells in the absence of interleukin-12 (IL-12) and IFNγ. Such IFNγ production was transcription factor T-bet-independent. Another T-box-containing transcription factor Eomes, but not T-bet, was induced both in GATA3-deficient CD4+ T cells differentiated under Th2 cell conditions, and in ...

  2. MGMT, GATA6, CD81, DR4, and CASP8 gene promoter methylation in glioblastoma

    Directory of Open Access Journals (Sweden)

    Skiriute Daina

    2012-06-01

    Full Text Available Abstract Background Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome. Methods The methylation status of MGMT, CD81, GATA6, DR4, and CASP8 in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis. Results The overwhelming majority (97.3% of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: MGMT in 51.3%, GATA6 in 68.4%, CD81 in 46.1%, DR4 in 41.3% and CASP8 in 56.8% of tumors. Methylation of MGMT was associated with younger patient age (p CASP8 with older (p MGMT methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p CASP8 was more frequent in patients who survived shorter than 36 months (p MGMT, GATA6 and CASP8 as independent predictors for glioblastoma patient outcome (p MGMT and GATA6 were independent predictors for patient survival in younger patients’ group, while there were no significant associations observed in older patients’ group when adjusted for therapy. Conclusions High methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of MGMT, GATA6 and CASP8 genes methylation in glioblastoma patient outcome.

  3. Gata3 acts downstream of beta-catenin signaling to prevent ectopic metanephric kidney induction.

    Directory of Open Access Journals (Sweden)

    David Grote

    2008-12-01

    Full Text Available Metanephric kidney induction critically depends on mesenchymal-epithelial interactions in the caudal region of the nephric (or Wolffian duct. Central to this process, GDNF secreted from the metanephric mesenchyme induces ureter budding by activating the Ret receptor expressed in the nephric duct epithelium. A failure to regulate this pathway is believed to be responsible for a large proportion of the developmental anomalies affecting the urogenital system. Here, we show that the nephric duct-specific inactivation of the transcription factor gene Gata3 leads to massive ectopic ureter budding. This results in a spectrum of urogenital malformations including kidney adysplasia, duplex systems, and hydroureter, as well as vas deferens hyperplasia and uterine agenesis. The variability of developmental defects is reminiscent of the congenital anomalies of the kidney and urinary tract (CAKUT observed in human. We show that Gata3 inactivation causes premature nephric duct cell differentiation and loss of Ret receptor gene expression. These changes ultimately affect nephric duct epithelium homeostasis, leading to ectopic budding of interspersed cells still expressing the Ret receptor. Importantly, the formation of these ectopic buds requires both GDNF/Ret and Fgf signaling activities. We further identify Gata3 as a central mediator of beta-catenin function in the nephric duct and demonstrate that the beta-catenin/Gata3 pathway prevents premature cell differentiation independently of its role in regulating Ret expression. Together, these results establish a genetic cascade in which Gata3 acts downstream of beta-catenin, but upstream of Ret, to prevent ectopic ureter budding and premature cell differentiation in the nephric duct.

  4. MGMT, GATA6, CD81, DR4, and CASP8 gene promoter methylation in glioblastoma

    International Nuclear Information System (INIS)

    Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome. The methylation status of MGMT, CD81, GATA6, DR4, and CASP8 in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis. The overwhelming majority (97.3%) of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: MGMT in 51.3%, GATA6 in 68.4%, CD81 in 46.1%, DR4 in 41.3% and CASP8 in 56.8% of tumors. Methylation of MGMT was associated with younger patient age (p < 0.05), while CASP8 with older (p < 0.01). MGMT methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p < 0.05), while methylation of CASP8 was more frequent in patients who survived shorter than 36 months (p < 0.05). Cox regression analysis showed patient age, treatment, MGMT, GATA6 and CASP8 as independent predictors for glioblastoma patient outcome (p < 0.05). MGMT and GATA6 were independent predictors for patient survival in younger patients’ group, while there were no significant associations observed in older patients’ group when adjusted for therapy. High methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of MGMT, GATA6 and CASP8 genes methylation in glioblastoma patient outcome

  5. Organization and differential expression of the GACA/GATA tagged somatic and spermatozoal transcriptomes in Buffalo Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Srivastava Jyoti

    2008-03-01

    Full Text Available Abstract Background Simple sequence repeats (SSRs of GACA/GATA have been implicated with differentiation of sex-chromosomes and speciation. However, the organization of these repeats within genomes and transcriptomes, even in the best characterized organisms including human, remains unclear. The main objective of this study was to explore the buffalo transcriptome for its association with GACA/GATA repeats, and study the structural organization and differential expression of the GACA/GATA repeat tagged transcripts. Moreover, the distribution of GACA and GATA repeats in the prokaryotic and eukaryotic genomes was studied to highlight their significance in genome evolution. Results We explored several genomes and transcriptomes, and observed total absence of these repeats in the prokaryotes, with their gradual accumulation in higher eukaryotes. Further, employing novel microsatellite associated sequence amplification (MASA approach using varying length oligos based on GACA and GATA repeats; we identified and characterized 44 types of known and novel mRNA transcripts tagged with these repeats from different somatic tissues, gonads and spermatozoa of water buffalo Bubalus bubalis. GACA was found to be associated with higher number of transcripts compared to that with GATA. Exclusive presence of several GACA-tagged transcripts in a tissue or spermatozoa, and absence of the GATA-tagged ones in lung/heart highlights their tissue-specific significance. Of all the GACA/GATA tagged transcripts, ~30% demonstrated inter-tissue and/or tissue-spermatozoal sequence polymorphisms. Significantly, ~60% of the GACA-tagged and all the GATA-tagged transcripts showed highest or unique expression in the testis and/or spermatozoa. Moreover, ~75% GACA-tagged and all the GATA-tagged transcripts were found to be conserved across the species. Conclusion Present study is a pioneer attempt exploring GACA/GATA tagged transcriptome in any mammalian species highlighting their

  6. Promoter analysis in living zebrafish embryos identifies a cis-acting motif required for neuronal expression of GATA-2

    OpenAIRE

    Meng, Anming; Tang, Hong; Ong, Bruce A.; Farrell, Michael J.; Lin, Shuo

    1997-01-01

    We have used zebrafish embryos to dissect the promoter activity of a gene with a complex expression pattern during embryogenesis. GATA-2 is a transcription factor required for hematopoiesis and is dynamically expressed in hematopoietic tissues and in the central nervous system. Using constructs containing zebrafish GATA-2 genomic flanking sequences and the green fluorescent protein (GFP) reporter gene, we demonstrate that distinct regulatory domains are required for hematopoietic, enveloping ...

  7. TRANSCRIPTIONAL FA CTORS FOXP3, GATA-3, PAX-5 AND THEIR COOPERAT IVE INTERACTIONS IN BRONCHIAL ASTHMA

    OpenAIRE

    V. N. Mineev; L. N. Sorokina; A. V. Eremeeva; M. A. Nyoma; A. S. Bedenko

    2013-01-01

    Abstract. The review article summarizes current information about transcriptional factors Fохр3, GATA- 3, РАХ-5 and their cooperative interactions. Predomination of one of these factors leads to production of corresponding cytokines and appropriate changes in T and B cell functions, thus causing development of different inflammatory events and typical symptoms. Focusing the discussion on Foxp3, GATA-3 and PAX- 5 is essential for understanding pathogenesis of inflammatory lung diseases, in par...

  8. GATA3 Expression Is Decreased in Psoriasis and during Epidermal Regeneration; Induction by Narrow-Band UVB and IL-4

    OpenAIRE

    Rácz, E.; Kurek, D.; Kant, M.; Baerveldt, E.M.; Florencia, E.; Mourits, S.; de Ridder, D.; Laman, J. D.; Van der Fits, L.; Prens, E.P.

    2011-01-01

    textabstractPsoriasis is characterized by hyperproliferation of keratinocytes and by infiltration of activated Th1 and Th17 cells in the (epi)dermis. By expression microarray, we previously found the GATA3 transcription factor significantly downregulated in lesional psoriatic skin. Since GATA3 serves as a key switch in both epidermal and T helper cell differentiation, we investigated its function in psoriasis. Because psoriatic skin inflammation shares many characteristics of epidermal regene...

  9. Suppression of erythropoietin gene expression by cadmium depends on inhibition of HIF-1, not stimulation of GATA-2

    Energy Technology Data Exchange (ETDEWEB)

    Obara, Naoshi; Imagawa, Shigehiko; Nakano, Yoko; Nagasawa, Toshiro [Division of Hematology, Institute of Clinical Medicine, University of Tsukuba, 305-8575, Tsukuba, Ibaraki (Japan); Suzuki, Norio; Yamamoto, Masayuki [Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, 305-8577, Tsukuba, Ibaraki (Japan)

    2003-05-01

    Long-term exposure of rats to cadmium (Cd) resulted in a marked suppression of erythropoietin (Epo) mRNA expression in the kidneys and the development of severe anemia. A recent report revealed that Cd inhibited hypoxia-inducible factor 1 (HIF-1) binding activity and Epo mRNA expression and protein production. However, Epo gene expression is also regulated by transcription factor GATA-2, which binds to the GATA binding site of the Epo promoter. To elucidate the mechanism of suppression of Epo by Cd, the effect of Cd on GATA-2 function was studied. Epo promoter/enhancer luciferase constructs, one with the wild-type promoter and another with a promoter with a mutant GATA site, were transfected into Hep3B cells. No significant difference in Epo promoter activity in these two types of cells was observed in the presence of Cd. The binding activity of GATA-2 was not affected by Cd. This study showed that Cd inhibited HIF-1 binding activity and Epo promoter activity, and then suppressed Epo protein production. Inhibition of Epo gene expression by Cd depends on suppression of HIF-1 binding activity, not on alteration of GATA function. (orig.)

  10. Identification of GATA-4 as a novel transcriptional regulatory component of regenerating islet-derived family members.

    Science.gov (United States)

    Lepage, David; Bruneau, Joannie; Brouillard, Geneviève; Jones, Christine; Lussier, Carine R; Rémillard, Anthony; Lemieux, Étienne; Asselin, Claude; Boudreau, François

    2015-12-01

    Intestinal epithelial cells are exposed to luminal bacterial threat and require adequate defense mechanisms to ensure host protection and epithelium regeneration against possible deleterious damage. Differentiated intestinal epithelial cells produce antimicrobial and regenerative components that protect against such challenges. Few intestinal specific transcription factors have been identified to control the switching from repression to activation of this class of gene. Herein, we show that gene transcription of some regenerating islet-derived (REG) family members is dependent on the transcription factor GATA-4. Silencing of GATA-4 expression in cultured intestinal epithelial cells identified Reg3β as a target gene using an unbiased approach of gene expression profiling. Co-transfection and RNA interference assays identified complex GATA-4-interactive transcriptional components required for the activation or repression of Reg3β gene activity. Conditional deletion of Gata4 in the mouse intestinal epithelium supported its regulatory role for Reg1, Reg3α, Reg3β and Reg3γ genes. Reg1 dramatic down-modulation of expression in Gata4 conditional null mice was associated with a significant decrease in intestinal epithelial cell migration. Altogether, these results identify a novel and complex role for GATA-4 in the regulation of REG family members gene expression. PMID:26477491

  11. Nuclear Receptor-Like Structure and Interaction of Congenital Heart Disease-Associated Factors GATA4 and NKX2-5

    OpenAIRE

    Kinnunen, Sini; Välimäki, Mika; Tölli, Marja; Wohlfahrt, Gerd; Darwich, Rami; Komati, Hiba; Nemer, Mona; Ruskoaho, Heikki

    2015-01-01

    Aims Transcription factor GATA4 is a dosage sensitive regulator of heart development and alterations in its level or activity lead to congenital heart disease (CHD). GATA4 has also been implicated in cardiac regeneration and repair. GATA4 action involves combinatorial interaction with other cofactors such as NKX2-5, another critical cardiac regulator whose mutations also cause CHD. Despite its critical importance to the heart and its evolutionary conservation across species, the structural ba...

  12. Investigating the DNA-binding ability of GATA-1-N-terminal zinc finger

    International Nuclear Information System (INIS)

    Erythroid transcription factor GATA-1 interacts with both DNA and other proteins through its zinc finger domains (ZnFs). While it has been known for me time that the C-terminal ZnF binds DNA at GATA sites, only recently has it been observed that the N-terminal finger (NF) is capable of interacting with GATC sites. Further, a number of naturally occurring mutations in NF (V205M, G208S, R216Q, D218G) that lead to anaemia and thrombocytopenia have been identified. We are interested in characterising the NF-DNA interaction and determining the effects of mutation upon this interaction. Using nuclear magnetic resonance (NMR) spectroscopy, we have observed an interaction between recombinant NF and a 16-mer DNA duplex containing a core GATC sequence. This result forms the basis from which residues in NF involved in DNA binding can be identified, and work is being carried out to improve the quality of the NMR data with the aim of determining the solution structure of the NF-DNA complex. The DNA-binding affinity of both wild-type and mutant NFs mentioned above is also being investigated using isothermal titration calorimetry. These data suggest that the strength of the interaction between NF and the 16-mer DNA duplex is in the sub-micromolar range, and comparisons between the DNA-binding affinities of the NF mutants are being made. Together, these studies will help us to understand how GATA-1 acts as a transcriptional regulator and how mutations in NF domain of GATA-1 may lead to blood disorders

  13. GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells

    OpenAIRE

    Kamata, Mayumi; Okitsu, Yoko; Fujiwara, Tohru; Kanehira, Masahiko; Nakajima, Shinji; Takahashi, Taro; Inoue, Ai; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Shimizu, Ritsuko; Yamamoto, Masayuki; Harigae, Hideo

    2014-01-01

    The bone marrow microenvironment comprises multiple cell niches derived from bone marrow mesenchymal stem cells. However, the molecular mechanism of bone marrow mesenchymal stem cell differentiation is poorly understood. The transcription factor GATA2 is indispensable for hematopoietic stem cell function as well as other hematopoietic lineages, suggesting that it may maintain bone marrow mesenchymal stem cells in an immature state and also contribute to their differentiation. To explore this ...

  14. The transcription factor GATA3 controls cell fate and maintenance of type 2 innate lymphoid cells

    OpenAIRE

    Hoyler, Thomas; Klose, Christoph S.N.; Souabni, Abdallah; Turqueti-Neves, Adriana; Pfeifer, Dietmar; Rawlins, Emma L.; Voehringer, David; Busslinger, Meinrad; Diefenbach, Andreas

    2012-01-01

    Innate lymphoid cells (ILCs) reside at mucosal surfaces and control immunity to intestinal infections. Type 2 innate lymphoid cells (ILC2) produce cytokines such as IL-5 and IL-13 and are required for immune defense against helminth infections and are involved in the pathogenesis of airway hyperreactivity. Here, we have investigated the role of the transcription factor GATA3 for ILC2 differentiation and maintenance. We showed that ILC2 and their lineage-specified bone marrow precursor (ILC2P)...

  15. Expression of hematopoietic transcription factors Runt, CBFβ and GATA during ontogenesis of scallop Chlamys farreri.

    Science.gov (United States)

    Yue, Feng; Wang, Lingling; Wang, Hao; Song, Linsheng

    2016-08-01

    Transcription factors Runx1, CBFβ and GATA1/2/3 play essential roles in regulating hematopoietic development during embryogenesis of vertebrate. In previous study, the orthologous genes of Runt, CBFβ and GATA1/2/3 have been identified from scallop Chlamys farreri and proved to have conserved function in regulating hemocyte production. Here, these three transcription factors were selected as hematopoietic markers to explore potential developmental events of hematopoiesis during ontogenesis of scallop. The transcripts of CfRunt, CfCBFβ and CfGATA were detected abundantly after 32-cell embryo, trochophore and morula stage, and reached to a peak level in 32-cell embryos and D-shaped veligers, pediveligers or gastrula respectively. Further whole-mount immunofluorescence assay showed that the immunoreactivity of CfRunt was firstly observed at 32-cell stage and then its distribution was specialized gradually to the mesoderm during gastrulation. By trochophore, the expression of CfRunt, CfCBFβ and CfGATA proteins occurred coincidently in two specific symmetry cell mass located bilaterally on prototroch, and then disappeared rapidly in D-shaped or umbonal vliger, respectively. However, remarkable expressions of the three transcription factors were observed consistently in a new sinus structure appeared at the dorsal anterior side of D-shaped and umbonal veliger. After bacterial challenge, the mRNA expression levels of the three transcription factors were up-regulated or down-regulated significantly in trochophore, D-shaped veliger and pediveliger, indicating the available hematopoietic regulation in scallop larvae. The results revealed that scallop might experience two waves of hematopoiesis during early development, which occurred in the bilateral symmetry cell mass of trochophore and the sinus structure of veliger. PMID:27012994

  16. The function and regulation of the GATA factor ELT-2 in the C. elegans endoderm.

    Science.gov (United States)

    Wiesenfahrt, Tobias; Berg, Janette Y; Osborne Nishimura, Erin; Robinson, Adam G; Goszczynski, Barbara; Lieb, Jason D; McGhee, James D

    2016-02-01

    ELT-2 is the major regulator of genes involved in differentiation, maintenance and function of C. elegans intestine from the early embryo to mature adult. elt-2 responds to overexpression of the GATA transcription factors END-1 and END-3, which specify the intestine, as well as to overexpression of the two GATA factors that are normally involved in intestinal differentiation, ELT-7 and ELT-2 itself. Little is known about the molecular mechanisms underlying these interactions, how ELT-2 levels are maintained throughout development or how such systems respond to developmental perturbations. Here, we analyse elt-2 gene regulation through transgenic reporter assays, ELT-2 ChIP and characterisation of in vitro DNA-protein interactions. Our results indicate that elt-2 is controlled by three discrete regulatory regions conserved between C. elegans and C. briggsae that span >4 kb of 5' flanking sequence. These regions are superficially interchangeable but have quantitatively different enhancer properties, and their combined activities indicate inter-region synergies. Their regulatory activity is mediated by a small number of conserved TGATAA sites that are largely interchangeable and interact with different endodermal GATA factors with only modest differences in affinity. The redundant molecular mechanism that forms the elt-2 regulatory network is robust and flexible, as loss of end-3 halves ELT-2 levels in the early embryo but levels fully recover by the time of hatching. When ELT-2 is expressed under the control of end-1 regulatory elements, in addition to its own endogenous promoter, it can replace the complete set of endoderm-specific GATA factors: END-1, END-3, ELT-7 and (the probably non-functional) ELT-4. Thus, in addition to controlling gene expression during differentiation, ELT-2 is capable of specifying the entire C. elegans endoderm. PMID:26700680

  17. GATA3 Inhibits Lysyl Oxidase Mediated Metastases of Human Basal Triple-Negative Breast Cancer Cells

    OpenAIRE

    Chu, Isabel M.; Michalowski, Aleksandra M.; Hoenerhoff, Mark; Kornelia M. Szauter; Luger, Dror; Sato, Misako; Flanders, Kathy; Oshima, Akira; Csiszar, Katalin; Green, Jeffrey E

    2011-01-01

    Discovery of mechanisms that impede the aggressive and metastatic phenotype of human basal triple-negative type breast cancers (BTNBC) could provide novel targets for therapy for this form of breast cancer that has a relatively poor prognosis. Previous studies have demonstrated that the expression of GATA3, the master transcriptional regulator of mammary luminal differentiation, can reduce the tumorigenicity and metastatic propensity of the human BTNBC MDA-MB-231 cell line (MB231), although t...

  18. GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility

    OpenAIRE

    Theodorou, V.; Stark, R.; Menon, S.; Carroll, J. S.

    2013-01-01

    Estrogen receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1 contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1-cooperating transcription factor mutated in breast tumors; however, its genomic properties are not fully defined. In order to investigate the composition of enha...

  19. Transcriptional Repression of Gata3 Is Essential for Early B Cell Commitment

    OpenAIRE

    Banerjee, Anupam; Northrup, Daniel; Boukarabila, Hanane; Jacobsen, Sten Erik W.; Allman, David

    2013-01-01

    Summary The mechanisms underlying the silencing of alternative fate potentials in very early B cell precursors remain unclear. Using gain- and loss-of-function approaches together with a synthetic Zinc-finger polypeptide (6ZFP) engineered to prevent transcription factor binding to a defined cis element, we show that the transcription factor EBF1 promotes B cell lineage commitment by directly repressing expression of the T-cell-lineage-requisite Gata3 gene. Ebf1-deficient lymphoid progenitors ...

  20. Continued Expression of GATA3 Is Necessary for Cochlear Neurosensory Development

    OpenAIRE

    Duncan, Jeremy S.; Fritzsch, Bernd

    2013-01-01

    Hair cells of the developing mammalian inner ear are progressively defined through cell fate restriction. This process culminates in the expression of the bHLH transcription factor Atoh1, which is necessary for differentiation of hair cells, but not for their specification. Loss of several genes will disrupt ear morphogenesis or arrest of neurosensory epithelia development. We previously showed in null mutants that the loss of the transcription factor, Gata3, results specifically in the loss ...

  1. c-kitpos GATA-4 high rat cardiac stem cells foster adult cardiomyocyte survival through IGF-1 paracrine signalling.

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    Nanako Kawaguchi

    Full Text Available BACKGROUND: Resident c-kit positive (c-kitpos cardiac stem cells (CSCs could be considered the most appropriate cell type for myocardial regeneration therapies. However, much is still unknown regarding their biological properties and potential. METHODOLOGY/PRINCIPAL FINDINGS: We produced clones of high and low expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs were co-cultured with adult rat ventricular cardiomyocytes, we observed increased survival and contractility of the cardiomyocytes, compared to cardiomyocytes cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there was a significant correlation between IGF-1 concentration and cardiomyocyte survival. We showed the activation of the IGF-1 receptor and its downstream molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF-1 receptor inhibited the survival of cardiomyocytes and prevented the activation of its signalling in cardiomyocytes in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus cardiomyocytes did extend the survival and contractility of cardiomyocytes cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs. CONCLUSION/SIGNIFICANCE: c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway.

  2. Predominance of Intraglomerular T-bet or GATA3 May Determine Mechanism of Transplant Rejection

    Science.gov (United States)

    Sun, Qiquan; Cheng, Dongrui; Zhang, Mingchao; He, Qunpeng; Chen, Zhaohong

    2011-01-01

    The transcription factors T-bet and GATA3 determine the differentiation of helper T cells into Th1 or Th2 cells, respectively. An altered ratio of their relative expression promotes the pathogenesis of certain immunological diseases, but whether this may also contribute to the pathogenesis of antibody-mediated rejection (ABMR) versus T cell-mediated rejection (TCMR) is unknown. Here, we characterized the intragraft expression of T-bet and GATA3 and determined the correlation of their levels with the presence of typical lesions of ABMR and TCMR. We found a predominant intraglomerular expression of T-bet in patients with ABMR, which was distinct from that in patients with TCMR. In ABMR, interstitial T-bet expression was typically located in peritubular capillaries, although the overall quantity of interstitial T-bet was less than that observed in TCMR. The expression of intraglomerular T-bet correlated with infiltration of CD4+ and CD8+ lymphocytes, which express T-bet, as well as intraglomerular CD68+ monocyte/macrophages, which do not express T-bet. The predominance of intraglomerular T-bet expression relative to GATA3 expression associated with poor response to treatment with bolus steroid. In summary, predominance of intraglomerular T-bet expression correlates with antibody-mediated rejection and resistance to steroid treatment. PMID:21289214

  3. A novel E2 box-GATA element modulates Cdc6 transcription during human cells polyploidization.

    Science.gov (United States)

    Vilaboa, Nuria; Bermejo, Rodrigo; Martinez, Pilar; Bornstein, Rafael; Calés, Carmela

    2004-01-01

    Cdc6 is a key regulator of the strict alternation of S and M phases during the mitotic cell cycle. In mammalian and plant cells that physiologically become polyploid, cdc6 is transcriptionally and post-translationally regulated. We have recently reported that Cdc6 levels are maintained in megakaryoblastic HEL cells, but severely downregulated by ectopic expression of transcriptional repressor Drosophila melanogaster escargot. Here, we show that cdc6 promoter activity is upregulated during megakaryocytic differentiation of HEL endoreplicating cells, and that Escargot interferes with such activation. Transactivation experiments showed that a 1.7 kb region located at 2800 upstream cdc6 transcription initiation site behaved as a potent enhancer in endoreplicating cells only. This activity was mainly dependent on a novel cis-regulatory element composed by an E2 box overlapping a GATA motif. Ectopic Escargot could bind this regulatory element in vitro and endogenous GATA-1 and E2A formed specific complexes in megakaryoblastic cells as well as in primary megakaryocytes. Chromatin Immunoprecipitation analysis revealed that both transcription factors were occupying the E2 box/GATA site in vivo. Altogether, these data suggest that cdc6 expression could be actively maintained during megakaryocytic differentiation through transcriptional mechanisms involving specific cis- and trans-regulatory elements. PMID:15590906

  4. Novel GATA6 mutations in patients with pancreatic agenesis and congenital heart malformations.

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    Christina S Chao

    Full Text Available Patients with pancreatic agenesis are born without a pancreas, causing permanent neonatal diabetes and pancreatic enzyme insufficiency. These patients require insulin and enzyme replacement therapy to survive, grow, and maintain normal blood glucose levels. Pancreatic agenesis is an uncommon condition but high-throughput sequencing methods provide a rare opportunity to identify critical genes that are necessary for human pancreas development. Here we present the clinical history, evaluation, and the genetic and molecular analysis from two patients with pancreatic agenesis. Both patients were born with intrauterine growth restriction, minor heart defects and neonatal diabetes. In both cases, pancreatic agenesis was confirmed by imaging studies. The patients are clinically stable with pancreatic enzymes and insulin therapy. In order identify the etiology for their disease, we performed whole exome sequencing on both patients. For each proband we identified a de novo heterozygous mutation in the GATA6 gene. GATA6 is a homeobox containing transcription factor involved in both early development of the pancreas and heart. In vitro functional analysis of one of the variants revealed that the mutation creates a premature stop codon in the coding sequence resulting in the production of a truncated protein with loss of activity. These results show how genetic mutations in GATA6 may lead to functional inactivity and pancreatic agenesis in humans.

  5. Transcription factor GATA-3 regulates the transcriptional activity of dopamine β-hydroxylase by interacting with Sp1 and AP4

    OpenAIRE

    Hong, Seok Jong; Choi, Hyun Jin; Hong, Sunghoi; Huh, Youngbuhm; Chae, Han; Kim, Kwang-Soo

    2008-01-01

    GATA-3 is a zinc finger transcription factor that is expressed in T cell lineages as well as in the nervous system during development. In this study, we report that forced expression of GATA-3 resulted in an increased number of dopamine β-hydroxylase (DBH)-expressing neurons in primary neural crest stem cell (NCSC) culture, suggesting that the DBH gene may be a downstream target gene of GATA-3. GATA-3 robustly transactivates the promoter function of the noradrenaline (NA)-synthesizing DBH gen...

  6. Enforced expression of GATA-3 during T cell development inhibits maturation of CD8 single-positive cells and induces thymic lymphoma in transgenic mice

    OpenAIRE

    Nawijn, Martijn,; Ferreira, Rita; Dingjan, Gemma; Kahre, O; Drabek, Dubravka; Karis, Alar; Hendriks, Rudi; Grosveld, Frank

    2001-01-01

    textabstractThe zinc finger transcription factor GATA-3 is of critical importance for early T cell development and commitment of Th2 cells. To study the role of GATA-3 in early T cell development, we analyzed and modified GATA-3 expression in vivo. In mice carrying a targeted insertion of a lacZ reporter on one allele, we found that GATA-3 transcription in CD4(+)CD8(+) double-positive thymocytes correlated with the onset of positive selection events, i.e., TCRalphabeta up-regulation and CD69 ...

  7. Gata-3 Negatively Regulates the Tumor-Initiating Capacity of Mammary Luminal Progenitor Cells and Targets the Putative Tumor Suppressor Caspase-14 ▿ §

    OpenAIRE

    Asselin-Labat, Marie-Liesse; Sutherland, Kate D.; Vaillant, François; Gyorki, David E; Wu, Di; Holroyd, Sheridan; Breslin, Kelsey; Ward, Teresa; Shi, Wei; Bath, Mary L.; Deb, Siddhartha; Fox, Stephen B.; Smyth, Gordon K; Lindeman, Geoffrey J; Visvader, Jane E.

    2011-01-01

    The transcription factor Gata-3 is a definitive marker of luminal breast cancers and a key regulator of mammary morphogenesis. Here we have explored a role for Gata-3 in tumor initiation and the underlying cellular mechanisms using a mouse model of “luminal-like” cancer. Loss of a single Gata-3 allele markedly accelerated tumor progression in mice carrying the mouse mammary tumor virus promoter-driven polyomavirus middle T antigen (MMTV-PyMT mice), while overexpression of Gata-3 curtailed tum...

  8. MicroRNA-208b Alleviates Post-Infarction Myocardial Fibrosis in a Rat Model by Inhibiting GATA4

    Science.gov (United States)

    Zhou, Chaoyuan; Cui, Qintao; Su, Guobao; Guo, Xiaoliang; Liu, Xiaochen; Zhang, Jie

    2016-01-01

    Background Myocardial infarction affects the health of many people. Post-infarction myocardial fibrosis has attracted much attention, but details of the mechanism remain elusive. In this study, the role of microRNA-208b (miR-208b) in modulating post-infarction myocardial fibrosis and the related mechanism were investigated. Material/Methods A rat model of myocardial infarction induced by ligating the left anterior descending artery was used to analyze the expression and roles of miR-208b by overexpression with the lentivirus vector of pre-miR-208b. Myocardial function was assessed and the expression of fibrosis-related factors type I collagen (COL1) and ACTA2 (alias αSMA) was detected. Myocardial fibroblasts isolated from newborn rats were transfected with luciferase reporter vectors containing wild-type or mutant Gata4 3′ UTR to verify the relationship between Gata4 and miR-208b. We then transfected the specific small interference RNA of Gata4 to detect changes in COL1 and ACTA2. Results miR-208b was down-regulated in hearts of model rats (P<0.01). Overexpressing miR-208b improved myocardial functions, such as reducing the infarction area (P<0.05) and promoting LVEF and LVFS (P<0.01), and inhibited COL1 and ACTA2 (P<0.01). Luciferase reporter assay proved Gata4 to be the direct target of miR-208b, with the target sequence in the 3′UTR. Inhibiting GATA4 resulted in the down-regulation of COL1 and ACTA2, suggesting that the role of miR-208b was achieved via regulating GATA4. Conclusions This study demonstrates the protective function of miR-208b via GATA4 in post-infarction myocardial fibrosis, providing a potential therapeutic target for treating myocardial fibrosis. PMID:27236543

  9. miR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation

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    Hsiao-Ning Huang

    2014-03-01

    Full Text Available Human embryonic stem cells (hESCs are functionally unique for their self-renewal ability and pluripotency, but the molecular mechanisms giving rise to these properties are not fully understood. hESCs can differentiate into embryoid bodies (EBs containing ectoderm, mesoderm, and endoderm. In the miR-200 family, miR-200c was especially enriched in undifferentiated hESCs and significantly downregulated in EBs. The knockdown of the miR-200c in hESCs downregulated Nanog expression, upregulated GATA binding protein 4 (GATA4 expression, and induced hESC apoptosis. The knockdown of GATA4 rescued hESC apoptosis induced by downregulation of miR-200c. miR-200c directly targeted the 3′-untranslated region of GATA4. Interestingly, the downregulation of GATA4 significantly inhibited EB formation in hESCs. Overexpression of miR-200c inhibited EB formation and repressed the expression of ectoderm, endoderm, and mesoderm markers, which could partially be rescued by ectopic expression of GATA4. Fibroblast growth factor (FGF and activin A/nodal can sustain hESC renewal in the absence of feeder layer. Inhibition of transforming growth factor-β (TGF-β/activin A/nodal signaling by SB431542 treatment downregulated the expression of miR-200c. Overexpression of miR-200c partially rescued the expression of Nanog/phospho-Smad2 that was downregulated by SB431542 treatment. Our observations have uncovered novel functions of miR-200c and GATA4 in regulating hESC renewal and differentiation.

  10. MicroRNA-26a protects against cardiac hypertrophy via inhibiting GATA4 in rat model and cultured cardiomyocytes.

    Science.gov (United States)

    Liu, Yan; Wang, Zhiqian; Xiao, Wenliang

    2016-09-01

    Pathological cardiac hypertrophy is characterized by deleterious changes developed in cardiovascular diseases, whereas microRNAs (miRNAs) are involved in the mediation of cardiac hypertrophy. To investigate the role of microRNA-26a (miR-26a) in regulating cardiac hypertrophy and its functioning mechanisms, overexpression and suppression of miR‑26a via its mimic and inhibitor in a transverse abdominal aortic constriction (TAAC)-induced rat model and in angiotensin II (Ang II)-induced cardiomyocytes (CMs) was performed. In the rat model, the heart weight (HW) compared with the body weight (BW), the CM area, and expression of the hypertrophy‑associated factors, atrial natriuretic factor (ANF) and β‑myosin heavy chain (β‑MHC), were assessed. In CMs, the protein synthesis rate was determined using a leucine incorporation assay. Mutation of the GATA‑binding protein 4 (GATA4) 3'‑untranslated region (UTR) and overexpression of GATA4 were performed to confirm whether GATA4 is the target of miR‑26a. The results indicated that miR-26a was significantly downregulated in the heart tissue of the rat model, as well as in Ang II‑induced CMs (Pregulate GATA4 with mutations in the 3'‑UTR, indicating that GATA4 was the direct target of miR‑26a. Overexpression of GATA4 abrogated the inhibitory functions of miR‑26a in cardiac hypertrophy. Taken together, the present study suggested an anti‑hypertrophic role of miR‑26a in cardiac hypertrophy, possibly via inhibition of GATA4. These findings may be useful in terms of facilitating cardiac treatment, with potential therapeutic targets and strategies. PMID:27485101

  11. The leukemia associated ETO nuclear repressor gene is regulated by the GATA-1 transcription factor in erythroid/megakaryocytic cells

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    Gullberg Urban

    2010-05-01

    Full Text Available Abstract Background The Eight-Twenty-One (ETO nuclear co-repressor gene belongs to the ETO homologue family also containing Myeloid Translocation Gene on chromosome 16 (MTG16 and myeloid translocation Gene-Related protein 1 (MTGR1. By chromosomal translocations ETO and MTG16 become parts of fusion proteins characteristic of morphological variants of acute myeloid leukemia. Normal functions of ETO homologues have as yet not been examined. The goal of this work was to identify structural and functional promoter elements upstream of the coding sequence of the ETO gene in order to explore lineage-specific hematopoietic expression and get hints to function. Results A putative proximal ETO promoter was identified within 411 bp upstream of the transcription start site. Strong ETO promoter activity was specifically observed upon transfection of a promoter reporter construct into erythroid/megakaryocytic cells, which have endogeneous ETO gene activity. An evolutionary conserved region of 228 bp revealed potential cis-elements involved in transcription of ETO. Disruption of the evolutionary conserved GATA -636 consensus binding site repressed transactivation and disruption of the ETS1 -705 consensus binding site enhanced activity of the ETO promoter. The promoter was stimulated by overexpression of GATA-1 into erythroid/megakaryocytic cells. Electrophoretic mobility shift assay with erythroid/megakaryocytic cells showed specific binding of GATA-1 to the GATA -636 site. Furthermore, results from chromatin immunoprecipitation showed GATA-1 binding in vivo to the conserved region of the ETO promoter containing the -636 site. The results suggest that the GATA -636 site may have a role in activation of the ETO gene activity in cells with erythroid/megakaryocytic potential. Leukemia associated AML1-ETO strongly suppressed an ETO promoter reporter in erythroid/megakaryocytic cells. Conclusions We demonstrate that the GATA-1 transcription factor binds and

  12. The GATA1-HS2 enhancer allows persistent and position-independent expression of a β-globin transgene.

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    Annarita Miccio

    Full Text Available Gene therapy of genetic diseases requires persistent and position-independent expression of a therapeutic transgene. Transcriptional enhancers binding chromatin-remodeling and modifying complexes may play a role in shielding transgenes from repressive chromatin effects. We tested the activity of the HS2 enhancer of the GATA1 gene in protecting the expression of a β-globin minigene delivered by a lentiviral vector in hematopoietic stem/progenitor cells. Gene expression from proviruses carrying GATA1-HS2 in both LTRs was persistent and resistant to silencing at most integration sites in the in vivo progeny of human hematopoietic progenitors and murine long-term repopulating stem cells. The GATA1-HS2-modified vector allowed correction of murine β-thalassemia at low copy number without inducing clonal selection of erythroblastic progenitors. Chromatin immunoprecipitation studies showed that GATA1 and the CBP acetyltransferase bind to GATA1-HS2, significantly increasing CBP-specific histone acetylations at the LTRs and β-globin promoter. Recruitment of CBP by the LTRs thus establishes an open chromatin domain encompassing the entire provirus, and increases the therapeutic efficacy of β-globin gene transfer by reducing expression variegation and epigenetic silencing.

  13. Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells.

    Science.gov (United States)

    Hosokawa, Hiroyuki; Tanaka, Tomoaki; Endo, Yusuke; Kato, Miki; Shinoda, Kenta; Suzuki, Akane; Motohashi, Shinichiro; Matsumoto, Masaki; Nakayama, Keiichi I; Nakayama, Toshinori

    2016-01-01

    Th2 cells produce Th2 cytokines such as IL-4, IL-5 and IL-13, but repress Th1 cytokine IFNγ. Recent studies have revealed various distinct memory-type Th2 cell subsets, one of which produces a substantial amount of IFNγ in addition to Th2 cytokines, however it remains unclear precisely how these Th2 cells produce IFNγ. We herein show that phosphorylation of Gata3 at Ser308, Thr315 and Ser316 induces dissociation of a histone deacetylase Hdac2 from the Gata3/Chd4 repressive complex in Th2 cells. We also identify Akt1 as a Gata3-phosphorylating kinase, and the activation of Akt1 induces derepression of Tbx21 and Ifng expression in Th2 cells. Moreover, T-bet-dependent IFNγ expression in IFNγ-producing memory Th2 cells appears to be controlled by the phosphorylation status of Gata3 in human and murine systems. Thus, this study highlights the molecular basis for posttranslational modifications of Gata3 that control the regulation of IFNγ expression in memory Th2 cells. PMID:27053161

  14. Systematic Cellular Disease Models Reveal Synergistic Interaction of Trisomy 21 and GATA1 Mutations in Hematopoietic Abnormalities.

    Science.gov (United States)

    Banno, Kimihiko; Omori, Sayaka; Hirata, Katsuya; Nawa, Nobutoshi; Nakagawa, Natsuki; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Sakuma, Tetsushi; Yamamoto, Takashi; Toki, Tsutomu; Ito, Etsuro; Yamamoto, Toshiyuki; Kokubu, Chikara; Takeda, Junji; Taniguchi, Hidetoshi; Arahori, Hitomi; Wada, Kazuko; Kitabatake, Yasuji; Ozono, Keiichi

    2016-05-10

    Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect of these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic mutations in GATA1. To better understand functional interplay between trisomy 21 and GATA1 mutations in hematopoiesis, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs) and genome-editing technologies. Comparative analysis of these engineered iPSCs demonstrated that trisomy 21 perturbed hematopoietic development through the enhanced production of early hematopoietic progenitors and the upregulation of mutated GATA1, resulting in the accelerated production of aberrantly differentiated cells. These effects were mediated by dosage alterations of RUNX1, ETS2, and ERG, which are located in a critical 4-Mb region of chromosome 21. Our study provides insight into the genetic synergy that contributes to multi-step leukemogenesis. PMID:27134169

  15. A cell cycle-regulated GATA factor promotes centromeric localization of CENP-A in fission yeast.

    Science.gov (United States)

    Chen, Ee Sin; Saitoh, Shigeaki; Yanagida, Mitsuhiro; Takahashi, Kohta

    2003-01-01

    CENP-A, the centromere-specific histone H3 variant, plays a crucial role in organizing kinetochore chromatin for precise chromosome segregation. We have isolated Ams2, a Daxx-like motif-containing GATA factor, and histone H4, as multicopy suppressors of cnp1-1, an S. pombe CENP-A mutant. While depletion of Ams2 results in the reduction of CENP-A binding to the centromere and chromosome missegregation, increasing its dosage restores association of a CENP-A mutant protein with centromeres. Conversely, overexpression of CENP-A or histone H4 suppresses an ams2 disruptant. The intracellular amount of Ams2 thus affects centromeric nucleosomal constituents. Ams2 is abundant in S phase and associates with chromatin, including the central centromeres through binding to GATA-core sequences. Ams2 is thus a cell cycle-regulated GATA factor that is required for centromere function. PMID:12535531

  16. Promyelocytic leukemia zinc finger protein activates GATA4 transcription and mediates cardiac hypertrophic signaling from angiotensin II receptor 2.

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    Ning Wang

    Full Text Available BACKGROUND: Pressure overload and prolonged angiotensin II (Ang II infusion elicit cardiac hypertrophy in Ang II receptor 1 (AT(1 null mouse, whereas Ang II receptor 2 (AT(2 gene deletion abolishes the hypertrophic response. The roles and signals of the cardiac AT(2 receptor still remain unsettled. Promyelocytic leukemia zinc finger protein (PLZF was shown to bind to the AT(2 receptor and transmit the hypertrophic signal. Using PLZF knockout mice we directed our studies on the function of PLZF concerning the cardiac specific transcription factor GATA4, and GATA4 targets. METHODOLOGY AND PRINCIPAL FINDINGS: PLZF knockout and age-matched wild-type (WT mice were treated with Ang II, infused at a rate of 4.2 ng·kg(-1·min(-1 for 3 weeks. Ang II elevated systolic blood pressure to comparable levels in PLZF knockout and WT mice (140 mmHg. WT mice developed prominent cardiac hypertrophy and fibrosis after Ang II infusion. In contrast, there was no obvious cardiac hypertrophy or fibrosis in PLZF knockout mice. An AT(2 receptor blocker given to Ang II-infused wild type mice prevented hypertrophy, verifying the role of AT(2 receptor for cardiac hypertrophy. Chromatin immunoprecipitation and electrophoretic mobility shift assay showed that PLZF bound to the GATA4 gene regulatory region. A Luciferase assay verified that PLZF up-regulated GATA4 gene expression and the absence of PLZF expression in vivo produced a corresponding repression of GATA4 protein. CONCLUSIONS: PLZF is an important AT(2 receptor binding protein in mediating Ang II induced cardiac hypertrophy through an AT(2 receptor-dependent signal pathway. The angiotensin II-AT(2-PLZF-GATA4 signal may further augment Ang II induced pathological effects on cardiomyocytes.

  17. The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription

    OpenAIRE

    Tanabe, Osamu; Shen, Yannan; Liu, Qinghui; Campbell, Andrew D.; Kuroha, Takashi; Yamamoto, Masayuki; Engel, James Douglas

    2007-01-01

    When the orphan nuclear receptors TR2 and TR4, the DNA-binding subunits of the DRED repressor complex, are forcibly expressed in erythroid cells of transgenic mice, embryos exhibit a transient mid-gestational anemia as a consequence of a reduction in the number of primitive erythroid cells. GATA-1 mRNA is specifically diminished in the erythroid cells of these TR2/TR4 transgenic embryos as it is in human CD34+ progenitor cells transfected with forcibly expressed TR2/TR4. In contrast, in loss-...

  18. FoxP3, GATA-3 and T-bet expression in elderly asthma

    OpenAIRE

    Vale-Pereira, Sofia; Todo-Bom, Ana; Geraldes, Luisa; Schmidt-Weber, Carsten; Akdis, Cesmi; Mota-Pinto, Anabela

    2011-01-01

    BACKGROUND: Asthma is a chronic inflammatory disorder in which Th2, Th1 and suppressive T cells (Tregs) play a role. The transcription factor FoxP3 plays a role in Treg differentiation while T-bet is important for Th1 and GATA-3 for Th2 differentiation from naïve T cells. Recent data show that age-related deregulation of Treg cells is a mechanism of senescence affecting several chronic diseases. It is crucial to understand the behaviour of these cell populations in asthma for elderly patients...

  19. GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry

    OpenAIRE

    Ku, Chia-Jui; Hosoya, Tomonori; Maillard, Ivan; Engel, James Douglas

    2012-01-01

    Maintaining hematopoietic stem cell (HSC) quiescence is a critical property for the life-long generation of blood cells. Approximately 75% of cells in a highly enriched long-term repopulating HSC (LT-HSC) pool (Lin−Sca1+c-KithiCD150+CD48−) are quiescent, with only a small percentage of the LT-HSCs in cycle. Transcription factor GATA-3 is known to be vital for the development of T cells at multiple stages in the thymus and for Th2 differentiation in the peripheral organs. Although it is well d...

  20. Ascitis quilosa en una gata: presentación de un caso

    OpenAIRE

    Amo, Alicia N. del; Piella, M.; Arias, Daniel Osvaldo; Tortora, M.; Scodellaro, Carla Floriana; Pintos, María Eugenia; Villanueva, Miriam; Diessler, Mónica Elizabeth; Massone, Adriana R.

    2003-01-01

    La ascitis quilosa es un hallazgo poco frecuente en la clínica de pequeños animales. En su mayoría se originan a partir de alteraciones intra-abdominales tales como ruptura de vasos linfáticos, neoplasias que obstruyan el drenaje de vasos linfáticos y cirrosis hepática. En el presente trabajo se describe un caso clínico de ascitis quilosa en una gata mestiza de pelo largo. Los hallazgos en los métodos complementarios que se realizaron, incluyendo el análisis bioquímico, citológico, radiológic...

  1. PU.1 Suppresses Th2 Cytokine Expression via Silencing of GATA3 Transcription in Dendritic Cells

    OpenAIRE

    Yashiro, Takuya; Kubo, Masato; Ogawa, Hideoki; Okumura, Ko; Nishiyama, Chiharu

    2015-01-01

    The transcription factor PU.1 is predominantly expressed in dendritic cells (DCs) and is essential for DC differentiation. Although there are several reports that PU.1 positively regulates the expression of DC-specific genes, whether PU.1 also has a suppressive effect on DCs is largely unknown. Here we demonstrate that PU.1 suppresses the expression of Th2 cytokines including IL-13 and IL-5 in bone marrow-derived DCs (BMDCs), through repression of the expression of GATA3, which is a master re...

  2. LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis

    OpenAIRE

    Maeda, Takahiro; Ito, Keisuke; Merghoub, Taha; Poliseno, Laura; Hobbs, Robin M.; Wang, Guocan; Dong, Lin; Maeda, Manami; Dore, Louis C.; Zelent, Arthur; Luzzatto, Lucio; Teruya-Feldstein, Julie; Weiss, Mitchell J.; Pandolfi, Pier Paolo

    2009-01-01

    GATA-1-dependent transcription is essential for erythroid differentiation and maturation. Suppression of programmed cell death is also thought to be critical for this process; however, the link between these two features of erythropoiesis has remained elusive. Here, we show that the POZ-Krüppel family transcription factor, LRF (also known as Zbtb7a/Pokemon), is a direct target of GATA1 and plays an essential anti-apoptotic role during terminal erythroid differentiation. We find that loss of L...

  3. Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1.

    OpenAIRE

    Osada, H; Grutz, G.; Axelson, H; Forster, A.; Rabbitts, T H

    1995-01-01

    The RBTN2 LIM-domain protein, originally identified as an oncogenic protein in human T-cell leukemia, is essential for erythropoiesis. A possible role for RBTN2 in transcription during erythropoiesis has been investigated. Direct interaction of the RBTN2 protein was observed in vivo and in vitro with the GATA1 or -2 zinc-finger transcription factors, as well as with the basic helix-loop-helix protein TAL1. By using mammalian two-hybrid analysis, complexes involving RBTN2, TAL1, and GATA1, tog...

  4. The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

    Directory of Open Access Journals (Sweden)

    Halsey Christina

    2012-08-01

    Full Text Available Abstract Background Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL where GATA1FL mutations are an essential driver for disease pathogenesis. Methods Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. Results We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. Conclusions These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL.

  5. Developmental Expression of an Amphioxus (Branchiostoma belcheri) Gene Encoding a GATA Transcription Factor%文昌鱼一个GATA基因在胚胎发育中的表达图式

    Institute of Scientific and Technical Information of China (English)

    张煜; 毛炳宇

    2009-01-01

    GATA factors are evolutionarily conserved and play crucial roles during embryonic development in both vertebrates and invertebrates. Vertebrate GATAs can be divided into two subgroups, the GATA1/2/3 and the GATA4/5/6 classes. Through genomic analysis, we have identified three GATA factors, representing the GATA1/2/3 and GATA4/5/6 subfamilies respectively, and one GATA like protein in the genome of the basal chordate amphioxus (Branchiostoma floridae, cephalochordata). Partial sequence of GATA123 in the amphioxus Branchiostoma belcheri (BbGATA123) was cloned and its expression pattern during early embryonic development was studied. Expression of BbGATA123 is first detected in the mesendoderm during gastrulation. Interestingly, in the late neurula and early larva stages, it is expressed strongly in the cerebral vesicle and the mid gut region. Its expression is compared to Otx, a gene known crucial for the development of anterior structures. Our observations suggest that GATA123, together with Otx, might play an important role in the development of amphioxus cerebral vesicle, the counterpart of the vertebrate brain.%GATA基因在脊椎动物和非脊椎动物的发育中行使重要的功能,该家族的成员在进化上也足非常保守的.脊椎动物的GATA基因分为两个亚群:GATA1/2/3和GATA4/5/6.通过生物信息分析,在文吕鱼的基因缓中找到了3个GATA基因:一个GATA1/2/3业家族基因,两个GATA4/5/6亚家族基因:还找到一个类GATA基因.还克隆了白氏文昌鱼(Branchiostoma belcheri)GATA123的一段序列,并研究了它在早期胚胎发育中的表达图式.结果表明GATA123在原肠胚的中内胚层表达,而在神经胚晚期和幼体早期,GATA123在脑泡和消化道中部区域表达.这种表达模式与头部发育的重要基因Otx相类似.结果提示在文吕鱼脑泡的发育过程中GATA123和Otx很可能共同发挥着重要的作用.

  6. A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing.

    Science.gov (United States)

    Yu, Wei-Ming; Appler, Jessica M; Kim, Ye-Hyun; Nishitani, Allison M; Holt, Jeffrey R; Goodrich, Lisa V

    2013-01-01

    Information flow through neural circuits is determined by the nature of the synapses linking the subtypes of neurons. How neurons acquire features distinct to each synapse remains unknown. We show that the transcription factor Mafb drives the formation of auditory ribbon synapses, which are specialized for rapid transmission from hair cells to spiral ganglion neurons (SGNs). Mafb acts in SGNs to drive differentiation of the large postsynaptic density (PSD) characteristic of the ribbon synapse. In Mafb mutant mice, SGNs fail to develop normal PSDs, leading to reduced synapse number and impaired auditory responses. Conversely, increased Mafb accelerates synaptogenesis. Moreover, Mafb is responsible for executing one branch of the SGN differentiation program orchestrated by the Gata3 transcriptional network. Remarkably, restoration of Mafb rescues the synapse defect in Gata3 mutants. Hence, Mafb is a powerful regulator of cell-type specific features of auditory synaptogenesis that offers a new entry point for treating hearing loss. DOI: http://dx.doi.org/10.7554/eLife.01341.001. PMID:24327562

  7. Notch signaling represses GATA4-induced expression of genes involved in steroid biosynthesis.

    Science.gov (United States)

    George, Rajani M; Hahn, Katherine L; Rawls, Alan; Viger, Robert S; Wilson-Rawls, Jeanne

    2015-10-01

    Notch2 and Notch3 and genes of the Notch signaling network are dynamically expressed in developing follicles, where they are essential for granulosa cell proliferation and meiotic maturation. Notch receptors, ligands, and downstream effector genes are also expressed in testicular Leydig cells, predicting a potential role in regulating steroidogenesis. In this study, we sought to determine if Notch signaling in small follicles regulates the proliferation response of granulosa cells to FSH and represses the up-regulation steroidogenic gene expression that occurs in response to FSH as the follicle grows. Inhibition of Notch signaling in small preantral follicles led to the up-regulation of the expression of genes in the steroid biosynthetic pathway. Similarly, progesterone secretion by MA-10 Leydig cells was significantly inhibited by constitutively active Notch. Together, these data indicated that Notch signaling inhibits steroidogenesis. GATA4 has been shown to be a positive regulator of steroidogenic genes, including STAR protein, P450 aromatase, and 3B-hydroxysteroid dehydrogenase. We observed that Notch downstream effectors HEY1, HEY2, and HEYL are able to differentially regulate these GATA4-dependent promoters. These data are supported by the presence of HEY/HES binding sites in these promoters. These studies indicate that Notch signaling has a role in the complex regulation of the steroidogenic pathway. PMID:26183893

  8. Optimizing the GATA-3 position weight matrix to improve the identification of novel binding sites

    Directory of Open Access Journals (Sweden)

    Nandi Soumyadeep

    2012-08-01

    Full Text Available Abstract Background The identifying of binding sites for transcription factors is a key component of gene regulatory network analysis. This is often done using position-weight matrices (PWMs. Because of the importance of in silico mapping of tentative binding sites, we previously developed an approach for PWM optimization that substantially improves the accuracy of such mapping. Results The present work implements the optimization algorithm applied to the existing PWM for GATA-3 transcription factor and builds a new di-nucleotide PWM. The existing available PWM is based on experimental data adopted from Jaspar. The optimized PWM substantially improves the sensitivity and specificity of the TF mapping compared to the conventional applications. The refined PWM also facilitates in silico identification of novel binding sites that are supported by experimental data. We also describe uncommon positioning of binding motifs for several T-cell lineage specific factors in human promoters. Conclusion Our proposed di-nucleotide PWM approach outperforms the conventional mono-nucleotide PWM approach with respect to GATA-3. Therefore our new di-nucleotide PWM provides new insight into plausible transcriptional regulatory interactions in human promoters.

  9. GATA3 mRNA expression, but not mutation, associates with longer progression-free survival in ER-positive breast cancer patients treated with first-line tamoxifen for recurrent disease.

    Science.gov (United States)

    Liu, Jingjing; Prager-van der Smissen, Wendy J C; Look, Maxime P; Sieuwerts, Anieta M; Smid, Marcel; Meijer-van Gelder, Marion E; Foekens, John A; Hollestelle, Antoinette; Martens, John W M

    2016-06-28

    In breast cancer, GATA3 mutations have been associated with a favorable prognosis and the response to neoadjuvant aromatase inhibitor treatment. Therefore, we investigated whether GATA3 mutations predict the outcome of tamoxifen treatment in the advanced setting. In a retrospective study consisting of 235 hormone-naive patients with ER-positive breast cancer who received tamoxifen as first-line treatment for recurrent disease, GATA3 mutations (in 14.0% of patients) did not significantly associate with either the overall response rate (ORR) or with the length of progression-free survival (PFS) after the start of tamoxifen therapy. Interestingly, among 148 patients for whom both mutation and mRNA expression data were available, GATA3 mutations associated with an increased expression of GATA3. However, only 23.7% of GATA3 high tumors had a mutation. Evaluation of the clinical significance of GATA3 mRNA revealed that it was associated with prolonged PFS, but not with the ORR, also in multivariate analysis. Thus, GATA3 mRNA expression, but not GATA3 mutation, is an independent predictor of prolonged PFS in ER-positive breast cancer patients who received first-line tamoxifen for recurrent disease. Besides GATA3 mutation, other mechanisms must exist that underlie increased GATA3 levels. PMID:27018307

  10. Multiplex Ligation-Dependent Probe Amplification Analysis of GATA4 Gene Copy Number Variations in Patients with Isolated Congenital Heart Disease

    Directory of Open Access Journals (Sweden)

    Valentina Guida

    2010-01-01

    Full Text Available GATA4 mutations are found in patients with different isolated congenital heart defects (CHDs, mostly cardiac septal defects and tetralogy of Fallot. In addition, GATA4 is supposed to be the responsible gene for the CHDs in the chromosomal 8p23 deletion syndrome, which is recognized as a malformation syndrome with clinical symptoms of facial anomalies, microcephaly, mental retardation, and congenital heart defects. Thus far, no study has been carried out to investigate the role of GATA4 copy number variations (CNVs in non-syndromic CHDs. To explore the possible occurrence of GATA4 gene CNVs in isolated CHDs, we analyzed by multiplex ligation-dependent probe amplification (MLPA a cohort of 161 non-syndromic patients with cardiac anomalies previously associated with GATA4 gene mutations. The patients were mutation-negative for GATA4, NKX2.5, and FOG2 genes after screening with denaturing high performance liquid chromatography. MLPA analysis revealed that normalized MLPA signals were all found within the normal range values for all exons in all patients, excluding a major contribution of GATA4 gene CNVs in CHD pathogenesis.

  11. RhIL-11 treatment normalized Th1/Th2 and T-bet/GATA-3 imbalance in in human immune thrombocytopenic purpura (ITP).

    Science.gov (United States)

    Lin, Ying; Zhou, Xieming; Guo, Wenjian; Li, Qianqian; Pan, Xiahui; Bao, Yunhua; He, Muqing; Zhu, Baoling; Lin, Xiaoji; Jin, Limin; Yao, Rongxin

    2016-09-01

    Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by reduction in platelet counts. T helper 1 (Th1) cells polarization with an increased shift of Th1/Th2 ratio has been reported in ITP. This shift is associated with transcription factor T-box expressed in T cells (T-bet) upregulation and GATA-binding protein 3 (GATA-3) downregulation, leading to an increased T-bet/GATA-3 ratio. Our previous in vitro study showed that recombinant human interleukin-11 (rhIL-11) could normalize Th1/Th2 imbalance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients, which co-occurred with T-bet/GATA-3 ratio restoration. In this report, we investigated whether rhIL-11 had therapeutic effect in clinical ITP patients and whether rhIL-11 treatment could normalize Th1/Th2 and T-bet/GATA-3 levels in vivo. We found rhIL-11 treatment had a response rate of 67.7% and significantly decreased Th1 and T-bet levels but increased Th2 and GATA-3 levels in ITP patients who showed good response, normalizing Th1/Th2 and T-bet/GATA-3 ratios similar to that in healthy controls. Thus our study suggested rhIL-11 was effective with tolerable adverse effects in ITP. The treatment strategy warrants further clinical investigation. PMID:27235596

  12. 中国人群Duffy血型基因启动子GATA-1序列研究%Study on a GATA-1 motif of Duffy gene promoter in Chinese population

    Institute of Scientific and Technical Information of China (English)

    苏宇清; 梁延连; 张印则; 吴凡

    2014-01-01

    目的 研究中国人群中Duffy血型基因启动子区域GATA-1盒子的遗传特点.方法 在中国人群中选择182例无偿献血者,用血清学方法鉴定Ddfy血型的表现型,提取基因组DNA,扩增测序Duffy血型基因启动子区域,其中包括GATA-1红细胞结合位点,同时使用PCR-SSP法检测Duffy基因型.结果 182例Duffy血型定型为Fy(a-b-)0例,Fy(a-b+)3例,Fy(a+b-)153例,Fy(a+b+)26例.Duffy血型基因分型PCR-SSP结果显示与其表现.型吻合.182例样本Duffy启动子区域的测序GATA-1的结合位点46位均为T/T纯合子.检出1例新的杂合子突变C-108T.结论 本文首次针对中国人群进行Duffy启动子区域GATA-1序列进行研究,测序结果显示,182例样本GATA-1结合位点均为正常野生型,Duffy血型基因启动子区域C-108T突变为首例报导.

  13. Subculture of Germ Cell-Derived Colonies with GATA4-Positive Feeder Cells from Neonatal Pig Testes

    Directory of Open Access Journals (Sweden)

    Kyung Hoon Lee

    2016-01-01

    Full Text Available Enrichment of spermatogonial stem cells is important for studying their self-renewal and differentiation. Although germ cell-derived colonies (GDCs have been successfully cultured from neonatal pig testicular cells under 31°C conditions, the short period of in vitro maintenance (<2 months limited their application to further investigations. To develop a culture method that allows for in vitro maintenance of GDCs for long periods, we subcultured the GDCs with freshly prepared somatic cells from neonatal pig testes as feeder cells. The subcultured GDCs were maintained up to passage 13 with the fresh feeder cells (FFCs and then frozen. Eight months later, the frozen GDCs could again form the colonies on FFCs as shown in passages 1 to 13. Immunocytochemistry data revealed that the FFCs expressed GATA-binding protein 4 (GATA4, which is also detected in the cells of neonatal testes and total testicular cells, and that the expression of GATA4 was decreased in used old feeder cells. The subcultured GDCs in each passage had germ and stem cell characteristics, and flow cytometric analyses revealed that ~60% of these cells were GFRα-1 positive. In conclusion, neonatal pig testes-derived GDCs can be maintained for long periods with GATA4-expressing testicular somatic cells.

  14. GATA-3 promotes T-cell specification by repressing B-cell potential in pro-T cells in mice

    NARCIS (Netherlands)

    M.E. García (Marcos); R.G.J. Klein Wolterink (Roel); F. Lemâitre (Fabrice); C. Le Goff (Carine); M. Hasan (Milena); R.W. Hendriks (Rudi); A. Cumano (Ana); J.P. di Santo (James)

    2013-01-01

    textabstractTranscription factors orchestrate T-lineage differentiation in the thymus. One critical checkpoint involves Notch1 signaling that instructs T-cell commitment at the expense of the B-lineage program. While GATA-3 is required for T-cell specification, its mechanism of action is poorly unde

  15. TRANSCRIPTIONAL FA CTORS FOXP3, GATA-3, PAX-5 AND THEIR COOPERAT IVE INTERACTIONS IN BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    V. N. Mineev

    2013-01-01

    Full Text Available Abstract. The review article summarizes current information about transcriptional factors Fохр3, GATA- 3, РАХ-5 and their cooperative interactions. Predomination of one of these factors leads to production of corresponding cytokines and appropriate changes in T and B cell functions, thus causing development of different inflammatory events and typical symptoms. Focusing the discussion on Foxp3, GATA-3 and PAX- 5 is essential for understanding pathogenesis of inflammatory lung diseases, in particular, bronchial asthma. The data obtained will be helpful in development of novel therapeutic strategies. Mechanisms of cooperative interactions of Fохр3, GATA-3 and РАХ-5, generally, remain poorly understood. In this article, we present modern, sometimes, controversial views on this issue. In particular, we are discussing regulation of Foxp3 expression, molecular interactions affecting production of PAX-5 factor, as well as addressing possible indirect interactions between these transcription factors via implementing GATA-3 and STAT6 functions.

  16. Mutagenesis of GATA motifs controlling the endoderm regulator elt-2 reveals distinct dominant and secondary cis-regulatory elements.

    Science.gov (United States)

    Du, Lawrence; Tracy, Sharon; Rifkin, Scott A

    2016-04-01

    Cis-regulatory elements (CREs) are crucial links in developmental gene regulatory networks, but in many cases, it can be difficult to discern whether similar CREs are functionally equivalent. We found that despite similar conservation and binding capability to upstream activators, different GATA cis-regulatory motifs within the promoter of the C. elegans endoderm regulator elt-2 play distinctive roles in activating and modulating gene expression throughout development. We fused wild-type and mutant versions of the elt-2 promoter to a gfp reporter and inserted these constructs as single copies into the C. elegans genome. We then counted early embryonic gfp transcripts using single-molecule RNA FISH (smFISH) and quantified gut GFP fluorescence. We determined that a single primary dominant GATA motif located 527bp upstream of the elt-2 start codon was necessary for both embryonic activation and later maintenance of transcription, while nearby secondary GATA motifs played largely subtle roles in modulating postembryonic levels of elt-2. Mutation of the primary activating site increased low-level spatiotemporally ectopic stochastic transcription, indicating that this site acts repressively in non-endoderm cells. Our results reveal that CREs with similar GATA factor binding affinities in close proximity can play very divergent context-dependent roles in regulating the expression of a developmentally critical gene in vivo. PMID:26896592

  17. T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription

    OpenAIRE

    Usui, Takashi; Preiss, Jan C.; Kanno, Yuka; Yao, Zheng Ju; Bream, Jay H.; O'Shea, John J.; Strober, Warren

    2006-01-01

    T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3. Here we show that CD4+ cells from T-bet−/− mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti–interleukin (IL)-4 blockade of IL-4 receptor (R) signaling. In addit...

  18. c-Myb, Menin, GATA-3, and MLL form a dynamic transcription complex that plays a pivotal role in human T helper type 2 cell development

    OpenAIRE

    Nakata, Yuji; Brignier, Anne C.; Jin, Shenghao; Shen, Yuan; Rudnick, Stephen I.; Sugita, Mayumi; Gewirtz, Alan M.

    2010-01-01

    GATA-3 and c-Myb are core elements of a transcriptionally active complex essential for human Th2 cell development and maintenance. We report herein mechanistic details concerning the role of these transcription factors in human peripheral blood Th2 cell development. Silencing c-Myb in normal human naive CD4+ cells under Th2 cell-promoting conditions blocked up-regulation of GATA-3 and interleukin-4, and in effector/memory CD4+ T cells, decreased expression of GATA-3 and Th2 cytokines. In prim...

  19. T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements

    OpenAIRE

    Kanhere, Aditi; Hertweck, Arnulf; Bhatia, Urvashi; Gökmen, M Refik; Perucha, Esperanza; Jackson, Ian; Lord, Graham M.; Jenner, Richard G.

    2012-01-01

    T-bet and GATA3 regulate the CD4+ T cell Th1/Th2 cell fate decision but little is known about the interplay between these factors outside of the murine Ifng and Il4/Il5/Il13 loci. Here we show that T-bet and GATA3 bind to multiple distal sites at immune regulatory genes in human effector T cells. These sites display markers of functional elements, act as enhancers in reporter assays and are associated with a requirement for T-bet and GATA3. Furthermore, we demonstrate that both factors bind d...

  20. Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations

    International Nuclear Information System (INIS)

    Guanine-adenine-thymine-adenine 2 (GATA2) mutated disorders include the recently described MonoMAC syndrome (Monocytopenia and Mycobacterium avium complex infections), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial MDS/AML (myelodysplastic syndrome/acute myeloid leukemia) (myeloid neoplasms), congenital neutropenia, congenital lymphedema (Emberger's syndrome), sensorineural deafness, viral warts, and a spectrum of aggressive infections seen across all age groups. While considerable efforts have been made to identify the mutations that characterize this disorder, pathogenesis remains a work in progress with less than 100 patients described in current literature. Varying clinical presentations offer diagnostic challenges. Allogeneic stem cell transplant remains the treatment of choice. Morbidity, mortality, and social costs due to the familial nature of the disease are considerable. We describe our experience with the disorder in three affected families and a comprehensive review of current literature

  1. Two GATA transcription factors are downstream effectors of floral homeotic gene action in Arabidopsis.

    Science.gov (United States)

    Mara, Chloe D; Irish, Vivian F

    2008-06-01

    Floral organogenesis is dependent on the combinatorial action of MADS-box transcription factors, which in turn control the expression of suites of genes required for growth, patterning, and differentiation. In Arabidopsis (Arabidopsis thaliana), the specification of petal and stamen identity depends on the action of two MADS-box gene products, APETALA3 (AP3) and PISTILLATA (PI). In a screen for genes whose expression was altered in response to the induction of AP3 activity, we identified GNC (GATA, nitrate-inducible, carbon-metabolism-involved) as being negatively regulated by AP3 and PI. The GNC gene encodes a member of the Arabidopsis GATA transcription factor family and has been implicated in the regulation of chlorophyll biosynthesis as well as carbon and nitrogen metabolism. In addition, we found that the GNC paralog, GNL (GNC-like), is also negatively regulated by AP3 and PI. Using chromatin immunoprecipitation, we showed that promoter sequences of both GNC and GNL are bound by PI protein, suggesting a direct regulatory interaction. Analyses of single and double gnc and gnl mutants indicated that the two genes share redundant roles in promoting chlorophyll biosynthesis, suggesting that in repressing GNC and GNL, AP3/PI have roles in negatively regulating this biosynthetic pathway in flowers. In addition, coexpression analyses of genes regulated by AP3, PI, GNC, and GNL indicate a complex regulatory interplay between these transcription factors in regulating a variety of light and nutrient responsive genes. Together, these results provide new insights into the transcriptional cascades controlling the specification of floral organ identities. PMID:18417639

  2. Genome-wide Analysis of Simultaneous GATA1/2, RUNX1, FLI1, and SCL Binding in Megakaryocytes Identifies Hematopoietic Regulators

    OpenAIRE

    Tijssen, Marloes R.; Cvejic, Ana; Joshi, Anagha; Hannah, Rebecca L.; Ferreira, Rita; Forrai, Ariel; Bellissimo, Dana C.; Oram, S. Helen; Smethurst, Peter A.; Wilson, Nicola K.; Wang, Xiaonan; Ottersbach, Katrin; Stemple, Derek L.; Green, Anthony R.; Ouwehand, Willem H.

    2011-01-01

    Summary Hematopoietic differentiation critically depends on combinations of transcriptional regulators controlling the development of individual lineages. Here, we report the genome-wide binding sites for the five key hematopoietic transcription factors—GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL—in primary human megakaryocytes. Statistical analysis of the 17,263 regions bound by at least one factor demonstrated that simultaneous binding by all five factors was the most enriched pattern and often...

  3. GATA1 mutation negative acute megakaryoblastic leukemia with acquired trisomy 21 presenting with extensive bone marrow necrosis in an adult: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Todd P. Williams

    2016-03-01

    Conclusions: To our knowledge, this is the first reported case of an adult with AMKL with acquired trisomy 21 in which the GATA1 mutation was investigated and the second reported case of AMKL presenting with extensive bone marrow necrosis. We will present a diagnostic approach to AMKL in which extensive bone marrow necrosis renders examination of the bone marrow difficult. Furthermore, we will examine the absence of the GATA1 mutation in a case of AMKL with trisomy 21 in an adult.

  4. Action of the Caenorhabditis elegans GATA factor END-1 in Xenopus suggests that similar mechanisms initiate endoderm development in ecdysozoa and vertebrates

    OpenAIRE

    Shoichet, Sarah A.; Malik, Talat H.; Rothman, Joel H.; Shivdasani, Ramesh A.

    2000-01-01

    In ecdysozoan protostomes, including arthropods and nematodes, transcription factors of the GATA family specify the endoderm: Drosophila dGATAb (ABF/Serpent) and Caenorhabditis elegans END-1 play important roles in generating this primary germ layer. end-1 is the earliest expressed endoderm-specific gene known in C. elegans and appears to initiate the program of gene expression required for endoderm differentiation, including a cascade of GATA factors required for development and maintenance ...

  5. Genome-Wide Gene Expression Profiling Revealed a Critical Role for GATA3 in the Maintenance of the Th2 Cell Identity.

    Directory of Open Access Journals (Sweden)

    Tetsuya Sasaki

    Full Text Available Functionally polarized CD4+ T helper (Th cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity.

  6. Isolation, characterization and genetic analysis of canine GATA4 gene in a family of Doberman Pinschers with an atrial septal defect

    Indian Academy of Sciences (India)

    Shin-Aeh Lee; Seung-Gon Lee; Hyeong-Sun Moon; Lopeti Lavulo; Kyoung-Oh Cho; Changbaig Hyun

    2007-12-01

    GATA4 is expressed early in the developing heart where it plays a key role in regulating the expression of genes encoding myocardial contractile proteins. Gene mutations in the human GATA4 have been implicated in various congenital heart defects (CHD), including atrial septal defect (ASD). Although ASD is the third most common CHD in humans, it is generally rare in dogs and cats. There is also no obvious predilection for ASD in dogs and cats, based on sex or breed. However, among dogs, the incidence rate of ASD is relatively high in Samoyeds and Doberman Pinschers, where its inheritance and genetic aetiology are not well understood. In this study, we identified and investigated the genetic aetiology of an ASD affected family in a pure breed dog population. Although the GATA4 gene was screened, we did not find any mutations that would result in the alteration of the coding sequence and hence, the predicted GATA4 structure and function. Although the aetiology of ASD is multifactorial, our findings indicate that GATA4 may not be responsible for the ASD in the dogs used in this study. However, this does not eliminate GATA4 as a candidate for ASD in other dog breeds.

  7. Evaluation of androgen receptor and GATA binding protein 3 as immunohistochemical markers in the diagnosis of metastatic breast carcinoma to the lung.

    Science.gov (United States)

    Hattori, Yukinori; Yoshida, Akihiko; Yoshida, Masayuki; Takahashi, Masahide; Tsuta, Koji

    2015-06-01

    Differentiating metastatic breast carcinoma in the lungs from primary lung tumors and mesotheliomas is important for determining prognosis and treatment. We evaluated novel breast specific markers, androgen receptor (AR) and GATA binding protein 3 (GATA3) immunohistostaining, for this differential, and compare to other traditional markers. The specimens comprised 33 metastatic breast carcinomas to the lung, 566 primary lung tumors (170 adenocarcinomas, 157 squamous cell carcinomas, 31 pleomorphic carcinomas, 115 large cell neuroendocrine carcinomas, 43 small cell carcinomas, and 49 typical carcinoids) and 42 malignant mesotheliomas. They were analyzed by immunohistochemistry using antibodies to AR, GATA3, estrogen receptor (ER), progesterone receptor (PgR), mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15). Of the metastatic breast carcinomas, immunohistostaining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 27 cases (81.8%), 24 cases (72.7%), 26 cases (78.8%), 13 cases (39.4%), 12 cases (36.4%), 9 cases (27.3%), respectively. Of primary lung tumors and mesotheliomas, staining of AR, GATA3, ER, PgR, mammaglobin, GCDFP-15 were positive in 18 cases (3%), 3 cases (0.5%), 4 cases (0.7%), 2 cases (0.3%), 0 case (0%), 2 cases (0.3%), respectively. Immunohistochemistry of AR and GATA3 are reliable for differentiating metastatic breast carcinoma from primary lung tumors and mesotheliomas. PMID:25727644

  8. The roles of GATA-4 during the heart development of vertebrates%转录因子GATA-4在脊椎动物心脏发育中的作用

    Institute of Scientific and Technical Information of China (English)

    郑嘉毅

    2012-01-01

    GA TA -4 transcription factor plays a critical role in the development of the heart. It belongs to the GATA family, which contains 2 conserved zinc finger DNA-binding domains. Deletion of GATA-4 may lead to embryonic death andmissense mutations of GA TA -4 at different sites are associated with different types of congenital heart defects. The present review focuses on the critical roles of GATA-4 on myocardial cell differentiation, embryonic development and cell apoptosisduring the heart development based on existing researches and articles, so as to provide a theoretical basis for the human diseases related to GA TA -4.%GATA-4是心脏发育过程中至关重要的转录因子,属于具有保守锌指结构的GA TA转录因子家族.GA TA-4基因缺失可致胚胎死亡,而不同位点的错义突变将引起不同类型的先天性心脏发育畸形.文章旨在通过对GA TA-4-4在心肌细胞分化、胚胎发育、细胞凋亡等方面所起的作用,对相关研究进展进行综述,探讨GA TA-4在心脏发育中的作用,从而为防治人类相关疾病提供理论依据.

  9. The GATA1-HS2 Enhancer Allows Persistent and Position-Independent Expression of a β-globin Transgene

    OpenAIRE

    Miccio, Annarita; Poletti, Valentina; Tiboni, Francesca; Rossi, Claudia; Antonelli, Antonella; MAVILIO, Fulvio; Ferrari, Giuliana

    2011-01-01

    Gene therapy of genetic diseases requires persistent and position-independent expression of a therapeutic transgene. Transcriptional enhancers binding chromatin-remodeling and modifying complexes may play a role in shielding transgenes from repressive chromatin effects. We tested the activity of the HS2 enhancer of the GATA1 gene in protecting the expression of a β-globin minigene delivered by a lentiviral vector in hematopoietic stem/progenitor cells. Gene expression from proviruses carrying...

  10. GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes

    OpenAIRE

    Lamartine Jérôme; Martin Michèle T; Berthier-Vergnes Odile; Malet Claude; Ginestet Chantal; Molina Manuella; Bonin Florian

    2009-01-01

    Abstract Background The general population is constantly exposed to low levels of radiation through natural, occupational or medical irradiation. Even if the biological effects of low-level radiation have been intensely debated and investigated, the molecular mechanisms underlying the cellular response to low doses remain largely unknown. Results The present study investigated the role of GATA3 protein in the control of the cellular and molecular response of human keratinocytes exposed to a 1...

  11. GATA3 Is Selectively Expressed in the Trophectoderm of Peri-implantation Embryo and Directly Regulates Cdx2 Gene Expression*

    OpenAIRE

    Home, Pratik; Ray, Soma; Dutta, Debasree; Bronshteyn, Illya; Larson, Melissa; Paul, Soumen

    2009-01-01

    During early mammalian development, genesis of the first two cell lineages, inner cell mass (ICM) and trophectoderm (TE), is dependent upon functions of key transcription factors that are expressed in a regulated and spatially restricted fashion. In this study, we demonstrate that during early mouse development, mRNA expression of transcription factor GATA3 is induced at the 4-cell stage and is consistently present during pre-implantation embryonic development. Interestingly, at the blastocys...

  12. LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis.

    Science.gov (United States)

    Maeda, Takahiro; Ito, Keisuke; Merghoub, Taha; Poliseno, Laura; Hobbs, Robin M; Wang, Guocan; Dong, Lin; Maeda, Manami; Dore, Louis C; Zelent, Arthur; Luzzatto, Lucio; Teruya-Feldstein, Julie; Weiss, Mitchell J; Pandolfi, Pier Paolo

    2009-10-01

    GATA-1-dependent transcription is essential for erythroid differentiation and maturation. Suppression of programmed cell death is also thought to be critical for this process; however, the link between these two features of erythropoiesis has remained elusive. Here, we show that the POZ-Krüppel family transcription factor, LRF (also known as Zbtb7a/Pokemon), is a direct target of GATA1 and plays an essential antiapoptotic role during terminal erythroid differentiation. We find that loss of Lrf leads to lethal anemia in embryos, due to increased apoptosis of late-stage erythroblasts. This programmed cell death is Arf and p53 independent and is instead mediated by upregulation of the proapoptotic factor Bim. We identify Lrf as a direct repressor of Bim transcription. In strong support of this mechanism, genetic Bim loss delays the lethality of Lrf-deficient embryos and rescues their anemia phenotype. Thus, our data define a key transcriptional cascade for effective erythropoiesis, whereby GATA-1 suppresses BIM-mediated apoptosis via LRF. PMID:19853566

  13. GATA3-driven expression of miR-503 inhibits prostate cancer progression by repressing ZNF217 expression.

    Science.gov (United States)

    Jiang, Xingkang; Chen, Yue; Du, E; Yang, Kuo; Zhang, Zhihong; Qi, Shiyong; Xu, Yong

    2016-09-01

    Although increasing evidence demonstrated that deregulation of mircoRNA-503 (miRNA-503) contributes to tumorigenesis, little is known about the biological role and intrinsic regulatory mechanisms of miR-503 in prostate cancer (PCa). In present study, we found that miR-503 was significantly downregulated in advanced PCa tissues and cell lines. Downregulation of miR-503 was strongly associated with aggressive clinical-pathological features and poor prognosis in PCa patients. Ectopic expression of miR-503 significantly inhibited tumor cells growth, cell migration and invasion in vitro and in vivo. Mechanistic studies revealed that ZNF217 was a direct target downstream target of miR-503. Knockdown of ZNF217 mimicked the tumor-suppressive effects of miR-503 overexpression on PCa invasion, whereas ZNF217 overexpression attenuated the tumor-suppressive function of miR-503. Subsequently, miR-503 further modulated the activation of ZNF217-downstream epithelial-mesenchymal transition (EMT) genes. Besides, we also found that GATA3 directly increased miR-503 expression and thus decreased ZNF217 expression, indicating the involvement of GATA3/miR-503/ZNF217 signaling in EMT process. Collectively, our results demonstrated that GATA3-driven expression of miR-503 inhibits PCa progression by repressing ZNF217 expression, and also implicated the potential application of miR-503 in PCa therapy. PMID:27267060

  14. Gain- and Loss-of-Function Mutations in the Breast Cancer Gene GATA3 Result in Differential Drug Sensitivity.

    Science.gov (United States)

    Mair, Barbara; Konopka, Tomasz; Kerzendorfer, Claudia; Sleiman, Katia; Salic, Sejla; Serra, Violeta; Muellner, Markus K; Theodorou, Vasiliki; Nijman, Sebastian M B

    2016-09-01

    Patterns of somatic mutations in cancer genes provide information about their functional role in tumourigenesis, and thus indicate their potential for therapeutic exploitation. Yet, the classical distinction between oncogene and tumour suppressor may not always apply. For instance, TP53 has been simultaneously associated with tumour suppressing and promoting activities. Here, we uncover a similar phenomenon for GATA3, a frequently mutated, yet poorly understood, breast cancer gene. We identify two functional classes of frameshift mutations that are associated with distinct expression profiles in tumours, differential disease-free patient survival and gain- and loss-of-function activities in a cell line model. Furthermore, we find an estrogen receptor-independent synthetic lethal interaction between a GATA3 frameshift mutant with an extended C-terminus and the histone methyltransferases G9A and GLP, indicating perturbed epigenetic regulation. Our findings reveal important insights into mutant GATA3 function and breast cancer, provide the first potential therapeutic strategy and suggest that dual tumour suppressive and oncogenic activities are more widespread than previously appreciated. PMID:27588951

  15. Identification of a novel pathway involving a GATA transcription factor in yeast and possibly in plant Zn uptake and homeostasis

    Institute of Scientific and Technical Information of China (English)

    Matthew J. Milner; Nicole S. Pence; Jiping Liu; Leon V. Kochian

    2014-01-01

    To gain a better understanding of the regulation of Zn homeostasis in plants and the degree of conservation of Zn homeostasis between plants and yeast, a cDNA library from the Zn/Cd hyperaccumulating plant species, Noccaea caerules-cens, was screened for its ability to restore growth under Zn limiting conditions in the yeast mutant zap1D. ZAP1 is a transcription factor that activates the Zn dependent transcrip-tion of yeast genes involved in Zn uptake, including ZRT1, the yeast high affinity Zn transporter. From this screen two members of the E2F family of transcription factors were found to activate ZRT1 expression in a Zn independent manner. The activation of ZRT1 by the plant E2F proteins involves E2F-mediated activation of a yeast GATA transcription factor which in turn activates ZRT1 expression. A ZRT1 promoter region necessary for activation by E2F and GATA proteins is upstream of two zinc responsive elements previously shown to bind ZAP1 in ZRT1. This activation may not involve direct binding of E2F to the ZRT1 promoter. The expression of E2F genes in yeast does not replace function of ZAP1; instead it appears to activate a novel GATA regulatory pathway involved in Zn uptake and homeostasis that is not Zn responsive.

  16. Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6.

    Science.gov (United States)

    Guye, Patrick; Ebrahimkhani, Mohammad R; Kipniss, Nathan; Velazquez, Jeremy J; Schoenfeld, Eldi; Kiani, Samira; Griffith, Linda G; Weiss, Ron

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) have potential for personalized and regenerative medicine. While most of the methods using these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or organoids. Here we present a novel approach for generating and then co-differentiating hiPSC-derived progenitors. With a genetically engineered pulse of GATA-binding protein 6 (GATA6) expression, we initiate rapid emergence of all three germ layers as a complex function of GATA6 expression levels and tissue context. Within 2 weeks we obtain a complex tissue that recapitulates early developmental processes and exhibits a liver bud-like phenotype, including haematopoietic and stromal cells as well as a neuronal niche. Collectively, our approach demonstrates derivation of complex tissues from hiPSCs using a single autologous hiPSCs as source and generates a range of stromal cells that co-develop with parenchymal cells to form tissues. PMID:26732624

  17. IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Kvist, Peter Helding; Holm, Thomas Lindebo; Holgersen, Kristine; Nielsen, Ole Haagen

    2015-01-01

    BACKGROUND: In the respiratory mucosa, interleukin (IL)-33, has been shown to enhance T helper 2 (TH2)-type responses through the master regulatory gene GATA-3. IL-33 is upregulated in ulcerative colitis (UC), and the aim was to assess if IL-33 holds a similar key position in the shaping of the...... were isolated from PAC IL-10 -/- mice and stimulated with IL-33.RESULTS: The colonic IL-33 expression was significantly upregulated all forms of colitis (P < 0.01) and correlated with disease severity score and inflammation (P < 0.001), and with GATA-3 expression levels (P < 0.01); no correlation with...... the TH1-specific T-bet expression was observed. MesLN T cells stimulated with IL-33 had increased GATA-3 expression, and showed an IL-33 dose-dependent increase in secreted TH2-type cytokines, whereas this effect was abolished by blocking IL-33 signaling. The non-TH2-type cytokine IL-17 was...

  18. Enforced expression of GATA-3 in transgenic mice inhibits Th1 differentiation and induces the formation of a T1/ST2-expressing Th2-committed T cell compartment in vivo

    OpenAIRE

    Nawijn, Martijn,; Dingjan, Gemma; Ferreira, Rita; Lambrecht, Bart; Karis, Alar; Savelkoul, Huub; Hendriks, Rudi; Grosveld, Frank

    2001-01-01

    textabstractThe transcription factor GATA-3 is essential for early T cell development and differentiation of naive CD4(+) T cells into Th2 effector cells. To study the function of GATA-3 during T cell-mediated immune responses in vivo, we investigated CD2-GATA3-transgenic mice in which GATA-3 expression is driven by the CD2 locus control region. Both in the CD4(+) and the CD8(+) T cell population the proportion of cells exhibiting a CD44(high)CD45RB(low)CD62L(low) Ag-experienced phenotype was...

  19. IFN-α suppresses GATA3 transcription from a distal exon and promotes H3K27 tri-methylation of the CNS-1 enhancer in human Th2 cells1

    OpenAIRE

    Huber, Jonathan P.; Gonzales-van Horn, Sarah R.; Roybal, Kole T.; Gill, Michelle A.; Farrar, J. David

    2014-01-01

    CD4+ T helper type 2 (Th2) development is regulated by the zinc finger transcription factor GATA3. Once induced by acute priming signals, such as IL-4, GATA3 poises the Th2 cytokine locus for rapid activation and establishes a positive feedback loop that maintains elevated GATA3 expression. Type I interferon (IFN-α/β) inhibits Th2 cells by blocking the expression of GATA3 during Th2 development and in fully committed Th2 cells. In this study, we have uncovered a unique mechanism by which IFN-...

  20. Seafloor mapping of the southeast Iberian margin (from Cabo de Palos to Cabo de Gata)

    Science.gov (United States)

    Lastras, Galderic; Leon, César; Elvira, Elena; Pascual, Laura; Muñoz, Araceli; de Cárdenas, Enrique; Acosta, Juan; Canals, Miquel

    2014-05-01

    We present the multibeam bathymetry and derived maps of the southeast Iberian margin from Cabo de Palos to Cabo de Gata, 37º35'N to 35º45'N and 2º10'W to 0º20'E, from the coastline down to the Algero-Balearic abyssal plain at depths exceeding 2600 m. The edition of of the maps is carried out within the Complementary Action VALORPLAT ("Scientific valorisation of multibeam bathymetry data from the Spanish continental shelf and slope"), funded by the Spanish Ministry of Economy and Competitivity. The multibeam bathymetry data of the slope and abyssal plain were obtained during different surveys in 2004, 2006 and 2007 on board R/V Vizconde de Eza with a Simrad EM300 multibeam echo-sounder as part of the CAPESME Project, a collaboration between the Spanish Institute of Oceanography (IEO) and General Secretariat of Fisheries (SGP), primarily aiming at creating maps of the fishing grounds of the Mediterranean continental margins of Spain. Multibeam bathymetry data from the continental shelf were obtained within the ESPACE project, also in a cooperative frame between IEO and SGP. The map series is constituted by a general map at 1:400,000 scale and 14 detailed maps at 1:75,000 scale, which include inset maps on slope gradients and seafloor nature (rock or sediment type), the later obtained with rock dredges and Shipeck sediment dredges. Both the detailed maps and the general map are available in paper print, and the whole collection is also distributed in an edited USB. The geological features displayed in the different maps include the continental shelf, with abundant geomorphic features indicative of past sea-level changes, the continental slope carved by the Palos, Tiñoso, Cartagena Este, Cartagena Oeste, Águilas, Almanzora, Alias, Garrucha and Gata submarine canyons, the Mazarrón, Palomares and Al-Mansour escarpments, the Abubácer, Maimonides and Yusuf ridges, the Águilas and Al-Mansour seamounts, and the Algero-Balearic abyssal plain where prominent

  1. Nuclear Receptor-Like Structure and Interaction of Congenital Heart Disease-Associated Factors GATA4 and NKX2-5.

    Directory of Open Access Journals (Sweden)

    Sini Kinnunen

    Full Text Available Transcription factor GATA4 is a dosage sensitive regulator of heart development and alterations in its level or activity lead to congenital heart disease (CHD. GATA4 has also been implicated in cardiac regeneration and repair. GATA4 action involves combinatorial interaction with other cofactors such as NKX2-5, another critical cardiac regulator whose mutations also cause CHD. Despite its critical importance to the heart and its evolutionary conservation across species, the structural basis of the GATA4-NKX2-5 interaction remains incompletely understood.A homology model was constructed and used to identify surface amino acids important for the interaction of GATA4 and NKX2-5. These residues were subjected to site-directed mutagenesis, and the mutant proteins were characterized for their ability to bind DNA and to physically and functionally interact with NKX2-5. The studies identify 5 highly conserved amino acids in the second zinc finger (N272, R283, Q274, K299 and its C-terminal extension (R319 that are critical for physical and functional interaction with the third alpha helix of NKX2-5 homeodomain. Integration of the experimental data with computational modeling suggests that the structural arrangement of the zinc finger-homeodomain resembles the architecture of the conserved DNA binding domain of nuclear receptors.The results provide novel insight into the structural basis for protein-protein interactions between two important classes of transcription factors. The model proposed will help to elucidate the molecular basis for disease causing mutations in GATA4 and NKX2-5 and may be relevant to other members of the GATA and NK classes of transcription factors.

  2. Afzelin attenuates asthma phenotypes by downregulation of GATA3 in a murine model of asthma.

    Science.gov (United States)

    Zhou, Wenbo; Nie, Xiuhong

    2015-07-01

    Asthma is a serious health problem causing significant mortality and morbidity globally. Persistent airway inflammation, airway hyperresponsiveness, increased immunoglobulin E (IgE) levels and mucus hypersecretion are key characteristics of the condition. Asthma is mediated via a dominant T-helper 2 (Th2) immune response, causing enhanced expression of Th2 cytokines. These cytokines are responsible for the various pathological changes associated with allergic asthma. To investigate the anti-asthmatic potential of afzelin, as well as the underlying mechanisms involved, its anti-asthmatic potential were investigated in a murine model of asthma. In the present study, BALB/c mice were systemically sensitized using ovalbumin (OVA) followed by aerosol allergen challenges. The effect of afzelin on airway hyperresponsiveness, eosinophilic infiltration, Th2 cytokine and OVA‑specific IgE production in a mouse model of asthma were investigated. It was found that afzelin‑treated groups suppressed eosinophil infiltration, allergic airway inflammation, airway hyperresponsiveness, OVA-specific IgE and Th2 cytokine secretion. The results of the present study suggested that the therapeutic mechanism by which afzelin effectively treats asthma is based on reduction of Th2 cytokine via inhibition of GATA-binding protein 3 transcription factor, which is the master regulator of Th2 cytokine differentiation and production. PMID:25738969

  3. MEF2 Cooperates With Forskolin/cAMP and GATA4 to Regulate Star Gene Expression in Mouse MA-10 Leydig Cells.

    Science.gov (United States)

    Daems, Caroline; Di-Luoffo, Mickaël; Paradis, Élise; Tremblay, Jacques J

    2015-07-01

    In Leydig cells, steroidogenic acute regulatory protein (STAR) participates in cholesterol shuttling from the outer to the inner mitochondrial membrane, the rate-limiting step in steroidogenesis. Steroid hormone biosynthesis and steroidogenic gene expression are regulated by LH, which activates various signaling pathways and transcription factors, including cAMP/Ca(2+)/CAMK (Ca(2+)/calmodulin-dependent kinase)-myocyte enhancer factor 2 (MEF2). The 4 MEF2 transcription factors are essential regulators of cell differentiation and organogenesis in numerous tissues. Recently, MEF2 was identified in Sertoli and Leydig cells of the testis. Here, we report that MEF2 regulates steroidogenesis in mouse MA-10 Leydig cells by acting on the Star gene. In MA-10 cells depleted of MEF2 using siRNAs (small interfering RNAs), STAR protein levels, Star mRNA levels, and promoter activity were significantly decreased. On its own, MEF2 did not activate the mouse Star promoter but was found to cooperate with forskolin/cAMP. By chromatin immunoprecipitation and DNA precipitation assays, we confirmed MEF2 binding to a consensus element located at -232 bp of the Star promoter. Mutation or deletion of the MEF2 element reduced but did not abrogate the MEF2/cAMP cooperation, indicating that MEF2 cooperates with other DNA-bound transcription factor(s). We identified GATA4 (GATA binding protein 4) as a partner for MEF2 in Leydig cells, because mutation of the GATA element abrogated the MEF2/cAMP cooperation on a reporter lacking a MEF2 element. MEF2 and GATA4 interact as revealed by coimmunoprecipitation, and MEF2 and GATA4 transcriptionally cooperate on the Star promoter. Altogether, our results define MEF2 as a novel regulator of steroidogenesis and Star transcription in Leydig cells and identify GATA4 as a key partner for MEF2-mediated action. PMID:25860031

  4. Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3.

    Directory of Open Access Journals (Sweden)

    Yu-Qin Deng

    Full Text Available Mast cell (MC degranulation is the foundation of the acute phase of allergic rhinitis (AR. Previously, downregulation of GATA binding protein 3 (GATA-3 was shown to suppress MC activation in an AR mouse model. Binding of microRNA-135a (miR-135a to GATA-3 was also observed, and overexpression of this miRNA decreased GATA-3 mRNA and protein expression. However, the effects of miR-135a on MCs during AR are currently unknown. In the present study, we utilized a lentiviral (LV vector to intranasally administer miR-135a to ovalbumin (OVA-sensitized AR mice. Following miR-135a treatment, the total serum IgE concentration observed during AR was significantly reduced. In the nasal mucosa, the expression of T-box expressed in T cells (T-bet was higher, whereas that of GATA-3 was lower in the AR mice following miRNA treatment. Notably, during AR, the ratio of type 1 T-helper cells (Th1 to type 2 (Th2 cells in the spleen is unbalanced, favoring Th2. However, administering miR-135a to the AR mice appeared to balance this ratio by increasing and decreasing the percentage of Th1 and Th2 cells, respectively. MiR-135a also appeared to strongly suppress the infiltration of eosinophils and MCs into the nasal mucosa, and it was specifically localized in the MCs, suggesting that its influence is modulated through regulation of GATA-3 in these cells. Additional work identifying the full therapeutic potential of miR-135a in the treatment of AR and diseases involving allergen-induced inflammation is warranted.

  5. A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression

    OpenAIRE

    Yamazaki, Hiromi; Suzuki, Mikiko; Otsuki, Akihito; Shimizu, Ritsuko; Bresnick, Emery H.; Engel, James Douglas; Yamamoto, Masayuki

    2014-01-01

    Chromosomal inversion between 3q21 and 3q26 results in high-risk acute myeloid leukemia (AML). Here, we identified a mechanism whereby a GATA2 distal hematopoietic enhancer (G2DHE or −77-kb enhancer) is brought into close proximity to the EVI1 gene in inv(3)(q21;q26) inversions, leading to leukemogenesis. We examined the contribution of G2DHE to leukemogenesis by creating a bacterial artificial chromosome (BAC) transgenic model that recapitulates the inv(3)(q21;q26) allele. Transgenic mice ha...

  6. Conserved POU/OCT- and GATA-binding sites in 5'-flanking promoter region of mammalian WNT8B orthologs.

    Science.gov (United States)

    Katoh, Masuko; Katoh, Masaru

    2007-05-01

    WNT family members are secreted-type glycoproteins regulating cell fate, planar cell polarity, cell adhesion, and cell movement. WNT signals are context-dependently transduced to the canonical pathway for the transcriptional up-regulation of MYC, CCND1, FGF20, JAG1, WISP1 and DKK1 genes, and also to the non-canonical pathway for the activation of RHOA, JNK, PKC, NFAT and NLK signaling cascades. We cloned and characterized the wild-type human WNT8B, while another group the aberrant human WNT8B with Gly230Ala and Arg284Leu amino-acid substitutions. Although WNT8B is undetectable in normal adult tissues by using Northern blot analyses, WNT8B is expressed in gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, and embryonal tumors. Here, comparative integromics on WNT8B orthologs were investigated by using bioinformatics (Techint) and human intelligence (Humint). Cow Wnt8b gene was identified within NW_001494361.1 genome sequence. Predicted sequence XM_582222.3 was an artificial cow Wnt8b with aberrant prediction for the first exon. Cow Wnt8b complete coding sequence was found to encode a 350-amino-acid protein, which showed 96.9% total-amino-acid identity with human WNT8B. Comparative proteomics revealed that N-terminal signal peptide, 22 Cys residues, two Asn-linked glycosylation sites, Gly230, and Arg284 of human WNT8B were conserved among mammalian WNT8B orthologs. Comparative genomics revealed that POU/OCT- and GATA-binding sites in the 5'-flanking promoter region were conserved among human, chimpanzee, cow, mouse, and rat WNT8B orthologs. In silico expression analyses revealed that human WNT8B was expressed in embryoid body derived from embryonic stem (ES) cells, hepatocyte progenitors derived from ES cells, fetal brain, diffuse-type gastric cancer, colorectal cancer, prostate cancer, and ovarian fibrotheoma. Based on the expression profiles of POU and GATA family transcription factors, it was revealed that WNT8B expression in hepatocyte

  7. Gata-3 Induces T Helper Cell Type 2 (Th2) Cytokine Expression and Chromatin Remodeling in Committed Th1 Cells

    OpenAIRE

    Lee, Hyun Jun; Takemoto, Naofumi; Kurata, Hirokazu; Kamogawa, Yumiko; Miyatake, Shoichiro; O'Garra, Anne; Arai, Naoko

    2000-01-01

    Committed T helper type 1 (Th1) and Th2 effector cells, resulting from chronic antigenic stimulation in interleukin (IL)-12 and IL-4, are implicated in the pathology of autoimmune and allergic diseases. Committed Th1 cells cannot be induced to change their cytokine profiles in response to antigenic stimulation and Th2 cytokine–inducing conditions. Here, we report that ectopic expression of GATA-3 induced Th2-specific cytokine expression not only in developing Th1 cells but also in otherwise i...

  8. Genome-Wide Gene Expression Profiling Revealed a Critical Role for GATA3 in the Maintenance of the Th2 Cell Identity

    OpenAIRE

    Sasaki, Tetsuya; Onodera, Atsushi; Hosokawa, Hiroyuki; Watanabe, Yukiko; Horiuchi, Shu; Yamashita, Junji; Tanaka, Hitoshi; Ogawa, Yasumasa; Suzuki, Yutaka; Nakayama, Toshinori

    2013-01-01

    Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytok...

  9. Analysis of the CCR3 promoter reveals a regulatory region in exon 1 that binds GATA-1

    Directory of Open Access Journals (Sweden)

    Koch Laura E

    2005-04-01

    Full Text Available Abstract Background CC Chemokine Receptor 3 (CCR3, the major chemokine receptor expressed on eosinophils, binds promiscuously to several ligands including eotaxins 1, 2, and 3. Even though the only cells that consistently accumulate following eotaxin administration in vivo are myeloid cells (primarily eosinophils, other cell types have recently been shown to express CCR3. It is therefore important to elucidate the molecular mechanisms regulating receptor expression. Results In order to define regions responsible for CCR3 transcription, a DNAse hypersensitive site was identified in the vicinity of exon 1. Coupled with our previous data implicating exon 1 in CCR3 transcription, we hypothesized that transcription factors bind to exon-1. Electrophoretic mobility shift analysis revealed that nuclear proteins in eosinophilic cells bound to exon 1. Furthermore, antibody interference and mutation studies demonstrated GATA-1 binding to exon 1. In order to test the 1.6-kb CCR3 promoter element (that includes exon 1 for in vivo function, this region was used to generate transgenic mice that expressed a reporter protein. Strong transgene expression was achieved, with the pattern of expression suggesting a broad acting promoter. Conclusion The transcription factor GATA-1 binds to CCR3 exon 1. The 1.6-kb CCR3 promoter element, that includes exon 1, is a strong promoter in vivo.

  10. IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1

    Science.gov (United States)

    Musaro, A.; McCullagh, K. J.; Naya, F. J.; Olson, E. N.; Rosenthal, N.

    1999-01-01

    Localized synthesis of insulin-like growth factors (IGFs) has been broadly implicated in skeletal muscle growth, hypertrophy and regeneration. Virally delivered IGF-1 genes induce local skeletal muscle hypertrophy and attenuate age-related skeletal muscle atrophy, restoring and improving muscle mass and strength in mice. Here we show that the molecular pathways underlying the hypertrophic action of IGF-1 in skeletal muscle are similar to those responsible for cardiac hypertrophy. Transfected IGF-1 gene expression in postmitotic skeletal myocytes activates calcineurin-mediated calcium signalling by inducing calcineurin transcripts and nuclear localization of calcineurin protein. Expression of activated calcineurin mimics the effects of IGF-1, whereas expression of a dominant-negative calcineurin mutant or addition of cyclosporin, a calcineurin inhibitor, represses myocyte differentiation and hypertrophy. Either IGF-1 or activated calcineurin induces expression of the transcription factor GATA-2, which accumulates in a subset of myocyte nuclei, where it associates with calcineurin and a specific dephosphorylated isoform of the transcription factor NF-ATc1. Thus, IGF-1 induces calcineurin-mediated signalling and activation of GATA-2, a marker of skeletal muscle hypertrophy, which cooperates with selected NF-ATc isoforms to activate gene expression programs.

  11. GATA3 induces human T-cell commitment by restraining Notch activity and repressing NK-cell fate.

    Science.gov (United States)

    Van de Walle, Inge; Dolens, Anne-Catherine; Durinck, Kaat; De Mulder, Katrien; Van Loocke, Wouter; Damle, Sagar; Waegemans, Els; De Medts, Jelle; Velghe, Imke; De Smedt, Magda; Vandekerckhove, Bart; Kerre, Tessa; Plum, Jean; Leclercq, Georges; Rothenberg, Ellen V; Van Vlierberghe, Pieter; Speleman, Frank; Taghon, Tom

    2016-01-01

    The gradual reprogramming of haematopoietic precursors into the T-cell fate is characterized by at least two sequential developmental stages. Following Notch1-dependent T-cell lineage specification during which the first T-cell lineage genes are expressed and myeloid and dendritic cell potential is lost, T-cell specific transcription factors subsequently induce T-cell commitment by repressing residual natural killer (NK)-cell potential. How these processes are regulated in human is poorly understood, especially since efficient T-cell lineage commitment requires a reduction in Notch signalling activity following T-cell specification. Here, we show that GATA3, in contrast to TCF1, controls human T-cell lineage commitment through direct regulation of three distinct processes: repression of NK-cell fate, upregulation of T-cell lineage genes to promote further differentiation and restraint of Notch activity. Repression of the Notch1 target gene DTX1 hereby is essential to prevent NK-cell differentiation. Thus, GATA3-mediated positive and negative feedback mechanisms control human T-cell lineage commitment. PMID:27048872

  12. Tissue-specific expression of GFP reporter gene in germline driven by GATA-2 promoter and enhancers in zebrafish

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    GATA-2,a transcription factor,is expressed in several types of blood cells and in the central nervous system (CNS),and regulates the differentiation of these cells.We have obtained five zebrafish transgenic germlines that carry and express the green fluorescent protein (GFP) gene ligated to various 5′flanking sequences of zebrafish GATA-2 gene.The spatial pattern of GFP expression varies,mainly depending on which regulatory sequence is used,among the germlines.In some of the germlines,the expression of GFP is restricted to the CNS and the enveloping layer (EVL) cells,while in some other lines GFP is observed only in the CNS.It is noted that the intensity of GFP in the transgenic fish remain unchanged after a six-generation passage of the transgenes.The transgenic fish could find its uses in the future in generating tissue-specific,even cellspecific mutant fish and in functional study of related genes through transgenesis.

  13. GATA-1 Inhibits PU.1 Gene via DNA and Histone H3K9 Methylation of Its Distal Enhancer in Erythroleukemia.

    Science.gov (United States)

    Burda, Pavel; Vargova, Jarmila; Curik, Nikola; Salek, Cyril; Papadopoulos, Giorgio Lucio; Strouboulis, John; Stopka, Tomas

    2016-01-01

    GATA-1 and PU.1 are two important hematopoietic transcription factors that mutually inhibit each other in progenitor cells to guide entrance into the erythroid or myeloid lineage, respectively. PU.1 controls its own expression during myelopoiesis by binding to the distal URE enhancer, whose deletion leads to acute myeloid leukemia (AML). We herein present evidence that GATA-1 binds to the PU.1 gene and inhibits its expression in human AML-erythroleukemias (EL). Furthermore, GATA-1 together with DNA methyl Transferase I (DNMT1) mediate repression of the PU.1 gene through the URE. Repression of the PU.1 gene involves both DNA methylation at the URE and its histone H3 lysine-K9 methylation and deacetylation as well as the H3K27 methylation at additional DNA elements and the promoter. The GATA-1-mediated inhibition of PU.1 gene transcription in human AML-EL mediated through the URE represents important mechanism that contributes to PU.1 downregulation and leukemogenesis that is sensitive to DNA demethylation therapy. PMID:27010793

  14. Halomonas indalinina sp.nov., a moderately halophilic bacterium isolated from a solar saltern in Cabo de Gata, Al,eria, southern Spain

    NARCIS (Netherlands)

    Cabrera, A.; Aguilera, M.; Fuentes Enriquez de Salamanca, S.; Incerti, C.; Russell, N.J.; Ramos-Cormenzana, A.; Monteoliva-Sanchez, M.

    2007-01-01

    moderately halophilic bacterium, strain CG2.1T, isolated from a solar saltern at Cabo de Gata, a wildlife reserve located in the province of Almería, southern Spain, was subjected to a polyphasic taxonomic study. This organism was an aerobic, motile, Gram-negative rod that produced orange-pigmented

  15. Enforced expression of Gata3 in T cells and group 2 innate lymphoid cells increases susceptibility to allergic airway inflammation in mice

    NARCIS (Netherlands)

    A. Kleinjan (Alex); R.G.J. Klein Wolterink (Roel); Y. Levani (Yelvi); M.J.W. de Bruijn (Marjolein); H.C. Hoogsteden (Henk); M. van Nimwegen (Menno); R.W. Hendriks (Rudi)

    2014-01-01

    textabstractAirway inflammation in allergic asthma reflects a threshold response of the innate immune system, including group 2 innate lymphoid cells (ILC2), followed by an adaptive Th2 cell-mediated response. Transcription factor Gata3 is essential for differentiation of both Th2 cells and ILC2. We

  16. A network including TGFβ/Smad4, Gata2, and p57 regulates proliferation of mouse hematopoietic progenitor cells.

    Science.gov (United States)

    Billing, Matilda; Rörby, Emma; May, Gillian; Tipping, Alex J; Soneji, Shamit; Brown, John; Salminen, Marjo; Karlsson, Göran; Enver, Tariq; Karlsson, Stefan

    2016-05-01

    Transforming growth factor β (TGFβ) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell function, as an early and direct target gene for TGFβ-induced Smad signaling in hematopoietic progenitor cells. We also report that Gata2 is involved in mediating a significant part of the TGFβ response in primitive hematopoietic cells. Interestingly, the cell cycle regulator and TGFβ signaling effector molecule p57 was found to be upregulated as a secondary response to TGFβ. We observed Gata2 binding upstream of the p57 genomic locus, and importantly, loss of Gata2 abolished TGFβ-stimulated induction of p57 as well as the resulting growth arrest of hematopoietic progenitors. Our results connect key molecules involved in hematopoietic stem cell self-renewal and reveal a functionally relevant network, regulating proliferation of primitive hematopoietic cells. PMID:26876150

  17. Dynamic regulation of permissive histone modifications and GATA3 binding underpin acquisition of granzyme A expression by virus-specific CD8(+) T cells.

    Science.gov (United States)

    Nguyen, Michelle L T; Hatton, Lauren; Li, Jasmine; Olshansky, Moshe; Kelso, Anne; Russ, Brendan E; Turner, Stephen J

    2016-02-01

    Numerous studies have focused on the molecular regulation of perforin (PFP) and granzyme B (GZMB) expression by activated cytotoxic T lymphocytes (CTLs), but little is known about the molecular factors that underpin granzyme A (GZMA) expression. In vitro activation of naïve CD8(+) T cells, in the presence of IL-4, enhanced STAT6-dependent GZMA expression and was associated with GATA3 binding and enrichment of transcriptionally permissive histone posttranslational modifications (PTMs) across the Gzma gene locus. While GZMA expression by effector influenza A virus specific CTLs was also associated with a similar permissive epigenetic signature, memory CTL lacked enrichment of permissive histone PTMs at the Gzma locus, although this was restored within recalled secondary effector CTLs. Importantly, GZMA expression by virus-specific CTLs was associated with GATA3 binding at the Gzma locus, and independent of STAT6-mediated signaling. This suggests regulation of GZMA expression is underpinned by differentiation-dependent regulation of chromatin composition at the Gzma locus and that, given GATA3 is key for CTL differentiation in response to infection, GATA3 expression is regulated by a distinct, IL-4 independent, signaling pathway. Overall, this study provides insights into the molecular mechanisms that control transcription of Gzma during virus-induced CD8(+) T-cell differentiation. PMID:26519105

  18. Transcription Factors Oct-1 and GATA-3 Cooperatively Regulate Th2 Cytokine Gene Expression via the RHS5 within the Th2 Locus Control Region.

    Directory of Open Access Journals (Sweden)

    Kiwan Kim

    Full Text Available The T helper type 2 (Th2 locus control region (LCR regulates Th2 cell differentiation. Several transcription factors bind to the LCR to modulate the expression of Th2 cytokine genes, but the molecular mechanisms behind Th2 cytokine gene regulation are incompletely understood. Here, we used database analysis and an oligonucleotide competition/electrophoretic mobility shift assays to search for transcription factors binding to RHS5, a DNase I hypersensitive site (DHS within the Th2 LCR. Consequently, we demonstrated that GATA-binding protein-3 (GATA-3, E26 transformation-specific protein 1 (Ets-1, octamer transcription factor-1 (Oct-1, and Oct-2 selectively associate with RHS5. Furthermore, chromatin immunoprecipitation and luciferase reporter assays showed that Oct-1 and Oct-2 bound within the Il4 promoter region and the Th2 LCR, and that Oct-1 and GATA-3 or Oct-2 synergistically triggered the transactivational activity of the Il4 promoter through RHS5. These results suggest that Oct-1 and GATA-3/Oct-2 direct Th2 cytokine gene expression in a cooperative manner.

  19. The utility of CDX2, GATA3, and DOG1 in the diagnosis of testicular neoplasms: an immunohistochemical study of 109 cases.

    Science.gov (United States)

    Osman, Hany; Cheng, Liang; Ulbright, Thomas M; Idrees, Muhammad T

    2016-02-01

    We identified 109 testicular tumors, including pure and mixed germ cell tumors and sex cord-stromal tumors, and conducted immunohistochemical staining for CDX2, DOG1, and GATA3 to address the potential utility of these readily available and commonly used markers in the evaluation of testicular tumors. Their expression has not been previously thoroughly examined in testicular germ cell tumors. The distribution, percentage, and intensity of positivity were assessed. CDX2 was positive in all yolk sac tumors, 25% of choriocarcinomas, 9% of seminomas, and 4% of embryonal carcinomas (sensitivity for yolk sac tumor, 100%; specificity, 89% [teratomas excluded]). CDX2 also stained glandular components within teratomas and identified inconspicuous yolk sac tumor components in 3 cases previously diagnosed as pure embryonal carcinoma. GATA3 was positive in all choriocarcinomas (sensitivity, 100%). Weak GATA3 immunostaining was also seen in 12% of yolk sac tumors and 2 of 2 primitive neuroectodermal tumors. DOG1 was negative in all tumors, but stained spermatocytes and spermatids and the luminal borders of the epididymis and rete testis of nonneoplastic testis. We conclude that CDX2 is a sensitive and relatively specific marker for yolk sac tumor among the nonteratomatous germ cell tumors. It may serve to screen for yolk sac tumor components often overlooked on hematoxylin and eosin-stained slides. GATA3 is helpful in the recognition of trophoblastic cells, especially of intermediate type. DOG1 is a sensitive marker for spermatocytes and needs to be further studied for its significance. PMID:26772394

  20. Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is partially mediated by translocation of miR-221 in microvesicles.

    Directory of Open Access Journals (Sweden)

    Bin Yu

    Full Text Available INTRODUCTION: microRNAs (miRs, a novel class of small non-coding RNAs, are involved in cell proliferation, differentiation, development, and death. In this study, we found that miR-221 translocation by microvesicles (MVs plays an important role in cardioprotection mediated by GATA-4 overexpressed mesenchymal stem cells (MSC. METHODS AND RESULTS: Adult rat bone marrow MSC and neonatal rat ventricle cardiomyocytes (CM were harvested as primary cultures. MSC were transduced with GATA-4 (MSC(GATA-4 using the murine stem cell virus (pMSCV retroviral expression system. Empty vector transfection was used as a control (MSC(Null. The expression of miRs was assessed by real-time PCR and localized using in situ hybridization (ISH. MVs collected from MSC cultures were characterized by expression of CD9, CD63, and HSP70, and photographed with electron microscopy. Cardioprotection during hypoxia afforded by conditioned medium (CdM from MSC cultures was evaluated by lactate dehydrogenase (LDH release, MTS uptake by CM, and caspase 3/7 activity. Expression of miR-221/222 was significantly higher in MSC than in CM and miR-221 was upregulated in MSC(GATA-4. MSC overexpression of miR-221 significantly enhanced cardioprotection by reducing the expression of p53 upregulated modulator of apoptosis (PUMA. Moreover, expression of PUMA was significantly decreased in CM co-cultured with MSC. MVs derived from MSC expressed high levels of miR-221, and were internalized quickly by CM as documented in images obtained from a Time-Lapse Imaging System. CONCLUSIONS: Our results demonstrate that cardioprotection by MSC(GATA-4 may be regulated in part by a transfer of anti-apoptotic miRs contained within MVs.

  1. 子痫前期患者外周血T-bet mRNA和GATA3 mRNA的表达水平的探讨%Explore the peripheral blood of patients with preeclampsia and T-bet mRNA expression levels of GATA3 Myrna

    Institute of Scientific and Technical Information of China (English)

    王燕云; 陈宝丽; 宋海澄; 左金玲

    2014-01-01

    Objective To investigate the peripheral blood of patients with preeclampsia T-bet mRNA and GATA3 mRNA expression and analyze the mechanism in the pathogenesis of preeclampsia. Methods Hospital 46 pregnant women with preeclampsia from January 2011 to De-cember 2012 were selected as the study group. At the same time,46 cases with normal pregnant women were selected as control group. T-bet mRNA and GATA3 mRNA expression in peripheral blood were detected. Results T-bet mRNA expression increased in the two groups. T-bet mRNA expression levels of the study group was significantly higher that of the control group. The difference was statistically significant( P ﹤0. 05). GATA3 mRNA expression was decreased in the study group and the control group. The study group GATA3 mRNA expression was signifi-cantly lower than the control group( P ﹤0. 05),and with statistically meaningful. T-bet mRNA/GATA3 mRNA expression ratios are presented in two groups. The data between the groups was statistically significant( P ﹤0. 05). Conclusion The patients with preeclampsia in T-bet mR-NA showed high expression,while GATA3 mRNA showed low expression. Both of which play a role in the pathogenesis of preeclampsia.%目的:探讨子痫前期患者外周血中的T-bet mRNA与GATA3 mRNA表达情况,分析其在子痫前期发病中的作用及机制。方法选取2011年1月到2012年12月间的46例子痫前期孕妇为研究组,并选取同期46例正常孕妇为对照组,检测两组外周血中的T-bet mRNA与GATA3 mRNA表达情况。结果 T-bet mRNA表达在两组中表达增强,研究组的T-bet mRNA表达量明显高于对照组,差异有统计学意义( P ﹤0.05)。GATA3 mRNA在两组中表达量减弱,研究组GATA3 mRNA表达量明显的低于对照组,差异有统计学意义( P ﹤0.05)。T-bet mRNA/GATA3 mRNA比值在两组中呈现正表达,差异有统计学意义( P ﹤0.05)。结论子痫前期患者外周血中的T-bet mRNA呈现高表达,而GATA

  2. 新疆维吾尔族寻常性银屑病患者皮损中转录因子GATA3的表达及意义%The expression and significance of GATA3 in lesions of psoriasis vulgaris Uygur patients in Xinjiang

    Institute of Scientific and Technical Information of China (English)

    马艳青; 罗东; 张艳君; 王慧琴; 赵宗峰; 吴卫东

    2014-01-01

    To investigate the expression and significance of the transcription factor GATA3 of JAK-STAT sig-naling pathway in lesions of psoriasis vulgaris Uygur patients in Xinjiang. Methods: The total RNA were extracted from 6 patients with psoriasis vulgaris and 5 healthy subjects and reversely transcribed in cDNA. RT2 profiler PCR array was used to detect the mRNA expression level of JAK/STAT signaling pathway related genes , and the expression of GATA3 proteins were detected by immunohistochemistry in 45 patients with psoriasis vulgaris and 21 healthy controls. Results: Compared with con-trol group, 17 candidate genes were identified that differentially expressed in psoriasis patients. The expression level of GATA3 mRNA existing in Xinjiang Uygur psoriatic lesions was down-regulated compared with the control group. The GATA3 protein were expressed at full-thickness epidermal cell nucleus in normal controls, while in tissue lesions of the pilot group the ex-pression were evidently decreased. There was statistical significance between those two groups (P<0.001). Conclusion: The ex-pression of GATA3 is significantly down-regulated within psoriasis epidermis in Xinjiang Uygur, which suggests that GATA3 may play a part in the pathogenesis of the Uygur psoriatic.%目的:探讨JAK-STAT信号转导通路中转录因子GATA3在新疆维吾尔族寻常性银屑病患者皮损组织中的表达水平及其意义。方法:分别提取6例新疆维吾尔族寻常性银屑病患者皮损组织(银屑病组)和5例新疆维吾尔族正常人皮肤组织(正常对照组)的总RNA,反转录合成cDNA,用RT2 profiler PCR Array检测JAK/STAT信号通路相关基因的mRNA表达水平,通过在线软件对数据进行分析,并采用免疫组化方法检测45例银屑病组和21例正常对照组中GATA3蛋白水平的表达情况,并进行相关分析。结果:新疆维吾尔族银屑病患者皮损组织与正常人皮肤组织对比,共有17个表达差异2

  3. Expressions of T-bet, GATA-3, RORγt and FoxP3 mRNA in peripheral blood of patients with allergic asthma%过敏性哮喘患者外周血T-bet、GATA-3、RORγt和FoxP3 mRNA的表达变化

    Institute of Scientific and Technical Information of China (English)

    施宇衡; 时国朝; 马佳韵; 艾香艳; 朱海星; 万欢英

    2011-01-01

    Objective To investigate the expressions of T-bet, GA TA-3, RORγt and FoxP3 mRNA in peripheral blood of patients with allergic asthma. Methods Seventeen patients with mild persistent and 13 patients with moderate-severe persistent house dust mite allergic asthma and 14 healthy controls were enrolled in this study.Expressions of T-bet,GATA-3,RORγt and FoxP3 mRNA in peripheral blood mononuclear cell (PBMC) were determined by quantitative fluorescence PCR. Results Expression of GATA-3 mRNA in mild and moderate-severe asthma patients was significantly higher than that in normal controls (P<0.01). Furthermore, expression of RORγt mRNA in patients with moderate-severe asthma was significantly higher than that in mild asthma patients and normal controls (P<0.01). However, there was no difference in expressions of T-bet and FoxP3 mRNA among these three groups (P>0.05). Conclusions GATA-3 expression was increased in allergic asthma,and RORγt expression was increased in moderate-severe allergic asthma. GA TA-3 and RORγt may play important role in the pathogenesis of allergic asthma.%目的:探讨特异性转录因子T-bet、GATA-3、RORγt和FoxP3 mRNA在过敏性哮喘患者外周血中的表达变化.方法:选择30例慢性持续期的屋尘螨过敏性哮喘患者,其中轻度哮喘17例、中重度哮喘13例,14名正常人作为对照.通过荧光实时定量PCR方法检测3组患者外周血单个核细胞(PBMC)中T-bet、GATA-3、RORγt和FoxP3mRNA的表达.结果:轻度和中重度哮喘患者的GATA-3 mRNA表达均显著高于正常人(均P0.05).结论:过敏性哮喘中GATA-3表达增加,中重度哮喘中RORγt表达增加,GATA-3和RORγt在哮喘发病中起着重要的作用.

  4. Vaginal Smear TNF-alpha, IL18, TLR4, and GATA3 mRNA Levels Correlate with Local Inflammation

    Directory of Open Access Journals (Sweden)

    Olga Bourmenskaya

    2014-12-01

    Full Text Available Background: A molecular approach to estimation of local inflammatory response associated with dysbiotic conditions of the vagina is reported. This approach is based on immune response gene transcription levels measured by qPCR assay. Methods and Results: qPCR analysis of 24 immune response gene transcripts in vaginal smears was performed for 215 women with vaginitis and 95 healthy controls. The data were sorted by comparison to local inflammatory response profiles assessed by conventional methods. The local inflammatory response in the vagina is found to correlate with TNF-alpha, IL18, TLR4, and GATA3 transcript levels. Sensitivity and specificity of the approach, as validated in accordance with conventional clinical examination results, are 94.9% and 93.7%, respectively. Conclusions: The noninvasive diagnostic approach to vaginal pathology based solely on its molecular characterization may prove to be clinically relevant.

  5. Germ-line GATA2 p.THR354MET mutation in familial myelodysplastic syndrome with acquired monosomy 7 and ASXL1 mutation demonstrating rapid onset and poor survival

    OpenAIRE

    Bödör, Csaba; Renneville, Aline; Smith, Matthew; Charazac, Aurélie; Iqbal, Sameena; Étancelin, Pascaline; Cavenagh, Jamie; Barnett, Michael J; Kramarzová, Karolina; Krishnan, Biju; Matolcsy, András; Preudhomme, Claude; Fitzgibbon, Jude; Owen, Carolyn

    2012-01-01

    While most myelodysplastic syndrome/acute myeloid leukemia cases are sporadic, rare familial cases occur and provide some insight into leukemogenesis. The most clearly defined familial cases result from inherited mutations in RUNX1 or CEBPA. Recently, novel germline mutations in GATA2 have been reported. We, therefore, investigated individuals from families with one or more first-degree relatives with myelodysplastic syndrome/acute myeloid leukemia with wild-type RUNX1 and CEBPA, for GATA2 mu...

  6. Dynamic shifts in occupancy by TAL1 are guided by GATA factors and drive large-scale reprogramming of gene expression during hematopoiesis.

    Science.gov (United States)

    Wu, Weisheng; Morrissey, Christapher S; Keller, Cheryl A; Mishra, Tejaswini; Pimkin, Maxim; Blobel, Gerd A; Weiss, Mitchell J; Hardison, Ross C

    2014-12-01

    We used mouse ENCODE data along with complementary data from other laboratories to study the dynamics of occupancy and the role in gene regulation of the transcription factor TAL1, a critical regulator of hematopoiesis, at multiple stages of hematopoietic differentiation. We combined ChIP-seq and RNA-seq data in six mouse cell types representing a progression from multilineage precursors to differentiated erythroblasts and megakaryocytes. We found that sites of occupancy shift dramatically during commitment to the erythroid lineage, vary further during terminal maturation, and are strongly associated with changes in gene expression. In multilineage progenitors, the likely target genes are enriched for hematopoietic growth and functions associated with the mature cells of specific daughter lineages (such as megakaryocytes). In contrast, target genes in erythroblasts are specifically enriched for red cell functions. Furthermore, shifts in TAL1 occupancy during erythroid differentiation are associated with gene repression (dissociation) and induction (co-occupancy with GATA1). Based on both enrichment for transcription factor binding site motifs and co-occupancy determined by ChIP-seq, recruitment by GATA transcription factors appears to be a stronger determinant of TAL1 binding to chromatin than the canonical E-box binding site motif. Studies of additional proteins lead to the model that TAL1 regulates expression after being directed to a distinct subset of genomic binding sites in each cell type via its association with different complexes containing master regulators such as GATA2, ERG, and RUNX1 in multilineage cells and the lineage-specific master regulator GATA1 in erythroblasts. PMID:25319994

  7. Y-GATA-H4、DYS448、DYS392在温州汉族群体中的遗传多态性

    Institute of Scientific and Technical Information of China (English)

    杨雷; 何秋莎; 吴淑珍; 包其郁

    2007-01-01

    采集温州地区300余例男性标本,对Y-GATA-H4、DYS448、DYS392的多态性进行了调查,以期获得有效的遗传背景资料,并能应用这些资料进行人类遗传学研究和法医学应用。

  8. The Stat6-regulated KRAB domain zinc finger protein Zfp157 regulates the balance of lineages in mammary glands and compensates for loss of Gata-3

    OpenAIRE

    Oliver, Carrie H.; Khaled, Walid T.; Frend, Hayley; Nichols, Jennifer; Watson, Christine J.

    2012-01-01

    Cell fate specification in mammary stem and progenitor cells is not well understood. In this study by Watson and colleagues, the authors identify a novel transcriptional regulator, Zfp157, as a target of Stat6. The authors demonstrate that Zfp157 regulates mammary progenitor cells by deleting Zfp157 in luminal cells, which resulted in a dramatic shift in the cellular composition of the mammary gland. In addition, the authors found that Gata-3 is not an essential regulator of mammary gland mor...

  9. Estrogen-Induced Aurora Kinase-A (AURKA) Gene Expression is Activated by GATA-3 in Estrogen Receptor-Positive Breast Cancer Cells

    OpenAIRE

    Jiang, Shoulei; Katayama, Hiroshi; Jin WANG; Li, Sara Antonia; Hong, Yan; Radvanyi, Laszlo; Li, Jonathan J.; Sen, Subrata

    2010-01-01

    Aurora-A is a proto-oncogenic mitotic kinase that is frequently overexpressed in human epithelial malignancies including in breast and ovarian cancers. The mechanism of transcriptional upregulation of Aurora-A in human breast cancer is not yet elucidated. We report herein that Aurora-A transcription is positively regulated by GATA-3 in response to estrogen in estrogen receptor α (ERα)-positive cells. Transient expression of aurora-A promoter deletion mutants in luciferase constructs identifie...

  10. Effects of Shen-Fu Injection on the Expression of T-Cell-Specific Transcription Factors T-bet/Gata-3 in Porcine Postresuscitation Lung Injury

    Directory of Open Access Journals (Sweden)

    Wei Gu

    2013-01-01

    Full Text Available Shen-Fu injection (SFI derived from the ancient traditional Chinese medicine. In this study, the effects of SFI on the expression of T-bet/GATA-3 and its potential mechanisms causing the shift of T cells from Th2 to Th1 on postresuscitation lung injury were examined in a porcine model of cardiac arrest. 30 pigs were randomly divided into SHAM ( and three return of spontaneous circulation (ROSC groups ( per group; 24 pigs were subjected to 8 min of electrically induced cardiac arrest and 2 min of basic life support, which received central venous injection of Shen-Fu (SFI, epinephrine (EP or saline (SA. After successful ROSC, 18 surviving pigs were sacrificed at 24 h after ROSC ( per group. The levels of serum and lung tissue interleukin (IL-4 and interferon (IFN-γ were measured by ELISA, and the protein and mRNA levels of GATA-3 and T-bet in the lung tissue were determined by western blotting and quantitative real-time polymerase chain reaction, respectively. Compared with the EP and SA groups, SFI treatment reduced the levels of IL-4 (, increased levels of IFN-γ (, and induced T-bet mRNA upregulation and GATA-3 mRNA downregulation (. SFI attenuated lung injury and regulated lung immune disorders. Therefore, SFI could protect postresuscitation lung injury by modulating a Th1/Th2 imbalance.

  11. The effects of galectin-1 on the gene expression of the transcription factors TBX21, GATA-3, FOXP3 and RORC.

    Science.gov (United States)

    Yakushina, V D; Vasil'eva, O A; Ryazantseva, N V; Novitsky, V V; Tashireva, L A

    2015-01-01

    CD4(+) T cells orchestrate the immune response by differentiating into T helper (Th) or regulatory (Treg) cell subsets that secrete distinct sets of cytokines. They also play a critical role in the pathogenesis of autoimmunity, asthma, allergy and, likely, cancer. The mechanisms involved in the regulation of CD4(+) T cell homeostasis by galectin-1 remain poorly characterized. To investigate whether galectin-1 modulates the differentiation of CD4(+) T cells, the effects of galectin-1 on the mRNA expression levels of TBX21, GATA-3, FOXP3 and RORC in activated peripheral blood mononuclear cells were examined. The expression levels of GATA-3 and FOXP3 mRNA were up-regulated after treatment with 1.0 μg/ml galectin-1 and were unchanged (for GATA-3) or slightly elevated (for FOXP3) compared with untreated cells when 2.0 μg/ml galectin-1 was added. At the same time, at both concentrations of galectin-1, we observed reduced TBX21 and RORC mRNA expression levels. These findings support the concept that galectin-1 skews the differentiation of CD4(+) T cells towards Th2 and Treg cells. PMID:25292313

  12. HDR syndrome: a follow-up genotype-phenotype analysis of a de novo missense Thr272Ile mutation in exon 4 of GATA3.

    Science.gov (United States)

    Gomes, T S; Gortner, L; Dockter, G; Leitner, D; Thakker, R V; Rohrer, T

    2012-11-01

    Hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) syndrome (MIM 146255) is a rare autosomal dominant disorder caused by mutations in the gene encoding GATA3, a dual zinc-finger transcription factor involved in vertebrate embryonic development. In this clinical case study we report on a follow-up of a phenotype associated with a GATA3 mutation. HDR syndrome was clinically diagnosed at age of 1.5 years in a boy with a de novo heterozygous missense (c.815C→T) mutation, Thr272Ile, in exon 4 of the GATA3 gene. Both parents were negative for Thr272Ile.At age of 17 months, the patient had a weight of 10.7, a body length of 78 cm, and a head circumference of 47.5 cm. By the age of 7 years, growth is age-appropriate, severe bilateral hearing loss (dB 60) was corrected by hearing aids. However, cognitive development (auditory sensory me-mory and language abilities) is at the lower ends of the test scores.In conclusion, a mildly impaired clinical course was achieved by the age of 7 years in a patient with HDR syndrome; this report adds to the body of data on genotype-phenotype analysis in HDR syndrome. · PMID:23203342

  13. GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Pierre-Yves Mantel

    2007-12-01

    Full Text Available Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg and inducible Treg (iTreg commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4 present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF-beta-mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy.

  14. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

    Energy Technology Data Exchange (ETDEWEB)

    Turowska, Agnieszka [sterna biologicals GmbH and Co. KG, Marburg (Germany); Librizzi, Damiano [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Baumgartl, Nadja [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Kuhlmann, Jens; Dicke, Tanja [sterna biologicals GmbH and Co. KG, Marburg (Germany); Merkel, Olivia [Department of Pharmaceutical Sciences, Wayne State University, Detroit (United States); Homburg, Ursula [sterna biologicals GmbH and Co. KG, Marburg (Germany); Höffken, Helmut [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Renz, Harald [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Garn, Holger, E-mail: garn@staff.uni-marburg.de [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany)

    2013-10-15

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

  15. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

    International Nuclear Information System (INIS)

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

  16. Avaliação da perda da coloração artificial de ágatas Color loss evaluation of artificially stained agates

    Directory of Open Access Journals (Sweden)

    Rodrigo de Almeida Silva

    2007-09-01

    Full Text Available O Rio Grande do Sul é um dos principais produtores de geodos de ágatas do mundo. As ágatas da região de Salto do Jacuí permitem a introdução de alguns corantes em seus poros, tornando-as coloridas. O objetivo do presente trabalho foi estudar a perda de cor de ágatas tingidas artificialmente, considerando diferentes ambientes de exposição. Estudaram-se ágatas coloridas pelos procedimentos clássicos (verde, vermelho, azul e preto e coloridas com corantes orgânicos (verde, vermelho, rosa e roxo. O procedimento experimental consistiu em expor as chapas de ágatas em três ambientes com luminosidades distintas: escuro, doméstico e ao ar livre. A evolução da cor foi avaliada pela técnica de colorimetria diferencial, usando o sistema colorimétrico CIE L*a*b*. Os resultados obtidos demonstram que os métodos clássicos de tingimento proporcionam cores permanentes, enquanto que os corantes orgânicos promovem cores instáveis. Dependendo do grau de luminosidade e tempo de exposição, a perda de cor pode ser praticamente total.The State of Rio Grande do Sul in Brazil is one of the main world producers of agates. The gray type of agates found in Salto do Jacuí is specially suited to be stained in various colours. The purpose of this work was to evaluate the colour loss of artificially stained agates, considering different exposure environments. Studies were carried out with agates stained by classical procedures (green, red, blue, and black and with organic dyes (green, red, pink, and purple. The experimental procedure consisted of displaying agate plates in three places with distinct luminosity: dark, indoor/domestic, and outdoor. The color variation was analyzed by differential colorimetry, using the CIE L*a*b* colorimetrical system. The results show that the classical procedures provided permanent colours, while the colour given by organic dyes was unstable. Depending on the luminosity and exposure time, the colour loss can be

  17. Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates with Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice during Murine Neurocysticercosis.

    Science.gov (United States)

    Mishra, Pramod K; Li, Qun; Munoz, Luis E; Mares, Chris A; Morris, Elizabeth G; Teale, Judy M; Cardona, Astrid E

    2016-06-01

    Neurocysticercosis (NCC) is one of the most common helminth parasitic diseases of the central nervous system (CNS) and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT) and eosinophil-deficient mice (ΔdblGATA) using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte infiltration due to

  18. Mutation of histone H3 serine 86 disrupts GATA factor Ams2 expression and precise chromosome segregation in fission yeast.

    Science.gov (United States)

    Lim, Kim Kiat; Ong, Terenze Yao Rui; Tan, Yue Rong; Yang, Eugene Guorong; Ren, Bingbing; Seah, Kwi Shan; Yang, Zhe; Tan, Tsu Soo; Dymock, Brian W; Chen, Ee Sin

    2015-01-01

    Eukaryotic genomes are packed into discrete units, referred to as nucleosomes, by organizing around scaffolding histone proteins. The interplay between these histones and the DNA can dynamically regulate the function of the chromosomal domain. Here, we interrogated the function of a pair of juxtaposing serine residues (S86 and S87) that reside within the histone fold of histone H3. We show that fission yeast cells expressing a mutant histone H3 disrupted at S86 and S87 (hht2-S86AS87A) exhibited unequal chromosome segregation, disrupted transcriptional silencing of centromeric chromatin, and reduced expression of Ams2, a GATA-factor that regulates localization of the centromere-specific histone H3 variant CENP-A. We found that overexpression of ams2(+) could suppress the chromosome missegregation phenotype that arose in the hht2-S86AS87A mutant. We further demonstrate that centromeric localization of SpCENP-A(cnp1-1) was significantly compromised in hht2-S86AS87A, suggesting synergism between histone H3 and the centromere-targeting domain of SpCENP-A. Taken together, our work presents evidence for an uncharacterized serine residue in fission yeast histone H3 that affects centromeric integrity via regulating the expression of the SpCENP-A-localizing Ams2 protein. [173/200 words]. PMID:26369364

  19. A novel interaction between megakaryocytes and activated fibrocytes increases TGF-β bioavailability in the Gata1(low) mouse model of myelofibrosis.

    Science.gov (United States)

    Zingariello, Maria; Ruggeri, Alessandra; Martelli, Fabrizio; Marra, Manuela; Sancillo, Laura; Ceglia, Ilaria; Rana, Rosa Alba; Migliaccio, Anna Rita

    2015-01-01

    Despite numerous circumstantial evidences, the pathogenic role of TGF-β in primary myelofibrosis (PMF), the most severe of the Philadelphia-negative myeloproliferative neoplasms, is still unclear because of the modest (2-fold) increases in its plasma levels observed in PMF patients and in the Gata1(low) mouse model. Whether myelofibrosis is associated with increased bioavailability of TGF-β bound to fibrotic fibres is unknown. Transmission electron-microscopy (TEM) observations identified that spleen from PMF patients and Gata1(low) mice contained megakaryocytes with abnormally high levels of TGF-β and collagen fibres embedded in their cytoplasm. Additional immuno-TEM observations of spleen from Gata1(low) mice revealed the presence of numerous activated fibrocytes establishing with their protrusions a novel cellular interaction, defined as peripolesis, with megakaryocytes. These protrusions infiltrated the megakaryocyte cytoplasm releasing collagen that was eventually detected in its mature polymerized form. Megakaryocytes, engulfed with mature collagen fibres, acquired the morphology of para-apoptotic cells and, in the most advanced cases, were recognized as polylobated heterochromatic nuclei surrounded by collagen fibres strictly associated with TGF-β. These areas contained concentrations of TGF-β-gold particles ~1000-fold greater than normal and numerous myofibroblasts, an indication that TGF-β was bioactive. Loss-of-function studies indicated that peripolesis between megakaryocytes and fibrocytes required both TGF-β, possibly for inducing fibrocyte activation, and P-selectin, possibly for mediating interaction between the two cell types. Loss-of-function of TGF-β and P-selectin also prevented fibrosis. These observations identify that myelofibrosis is associated with pathological increases of TGF-β bioavailability and suggest a novel megakaryocyte-mediated mechanism that may increase TGF-β bioavailability in chronic inflammation. PMID:27069753

  20. A novel interaction between megakaryocytes and activated fibrocytes increases TGF-β bioavailability in the Gata1low mouse model of myelofibrosis

    Science.gov (United States)

    Zingariello, Maria; Ruggeri, Alessandra; Martelli, Fabrizio; Marra, Manuela; Sancillo, Laura; Ceglia, Ilaria; Rana, Rosa Alba; Migliaccio, Anna Rita

    2015-01-01

    Despite numerous circumstantial evidences, the pathogenic role of TGF-β in primary myelofibrosis (PMF), the most severe of the Philadelphia-negative myeloproliferative neoplasms, is still unclear because of the modest (2-fold) increases in its plasma levels observed in PMF patients and in the Gata1low mouse model. Whether myelofibrosis is associated with increased bioavailability of TGF-β bound to fibrotic fibres is unknown. Transmission electron-microscopy (TEM) observations identified that spleen from PMF patients and Gata1low mice contained megakaryocytes with abnormally high levels of TGF-β and collagen fibres embedded in their cytoplasm. Additional immuno-TEM observations of spleen from Gata1low mice revealed the presence of numerous activated fibrocytes establishing with their protrusions a novel cellular interaction, defined as peripolesis, with megakaryocytes. These protrusions infiltrated the megakaryocyte cytoplasm releasing collagen that was eventually detected in its mature polymerized form. Megakaryocytes, engulfed with mature collagen fibres, acquired the morphology of para-apoptotic cells and, in the most advanced cases, were recognized as polylobated heterochromatic nuclei surrounded by collagen fibres strictly associated with TGF-β. These areas contained concentrations of TGF-β-gold particles ~1000-fold greater than normal and numerous myofibroblasts, an indication that TGF-β was bioactive. Loss-of-function studies indicated that peripolesis between megakaryocytes and fibrocytes required both TGF-β, possibly for inducing fibrocyte activation, and P-selectin, possibly for mediating interaction between the two cell types. Loss-of-function of TGF-β and P-selectin also prevented fibrosis. These observations identify that myelofibrosis is associated with pathological increases of TGF-β bioavailability and suggest a novel megakaryocyte-mediated mechanism that may increase TGF-β bioavailability in chronic inflammation. PMID:27069753

  1. GATA-Dependent Glutaminolysis Drives Appressorium Formation in Magnaporthe oryzae by Suppressing TOR Inhibition of cAMP/PKA Signaling.

    Directory of Open Access Journals (Sweden)

    Margarita Marroquin-Guzman

    2015-04-01

    Full Text Available Fungal plant pathogens are persistent and global food security threats. To invade their hosts they often form highly specialized infection structures, known as appressoria. The cAMP/ PKA- and MAP kinase-signaling cascades have been functionally delineated as positive-acting pathways required for appressorium development. Negative-acting regulatory pathways that block appressorial development are not known. Here, we present the first detailed evidence that the conserved Target of Rapamycin (TOR signaling pathway is a powerful inhibitor of appressorium formation by the rice blast fungus Magnaporthe oryzae. We determined TOR signaling was activated in an M. oryzae mutant strain lacking a functional copy of the GATA transcription factor-encoding gene ASD4. Δasd4 mutant strains could not form appressoria and expressed GLN1, a glutamine synthetase-encoding orthologue silenced in wild type. Inappropriate expression of GLN1 increased the intracellular steady-state levels of glutamine in Δasd4 mutant strains during axenic growth when compared to wild type. Deleting GLN1 lowered glutamine levels and promoted appressorium formation by Δasd4 strains. Furthermore, glutamine is an agonist of TOR. Treating Δasd4 mutant strains with the specific TOR kinase inhibitor rapamycin restored appressorium development. Rapamycin was also shown to induce appressorium formation by wild type and Δcpka mutant strains on non-inductive hydrophilic surfaces but had no effect on the MAP kinase mutant Δpmk1. When taken together, we implicate Asd4 in regulating intracellular glutamine levels in order to modulate TOR inhibition of appressorium formation downstream of cPKA. This study thus provides novel insight into the metabolic mechanisms that underpin the highly regulated process of appressorium development.

  2. Expansion of CD4(+ CD25(+ and CD25(- T-Bet, GATA-3, Foxp3 and RORγt cells in allergic inflammation, local lung distribution and chemokine gene expression.

    Directory of Open Access Journals (Sweden)

    You Lu

    Full Text Available Allergic asthma is associated with airway eosinophilia, which is regulated by different T-effector cells. T cells express transcription factors T-bet, GATA-3, RORγt and Foxp3, representing Th1, Th2, Th17 and Treg cells respectively. No study has directly determined the relative presence of each of these T cell subsets concomitantly in a model of allergic airway inflammation. In this study we determined the degree of expansion of these T cell subsets, in the lungs of allergen challenged mice. Cell proliferation was determined by incorporation of 5-bromo-2'-deoxyuridine (BrdU together with 7-aminoactnomycin (7-AAD. The immunohistochemical localisation of T cells in the lung microenvironments was also quantified. Local expression of cytokines, chemokines and receptor genes was measured using real-time RT-PCR array analysis in tissue sections isolated by laser microdissection and pressure catapulting technology. Allergen exposure increased the numbers of T-bet(+, GATA-3(+, RORγt(+ and Foxp3(+ cells in CD4(+CD25(+ and CD4(+CD25(- T cells, with the greatest expansion of GATA-3(+ cells. The majority of CD4(+CD25(+ T-bet(+, GATA-3(+, RORγt(+ and Foxp3(+ cells had incorporated BrdU and underwent proliferation during allergen exposure. Allergen exposure led to the accumulation of T-bet(+, GATA-3(+ and Foxp3(+ cells in peribronchial and alveolar tissue, GATA-3(+ and Foxp3(+ cells in perivascular tissue, and RORγt(+ cells in alveolar tissue. A total of 28 cytokines, chemokines and receptor genes were altered more than 3 fold upon allergen exposure, with expression of half of the genes claimed in all three microenvironments. Our study shows that allergen exposure affects all T effector cells in lung, with a dominant of Th2 cells, but with different local cell distribution, probably due to a distinguished local inflammatory milieu.

  3. Geología, caracterización y aplicaciones de las rocas zeolíticas del complejo volcánico de Cabo de Gata (Almeria)

    OpenAIRE

    Costafreda Mustelier, Jorge Luis

    2008-01-01

    El presente trabajo tiene la finalidad de caracterizar las rocas zeolíticas que afloran en el yacimiento San José-Los Escullos y sus alrededores, en la zona de Cabo de Gata, Almería, dentro del complejo volcánico del Sureste de España, y determinar sus posibles aplicaciones en la fabricación de morteros y cementos puzolánicos. Los hitos seguidos para el desarrollo de los temas que conforman esta investigación, parten de un reconocimiento geológico del área donde yacen estos materiales, con el...

  4. HEMANGIOMA HEPÁTICO PRIMÁRIO EM GATA PERSA COM DOENÇA RENAL POLICÍSTICA PRIMARY HEPATIC HEMANGIOMA IN PERSIAN CAT WITH POLYCYSTIC KIDNEY DISEASE

    OpenAIRE

    Valdemiro Amaro da Silva Júnior; Frederico Celso Lyra Maia; Fábio Luiz da Cunha Brito

    2008-01-01

    Hemangiomas primários do fígado são neoplasias benignas que podem comprometer a sobrevivência do animal, em virtude da compressão de vasos, ductos e hepatócitos adjacentes, especialmente pela possibilidade de rupturas e morte por hipovolemia. Por serem raros em felinos, objetiva-se relatar o caso de uma gata Persa, com 10 anos de idade, cujos sinais clínicos eram: aumento de volume abdominal, vômitos intermitentes, apatia e anorexia, além de cios irregular...

  5. A high-resolution map of genes, microsatellite markers, and new dinucleotide repeats from UBE1 to the GATA locus in the region Xp11.23

    Energy Technology Data Exchange (ETDEWEB)

    Kwan, Sau-Ping; Hagemann, T.L. [Rush Medical School, Chicago, IL (United States); Rosen, F.S. [Harvard Medical School, Boston, MA (United States)] [and others

    1995-09-01

    Several new genes and markers have recently been identified on the proximal short arm of the human X chromosome in the area of Xp11.23. We had previously generated at YAC contig in this region extending from UBE1 to the OATL1 locus. In this report two polymorphic dinucleotide repeats, DXS6949 and DXS6950, were isolated and characterized from the OATL1 locus. A panel of YAC deletion derivatives from the distal portion of the contig was used in conjunction with the rest of the YAC map to position the new microsatellites and order other markers localizing to this interval. The marker order was determined to be DXS1367-ZNF81-DXS6849-ZNF21-DXS6616-DXS6950-DXS6949. In the proximal region below OATL1, we have isolated a pair of YACs from the GATA locus, B1026 and C01160. Mapping within these YACs indicates the orientation of DXS1126 and DXS1240, while a cosmid near the OATL1 region reveals the overlap between the YAC contigs from the two loci. This cosmid contains the gene responsible for Wiskott-Aldrich syndrome (WAS) and localizes the disease gene between OATL1 and GATA. These data enable the expansion of the present physical map of the X chromosome from UBE1 to the GATA locus, covering a large portion of the Xp11.23 region. Genetic crossovers in Xp11.23 support the marker orientation and the position of WAS, contrary to previous reports. With the integration of both physical and genetic maps we have predicted the following marker order: Xpter-UBE1-SYN1/ARAF1/TIMP1/DXS1367-ZNF81-DXS-6849-ZNF21-DXSy6616-(OATL1, DXS6950-DXS6949)-WAS-(GATA,DXS1126)-DXS12410-Xcen. This orientation identifies DXS6949 and DXS1126 as the nearest flanking polymorphic markers for WAS and provides useful anchor positions for the analysis of other disease genes that have been localized to this area including three different retinal defects and X-linked nephrolithiasis. 39 refs., 3 figs., 1 tab.

  6. Halomonas indalinina sp.nov., a moderately halophilic bacterium isolated from a solar saltern in Cabo de Gata, Al,eria, southern Spain

    OpenAIRE

    Cabrera, A.; Aguilera, M.; Fuentes Enriquez de Salamanca, S.; Incerti, C.; Russell, N J; Ramos-Cormenzana, A.; Monteoliva-Sanchez, M.

    2007-01-01

    moderately halophilic bacterium, strain CG2.1T, isolated from a solar saltern at Cabo de Gata, a wildlife reserve located in the province of Almería, southern Spain, was subjected to a polyphasic taxonomic study. This organism was an aerobic, motile, Gram-negative rod that produced orange-pigmented colonies. Strain CG2.1T was able to grow at salinities of 3¿25 % (w/v) and at temperatures of 15¿40 °C. The pH range for growth was 5¿9. Strain CG2.1T was a heterotroph capable of utilizing various...

  7. Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment

    OpenAIRE

    Yamane, Hidehiro; Zhu, Jinfang; Paul, William E.

    2005-01-01

    T cell receptor (TCR) signaling plays an important role in early interleukin (IL)-4 production by naive CD4 + T cells. This “antigen-stimulated” early IL-4 is sufficient for in vitro Th2 differentiation. Here, we provide evidence that early IL-4 production by naive CD4 + T cells stimulated with cognate peptide requires TCR-induced early GATA-3 expression and IL-2 receptor signaling, both of which are controlled by the degree of activation of extracellular signal-regulated kinase (ERK). Stimul...

  8. The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins.

    OpenAIRE

    Wadman, I A; Osada, H; Grütz, G G; Agulnick, A D; Westphal, H; Forster, A.; Rabbitts, T H

    1997-01-01

    The LIM-only protein Lmo2, activated by chromosomal translocations in T-cell leukaemias, is normally expressed in haematopoiesis. It interacts with TAL1 and GATA-1 proteins, but the function of the interaction is unexplained. We now show that in erythroid cells Lmo2 forms a novel DNA-binding complex, with GATA-1, TAL1 and E2A, and the recently identified LIM-binding protein Ldb1/NLI. This oligomeric complex binds to a unique, bipartite DNA motif comprising an E-box, CAGGTG, followed approxima...

  9. The degree of leukocytosis and urine GATA-3 mRNA levels are risk factors for severe acute kidney injury in Puumala virus nephropathia epidemica.

    Directory of Open Access Journals (Sweden)

    Daniel H Libraty

    Full Text Available Puumala hantavirus (PUUV infection, also known as nephropathia epidemica, is the most common cause of hemorrhagic fever with renal syndrome (HFRS in Europe. The pathogenesis of PUUV nephropathia epidemica is complex and multifactorial, and the risk factors for severe acute kidney injury (AKI during acute PUUV infection are not well defined. We conducted a prospective study of hospitalized patients with PUUV infection in Tampere, Finland to identify acute illness risk factors for HFRS severity. Serial daily blood and urine samples were collected throughout acute illness and at 2 week and 6 month convalescent visits. By univariate analyses, the maximum white blood cell count during acute illness was a risk factor for severe AKI. There were no significant associations between PUUV-induced AKI severity and platelet counts, C-reactive protein, or alanine aminotransferase levels. Maximum plasma interleukin (IL-6, urine IL-6, and urine IL-8 concentrations were positively associated with PUUV-induced AKI. Finally, the maximum urinary sediment GATA-3 mRNA level was positively correlated with the peak fold-change in serum creatinine, regardless of AKI severity classification. By multivariate analyses, we found that the maximum levels of leukocytes and urinary sediment GATA-3 mRNA during acute illness were independent risk factors for severe PUUV-induced AKI. We have identified novel acute illness risk factors for severe PUUV-induced AKI.

  10. Expression analysis and localization of wt1, ad4bp/sf-1 and gata4 in the testis of catfish, Clarias batrachus: Impact of wt1-esiRNA silencing.

    Science.gov (United States)

    Murugananthkumar, Raju; Senthilkumaran, Balasubramanian

    2016-08-15

    In teleosts, a comprehensive role or interaction of wt1, ad4bp/sf-1 and gata4 genes in relation to gonadal development and/or recrudescence was never attempted. Present study aimed to identify the involvement of these genes during testicular development of catfish, Clarias batrachus. Dominant expression of wt1 and gata4 was observed in developing and adult testis, while ad4bp/sf-1 showed steady expression. Localization of these genes in adult testis revealed their presence in spermatogonia, spermatocytes and interstitial/Leydig cells. Significant high expression during pre-spawning and spawning phases, and upregulated levels of these genes after hCG induction authenticated gonadotropic regulation. Transient silencing of wt1-esiRNA displayed decrease in wt1 expression, which further downregulated the expression of ad4bp/sf-1 and gata4, and certain steroidogenic enzyme genes related to androgen production. These results suggest that wt1 might target ad4bp/sf-1 and gata4 expression, and also have regulatory influence either indirectly or directly on the steroidogenic enzyme genes of catfish. PMID:27173028

  11. Smad4 mediated BMP2 signal is essential for the regulation of GATA4 and Nkx2.5 by affecting the histone H3 acetylation in H9c2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Si, Lina; Shi, Jin; Gao, Wenqun [Heart Centre, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China); Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China); Zheng, Min [Heart Centre, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China); Liu, Lingjuan; Zhu, Jing [Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China); Tian, Jie, E-mail: jietian@cqmu.edu.cn [Heart Centre, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing 400014 (China)

    2014-07-18

    Highlights: • BMP2 can upregulated cardiac related gene GATA4, Nkx2.5, MEF2c and Tbx5. • Inhibition of Smad4 decreased BMP2-induced hyperacetylation of histone H3. • Inhibition of Smad4 diminished BMP2-induced overexpression of GATA4 and Nkx2.5. • Inhibition of Smad4 decreased hyperacetylated H3 in the promoter of GATA4 and Nkx2.5. • Smad4 is essential for BMP2 induced hyperacetylated histone H3. - Abstract: BMP2 signaling pathway plays critical roles during heart development, Smad4 encodes the only common Smad protein in mammals, which is a pivotal nuclear mediator. Our previous studies showed that BMP2 enhanced the expression of cardiac transcription factors in part by increasing histone H3 acetylation. In the present study, we tested the hypothesis that Smad4 mediated BMP2 signaling pathway is essential for the expression of cardiac core transcription factors by affecting the histone H3 acetylation. We successfully constructed a lentivirus-mediated short hairpin RNA interference vector targeting Smad4 (Lv-Smad4) in rat H9c2 embryonic cardiac myocytes (H9c2 cells) and demonstrated that it suppressed the expression of the Smad4 gene. Cultured H9c2 cells were transfected with recombinant adenoviruses expressing human BMP2 (AdBMP2) with or without Lv-Smad4. Quantitative real-time RT-PCR analysis showed that knocking down of Smad4 substantially inhibited both AdBMP2-induced and basal expression levels of cardiac transcription factors GATA4 and Nkx2.5, but not MEF2c and Tbx5. Similarly, chromatin immunoprecipitation (ChIP) analysis showed that knocking down of Smad4 inhibited both AdBMP2-induced and basal histone H3 acetylation levels in the promoter regions of GATA4 and Nkx2.5, but not of Tbx5 and MEF2c. In addition, Lv-Smad4 selectively suppressed AdBMP2-induced expression of HAT p300, but not of HAT GCN5 in H9c2 cells. The data indicated that inhibition of Smad4 diminished both AdBMP2 induced and basal histone acetylation levels in the promoter regions of

  12. Smad4 mediated BMP2 signal is essential for the regulation of GATA4 and Nkx2.5 by affecting the histone H3 acetylation in H9c2 cells

    International Nuclear Information System (INIS)

    Highlights: • BMP2 can upregulated cardiac related gene GATA4, Nkx2.5, MEF2c and Tbx5. • Inhibition of Smad4 decreased BMP2-induced hyperacetylation of histone H3. • Inhibition of Smad4 diminished BMP2-induced overexpression of GATA4 and Nkx2.5. • Inhibition of Smad4 decreased hyperacetylated H3 in the promoter of GATA4 and Nkx2.5. • Smad4 is essential for BMP2 induced hyperacetylated histone H3. - Abstract: BMP2 signaling pathway plays critical roles during heart development, Smad4 encodes the only common Smad protein in mammals, which is a pivotal nuclear mediator. Our previous studies showed that BMP2 enhanced the expression of cardiac transcription factors in part by increasing histone H3 acetylation. In the present study, we tested the hypothesis that Smad4 mediated BMP2 signaling pathway is essential for the expression of cardiac core transcription factors by affecting the histone H3 acetylation. We successfully constructed a lentivirus-mediated short hairpin RNA interference vector targeting Smad4 (Lv-Smad4) in rat H9c2 embryonic cardiac myocytes (H9c2 cells) and demonstrated that it suppressed the expression of the Smad4 gene. Cultured H9c2 cells were transfected with recombinant adenoviruses expressing human BMP2 (AdBMP2) with or without Lv-Smad4. Quantitative real-time RT-PCR analysis showed that knocking down of Smad4 substantially inhibited both AdBMP2-induced and basal expression levels of cardiac transcription factors GATA4 and Nkx2.5, but not MEF2c and Tbx5. Similarly, chromatin immunoprecipitation (ChIP) analysis showed that knocking down of Smad4 inhibited both AdBMP2-induced and basal histone H3 acetylation levels in the promoter regions of GATA4 and Nkx2.5, but not of Tbx5 and MEF2c. In addition, Lv-Smad4 selectively suppressed AdBMP2-induced expression of HAT p300, but not of HAT GCN5 in H9c2 cells. The data indicated that inhibition of Smad4 diminished both AdBMP2 induced and basal histone acetylation levels in the promoter regions of

  13. The Novel Marker GATA3 is Significantly More Sensitive Than Traditional Markers Mammaglobin and GCDFP15 for Identifying Breast Cancer in Surgical and Cytology Specimens of Metastatic and Matched Primary Tumors.

    Science.gov (United States)

    Sangoi, Ankur R; Shrestha, Bijayee; Yang, George; Mego, Ourhay; Beck, Andrew H

    2016-04-01

    Traditional markers mammaglobin and GCDFP15 show good specificity but lack sensitivity and can be difficult to interpret in small tissue samples. We undertook a comparative study of the novel nuclear marker GATA3 (expression typically restricted to breast and urothelial carcinomas) and GCDFP15 and mammaglobin. We first compared quantitative mRNA expression levels of these 3 markers across a diverse set of over 6000 tumors and 500 normal samples from The Cancer Genome Atlas which showed dramatically higher GATA3 expression (>10-fold higher) in breast cancer as compared with GCDFP15 or mammaglobin (both PGATA3 may represent a more sensitive marker of breast cancer than GCDFP15 or mammaglobin. We next examined protein expression by immunohistochemistry in 166 cases (including surgical and cytology specimens) of metastatic breast carcinoma and 54 cases with available matched primaries. One whole-slide section from each case was stained for monoclonal GATA3 (L50-823), monoclonal mammaglobin (31A5), and monoclonal GCDFP15 (EP1582Y). Staining intensity (0 to 3+) and extent (0% to 100%) were scored with an H-score calculated (range, 0 to 300). Sensitivities by varying H-score cutoffs for a positive result in metastatic breast carcinoma among GATA3/GCDFP15/mammaglobin, respectively, were as follows: any H-score=95%/65%/78%, H-score>50=93%/37%/47%, H-score>100=90%/25%/27%, H-score>150=86%/21%/19%, H-score>200=73%/18%/9%, H-score>250=66%/14%/6%. Significant staining differences by specimen type, tumor subtype/grade, or ER/PR/HER2 status were not identified. Significantly stronger correlation was observed between primary/metastatic GATA3 expression [Pearson's correlation=0.81 (0.68-0.89)] as compared with the primary/metastatic correlations of GCDFP15 [Pearson's correlation=0.57 (0.33-0.74)] and mammaglobin [Pearson's correlation=0.50 (0.24-0.70)] (both PGATA3 stains a significantly higher proportion of both primary and metastatic breast carcinomas than GCDFP15 or mammaglobin

  14. Method of determination of the leaf area of the potato cultivar Ágata from linear dimensionsMétodo de determinação da área foliar da cultivar de batata Ágata a partir de dimensões lineares

    Directory of Open Access Journals (Sweden)

    Sidnei Osmar Jadoski

    2012-12-01

    Full Text Available The cultivar Ágata is currently the most widely cultivated in areas of potato production in Brazil, however, are necessaries basic information about its characteristics, especially on the development of the canopy. The work was developed in experimental area of the Unit of Research in Potato Culture and Microclimate for Agriculture, in the department of Agronomy of the UniversidadeEstadual do Centro Oeste (Unicentro, in Guarapuava (PR. The aim was to evaluate the efficiency of the adjustment of different mathematic models to determine the leaf area of potato plants of the cultivar Ágata. The evaluations were performed considering the dimensions of a 100 seeds of several sizes which were randomly collected in the phase of maximum vegetative development of plants. The data obtained were submitted to analysis of regression, being tested six different mathematic models: linear, quadratic, cubic functions and the exponential models from growth, Gauss and Lorentz, using the length and the height of leaves as independent variable to the adjustment in function of the real leaf area measured in laboratory. The variable length and the product of length x width of the leaf were those who presented the best results of adjustments to the models tested. With more emphasis to the length, for which all the models testes present statistical significance. It was concluded that the leaf length is the most appropriated parameter to be used in evaluation of the leaf area of potato plants cultivar Ágata, being the exponential function of growth and Lorentz the less recommended since its lowest adjustment coefficient. A cultivar Ágata é atualmente a mais cultivada nas lavouras de produção de batata no Brasil, contudo, ainda são necessárias informações básicas sobre suas características, especialmente sobre o desenvolvimento do dossel vegetativo.O trabalho foi desenvolvido em área experimental da Unidade de Pesquisa em Bataticultura e Microclima para a

  15. Análisis e interpretación de los materiales volcánicos del Cerro de los Frailes (Cabo de Gata. Almería

    Directory of Open Access Journals (Sweden)

    Fernández Soler, J. M.

    1987-12-01

    Full Text Available The formation of Los Frailes volcano had two stages, which produced amphibole andesites (Frailes-I and two-pyroxene andesites (Frailes-II respectively, Iying on the extension of the dacites and andesites of the southernmost Cabo de Gata volcanoes (Revancha-Sabinal. The FRAILES-I stage is discontinuous, and has mainly produced domes and autoclastic breccias, in addition to an intermediate level of pumice-and-ash flow; this unit has some intercalated sedimentary levels. To the NE it is covered by a formation of sedimentary and hydroclastic rocks. The Frailes-II stage is continuous, and has formed some lava flows, the two summit domes, and sorne pyroclastic rocks of scarcely explosive origin. Other volcanic features are some domes and dikes of biotite-amphibole dacites, which affect to the Frailes-I-group; these are the southern continuation of the dacitic volcanic group of Rodalquilar-Rellana-Garbanzal. The generally accepted idea of a succesion in Cabo de Gata of cycles which started very explosively and ended with subvolcanic extrussions (domes does not seem to be very realistic at least in the building of Los Frailes. A review of geochronological data, and the field disposition of the described materials does not discard the hypothesis that the pyroxene andesites of FrailesI-I might have been formed simultaneously or even than later the ignimbritic dacites of the Rodalquilar group.La formación del volcán de Los Frailes se produjo en dos ciclos, de composiciones andesítica anfibólica (Frailes-I y andesitica de dos piroxenos (Frailes-II, apoyadas sobre la prolongación hacia el este de las andesitas y dacitas del extremo sur de Cabo de Gata (edificio de Revancha-Sabinal-Cabo de Gata. El ciclo Frailes-I es discontínuo y ha formado domos y brechas autoclásticas principalmente, mas un nivel intermedio de colada piroclástica pumítica; este ciclo contiene niveles sedimentarios intercalados. Al NE es cubierto por una formación de rocas

  16. Analgesia da farmacopuntura com meloxicam ou da aquapuntura preemptivas em gatas submetidas à ovariosalpingohisterectomia Analgesia of preemptive pharmacopuncture with meloxicam or aquapuncture in cats undergoing ovariohysterectomy

    OpenAIRE

    Nicole Ruas de Sousa; Stelio Pacca Loureiro Luna; Maria Luísa Buffo de Cápua; Alfredo Feio da Maia Lima; Flávia Augusta de Oliveira; Bruno Massa de Viveiros; Luciano Barbosa

    2012-01-01

    Objetivou-se avaliar o efeito analgésico da farmacopuntura com meloxicam e da aquapuntura preemptivas em gatas submetidas à OSH. Foram utilizados 29 animais considerados sadios após exame clínico e laboratorial com idade de 11,59±6,21 meses e peso de 2,50±0,58kg distribuídos em quatro grupos: aquapuntura (GA; n=7; 0,1ml de solução fisiológica nos acupontos BP6, VB34, F3 e E36 bilaterais), meloxicam (GM; n=8; 0,1mg kg-1 de meloxicam por via subcutânea), farmacopuntura (GMFV; n=7; 0,01mg kg-1 d...

  17. Relación entre parámetros ultrasonográficos y edad gestacional en la gata doméstica

    OpenAIRE

    García Mitacek, María Carla; Praderio, Romina; Bonaura, María Candela; Sota, Rodolfo Luzbel de la; Stornelli, María Alejandra

    2012-01-01

    Existen diferentes métodos para el diagnóstico de la gestación en felinos, sin embargo el examen ultrasonográfico permite confirmar la preñez en forma temprana y brinda información sobre el desarrollo embrionario-fetal. El objetivo del trabajo fue relacionar diferentes parámetros ultrasonográficos con el día de gestación. Se utilizaron gatas (n=10) mestizas, de entre 24 y 36 meses de edad. El diagnóstico de gestación se realizó por ecografía 20 días posteriores al día del servicio. Se realizó...

  18. A expressão da COX-2 em patologias da glândula mamária da gata

    OpenAIRE

    Sousa, Rui Pedro Meireles de

    2010-01-01

    Pelo menos 80-85% dos tumores da glândula mamária dos felídeos são malignos. Estes tumores ocorrem em média entre os 10-11 anos de idade e são o terceiro tumor mais frequente nesta espécie, precedidos dos tumores hematopoiéticos e cutâneos. A incidência destes tumores nos felídeos é inferior em cerca de metade aos dos canídeos e humanos. Contudo, as neoplasias mamárias correspondem a 17% de todos os tumores que ocorrem na gata, que metastizam com frequência, principalmente para o pulmão e gân...

  19. Esterilização em gatas mediante salpingectomia parcial (incluindo prenhes versus ovariossalpingohisterectomia Sterilization in queens by partial salpingectomy (including pregnant versus ovariohysterectomy

    Directory of Open Access Journals (Sweden)

    Amanda Camilo Silva

    2012-03-01

    Full Text Available A ligadura ou laqueadura das tubas uterinas é uma forma de contracepção bastante utilizada na medicina humana. Ela consiste na oclusão mecânica e/ou ressecção parcial desta estrutura (salpingectomia parcial. Nesta pesquisa, procurou-se utilizar uma técnica de contracepção definitiva em gatas prenhes, que não comprometesse a gestação em curso, o parto, nem os conceptos, tendo em vista a frequência da visualização de útero gravídico nas campanhas de castração. Avaliou-se também o ganho de peso e mudanças de comportamento das gatas submetidas à salpingectomia parcial, comparando-as com as submetidas à ovariossalpingohisterectomia (OSH, além de comparar o tempo cirúrgico entre os dois procedimentos. Para tal, foram utilizadas 40 gatas, distribuídas em dois grupos de 20 animais, GA: salpingectomia parcial, e GB: OSH; sendo o primeiro subdividido em GA1 contendo 10 gatas prenhes e GA2 contendo 10 não prenhes. Todos os animais foram reavaliados com sete, 60, 180 e 365 dias. O tempo cirúrgico apresentou diferença estatisticamente significativa entre os grupos, sendo o GB mais demorado. Nas gatas do grupo GA1, o curso gestacional e o parto foram normais. No total, foram visualizadas 51 vesículas embrionárias, nasceram 49 fetos vivos e ocorreram duas reabsorções fetais. Dentre os 49 fetos, sete (14,28% apresentaram a anormalidade genu recurvatum. Quanto à fertilidade, os animais do grupo A que ciclaram e copularam não engravidaram. Apenas o grupo B apresentou aumento de peso médio (20,34% estatisticamente significativo. Com relação aos parâmetros comportamentais, o grupo B apresentou maiores alterações quanto ao aumento na ingestão de alimentos, aumento da letargia e diminuição do período de vigília. Concluiu-se que a técnica de salpingectomia parcial realizada em gatas é um método contraceptivo 100% eficaz, de rápida execução, que pode ser empregado durante a identificação transcirúrgica do estado

  20. Caracterização química e física de batatas ágata e monalisa minimamente processadas Chemical and physical characterization of fresh-cut potatoes

    Directory of Open Access Journals (Sweden)

    Lívia L. O. Pineli

    2006-03-01

    Full Text Available O objetivo deste trabalho foi caracterizar química e fisicamente batatas minimamente processadas durante o armazenamento refrigerado. Batatas (Solanum tuberosum, L. ágata e monalisa foram minimamente processadas como minibatatas. Após o processamento, as batatas foram acondicionadas sob vácuo parcial e, posteriormente, armazenadas em câmaras frias a 5 e 15ºC, por nove dias. A cada três dias, foram avaliadas as seguintes variáveis: firmeza, atividade da polifenoloxidase e peroxidase, açúcares solúveis totais, amido e vitamina C total. Nas batatas armazenadas a 15ºC, constatou-se que, após nove dias de armazenamento, sua firmeza era 3,3 vezes menor em batatas monalisa e 4,3 vezes menor para a cultivar ágata, quando comparadas com o produto recém-processado. A atividade da polifenoloxidase mostrou-se praticamente estável em batatas monalisa armazenadas a 5ºC. Batatas monalisa minimamente processadas apresentaram maior atividade da peroxidase a 5ºC, sendo 86% maior do que a atividade desta enzima em batatas ágata ao final do período experimental. O teor inicial de açúcares solúveis totais nas batatas minimamente processadas era 28% maior na cultivar monalisa, quando comparada com tubérculos de ágata. As duas cultivares apresentaram tendência de elevação do teor de amido nos primeiros três dias, para as duas temperaturas estudadas. Em ambas as cultivares, armazenamento a 5ºC possibilitou maior manutenção dos teores de vitamina C.The present work was carried out aiming to evaluate chemical and physical characteristics of fresh-cut potatoes stored under 5 and 15°C. Potatoes, (Solanum tuberosum L. ágata and Monalisa were minimally processed as baby potatoes. After processing, the material was packed under partial vacuum and stored at 5 and 15°C for nine days. Every three days tubers were evaluated for firmness, enzymatic activity (polyphenoloxidase and peroxidase, total soluble sugars, starch, and total vitamin C

  1. Briófitos como bioindicadores de calidad botánica en zonas áridas del SE español: Sierras de Filabres, Cabrera, Alhamilla y Cabo de Gata (Almería, España)

    OpenAIRE

    Ros Ferré, Rosa María; Guerra Montes, Juan; García Zamora, Pedro

    1999-01-01

    Briófitos como bioindicadores de calidad botánica en zonas áridas del Sudeste español: Sierras de Filabres, Cabrera, Alhamilla y Cabo de Gata (Almería, España). Basado en el estudio de la flora y vegetación briofíticas de las sierras de Filabres, Cabrera, Alhamilla y Cabo de Gata, se ha realizado la evaluación fitobiológica de las mismas aplicando un coeficiente de calidad botánica a una serie de localidades elegidas en el seno de estos sistemas montañosos. De este modo se han cartografiado l...

  2. Deposición atmosférica de bioelementos y su modificación por la cubierta vegetal en bosques de Quercus pyrenaica de la Sierra de Gata (Salamanca)

    OpenAIRE

    Moreno, G.; Gallardo, Juan. F.; Cuadrado, S.

    1994-01-01

    [EN]Water and several bioelements dynamics have been studied over three years in Quercus pyrenaica forest ecosystems, in the "Sierra de Gata" mountains (Salamanca Province, Spain); four permanent forest plots were selected following a rainfall gradient (annual mean precipitation ranges form 720 to 1580 mm). The site is presumed to be unpolluted. The aim of this study was to examine bulk precipitation, dry deposistion, throughfall and stemflow in order to determine the mechanisms involved in c...

  3. Evaluation of mRNA expression of the transcription factors of Th1 and Th2 subsets (T-bet and GATA-3 in periodontal health and disease - A pilot study in south Indian population

    Directory of Open Access Journals (Sweden)

    Nichenametla Rajesh

    2015-01-01

    Full Text Available Background: Based on their respective pro- or anti-inflammatory cytokine profiles, the Th1/Th2 paradigm explains pathogenic mechanisms involved in periodontal disease. Establishment of Th1 and Th2 subsets from a naive T-cell precursor depends on transcriptional regulation. The aim of this study was to compare the expression of master transcription factor regulators T-bet and GATA-3, respectively, to indicate the predominance of Th1 and Th2 subsets in the presence and absence of periodontal disease. Materials and Methods: A gingival tissue biopsy sample was obtained from each of 10 severe periodontitis patients (>5 mm attachment loss and 10 periodontally healthy patients (no attachment loss. Biopsies were immediately processed by real-time reverse transcriptase polymerase chain reaction and the difference in mRNA expression of T-bet and GATA-3 was assessed for each group. Results: The mRNA expression of T-bet was marginally increased about 1.31-fold in disease, while the GATA-3 levels showed a significant decrease of 4.39-fold in disease. Conclusion: The advanced periodontal lesions lack Th2 cells, which produce anti-inflammatory cytokines. The biopsies were therefore dominated by Th1 cells, which activate macrophages and osteoclasts.

  4. Caracterização química e física de batatas 'Ágata' minimamente processadas, embaladas sob diferentes atmosferas modificadas ativas Chemical and physical characterization of fresh-cut 'Ágata' potatoes packed under different active modified atmospheres

    Directory of Open Access Journals (Sweden)

    Lívia Lacerda Oliveira Pineli

    2005-10-01

    Full Text Available O objetivo deste trabalho foi avaliar as alterações químicas e físicas em batatas 'Ágata' minimamente processadas, embaladas sob diferentes atmosferas, durante o armazenamento refrigerado. Batatas 'Ágata' foram minimamente processadas como minibatatas e embaladas em filmes de náilon multicamadas. Os tratamentos aplicados no momento da embalagem foram o vácuo parcial e as misturas 10%CO2, 2%O2, 88%N2 ou 5%CO2, 5%O2, 90%N2. Em seguida, foram armazenadas a 5ºC. A cada três dias, amostras foram avaliadas quanto ao índice de escurecimento, atividade da polifenoloxidase e peroxidase, firmeza, sólidos solúveis totais e acidez titulável. O armazenamento sob vácuo parcial foi o mais eficaz no controle do escurecimento, da minimização da atividade da polifenoloxidase e da peroxidase, prevenindo alterações nos teores de sólidos solúveis totais, redução da firmeza, encharcamento da embalagem e maior acidez titulável. Os demais tratamentos apresentaram rápido desenvolvimento do escurecimento, aumento de firmeza em decorrência de ressecamento dos tubérculos, elevação nos sólidos solúveis totais e menor desenvolvimento da acidez em comparação ao tratamento sob vácuo parcial. A utilização de vácuo parcial foi a mais recomendada para a manutenção da qualidade das minibatatas. Todavia, outros tratamentos que busquem a manutenção da firmeza e frescor, sem o desenvolvimento de off-flavors e sem escurecimento, devem ser avaliados.The objective of this work was to evaluate chemical and physical characteristics of fresh-cut 'Ágata' potatoes packed under different active modified atmospheres, during refrigerated storage. 'Ágata' potatoes were minimally processed as baby potatoes and packed in nylon multilayer films. The treatments applied were partial vacuum, and atmospheres with 10%CO2, 2%O2, 88%N2 and 5%CO2, 5%O2, 90%N2. After that, they were stored at 5ºC. Every three days, tubers were evaluated for browning index

  5. Energy

    International Nuclear Information System (INIS)

    This chapter of the environmental control report deals with the environmental impact of energy production, energy conversion, atomic energy and renewable energy. The development of the energy consumption in Austria for the years 1993 to 1999 is given for the different energy types. The development of the use of renewable energy sources in Austria is given, different domestic heat-systems are compared, life cycles and environmental balance are outlined. (a.n.)

  6. Color landscape plan of the concrete Consideration on the harmony of concrete and landscape; Konkurito no shikisai keikan keikaku. Keikan to konkurito no chowa wo kangaeru

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, Hiroshi [Landscape Planning and Design with Concrete and Color, Tokyo (Japan)

    1999-03-10

    In Ministry of Construction, they positively promote the natural river make, and they have announced the basic design with the aim of river which does not use the concrete and river in which the concrete is not seen. It is the design control in using the concrete to be necessary for this. They introduced color landscape plan of the pile block of the concrete as a case in aiming at the harmony of concrete and landscape of being more concrete. They introduced concrete product which could express the local color characteristics of colors of the concrete which it does not suit for the landscape, usage of the concrete, concrete of the warm color, colors of concrete product of France, examples of the Disneyland, colors concrete lied, landscapes and cost, etc. (NEDO)

  7. Biología de la gestación en la gata doméstica (Felis catus Biology of pregnancy in the domestic cat (Felis catus

    Directory of Open Access Journals (Sweden)

    A.E SANCHEZ

    2002-01-01

    Full Text Available La gata es una hembra poliéstrica estacional en la cual el estímulo coital desencadena la liberación de LH y la ovulación, fenómenos que ocurren dentro de las primeras 50 horas postcoito. La fecundación de los ovocitos ocurre en el oviducto dentro de 30 horas post-ovulación. El transporte embrionario en oviducto toma alrededor de 132 horas y al momento de ingresar al útero los embriones se encuentran al estado de mórula compacta. A continuación los blastocistos migran entre los cuernos uterinos por aproximadamente 80 horas, hasta producirse la implantación 12 a 13 días post-coito. Durante la etapa preimplantacional existe un aumento significativo de la progesterona sérica así como de los receptores luteales a LH. A partir de la segunda mitad de la gestación, decae la producción de progesterona y aumenta la secreción de prolactina, postulándose que esta última sería el principal agente luteotrófico en la gata. También durante la segunda mitad de la gestación aumenta la secreción de relaxina. La producción y rol de la progesterona en la gestación tardía es un tema controversial. Se ha demostrado que la placenta felina posee actividad esteroidogénica y capacidad de sintetizar progesterona, lo cual sugiere que estaría relacionada con el soporte hormonal de la preñezThe domestic cat can be defined as a seasonal poliestrous female. During mating the physical stimulus produce the release of LH and ovulation, which occur during the first 50 hours post mating. The fertilization of oocytes takes place inside the oviduct during the 30 hours post ovulation. The embryos transport on the oviduct takes about 132 hours and when embryos reach the uterus they are already a compacted morulae. After this, the blastocyst migrates to both uterine horns for a period of 80 hours aproximately until implantation ocurrs 12 to 13 days after mating. During the preimplantation period, there is a significant increase in blood progesterone and

  8. Flora y vegetación marina y litoral del Cabo de Gata y el puerto de Roquetas del Mar (Almería). Primera aproximación

    OpenAIRE

    Ballesteros, Enric; Catalan, Jordi

    1983-01-01

    Se comentan las principales comunidades vegetales, litorales y submarinas de la zona del Cabo de Gata y el Puerto de Roquetas, presentándose una serie de inventarios fitosociológicos y unos esquemas de zonación de algunos puntos concretos de la costa. La realización de dichos inventarios y la recolección de especies mediante un muestreo selectivo han permitido confeccionar una lista de 15 Cianófitos, 163 algas superiores, 3 fanerógamas y 2 liqúenes. Asimismo se describ...

  9. A Positive GATA Element and a Negative Vitamin D Receptor-Like Element Control Atrial Chamber-Specific Expression of a Slow Myosin Heavy-Chain Gene during Cardiac Morphogenesis

    OpenAIRE

    Wang, Gang Feng; Nikovits, William; Schleinitz, Mark; Stockdale, Frank E.

    1998-01-01

    We have used the slow myosin heavy chain (MyHC) 3 gene to study the molecular mechanisms that control atrial chamber-specific gene expression. Initially, slow MyHC 3 is uniformly expressed throughout the tubular heart of the quail embryo. As cardiac development proceeds, an anterior-posterior gradient of slow MyHC 3 expression develops, culminating in atrial chamber-restricted expression of this gene following chamberization. Two cis elements within the slow MyHC 3 gene promoter, a GATA-bindi...

  10. Propuesta de un sistema de seguimiento y alerta para la gestión de espacios protegidos: el caso del Parque Natural Cabo de Gata-Níjar (Almería, España)

    OpenAIRE

    Oyarzábal, Mariano; Oyonarte Gutiérrez, Cecilio; Giorno, Agustín

    2008-01-01

    La mayoría de las áreas protegidas del mundo carecen de un sistema de seguimiento y alerta con implicancias directas en la gestión. Este trabajo propone, a partir del caso del Parque Natural Cabo de Gata-Níjar, posibles aplicaciones de un sistema de seguimiento. El sistema está basado en la más moderna tecnología satelital y fue originalmente desarrollado para uso agropecuario. En concreto, se propone la caracterización en un contexto histórico del funcionamiento de la vegetación del...

  11. Comparative Analysis of Nkx2-5/GATA4/TBX5 Expression in Chicken, Quail and Chicken-quail Hybrids during the Early Stage of Cardiac Development in Embryos

    OpenAIRE

    Ban, Qian; Liu, Xiaojun; Hui, Wenqiao; Chen, Danying; Zhao, Zongsheng; Jia, Bin

    2013-01-01

    The present study makes an investigation into expression of genes related to cardiac development in chicken, quail and chicken-quail hybrids during the early stage of embryogenesis. Real-time PCR was used to detect mRNA expressions of Nkx2-5, GATA4 and TBX5 in the heart of chicken, quail and chicken-quail hybrids embryos during the 3rd to 7th days of incubation. Results showed that NKX2-5 mRNA displayed a similar expression trend in chicken, quail and chicken-quail hybrids. The initial and hi...

  12. Traduzir Teatro no Estado Novo: Gata em Telhado de Zinco Quente (1959), tradução de Sérgio Guimarães, do original Cat on a Hot Tin Roof (1955), de Tennessee Williams

    OpenAIRE

    Lopes, Hélder Pedro Nascimento

    2014-01-01

    À luz da viragem cultural dos Estudos de Tradução ocorrida nos anos 80 e tendo em conta a interdisciplinaridade abordada nos campos literário, cultural e histórico pela Manipulation School (Lefevere, Bassnett, Lambert, Hermans e Toury), na esteira de Itamar Even-Zohar com a Teoria dos Polissistemas (1979), a presente dissertação pretende analisar a tradução portuguesa da peça Cat on a Hot Tin Roof (1955), da autoria de Tennessee Williams, intitulada Gata em Telhado de Zinco Que...

  13. Avaliação da analgesia pós-operatória da metadona, da cetamina ou da sua associação em gatas submetidas a ovariossalpingo-histerectomia

    OpenAIRE

    V.S. Padilha; R. Tocheto; S.L. Beier; J. Volpato; N. Oleskovicz

    2015-01-01

    A prevenção e o controle da dor são componentes básicos para um procedimento anestésico adequado. Objetivou-se com este estudo avaliar a analgesia pós-operatória da cetamina, em dose subanestésica, da metadona e da associação de ambas pela via intramuscular em felinos. Foram utilizadas 24 gatas, hígidas, submetidas à ovariossalpingo-histerectomia eletiva. No dia anterior ao início do estudo, os animais foram anestesiados para colocação de cateter na veia jugular, para posterior coleta de sang...

  14. Dexmedetomidina epidural em gatas submetidas à ovariosalpingohisterectomia sob anestesia total intravenosa com propofol e pré-medicadas com cetamina S(+) e midazolam Epidural dexmedetomidine in cats submitted to ovariosalpingohisterectomy under intravenous total anesthesia with propofol and pre medicated with ketamine (S) and midazolam

    OpenAIRE

    Otávia Dorigon; Nilson Oleskovicz; Aury Nunes de Moraes; Ademar Luiz Dallabrida; Fabíola Niederauer Flôres; André Vasconcelos Soares; Thiago José Mores

    2009-01-01

    O objetivo deste estudo foi avaliar os efeitos da administração epidural de dexmedetomidina em gatas submetidas à ovariosalpingohisterectomia (OSH), sob infusão contínua de propofol. Para tanto, foram utilizadas 12 gatas adultas, hígidas, com peso médio de 3,3±0,4kg, e entre um e quatro anos de idade. Como medicação pré-anestésica, os animais receberam cetamina S(+) (5mg kg-1) e midazolam(0,5mg kg-1), pela via intramuscular, e propofol como agente indutor (4mg kg-1), pela via intraveno...

  15. Experimental studies on a Savonius rotor with casing; Casing wo motsu Savonius gata turbine no tokusei ni kansuru jikkenteki kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Tan, S. [Tsuruoka National College of Technology, Yamagata (Japan); Shimizu, Y. [Mie University, Mie (Japan). Faculty of Engineering; Kikuyama, K. [Nagoya University, Nagoya (Japan). Faculty of Engineering

    1997-07-25

    The Savonius turbine, which works at low rotatory speeds and gives a high degree of torque, has been used for a wind turbines. In order to examine the feasibility of applying the turbine as a wave energy conversion system, a Savonius rotor was installed in a casing and its performance was studied experimentally to examine the various geometrical configurations of the rotor and casing. When optimally configured, the turbine exhibits higher efficiency than a wind turbine without a casing during steady flow conditions. 6 refs., 17 figs., 1 tab.

  16. Energy

    CERN Document Server

    Foland, Andrew Dean

    2007-01-01

    Energy is the central concept of physics. Unable to be created or destroyed but transformable from one form to another, energy ultimately determines what is and isn''t possible in our universe. This book gives readers an appreciation for the limits of energy and the quantities of energy in the world around them. This fascinating book explores the major forms of energy: kinetic, potential, electrical, chemical, thermal, and nuclear.

  17. Construction of two YAC contigs in human xp11.23-p11.22, one encompassing the loci OATL1, GATA, TFE3, and SYP, the other linking DXS255 to DXS146

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, S.E.; Hatchwell, E.; Chand, A.; Ockenden, N.; Craig, I.W. [Univ. of Oxford, Oxford (United Kingdom)] [and others

    1995-09-20

    We have constructed two YAC contigs in the Xp11.23-p11.22 interval of the human X chromosome, a region that was previously poorly characterized. One contig, of at least 1.4 Mb, links the pseudogene OATL1 to the genes GATA1, TFE3, and SYP and also contains loci implicated in Wiskott-Aldrich syndrome and synovial sarcoma. A second contig, mapping proximal to the first, is estimated to be over 2.1 Mb and links the hypervariable locus DXS255 to DXS146, and also contains a chloride channel gene that is responsible for hereditary nephrolithiasis. We have used plasmid rescue, inverse PCR, and Alu-PCR to generate 20 novel markers from this region, 1 of which is polymorphic, and have positioned these relative to one another on the basis of YAC analysis. The order of previously known markers within our contigs, Xpter-OATL1-GATA-TFE3-SYP-DXS255-DXS146-Xcen, agrees with genomic pulsed-field maps of the region. In addition, we have constructed a rare-cutter restriction map for a 710-kb region of the DXS255-DXS146 contig and have identified three CpG islands. These contigs and new markers will provide a useful resource for more detailed analysis of Xp11.23-p11.22, a region implicated in several genetic diseases. 32 refs., 2 figs., 2 tabs.

  18. Caudal brain infarctions in a kitten – case reportInfartos em região encefálica caudal em gata filhote – relato de caso

    Directory of Open Access Journals (Sweden)

    Lucas Alécio Gomes

    2013-05-01

    Full Text Available Stroke is uncommon in animals compared with humans because of the lower incidence of atherosclerosis and primary hypertension. However with advanced imaging, vascular disease is being recognized with increasing frequency in veterinary medicine. Cerebrovascular disease can be subdivided into infarction and hemorrhage, although the two categories overlap in the case of hemorrhagic infarcts. The aim of thisarticle is to report the neurological manifestations associated with stroke (infarctions in at two-month old, domestic shorthair cat. Neurological evaluation revealed head tilt, tetraparesis, proprioceptive deficits in all four limbs, and decreased pupillary light reflex. Further, manifestations of neurological dysfunctions were acute and progressive. At the necropsy, grossly there were hemorrhage and necrosis at mid-brain and cerebellum. Histopathology confirmed liquefactive necrosis at the mid-brain and cerebellum. The neurological manifestations associated with the pathological findings are suggestive of an anoxic infarction probably due to vascular occlusion. Em animais é baixa a incidência de arterosclerose e hipertensão primária. Devido a tal característica, infarto cerebral é incomum nos mesmos. Entretanto, com o avanço das modalidades de imagem, doença vascular está sendo reconhecida com maio frequência na medicina veterinária. Doença cerebrovascular pode ser subdividida em infarto e hemorragia, embora as duas categorias se interponham no caso de infartos hemorrágicos. Assim sendo, o objetivo deste artigo é descrever as manifestações neurológicas associadas a acidente vascular (infartos em uma gata de dois meses de idade, sem raça definida e domiciliada. Na avaliação neurológica observou-se inclinação de cabeça, tetraparesia, déficits proprioceptivos nos quatro membros e diminuição do reflexo pupilar a luz. Além disso, os problemas neurológicos foram agudos e progressivos. Na necropsia macroscopicamente

  19. Helicase-like transcription factor (Hltf regulates G2/M transition, Wt1/Gata4/Hif-1a cardiac transcription networks, and collagen biogenesis.

    Directory of Open Access Journals (Sweden)

    Rebecca A Helmer

    Full Text Available HLTF/Hltf regulates transcription, remodels chromatin, and coordinates DNA damage repair. Hltf is expressed in mouse brain and heart during embryonic and postnatal development. Silencing Hltf is semilethal. Seventy-four percent of congenic C57BL/6J Hltf knockout mice died, 75% within 12-24 hours of birth. Previous studies in neonatal (6-8 hour postpartum brain revealed silencing Hltf disrupted cell cycle progression, and attenuated DNA damage repair. An RNA-Seq snapshot of neonatal heart transcriptome showed 1,536 of 20,000 total transcripts were altered (p < 0.05 - 10 up- and 1,526 downregulated. Pathway enrichment analysis with MetaCore™ showed Hltf's regulation of the G2/M transition (p=9.726E(-15 of the cell cycle in heart is nearly identical to its role in brain. In addition, Brca1 and 12 members of the Brca1 associated genome surveillance complex are also downregulated. Activation of caspase 3 coincides with transcriptional repression of Bcl-2. Hltf loss caused downregulation of Wt1/Gata4/Hif-1a signaling cascades as well as Myh7b/miR499 transcription. Hltf-specific binding to promoters and/or regulatory regions of these genes was authenticated by ChIP-PCR. Hif-1a targets for prolyl (P4ha1, P4ha2 and lysyl (Plod2 collagen hydroxylation, PPIase enzymes (Ppid, Ppif, Ppil3 for collagen trimerization, and lysyl oxidase (Loxl2 for collagen-elastin crosslinking were downregulated. However, transcription of genes for collagens, fibronectin, Mmps and their inhibitors (Timps was unaffected. The collective downregulation of genes whose protein products control collagen biogenesis caused disorganization of the interstitial and perivascular myocardial collagen fibrillar network as viewed with picrosirius red-staining, and authenticated with spectral imaging. Wavy collagen bundles in control hearts contrasted with collagen fibers that were thin, short and disorganized in Hltf null hearts. Collagen bundles in Hltf null hearts were tangled and

  20. Energy

    CERN Document Server

    Robertson, William C

    2002-01-01

    Confounded by kinetic energy? Suspect that teaching about simple machines isn t really so simple? Exasperated by electricity? If you fear the study of energy is beyond you, this entertaining book will do more than introduce you to the topic. It will help you actually understand it. At the book s heart are easy-to-grasp explanations of energy basics work, kinetic energy, potential energy, and the transformation of energy and energy as it relates to simple machines, heat energy, temperature, and heat transfer. Irreverent author Bill Robertson suggests activities that bring the basic concepts of energy to life with common household objects. Each chapter ends with a summary and an applications section that uses practical examples such as roller coasters and home heating systems to explain energy transformations and convection cells. The final chapter brings together key concepts in an easy-to-grasp explanation of how electricity is generated. Energy is the second book in the Stop Faking It! series published by NS...

  1. Energy.

    Science.gov (United States)

    Chambers, David W

    2012-01-01

    Energy is the capacity to do the things we are capable of and desire to accomplish. Most often this is thought of in terms of PEP--personal energy potential--a reservoir of individual vivacity and zest for work. Like a battery, energy can be conceived of as a resource that is alternatively used and replenished. Transitions between activities, variety of tasks, and choices of what to spend energy on are part of energy management. Energy capacity can be thought of at four levels: (a) so little that harm is caused and extraordinary steps are needed for recovery, (b) a deficit that slightly impairs performance but will recover naturally, (c) the typical range of functioning, and (d) a surplus that may or may not be useful and requires continual investment to maintain. "Flow" is the experience of optimal energy use when challenges balance capacity as a result of imposing order on our environment. There are other energy resources in addition to personal vim. Effective work design reduces demands on energy. Money, office design, and knowledge are excellent substitutes for personal energy. PMID:22856055

  2. GATA Transcription Factors and Cancer

    OpenAIRE

    Zheng, Rena; Blobel, Gerd A.

    2010-01-01

    It has been almost a quarter century since it was first appreciated that a class of oncogenes contained in rapidly transforming avian retroviruses encoded DNA-binding transcription factors. As with other oncogenes, genetic recombination with the viral genome led to their overexpression or functional alteration. In the years that followed, alterations of numerous transcription factors were shown to be causatively involved in various cancers in human patients and model organisms. Depending on t...

  3. HEMANGIOMA HEPÁTICO PRIMÁRIO EM GATA PERSA COM DOENÇA RENAL POLICÍSTICA PRIMARY HEPATIC HEMANGIOMA IN PERSIAN CAT WITH POLYCYSTIC KIDNEY DISEASE

    Directory of Open Access Journals (Sweden)

    Valdemiro Amaro da Silva Júnior

    2008-07-01

    Full Text Available

    Hemangiomas primários do fígado são neoplasias benignas que podem comprometer a sobrevivência do animal, em virtude da compressão de vasos, ductos e hepatócitos adjacentes, especialmente pela possibilidade de rupturas e morte por hipovolemia. Por serem raros em felinos, objetiva-se relatar o caso de uma gata Persa, com 10 anos de idade, cujos sinais clínicos eram: aumento de volume abdominal, vômitos intermitentes, apatia e anorexia, além de cios irregulares. No exame radiográfico se observou massa tecidual radiopaca no fígado. Na ultra-sonografia hepática, percebiam-se contornos irregulares, parênquima heterogêneo, hiperecogênico, com áreas cavitárias, sugestivo de neoplasia e cistos. No exame macroscópico, visibilizaram-se ascite sanguinolenta, esteatose hepática e massa neoplásica única com 12 cm de comprimento por 8 cm de largura e diversos cistos. Os ovários e rins se apresentavam policísticos e havia hiperplasia endometrial cística. Microscopicamente foram diagnosticadas no fígado formações císticas limitadas por endotélio e delgada cápsula de tecido conjuntivo, esteatose e hepatite periportal mononuclear-linfocitária com proliferação de ductos bilíferos. A massa tumoral originava-se a partir do tecido conjuntivo da cápsula hepática e se caracterizava pela presença de brotos vasculares oriundos de células endoteliais, com dilatação e anastomose de vasos nas áreas mais superficiais. Os achados observados são compatíveis com o diagnóstico de hemangioma hepático primário do tipo capilar-cavernoso. Nos ovários, no útero, nos rins e fígado, constatou-se doença policística.

     

    PALAVRAS-CHAVES: Fígado, gato, neoplasia vascular.

    Primaries hepatics hemangiomas are benign tumors that may compel limitations to animal survival owing to the compression of blood vessels, ducts and contiguous hepatocytes, especially due a

  4. Energies

    International Nuclear Information System (INIS)

    This special dossier 'energies' is made of 6 contributions dealing with: the EPR, the European Pressurized Reactor (Bertrand Barre); nuclear weapons proliferation, the real threat (Bernard Lerouge); Proliferation in a globalizing economy (Georges Le Guelte); the compared efficiency of US and Electricite de France's nuclear parks in exploitation (Laurent Stricker, Jacques Leclercq); Why financing and how to finance the security of power supply (Fabien Chone); thoughts on the calls for competition of electricity production (Jacques Clade)

  5. Analgesia da farmacopuntura com meloxicam ou da aquapuntura preemptivas em gatas submetidas à ovariosalpingohisterectomia Analgesia of preemptive pharmacopuncture with meloxicam or aquapuncture in cats undergoing ovariohysterectomy

    Directory of Open Access Journals (Sweden)

    Nicole Ruas de Sousa

    2012-07-01

    Full Text Available Objetivou-se avaliar o efeito analgésico da farmacopuntura com meloxicam e da aquapuntura preemptivas em gatas submetidas à OSH. Foram utilizados 29 animais considerados sadios após exame clínico e laboratorial com idade de 11,59±6,21 meses e peso de 2,50±0,58kg distribuídos em quatro grupos: aquapuntura (GA; n=7; 0,1ml de solução fisiológica nos acupontos BP6, VB34, F3 e E36 bilaterais, meloxicam (GM; n=8; 0,1mg kg-1 de meloxicam por via subcutânea, farmacopuntura (GMFV; n=7; 0,01mg kg-1 de meloxicam, diluído em 0,8ml de solução fisiológica, distribuído nos acupontos BP6, VB34, F3 e E36 bilaterais e subdose de meloxicam (GMFF; n=7; 0,01mg kg-1 de meloxicam diluído em solução fisiológica por via SC na região interescapular. Os animais foram submetidos à OSH por meio de técnica cirúrgica minimamente invasiva. Os momentos de avaliação pós-cirúrgica foram 1h, 2h, 6h, 8h, 12h e 24h após o término da cirurgia por avaliador encoberto. Todos os parâmetros avaliados no dia anterior à cirurgia foram considerados como valores basais. Para a avaliação da sedação, utilizou-se a escala analógica visual e o escore do grau de sedação. Para a avaliação da dor, foram utilizadas a escala analógica visual (EAV, a escala descritiva de dor (EDD e o grau de hiperalgesia com o auxílio dos monofilamentos de Von Frey. O resgate analgésico foi realizado com morfina na dose de 0,2mg kg-1 por via intramuscular (IM, quando a pontuação na EDD ultrapassava 33% da total. A análise estatística foi realizada por meio do programa Sigma-Stat 3.1, utilizando-se a análise de variância paramétrica e não paramétrica e respectivos teste de Tukey e de Dunn para as comparações, com significância de 5% (PThe aim of this study was to evaluate the analgesic effect of preemptive pharmacopuncture with meloxicam or aquapuncture in cats undergoing ovariohysterectomy. Twenty-nine healthy animals, aged 11.59±6.21 and weighing 2.50±0.58kg

  6. Evaluación de respuesta ovárica y calidad de ovocitos en gatas tratadas con hormona folículo estimulante (FSH) utilizando dos esquemas de administración Evaluation of ovarian response and oocyte quality in domestic cats treated with two administration schemes of follicle stimulating hormone (FSH)

    OpenAIRE

    A. E. SANCHEZ; M. E. SILVA

    2003-01-01

    El objetivo de este trabajo fue estudiar el efecto del tratamiento gonadotrófico con FSH sobre las características foliculares y ovocitarias de gatas adultas, y comparar dos esquemas de administración de FSH en términos del número de ovocitos potencialmente aptos para MIV. Usando veinte gatas adultas, aleatoriamente, se formaron tres grupos de tratamiento. Grupo SC (n=7) 5 mg/ día de FSH por 4 días, vía subcutánea; Grupo IM (n=6) 2 mg/día de FSH por 5 días, vía intramuscular y un Grupo Contro...

  7. Myocardial Gene Expression of T-bet, GATA-3, Ror-γt, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed TH1-Type Response

    Directory of Open Access Journals (Sweden)

    Luciana Gabriel Nogueira

    2014-01-01

    Full Text Available Background. Chronic Chagas disease cardiomyopathy (CCC, a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC. Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg in CCC, NIC, and heart donor myocardial samples. Methods and Results. Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13 or associated with Treg (TGF-β and IL-10 were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. Conclusions. Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3+CTLA4+ Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation.

  8. Modeling of wind power generating system with a propeller type windmill by neural networks; Neural network wo mochiita propeller gata fusha hatsuden system no modeling

    Energy Technology Data Exchange (ETDEWEB)

    Sakaguchi, E.; Tanaka, T.; Tomiya, T. [Anan College of Technology, Tokushima (Japan); Suzuki, T. [The University of Tokushima, Tokushima (Japan)

    1997-07-01

    One of the expected sources of natural energy for the future is wind energy, which has been actively studied as a substitute sources of energy for the world. Not only about wind energy, natural energies of ocean, sun, etc. are clean and safe, but fluctuation of properties are large and has poor reproducibility, so that most important subject is to find out methods to take out those energies effectively. To simulate and control windmill power system by control sequence, we need to obtain the accurate model of the wind power generating system previously. It is well-known that neural networks are useful for many problems in nonlinear system because of the ability of learning and nonlinear representation. We apply the neural network method to model a small-scale windmill power system which has a propeller type windmill with a dc generator. We manifested the validity of the proposed method by simulation results from both the simulated results for sinusoidal change of wind speed and natural wind speed by random sequence. Finally, the simulation results are illustrated to show the effectiveness of the modeling method used here for field data of wind speed and windmill speed. 14 refs., 20 figs., 1 tab.

  9. Avaliação da analgesia pós-operatória da metadona, da cetamina ou da sua associação em gatas submetidas a ovariossalpingo-histerectomia

    Directory of Open Access Journals (Sweden)

    V.S. Padilha

    2015-04-01

    Full Text Available A prevenção e o controle da dor são componentes básicos para um procedimento anestésico adequado. Objetivou-se com este estudo avaliar a analgesia pós-operatória da cetamina, em dose subanestésica, da metadona e da associação de ambas pela via intramuscular em felinos. Foram utilizadas 24 gatas, hígidas, submetidas à ovariossalpingo-histerectomia eletiva. No dia anterior ao início do estudo, os animais foram anestesiados para colocação de cateter na veia jugular, para posterior coleta de sangue para mensuração da concentração sérica do cortisol. No dia do experimento, os animais foram alocados aleatoriamente em três grupos (n=oito, os quais receberam cetamina (GC, na dose de 0,5mg/kg; ou metadona (GM, na dose de 0,3mg/kg; ou cetamina e metadona (GCM, nas doses de 0,5mg/kg e 0,3mg/kg, respectivamente, todos pela via intramuscular. Todos os grupos receberam os fármacos 20 minutos antes da indução anestésica, a qual foi realizada com propofol, e a manutenção com isoflurano. Os parâmetros avaliados foram a mensuração do cortisol nos momentos M0 (basal - antes da cirurgia, M1(transoperatório, M2, M3, M4, M8, M12 e M24 (duas, três, quatro, oito, 12 e 24 horas após o término da cirurgia,e a do escore de dor por meio da escala multidimensional de dor aguda em felinos nos momentos M0, M2, M3, M4, M8, M12 e M24. Os valores de cortisol foram maiores no GC em comparação ao GM e ao GCM em M2 e M3. Os escores de dor foram maiores no GC nos momentos M2 e M3 em comparação ao GM e ao GCM, respectivamente. No somatório de pontos, no M2, o GC apresentou valores maiores que o GM e o GCM, e, no M4, o GC obteve valores maiores que o GCM. Em relação ao número de resgates no pós-operatório no GC, 8/8 dos animais necessitaram de resgate, no GM 5/8 e no GCM 3/8. Conclui-se que a associação de metadona e cetamina em gatas submetidas à OSH eletiva promove analgesia pós-operatória adequada e, assim, reduz o requerimento de

  10. Modulation of cytokines and transcription factors (T-Bet and GATA3 in CD4 enriched cervical cells of Chlamydia trachomatis infected fertile and infertile women upon stimulation with chlamydial inclusion membrane proteins B and C

    Directory of Open Access Journals (Sweden)

    Salhan Sudha

    2009-08-01

    Full Text Available Abstract Background Chlamydial Inclusion membrane proteins (Incs, are involved in biochemical interactions with host cells and infecting Chlamydiae. We have previously reported the role of two Chlamydia trachomatis (CT Incs, namely IncB and IncC in generating host immunity in CT infected women. Emerging data shows involvement of Inc stimulated CD4 positive T cells in aiding host immunity in infected fertile and infertile women through the secretion of interferon gamma. However the lack of data on the intra-cytokine interplay to these Incs in infected cell milieu prompted us to investigate further. Methods A total of 14 CT-positive fertile, 18 CT-positive infertile women and 25 uninfected controls were enrolled in this study. CD8 depleted, CD4 enriched cervical cells were isolated and upon stimulation with IncB and IncC, modulation of cytokines (Interleukin (IL-1 Beta, IL-4, IL-5, IL-6, IL-10, Interferon-gamma, IL-12, IL-23, Tumor Necrosis Factor-alpha and Granulocyte macrophage colony-stimulating factor (GM-CSF and T cell lineage regulating transcription factors T-Bet and GATA3 was determined by real-time reverse-transcriptase (RT-PCR and ELISA. Results Significant higher expression (P Conclusion Overall our data shows that CT IncB and IncC are able to upregulate expression of cytokines, namely interferon-gamma, IL-12, IL-23 and GM-CSF in CT-positive fertile women while expression of IL-1 Beta, IL-4, IL-5, IL-6 and IL-10 were upregulated in CT-positive infertile women. Our study also suggests that Incs are able to modulate expression of T cell lineage determinants indicating their involvement in regulation of immune cells.

  11. La migración holocena del ambiente litoral y su influencia en la génesis y distribución de las facies sedimentarias de la plataforma continental: el ejemplo de Cabo de Gata (Almería-España)

    OpenAIRE

    A. Vázquez; Zamarreño, I.

    1985-01-01

    [ES] Se establecen las estabilizaciones del nivel del mar durante la transgresión Holocena a partir de la comparación de las terrazas cartografiadas en la plataforma continental del Cabo de Gata y las líneas de costa, deducidas del grado de fracturación de los bivalvos en muestras alineadas en perfiles perpendiculares a la costa actual y paralelos entre sí. La existencia y distribución de sedimentos litorales en gran parte de la plataforma se explica por el bajo índice de...

  12. Energies; Energies

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-07-01

    In the framework of the National Debate on the energies in a context of a sustainable development some associations for the environment organized a debate on the nuclear interest facing the renewable energies. The first part presents the nuclear energy as a possible solution to fight against the greenhouse effect and the associated problem of the wastes management. The second part gives information on the solar energy and the possibilities of heat and electric power production. A presentation of the FEE (French wind power association) on the situation and the development of the wind power in France, is also provided. (A.L.B.)

  13. Numerical estimation of stability and improvement for coolant passage design in Hollow type CICC; Hollow gata CICC no reikyaku ryuro kaizen to anteisei no suchiteki kento

    Energy Technology Data Exchange (ETDEWEB)

    Miyauchi, M. [Yamagata Univ., Yamagata (Japan); Yoshiki, H. [The Univ. of Tokyo, Tokyo (Japan)

    1999-06-07

    The Hollow type CICC has a central channel (Hole) and is separated from surrounding bundle by a spiral tape with a gap, heat of a strand can effectively be convected to the Hole zone. However, even strong convection currents are induced in two ends of a thermal generating zone, but the heat is accumulated in the central part, and stability margin drops while relatively a long time heat has input for about 100 msec. In this study, the helium deposit inside the heating zone is reduced by a little design changing of the spiral tape that separates the bundle and the hole and efforts of improving stability of low energy density against heating are attempted. The instability caused by low energy and a long time heat invasion of the CICC appears also in simulation of Zanino at el. using a MITHRANDIR code. At this time, a method for calculating overflow of helium flowing to the bundle/Hole taking references of a branch current model and a joint flow model that are used in engine simulations is developed. (NEDO)

  14. Evaluación de respuesta ovárica y calidad de ovocitos en gatas tratadas con hormona folículo estimulante (FSH utilizando dos esquemas de administración Evaluation of ovarian response and oocyte quality in domestic cats treated with two administration schemes of follicle stimulating hormone (FSH

    Directory of Open Access Journals (Sweden)

    A. E. SANCHEZ

    2003-01-01

    Full Text Available El objetivo de este trabajo fue estudiar el efecto del tratamiento gonadotrófico con FSH sobre las características foliculares y ovocitarias de gatas adultas, y comparar dos esquemas de administración de FSH en términos del número de ovocitos potencialmente aptos para MIV. Usando veinte gatas adultas, aleatoriamente, se formaron tres grupos de tratamiento. Grupo SC (n=7 5 mg/ día de FSH por 4 días, vía subcutánea; Grupo IM (n=6 2 mg/día de FSH por 5 días, vía intramuscular y un Grupo Control (n=7. Las gatas fueron ovariectomizadas y se realizó recuento, medición de folículos y recuperación de ovocitos. Los folículos fueron agrupados en dos categorías: o = 2 mm (considerados como preovulatorios. El tratamiento gonadotrófico aumentó (P o = 2 mm, comparado con el grupo control, independiente del esquema de administración de FSH. El tratamiento gonadotrófico, también aumentó (P o = 2 mm versus folículosThe purpose of this work was to study the effects of FSH administration upon follicular and oocyte characteristics of female cats. Two FSH administration schemes were compared and their effects on the number of follicles and good grade oocytes for IVM obtained by follicular punction was determined. Twenty adults female cats were randomly distributed on 3 experimental groups: Group SC (n=7 recieved 5 mg/day of FSH for 4 days, subcutaneoulsy; Group IM (n=6 recieved 2 mg/day of FSH for 5 days, intramuscular and Control Group (n=7 which did not recieve any treatment. The ovaries were surgically removed from all female cats and follicles were counted and measured and the oocytes were recovered. Follicles were clasified according to their diameter on or = 2 mm (preovulatory. Gonadotrophine treatment increased the total number of follicles and follicles with > or = 2 mm diameter when compared to control group (P or = 2 mm than for follicles with < 2 mm diameter. It can be concluded that intramuscular or subcutaneus administration of

  15. GATA Negative Pressure Wound Therapy System

    OpenAIRE

    Yıldız, Şenol; Uzun, Günalp; Mutluoglu, Mesut; Memis, Ali

    2014-01-01

    The use of negative pressure wound therapy (NPWT) systems has been shown to promote wound healing. NPWT systems promise a fast and efficient way of preparing wounds for closure by either secondary intention or delayed primary closure, as well as for skin grafting and flap covering. While many of its benefits are established, commercial NPWT systems are not readily available and may be extremely costly for the patient. In the current report, we describe an equivalent alternative of NPWT at a s...

  16. Leucogram and serum acute phase protein concentrations in queens submitted to conventional or videolaparoscopic ovariectomy Leucograma e concentrações séricas de proteínas de fase aguda de gatas submetidas à ovariectomia convencional ou por videolaparoscopia

    Directory of Open Access Journals (Sweden)

    A.E. Alves

    2010-02-01

    Full Text Available Thirty health queens were submitted to ovariectomy by conventional technique or by videolaparoscopy. In order to study the intensity of inflammatory response by means of acute phase protein analysis and white blood cell count, serum samples were taken before and until 144 hours after the surgical procedures. The protein concentrations that were significantly increased 24 hours after surgical procedures were: ceruloplasmin, hemopexin, haptoglobin, and α1-acid glycoprotein, 69.8%, 103.5%, 117.3%, and 199.0%, respectively, for conventional ovariectomy; and 22.3%, 46.1%, 79.8%, and 74.6%, respectively, for laparoscopic ovariectomy. Therefore, inflammatory response was more intense in queens submitted to conventional ovariectomy. Results indicate that the increase or decrease in acute phase proteins, as well as in white blood cells count, may be useful in the evaluation of inflammatory response induced by these surgical procedures.Trinta gatas, saudáveis, foram submetidas à ovariectomia pela técnica convencional e por videolaparoscopia. Amostras de sangue foram obtidas com o objetivo de verificar a intensidade da resposta inflamatória por meio da análise das concentrações de proteinas de fase aguda e contagem de leucócitos antes e até 144 horas após procedimento cirúrgico. As proteínas que apresentaram aumento significativo 24 horas após a cirurgia foram: ceruloplasmina, hemopexina, haptoglobina e α1-glicoproteína ácida, 69,8%, 103,5%, 117,3% e 199,0%, respectivamente, para ovariectomia convencional, e 22,3%, 46,1%, 79,8% e 74,6%, respectivamente, para ovariectomia por videolaparoscopia. A resposta inflamatória foi mais evidente nas gatas submetidas à ovariectomia convencional. Os resultados mostram aumento e diminuição na concentração de proteínas de fase aguda e na contagem de leucócitos, podendo ser utilizados na avaliação da resposta inflamatória induzida por procedimentos cirúrgicos.

  17. Estudo retrospectivo de ovariossalpingo-histerectomia em cadelas e gatas atendidas em Hospital Veterinário Escola no período de um ano Retrospective ovariosalpingohisterectomy study in bitches and queens assisted at a Veterinary School Hospital during one year

    Directory of Open Access Journals (Sweden)

    C.P. Balthazar da Silveira

    2013-04-01

    Full Text Available Realizou-se um estudo retrospectivo das indicações de ovariossalpingo-histerectomia - eletiva e terapêutica - no período de um ano. Foram analisados 193 prontuários de cadelas e gatas atendidas em Hospital Veterinário Escola, entre março de 2010 e março de 2011, levando em consideração a espécie, a idade e o uso ou não de anticoncepcional. Constatou-se que a demanda de OSH com caráter terapêutico (78,8% é consideravelmente mais alta que a eletiva (21,2%. Observou-se que as anormalidades reprodutivas detectadas com maior frequência foram piometra (53,36% e complicações obstétricas (25,38% e que o uso de anticoncepcional foi o fator relevante para o delineamento desses quadros.An ovariosalpingohisterectomy procedure indication - elective and therapeutic - retrospective study was conducted during one year. Record files from 193 bitches and queens assisted at a Veterinary School Hospital between March 2010 and March 2011 were analyzed, considering species, age and contraceptive use. It was possible to conclude that the therapeutic OSH demand (78.8% is remarkably superior to the elective OSH request (21.2%. It was also observed that the most frequently detected reproductive abnormalities were pyometra (53.36% and gestational complications (25.38%, and also that the use of contraceptives is a relevant factor for those events.

  18. Wind energy; Energie eolienne

    Energy Technology Data Exchange (ETDEWEB)

    Vachey, C.

    2000-05-01

    This public information paper presents the wind energy resource in the Languedoc Roussillon region, explains how a wind turbine works, the different types of utilization and the cost of the wind energy. The environmental impacts of the wind energy, on the noise and the landscape, are also discussed. (A.L.B.)

  19. UK energy

    International Nuclear Information System (INIS)

    The book describes the relationship between the energy needs and energy policies, in the United Kingdom. The global energy scene in relation to the U.K., and the development of energy policies, is discussed. Energy demand and supply in the UK, including nuclear power, is described. Energy conservation, energy prospects and energy policy objectives are also examined. (U.K.)

  20. Energy: nuclear energy

    International Nuclear Information System (INIS)

    Convinced that the nuclear energy will be the cleaner, safer, more economical and more respectful of the environment energy of the future, the author preconizes to study the way it can be implemented, to continue to improve its production, to understand its virtues and to better inform the public. He develops this opinion in the presentation of the principal characteristics of the nuclear energy: technology, radioactive wastes, radiation protection, the plutonium, the nuclear accidents, the proliferation risks, the economics and nuclear energy and competitiveness, development and sustainability. (A.L.B.)

  1. Wind energies; Energies eoliennes

    Energy Technology Data Exchange (ETDEWEB)

    Martin, J.

    1997-01-01

    The main part of this study is focused on the wind turbine, including a full overview of turbine types, with in each case advantages, disadvantages and conditions of use. Subsidiary elements are mentioned, for support or energy conversion (into electricity, water pumping, heat generation). A glimpse is added to energy storage, and an economic balance is stroke. (D.L.)

  2. Energy crisis

    International Nuclear Information System (INIS)

    From energy policy to the problem of public acceptance of nuclear power, problems like energy supply, energy strategies, the race of industrial countries for the short energy reserves, the West German energy demand until the year 2.000, energy conservation, and the controversy over increased use of nuclear energy are reviewed. (GL)

  3. Tidal energy

    International Nuclear Information System (INIS)

    Together with wave energy, ocean thermal energy, and the often overlooked energy from ocean curents tidal energy belongs to those renewable energy sources that can be subsumed under the generic term of ocean energy. All that these energy sources have in common, however, is that they are found in the ocean. The present article discusses tidal energy with respect to the four principal factors determining the scope of a renewable energy source, namely global, technical, and economic availability and ecological acceptability. (orig.)

  4. Energy Drinks

    Science.gov (United States)

    ... energy drinks with alcohol. About 25 percent of college students consume alcohol with energy drinks, and they binge- ... are. Excessive energy drink consumption may disrupt teens’ sleep patterns and may fuel risk-taking behavior. Many energy ...

  5. Renewable Energy

    OpenAIRE

    Destouni, Georgia; Frank, Harry

    2010-01-01

    The Energy Committee of the Royal Swedish Academy of Sciences has in a series of projects gathered information and knowledge on renewable energy from various sources, both within and outside the academic world. In this article, we synthesize and summarize some of the main points on renewable energy from the various Energy Committee projects and the Committee’s Energy 2050 symposium, regarding energy from water and wind, bioenergy, and solar energy. We further summarize the Energy Committee’s ...

  6. Energy Technology.

    Science.gov (United States)

    Eaton, William W.

    Reviewed are technological problems faced in energy production including locating, recovering, developing, storing, and distributing energy in clean, convenient, economical, and environmentally satisfactory manners. The energy resources of coal, oil, natural gas, hydroelectric power, nuclear energy, solar energy, geothermal energy, winds, tides,…

  7. Energy intermittency

    CERN Document Server

    Sorensen, Bent

    2014-01-01

    The first book to consider intermittency as a key point of an energy system, Energy Intermittency describes different levels of variability for traditional and renewable energy sources, presenting detailed solutions for handling energy intermittency through trade, collaboration, demand management, and active energy storage. Addressing energy supply intermittency systematically, this practical text:Analyzes typical time-distributions and intervals between episodes of demand-supply mismatch and explores their dependence on system layouts and energy source characteristicsSimulates scenarios regar

  8. Dossier Energy

    International Nuclear Information System (INIS)

    Several aspects with respect to energy are discussed in a special section of this magazine: the security of energy supply in a liberalized market, saving energy by outsourcing (e.g. compressed air contracting), the profits of a liberalized energy market for businesses, incentives for energy saving projects and innovations, an energy efficiency project at Ineos Silicas (producer of zeolites), and energy efficient electronic equipment

  9. GATA: A graphic alignment tool for comparative sequenceanalysis

    Energy Technology Data Exchange (ETDEWEB)

    Nix, David A.; Eisen, Michael B.

    2005-01-01

    Several problems exist with current methods used to align DNA sequences for comparative sequence analysis. Most dynamic programming algorithms assume that conserved sequence elements are collinear. This assumption appears valid when comparing orthologous protein coding sequences. Functional constraints on proteins provide strong selective pressure against sequence inversions, and minimize sequence duplications and feature shuffling. For non-coding sequences this collinearity assumption is often invalid. For example, enhancers contain clusters of transcription factor binding sites that change in number, orientation, and spacing during evolution yet the enhancer retains its activity. Dotplot analysis is often used to estimate non-coding sequence relatedness. Yet dot plots do not actually align sequences and thus cannot account well for base insertions or deletions. Moreover, they lack an adequate statistical framework for comparing sequence relatedness and are limited to pairwise comparisons. Lastly, dot plots and dynamic programming text outputs fail to provide an intuitive means for visualizing DNA alignments.

  10. 256Mbit NAND type EEPROM; 256Mbit NAND gata EEPROM

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    Development has been made on a 256Mbit NAND type EEPROM (read-out only memory capable of electrical and collective erasure and rewriting) having the world`s smallest chip size of about 130 mm {sup 2} and having the industry`s largest capacity. The development was made possible by using a technology for micro fine processing of 0.25 {mu} m and a shallow trench isolation (STI) technology to provide slots between elements and isolate the elements. The NAND type EEPROM is used widely for memory media for image data of electronic still cameras, memory cards, and semiconductor disks. Replacement of magnetic disks (MD) into a semiconductor memory (SmartMedia{sub TM}) is intended in the future music market, where demand is predicted to increase for the NAND type EEPROM of large capacity. The product package lined up include the SmartMedia{sub TM} as small flash memory card and the Thin Small Outline Package (TSOP). The SmartMedia{sub TM} mounting two 256 Mbit chips, scheduled of commercialization in the spring of 1999, can record as much as one CD can, and will be a product that will open up a new music market. (translated by NEDO)

  11. KAMPILLAKADI GHRITA IN GARBHASHAYA GREEVA GATA VRANA (CERVICAL EROSION

    Directory of Open Access Journals (Sweden)

    Dhiman Kamini

    2012-04-01

    Full Text Available Certain diseases may not be life threatening but troublesome and irritating to an individual in day to day routine activity. “Cervical erosion” is one among them increasing day by day and demanding greater concern over it. It is a benign condition but if left untreated may leads up to infertility and predisposes to cervical malignancy. Cauterization is the known treatment for cervical erosion but chances of recurrence of the disease are high. Keeping this fact in mind the present clinical study has been undertaken. The total effect of drug was evaluated on the basis of signs and symptoms after completion of therapy. The data obtained in clinical study before and after treatment was expressed in terms of Mean, Standard Deviation (+SD and Standard Error (+SE. Group-I revealed better results than Group-II over total criteria of assessment.

  12. Electric locomotive EH500; EH500 gata denki kikansha

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    The advanced AC/DC electric locomotive delivered to Japan Freight Railway Co. is in wagon traction test on real lines after confirmation of the basic performance. The locomotive adopts a PWM converter using IGBT devices for the main circuit equipment to reduce harmonics and improve a power factor, and also adopts vector control by fast MPU to attain high-adhesion control and excellent traction performance. The locomotive allows through operation over the DC/AC section from Tokyo to Hokkaido without any locomotive exchange with expectation of fast freight transport. Main specifications are as follows: (1) Electric system: DC 1,500V, AC 20kV-50/60Hz, (2) Axle arrangement type: (Bo-Bo)- (Bo-Bo) (Bo: double driving axle bogie), (3) Total operation mass: 134.4t, (4) Rated output: 4,000kW (one hour), and (5) Maximum operation speed: 110km/h. (translated by NEDO)

  13. GATA: a graphic alignment tool for comparative sequence analysis

    OpenAIRE

    Nix David A; Eisen Michael B

    2005-01-01

    Abstract Background Several problems exist with current methods used to align DNA sequences for comparative sequence analysis. Most dynamic programming algorithms assume that conserved sequence elements are collinear. This assumption appears valid when comparing orthologous protein coding sequences. Functional constraints on proteins provide strong selective pressure against sequence inversions, and minimize sequence duplications and feature shuffling. For non-coding sequences this collineari...

  14. Energy sustainability through green energy

    CERN Document Server

    Sharma, Atul

    2015-01-01

    This book shares the latest developments and advances in materials and processes involved in the energy generation, transmission, distribution and storage. Chapters are written by researchers in the energy and materials field. Topics include, but are not limited to, energy from biomass, bio-gas and bio-fuels; solar, wind, geothermal, hydro power, wave energy; energy-transmission, distribution and storage; energy-efficient lighting buildings; energy sustainability; hydrogen and fuel cells; energy policy for new and renewable energy technologies and education for sustainable energy development

  15. Energy assessments

    International Nuclear Information System (INIS)

    Energy industry initiatives during the 1970s and during the 1990s are compared. During the 1970s, the objective was to reduce energy consumption and to reduce dependency on foreign fuel. Today, the emphasis is on reducing energy costs and to improve net operating income. The challenges posed by the drive to reduce energy costs are discussed. As a tool in the drive to reduce energy cost, the energy assessment process was described. The process entails a detailed analysis of energy consumption, an investigation of energy rates and an assessment of site conditions and equipment, with a view towards an optimum combination that will lead to energy cost reductions

  16. Energy resources

    CERN Document Server

    Simon, Andrew L

    1975-01-01

    Energy Resources mainly focuses on energy, including its definition, historical perspective, sources, utilization, and conservation. This text first explains what energy is and what its uses are. This book then explains coal, oil, and natural gas, which are some of the common energy sources used by various industries. Other energy sources such as wind, solar, geothermal, water, and nuclear energy sources are also tackled. This text also looks into fusion energy and techniques of energy conversion. This book concludes by explaining the energy allocation and utilization crisis. This publ

  17. Energy Demand

    OpenAIRE

    Stehfest, E. et al.

    2014-01-01

    Key policy issues – How will energy demand evolve particularly in emerging and medium- and low- income economies? – What is the mix of end-use energy carriers to meet future energy demand? – How can energy efficiency contribute to reducing the growth rate of energy demand and mitigate pressures on the global environment?

  18. Solar Energy.

    Science.gov (United States)

    Eaton, William W.

    Presented is the utilization of solar radiation as an energy resource principally for the production of electricity. Included are discussions of solar thermal conversion, photovoltic conversion, wind energy, and energy from ocean temperature differences. Future solar energy plans, the role of solar energy in plant and fossil fuel production, and…

  19. Energy Demand

    NARCIS (Netherlands)

    Stehfest, E. et al.

    2014-01-01

    Key policy issues – How will energy demand evolve particularly in emerging and medium- and low- income economies? – What is the mix of end-use energy carriers to meet future energy demand? – How can energy efficiency contribute to reducing the growth rate of energy demand and mitigate pressures on t

  20. Energy audit and energy security

    OpenAIRE

    Beata Agnieszka Kulessa

    2013-01-01

    In article, we present the issue of energy security. This article to answer the questions concerning the future of energy in Poland. These activities are directly related to energy security and the reduction of CO2 emissions. One element of this plan is the introduction in the EU energy certification of buildings. The energy certificates in Poland launched on 01.01.2009 and implements the objectives adopted by the European Union and contribute to energy security, increasing energy efficiency ...

  1. Dexmedetomidina epidural em gatas submetidas à ovariosalpingohisterectomia sob anestesia total intravenosa com propofol e pré-medicadas com cetamina S(+ e midazolam Epidural dexmedetomidine in cats submitted to ovariosalpingohisterectomy under intravenous total anesthesia with propofol and pre medicated with ketamine (S and midazolam

    Directory of Open Access Journals (Sweden)

    Otávia Dorigon

    2009-06-01

    Full Text Available O objetivo deste estudo foi avaliar os efeitos da administração epidural de dexmedetomidina em gatas submetidas à ovariosalpingohisterectomia (OSH, sob infusão contínua de propofol. Para tanto, foram utilizadas 12 gatas adultas, hígidas, com peso médio de 3,3±0,4kg, e entre um e quatro anos de idade. Como medicação pré-anestésica, os animais receberam cetamina S(+ (5mg kg-1 e midazolam(0,5mg kg-1, pela via intramuscular, e propofol como agente indutor (4mg kg-1, pela via intravenosa. Em seguida, os animais foram intubados para receber oxigênio a 100% , por meio de sistema sem reinalação de gases, e a infusão contínua de propofol (0,3mg kg-1 min-1 foi iniciada. Os animais foram alocados em dois grupos, nos quais foram administrados dexmedetomidina (2µg kg-1 por via epidural (GDEX, n=06 e, no grupo controle (GSAL, n=06, solução salina 0,9% pela mesma via. O volume total da solução para administração epidural foi completado com solução salina e ajustado para 0,26ml kg-1 em ambos os grupos. No GSAL, houve necessidade de administração de fentanil imediatamente após o início da cirurgia (T10 em 33,33% dos pacientes. Durante a infusão contínua de propofol, o reflexo palpebral medial esteve presente em 66,6% dos animais do GSAL e em 16,6% dos animais do GDEX. O globo ocular permaneceu centralizado em todos os animais do GSAL e rotacionado em 83,4% dos animais do GDEX. Foi observada redução da freqüência cardíaca após a indução anestésica em ambos os grupos. A pressão arterial média foi menor no T0 e no T5, no GDEX, e maior no T10, no GSAL, em relação ao basal. A freqüência respiratória foi menor no GDEX nos tempos T20 e T30 em relação a GSAL. A SaO2 e a PaO2 foram maiores de T5 até T40 para ambos os grupos em comparação ao basal. Para a PaCO2, foram observados valores maiores de T5 até T40 para o GDEX e maiores no T5, T10 e T20, no GSAL, em relação aos valores basais. Na recuperação anest

  2. Energy, tourism

    OpenAIRE

    Frantál, B. (Bohumil)

    2015-01-01

    The chapter provides a general definition of energy and resume the role and environmental impacts of tourism as one of the largest global industries and energy consumers.Then the energy tourism nexus is conceptualized from three perspectives: The first is energy as a driver of tourism. The second is energy as a constraint of tourism. The third is energy as an attraction and object of tourists´interests.

  3. Hubble Energy

    OpenAIRE

    Macleod, Alasdair

    2004-01-01

    Light received from a cosmological source is redshifted with an apparent loss of energy, a problem first pointed out by Edwin Hubble in 1936. A new type of energy called Hubble Energy is introduced to restore the principle of energy conservation. The energy has no inertial or gravitational effect but retards radial motion in a manner consistent with the anomalous acceleration experienced by the Pioneer probes leaving the solar system. The energy is predicted to have important effects on the s...

  4. Energy memento

    International Nuclear Information System (INIS)

    This memento about energy provides a series of tables with numerical data relative to energy resources and uses in France, in the European Union and in the rest of the world: energy consumption (primary energy, forecasting, CO2 emissions, energy independence, supplies, uses and imports, demand scenarios, energy savings..), power production (production, forecasting, loads, consumption, hydro-power, thermal equipment, exports), nuclear power (production, forecasting, reactors population, characteristics of French PWRs, uranium needs and fuel cycle), energy resources (renewable energies, fossil fuels and uranium reserves and production), economic data (gross national product, economic and energy indicators, prices and cost estimations), energy units and conversion factors (counting, calorific value of coals, production costs, energy units). (J.S.)

  5. Energy Storage and Renewable Energy.

    OpenAIRE

    Durmaz, Tunç

    2014-01-01

    I consider an economy with fossil fuel and renewable energy and energy storage, and search for the conditions that lead to welfare improvements when energy is stored. I then solve for the optimal decision rule and analyze the long-run tendencies of the economy-energy variables. The findings are threefold. First, energy storage is fostered by the convexity of the marginal utility (prudence), the marginal cost function for fossil fuel energy, and the degree of intermittency. Second, considering...

  6. Energy Theater

    Science.gov (United States)

    Daane, Abigail R.; Wells, Lindsay; Scherr, Rachel E.

    2014-01-01

    Energy Theater is a dynamic, full-body activity that engages all students in representing the flow of energy in various phenomena, such as a light bulb burning steadily or a refrigerator cooling food. In Energy Theater, each participant acts as a unit of energy that has one form at a time. Regions on the floor correspond to objects in a physical…

  7. Geothermal Energy.

    Science.gov (United States)

    Conservation and Renewable Energy Inquiry and Referral Service (DOE), Silver Spring, MD.

    An introduction to geothermal energy is provided in this discussion of: (1) how a geothermal reservoir works; (2) how to find geothermal energy; (3) where it is located; (4) electric power generation using geothermal energy; (5) use of geothermal energy as a direct source of heat; (6) geopressured reservoirs; (7) environmental effects; (8)…

  8. Advantage Energy

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    Increased focus has been placed on the issues of energy access and energy poverty over the last number of years, most notably indicated by the United Nations (UN) declaring 2012 as the 'International Year of Sustainable Energy for All'. Although attention in these topics has increased, incorrect assumptions and misunderstandings still arise in both the literature and dialogues. Access to energy does not only include electricity, does not only include cook stoves, but must include access to all types of energy that form the overall energy system. This paper chooses to examine this energy system using a typology that breaks it into 3 primary energy subsystems: heat energy, electricity and transportation. Describing the global energy system using these three subsystems provides a way to articulate the differences and similarities for each system's required investments needs by the private and public sectors.

  9. Nuclear energy and energy security

    International Nuclear Information System (INIS)

    Do Georgia needs nuclear energy? Nuclear energy is high technology and application of such technology needs definite level of industry, science and society development. Nuclear energy is not only source of electricity production - application of nuclear energy increases year-by-year for medical, science and industrial use. As an energy source Georgia has priority to extend hydro-power capacity by reasonable use of all available water resources. In parallel regime the application of energy efficiency and energy conservation measures should be considered but currently this is not prioritized by Government. Meanwhile this should be taken into consideration that attempts to reduce energy consumption by increasing energy efficiency would simply raise demand for energy in the economy as a whole. The Nuclear energy application needs routine calculation and investigation. For this reason Government Commission is already established. But it seems in advance that regional nuclear power plant for South-Caucasus region would be much more attractive for future

  10. Energy efficiency through energy audit

    International Nuclear Information System (INIS)

    Energy is an essential factor to economic and social development and improved standards of living in developing countries. Nigeria in particular. There is a strong need for greater energy efficiency in every sector of economy in order to reduce costs. enhance competitiveness, conserve energy resources and reduce environmental impacts associated with production, distribution and use of energy. Energy auditing and monitoring has a significant role in any energy management and conservation project. Energy auditing as an important part of industrial energy management on plant level, represents a complex of activities aiming at the efficient use of energy. The activities are undertaken by a team of experts who use a set of measuring instruments to monitor and evaluate all the necessary data to elaborate a package of recommendations on improvements in the field of energy efficiency and possible product quality. The inefficient conversion and use of energy have been identified as a central problem for all developing countries, Nigeria inclusive, since they all consume significantly higher amounts of energy per unit of GDP than OECD countries. This aggravates energy-related environmental problems and is also a burden on domestic resources and foreign exchange. Energy prices have risen drastically in many developing countries, while energy intensities remain high. Price changes alone are not rapidly translating energy efficiency improvements. Identifying and removing the obstacles to greater energy efficiency should be priority for government in developing countries. This is why the Energy Commission, an apex organ of government on Energy matters in all its ramifications is out to encourage relatively low-cost energy audits for the Textile industries - such audits can identify ''good house-keeping's' measures, such as simply process improvements, that reduce energy consumption and operating costs. This will be followed by the training of plant workers/energy managers

  11. Green energy

    OpenAIRE

    Olteanu, Victor

    2014-01-01

    Strategic plans in the energy sector have the overall objective of the use of renewable energy, especially wind power, hydroelectricity, biomass intending a considerable increase in the share it has in total energy production. Thus, chase is moving towards an economy based on low carbon consumption and improve performance standards for the production, distribution and use of energy, helping to reduce greenhouse gas emissions, increase the use of renewable resources for energy production, to l...

  12. Energy Leapfrogging

    OpenAIRE

    van Benthem, Arthur A.

    2015-01-01

    Today's less developed countries (LDCs) have access to energy technologies that did not exist when today's richer countries were at similar stages of development. Do LDCs therefore consume less energy per capita than rich countries in the past? And is their economic growth associated with a lower growth in energy consumption? Can they "leapfrog" to a lower-carbon economy? I use data on energy consumption, prices, and gross domestic product for 76 countries to estimate the energy intensity of ...

  13. Energy waste

    OpenAIRE

    KOOPAEE-ZADEH, Jaber

    2015-01-01

    Abstract. Energy restore depends on the residue thermal value. The energy restore unit should receive the material energy continuesly to sustain. The material suitability problem consists of two components of quality and quantity both of which can be measured and adopted in a proper place for the energy restore unit. But, still in many countries the residues conversion has a lower priority than separatio in origin, restore and compost production. So, the measured thermal energy in the plannin...

  14. Deciphering energy

    International Nuclear Information System (INIS)

    In this book, the author aims at giving some explanations about the various terms regarding energy which are present in our everyday life, in speeches, in papers and magazines, on the air, in our energy bills, for instance: energy poverty, price of a barrel of oil, resources and proved reserves, intermittency and energy storage, fossil and renewable energies, and so on. In a first part, the author addresses issues ranging from the development needs of a society to the energy assessment of a country, i.e.: nature and quantity of needs in services provided by energy, analysis of the required quantity of energy products needed to satisfy these needs, stages between primary resources and service delivery, description of the French consumption of available final energy products (per product and per economic sector). In the second part, he addresses energy supply, energy sectors and environmental issues, thus focusing on the front end of the energy system, i.e. ways of production from primary energy resources to final energy products: main physical characteristics and description of the different fissile, fossil and renewable energies, description of the main sectors of production of final energy products (fuels, electricity, heat) with a specific attention to electricity. In this part, local, regional and global environmental issues related to the exploitation of these energy sectors are discussed: sources of atmospheric pollution related to energy, relationship between energy and global warming, role of the different greenhouse gases emitted by these sectors, and quantitative analysis of these emissions. The third part addresses the economy of energy systems. The author proposes a cost assessment method which can be used for the production analysis as well as the economic analysis of a specific energy product. He also described external costs and profits, and methods to take those hidden costs and profits into account. Other economic tools are discussed and compared

  15. Energy Consumption vs. Energy Requirement

    Science.gov (United States)

    Fan, L. T.; Zhang, Tengyan; Schlup, John R.

    2006-01-01

    Energy is necessary for any phenomenon to occur or any process to proceed. Nevertheless, energy is never consumed; instead, it is conserved. What is consumed is available energy, or exergy, accompanied by an increase in entropy. Obviously, the terminology, "energy consumption" is indeed a misnomer although it is ubiquitous in the…

  16. Energy audit and energy security

    Directory of Open Access Journals (Sweden)

    Beata Agnieszka Kulessa

    2013-07-01

    Full Text Available In article, we present the issue of energy security. This article to answer the questions concerning the future of energy in Poland. These activities are directly related to energy security and the reduction of CO2 emissions. One element of this plan is the introduction in the EU energy certification of buildings. The energy certificates in Poland launched on 01.01.2009 and implements the objectives adopted by the European Union and contribute to energy security, increasing energy efficiency in construction and environmental protection.

  17. Energy perspective

    Energy Technology Data Exchange (ETDEWEB)

    1979-05-01

    Representatives of the three national political parties in Canada were interviewed to find their views on energy policy. Speaking for the Liberal Party, Energy Minister Allistair Gillespie recommends a 3.5% energy growth, expansion of the home insulation program, and development of nuclear petroleum, and renewable energy. He made no specific recommendations for transport. Tommy Douglas of the National Democratic Party (NDP) wants a 6% growth in renewable energy by 2000 and calls for and expanded role of government research, development, and financial assistance in conservation and renewable energy sources, along with a moratorium on nuclear energy if indicated by a national energy inquiry. Tory spokesman Stan Schellenberger supports solar energy development and a limited government role other than tax incentives, limited exports, and efficient public transportation.

  18. Energy studies

    CERN Document Server

    Shepherd, W

    2003-01-01

    How is the future world energy demand to be met? The rates of use of the fossil fuels - coal, oil and natural gas - are increasing all over the world. The remaining stocks are finite and are not renewable. This important book considers the various options of renewable energy, including water energy, wind energy and biomass, solar thermal and solar photovoltaic energy. And should the nuclear option remain open? The book examines the environmental implications and economic viability of all fossil and renewable sources, introduces more distant future options of geothermal energy and nuclear fusio

  19. Energy systems

    International Nuclear Information System (INIS)

    Up to the present the production, transmission and distribution of energy has been considered mostly as a fragmented problem; at best only subsystems have been considered. Today the scale of energy utilization is increasing rapidly, and correspondingly, the reliance of societies on energy. Such strong quantitative increases influence the qualitative nature of energy utilization in most of its aspects. Resources, reserves, reliability and environment are among the key words that may characterize the change in the nature of the energy utilization problem. Energy can no longer be considered an isolated technical and economical problem, rather it is embedded in the ecosphere and the society-technology complex. Restraints and boundary conditions have to be taken into account with the same degree of attention as in traditional technical problems, for example a steam turbine. This results in a strong degree of interweaving. Further, the purpose of providing energy becomes more visible, that is, to make survival possible in a civilized and highly populated world on a finite globe. Because of such interweaving and finiteness it is felt that energy should be considered as a system and therefore the term 'energy systems' is used. The production of energy is only one component of such a system; the handling of energy and the embedding of energy into the global and social complex in terms of ecology, economy, risks and resources are of similar importance. he systems approach to the energy problem needs more explanation. This paper is meant to give an outline of the underlying problems and it is hoped that by so doing the wide range of sometimes confusing voices about energy can be better understood. Such confusion starts already with the term 'energy crisis'. Is there an energy crisis or not? Much future work is required to tackle the problems of energy systems. This paper can only marginally help in that respect. But it is hoped that it will help understand the scope of the

  20. Energy security

    International Nuclear Information System (INIS)

    In the case of Cuba, energy security goes beyond the typical security framework of energy supply to encompass the economic blockade which affects Cuba's access to some markets for its traditional products and obstructs international credit options. Recent problems concerning security of national energy supply include: - Shortages of foreign exchange necessary for the purchase of fuel and spare parts, for new investments and for the implementation of programmes supporting the rational use of energy. - High dependence on imported energy, including oil and petroleum products. -Use of domestic crude oil, with energy performance slightly below that of the imported fuels it replaces, especially fuel oil. The main negative aspect is the high sulphur content, which has adverse operational and environmental effects. - Interruptions in energy services resulting from hurricanes and tropical storms, and from breakdowns and accidents related to the transport of fuels, especially coastal transport. The strategies employed to improve Cuba's energy security situation are based on: - Increased economic competitiveness; - Fuel conservation and rational use of energy; - Efficient exploration and use of oil and natural gas; - Development of renewable energy sources; - Legal and institutional support of activities in the energy sector; - Active involvement in the international arena focused on regional integration efforts and international forums related to technological, energy and environmental issues, and on strengthening bilateral alliances aimed at creating the necessary environment for trade, technological transfer and foreign investment for guaranteeing national energy supply

  1. Geothermal Energy

    Energy Technology Data Exchange (ETDEWEB)

    Steele, B.C.; Harman, G.; Pitsenbarger, J. [eds.

    1996-02-01

    Geothermal Energy Technology (GET) announces on a bimonthly basis the current worldwide information available on the technologies required for economic recovery of geothermal energy and its use as direct heat or for electric power production.

  2. Energy Statistics

    International Nuclear Information System (INIS)

    For the years 1992 and 1993, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy Review appear in more detail from the publication Energiatilastot - Energy Statistics issued annually, which also includes historical time series over a longer period. The tables and figures shown in this publication are: Changes in the volume of GNP and energy consumption; Coal consumption; Natural gas consumption; Peat consumption; Domestic oil deliveries; Import prices of oil; Price development of principal oil products; Fuel prices for power production; Total energy consumption by source; Electricity supply; Energy imports by country of origin in 1993; Energy exports by recipient country in 1993; Consumer prices of liquid fuels; Consumer prices of hard coal and natural gas, prices of indigenous fuels; Average electricity price by type of consumer; Price of district heating by type of consumer and Excise taxes and turnover taxes included in consumer prices of some energy sources

  3. Energy consumption and energy prices

    International Nuclear Information System (INIS)

    Data are presented on energy consumption and energy prices related to a number of OECD (Organisation for Economic Co-operation and Development) lands covering the period 1951-1990. The information sources are described and the development of energy consumption and prices in Denmark are illustrated in relation to these other countries. The energy intensity (the relation between energy consumption and the gross national product) is dealt with. Here it is possible to follow development during the whole post-war period. It is generally understood that Denmark saved large amounts of energy after 1973-74 but, taken over the whole post-war period, savings and decline in energy-gross national product relations are less dramatic compared to conditions in other OECD countries. Energy coefficients or elasticities show the relative rise in consumption compared to the relative rise in gross national product (growth rate). This is shown to be typically unstable and an eventual connection with the amount of energy price increase and/or the growth rate of the national economy is considered. Results of Granger causuality tests on energy consumption, national income and energy prices are presented. Effective energy prices were very low in Denmark up to 1970 when they suddenly began to increase. Since the oil crisis Denmark's energy consumption has fallen whereas the other countries have used rather more energy than before. Effective promotion of energy savings must be seen in relation to the fact that the 1970 basis level of energy consumption and intensity was unusually high. The high effective energy prices have also encouraged energy savings in Denmark. (AB)

  4. Atomic energy

    CERN Multimedia

    1996-01-01

    Interviews following the 1991 co-operation Agreement between the Department of Atomic Energy (DAE) of the Government of India and the European Organization for Nuclear Research (CERN) concerning the participation in the Large Hadron Collider Project (LHC) . With Chidambaram, R, Chairman, Atomic Energy Commission and Secretary, Department of Atomic Energy, Department of Atomic Energy (DAE) of the Government of India and Professor Llewellyn-Smith, Christopher H, Director-General, CERN.

  5. Energy trading

    Energy Technology Data Exchange (ETDEWEB)

    Beckmann, K.; Schroeter, S.

    2009-05-15

    Two brief articles and two interviews deal with the subject of energy trading. Power and gas exchanges in Europe multiply, but, experts say, we are nowhere near a mature, integrated European energy market as yet. Trading regulations need to be improved and harmonised and interconnections expanded. European Energy Review assesses the state of energy trading in Europe and interviews the ceo's of NordPool (the Nordic power exchange) and APX (Amsterdam Power Exchange)

  6. Energy storage

    CERN Document Server

    Brunet, Yves

    2013-01-01

    Energy storage examines different applications such as electric power generation, transmission and distribution systems, pulsed systems, transportation, buildings and mobile applications. For each of these applications, proper energy storage technologies are foreseen, with their advantages, disadvantages and limits. As electricity cannot be stored cheaply in large quantities, energy has to be stored in another form (chemical, thermal, electromagnetic, mechanical) and then converted back into electric power and/or energy using conversion systems. Most of the storage technologies are examined: b

  7. Nuclear energy

    OpenAIRE

    Bucaille, Alain; Shihab-Eldin, Adnan; Bauquis, Pierre-René

    2007-01-01

    Nuclear energy can play a role in carbon free production of electrical energy, thus making it interesting for tomorrow’s energy mix. However, several issues have to be addressed. In fission technology, the design of so-called fourth generation reactors show great promise, in particular in addressing materials efficiency and safety issues. If successfully developed, such reactors may have an important and sustainable part in future energy production. Working fusion reactors may be even more ma...

  8. Energy audit for energy conservation

    International Nuclear Information System (INIS)

    Energy audit is a very effective management tool for betterment of plant performance. The energy audit has a problem solving approach rather than a fault finding technique. The energy conservation is a rational use of energy. It has been the experience of the developed countries that energy is one issue which results into cost savings with relatively much less efforts/cost in comparison with other resources used in production, development and adoption of energy efficiency equipment and practices in most of production process has been the result of same technique. (author). 1 tab

  9. Energy Storage.

    Science.gov (United States)

    Eaton, William W.

    Described are technological considerations affecting storage of energy, particularly electrical energy. The background and present status of energy storage by batteries, water storage, compressed air storage, flywheels, magnetic storage, hydrogen storage, and thermal storage are discussed followed by a review of development trends. Included are…

  10. Energy efficiency

    International Nuclear Information System (INIS)

    This road-map proposes by the Group Total aims to inform the public on the energy efficiency. It presents the energy efficiency and intensity around the world with a particular focus on Europe, the energy efficiency in industry and Total commitment. (A.L.B.)

  11. Geothermal energy

    International Nuclear Information System (INIS)

    This chapter discusses the role of geothermal energy may have on the energy future of the US. The topics discussed in the chapter include historical aspects of geothermal energy, the geothermal resource, hydrothermal fluids, electricity production, district heating, process heating, geopressured brines, technology and costs, hot dry rock, magma, and environmental and siting issues

  12. Energy taxation

    International Nuclear Information System (INIS)

    This study presents the energy taxation, as an energy policy tool, applied to the fossil fuels and to the electric power. Taxes, tax revenue and taxation in function of the energy content or the carbon content are discussed. Many tables and statistical data illustrate this analysis and allow the comparison with other countries in Europe. (A.L.B.)

  13. Energy alternatives

    International Nuclear Information System (INIS)

    Due to sharp rise in oil proces after the 1973 Arab-Israeli War, world attention has been focussed on the energy problem. At present the energy problem is limited to the cost and reliability of supply, even though there are enough supplies to go round. However, in the future the problem will be of availability, because in spite of the full exploitation of currently available conventional energy sources, the supply will fall short of demand which will always be increasing. Hence, there is need to develop alternate energy sources, including fast breeder reactors, fusion reactors and MHD. Economic and technical aspects of these energy are discussed. (M.G.B.)

  14. Wind Energy

    Energy Technology Data Exchange (ETDEWEB)

    Beurskens, H.J.M. [SET Analysis, Kievitlaan 26, 1742 AD Schagen (Netherlands); Brand, A.J. [Energy research Centre of the Netherlands ECN, Unit Wind Energy, P.O. Box 1, 1755 ZG Petten (Netherlands)

    2013-02-15

    Over the years, wind energy has become a major source of renewable energy worldwide. The present chapter addresses the wind resource, which is available for exploitation for large-scale electricity production, and its specific physical properties. Furthermore, the technical options available to convert the energy of the air flow into mechanical energy and electricity are described. Specific problems of large-scale integration of wind energy into the grid as well as the present and future market developments are described in this chapter. Finally, environmental aspects are discussed briefly.

  15. Applied energy an introduction

    CERN Document Server

    Abdullah, Mohammad Omar

    2012-01-01

    Introduction to Applied EnergyGeneral IntroductionEnergy and Power BasicsEnergy EquationEnergy Generation SystemsEnergy Storage and MethodsEnergy Efficiencies and LossesEnergy industry and Energy Applications in Small -Medium Enterprises (SME) industriesEnergy IndustryEnergy-Intensive industryEnergy Applications in SME Energy industriesEnergy Sources and SupplyEnergy SourcesEnergy Supply and Energy DemandEnergy Flow Visualization and Sankey DiagramEnergy Management and AnalysisEnergy AuditsEnergy Use and Fuel Consumption StudyEnergy Life-Cycle AnalysisEnergy and EnvironmentEnergy Pollutants, S

  16. Energy 93, energy in Israel

    International Nuclear Information System (INIS)

    For the first time this report includes a chapter entitles 'energy and peace'. Following is an overview of israel's energy economy and some principal initiatives in its various sectors during 1992/93 period. 46 figs, 13 tabs

  17. Energy Law

    International Nuclear Information System (INIS)

    The author is trying very hard to present a systematic and compact description of the energy law as a whole. For reasons metioned in the first chapter, the energy law confines itself to the law relating to energy supplied by means of pipelines and transmission lines. Energy law and the law relating supplied by means of pipelines are therefore synonyms. There is no special energy law except the one relating to energy supplied by means of pipelines. The book - intended to be read by experts and undergraduates - discusses the subject and systematics of energy law, energy control, price regulations for electricity supply industry and for the gas supply industry, the law relating to pipe-laying, licence fees and law on cartels, supply obligations of the electricity supply utilities, legal issues of energy supply contracts, liability for supply disruptions, the legal nature of public energy supply, planning law, the relating to plant licensing, atomic law, legal protection in plant licensing procedures, the current structure of industry supplying energy by means of pipelines and, finally, reform demands. (orig.)

  18. Energy applications: enabling energy services

    OpenAIRE

    Wood, James

    2012-01-01

    Master in Business Administration The energy services industry is not only misunderstood due to its diversity of value propositions, it has also been largely ignored as a major short term means of tackling climate change, ensuring energy supply security, and mitigating against rising energy costs (the three typical national energy policy goals frequently quoted around the world). Private sector business models have not been sufficiently identified, designed, incorporated, and evolved to...

  19. Transporation Energy

    Energy Technology Data Exchange (ETDEWEB)

    Clifford Mirman; Promod Vohra

    2012-06-30

    This Transportation Energy Project is comprised of four unique tasks which work within the railroad industry to provide solutions in various areas of energy conservation. These tasks addressed: energy reducing yard related decision issues; alternate fuels; energy education, and energy storage for railroad applications. The NIU Engineering and Technology research team examined these areas and provided current solutions which can be used to both provide important reduction in energy usage and system efficiency in the given industry. This project also sought a mode in which rural and long-distance education could be provided. The information developed in each of the project tasks can be applied to all of the rail companies to assist in developing efficiencies.

  20. Energy needs

    International Nuclear Information System (INIS)

    There seems to be a trend towards expecting energy conservation to be a panacea for the world's ills. In fact, a global perspective on energy needs shows that more, not less, energy is needed and technological innovation in energy sources is essential in order to meet the needs of more than just the developed countries. Energy-intensive technology is the amplification of our natural resources rather than their depletion. A fundamental bioethical principle must be established if we are to analyze and organize scientific evidence about hazards from currently feasible energy resources, and separate genuine from counterfeit claims to credibility. In particular, public fears about radiation hazards and radioactive waste disposal are influenced too much by rhetorical cleverness and forensic skills of a vociferous minority. Potential hazard management is ethically equitable only if it is proportioned to actual basic harm that can be identified and reduced by expenditures of human effort, time and money

  1. Wind energy.

    Science.gov (United States)

    Leithead, W E

    2007-04-15

    From its rebirth in the early 1980s, the rate of development of wind energy has been dramatic. Today, other than hydropower, it is the most important of the renewable sources of power. The UK Government and the EU Commission have adopted targets for renewable energy generation of 10 and 12% of consumption, respectively. Much of this, by necessity, must be met by wind energy. The US Department of Energy has set a goal of 6% of electricity supply from wind energy by 2020. For this potential to be fully realized, several aspects, related to public acceptance, and technical issues, related to the expected increase in penetration on the electricity network and the current drive towards larger wind turbines, need to be resolved. Nevertheless, these challenges will be met and wind energy will, very likely, become increasingly important over the next two decades. An overview of the technology is presented. PMID:17272245

  2. Energy Security

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    With an increasing number of countries becoming industrialized, energy, the so-called blood of modern economies, is becoming increasingly important Energy security has become an important factor that directly influences world economic stability and international relations. In an article posted on People's Daily Online, Liu Jianfei, professor at the International Strategic Research Center of the Party School of the Central Committee of the Communist Party of China, shares his opinions on energy security.

  3. Energy quality

    OpenAIRE

    Stern, David I.

    2009-01-01

    This paper develops economic definitions of energy quality for individual fuels and energy aggregates. There are both use- and exchange-value concepts as well as marginal and total measures of energy quality. A factor augmentation or quality coefficients approach corresponds to the use-value definition while indicators based on distance functions and relative prices are exchange-value based definitions. These indicators are identical when the elasticity of substitution between fuels is infini...

  4. Energy Savers

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The government has mandated a reduction in energy use this year, but many wonder whether and how that goal can be achieved Pressure is mounting for China to reduce its energy consumption, but many say the government's target of cutting energy use per unit of gross domestic product (GDP) by 4 percent this year will be a major hurdle. Nearly half of the provinces and

  5. Geothermal energy

    International Nuclear Information System (INIS)

    Objective of this brochure is to present the subject Geothermics and the possible use of geothermal energy to the public. The following aspects will be refered to: -present energy situation -geothermal potential -use of geothermal energy -environemental aspects -economics. In addition, it presents an up-dated overview of geothermal projects funded by the German government, and a list of institutions and companies active in geothermal research and developments. (orig./HP)

  6. Wind Energy

    Energy Technology Data Exchange (ETDEWEB)

    Ganley, Jason; Zhang, Jie; Hodge, Bri-Mathias

    2016-03-15

    Wind energy is a variable and uncertain renewable resource that has long been used to produce mechanical work, and has developed into a large producer of global electricity needs. As renewable sources of energy and feedstocks become more important globally to produce sustainable products, many different processes have started adopting wind power as an energy source. Many times this is through a conversion to hydrogen through electrolysis that allows for a more continuous process input. Other important pathways include methanol and ammonia. As the demand for sustainable products and production pathways increases, and wind power capital costs decrease, the role of wind power in chemical and energy production seems poised to increase significantly.

  7. Energy economics

    International Nuclear Information System (INIS)

    The energy demand is strongly conditioned by the consuming equipments. Depending on the uses, some energy sources can be substituted, while for some others the choice is limited or impossible. The energy offer comes mainly from non-renewable resources, and taking into consideration the geographical localization of these resources, economics are geopolitics are indissociable despite the development of markets. Necessary for the economic development, energy cannot be consumed without impact on the environment, which raises some worrying questions, like the one of global warming. (J.S.)

  8. Energy glossary

    International Nuclear Information System (INIS)

    This glossary has been prepared in conjunction with the 'Energy in Minnesota' Workshop. The workshop was held in response to legislator's needs for information on a spectrum of energy related issues. The definitions which are provided here are terms frequently used in discussing energy issues. The glossary has been divided into two parts. The first section includes general terms related to energy. The second section includes only nuclear terms. This separation has been made because of the large amount of specialized terminology in nuclear technology. The sources from which all the terms are excerpted are listed at the end of the glossary. Additional definitions and information may be found in these references

  9. Energy: nuclear energy; Energies: l'energie nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Lung, M. [Societe Generale pour les Techniques Nouvelles (SGN), 78 - Saint-Quentin-en-Yvelines (France)

    2000-11-01

    Convinced that the nuclear energy will be the cleaner, safer, more economical and more respectful of the environment energy of the future, the author preconizes to study the way it can be implemented, to continue to improve its production, to understand its virtues and to better inform the public. He develops this opinion in the presentation of the principal characteristics of the nuclear energy: technology, radioactive wastes, radiation protection, the plutonium, the nuclear accidents, the proliferation risks, the economics and nuclear energy and competitiveness, development and sustainability. (A.L.B.)

  10. Geothermal energy

    International Nuclear Information System (INIS)

    Geothermal energy has shown a revival for several years and should strongly develop in a near future. Its potentiality is virtually unexhaustible. Its uses are multiple and various: individual and collective space heating, heat networks, power generation, heat storage, heat exchanges etc.. Re-launched by the demand of renewable energy sources, geothermal energy has become credible thanks to the scientific works published recently which have demonstrated its economical and technical relevance. Its image to the public is changing as well. However, lot of work remains to do to make geothermal energy a real industry in France. Several brakes have to be removed rapidly which concern the noise pollution of geothermal facilities, the risk of bad results of drillings, the electricity costs etc. This dossier gives an overview of today's main research paths in the domain of geothermal energy: 1 - geothermal energy in France: historical development, surface and deep resources, ambitions of the French national energy plan (pluri-annual investment plan for heat generation, incentives, regional 'climate-air-energy' schemes), specific regulations; 2 - geothermal energy at the city scale - sedimentary basins: Ile-de-France 40 years of Dogger reservoir exploitation, potentialities of clastic reservoirs - the Chaunoy sandstones example; 3 - geothermal power generation: conventional reservoirs - the Bouillante model (Guadeloupe, French Indies); the Soultz-sous-Forets pilot plant (Bas-Rhin, France); the supercritical reservoirs - the Krafla geothermal area (Iceland). (J.S.)

  11. Solar energy

    Science.gov (United States)

    Rapp, D.

    1981-01-01

    The book opens with a review of the patterns of energy use and resources in the United States, and an exploration of the potential of solar energy to supply some of this energy in the future. This is followed by background material on solar geometry, solar intensities, flat plate collectors, and economics. Detailed attention is then given to a variety of solar units and systems, including domestic hot water systems, space heating systems, solar-assisted heat pumps, intermediate temperature collectors, space heating/cooling systems, concentrating collectors for high temperatures, storage systems, and solar total energy systems. Finally, rights to solar access are discussed.

  12. Energy fiscality

    International Nuclear Information System (INIS)

    This report gives a general presentation of energy fiscality in France: taxes on energy, mechanisms of stabilization of government's fiscal incomes in case of significant oil prices change, some particularities of energy taxes, the fiscality according to the energy content and according to the carbon content. The fiscality of petroleum products (automotive fuels and other products), natural gas and electricity in France is presented in appendixes together with a comparison of the fiscality in use in the rest of Europe (automotive fuels, domestic fuels, natural gas and electricity for domestic use and for industrial use). (J.S.)

  13. ЭКСПРЕССИЯ ТРАНСКРИПЦИОННОГО ФАКТОРА GATA-3 В ЛИМФОЦИТАХ ПЕРИФЕРИЧЕСКОЙ КРОВИ БОЛЬНЫХ БРОНХИАЛЬНОЙ АСТМОЙ

    OpenAIRE

    Минеев, В.; Сорокина, Л.; Нёма, М.; Трофимов, В.

    2010-01-01

    Цель исследования – изучить экспрессию GATA-3 в лимфоцитах периферической крови у больных БА. Материалы и методы. Обследовано 10 практически здоровых лиц, 15 больных аллергической (атопической) БА и 15 больных неаллергической БА. Применяли методику Western blotting в соответствии со стандартным протоколом (Amersham) с использованием соответствующих антител: анти-GATA-3 (Abcam, Великобритания). Уровень белка определяли по уровню β-актина (Sigma Aldrich, США). Результаты. Выявлено, что уровень ...

  14. Energy 2050

    International Nuclear Information System (INIS)

    The symposium is focused on key issues emanating from the Academy's in-depth energy studies during 2005-2009. The symposium objectives are: - to formulate an outlook for environmentally friendly energy by 2050; - to understand how and when the current dependence on fossil fuels can be replaced by a sustainable energy system; - to find ways to mitigate the effects of CO2 emissions; e.g. efficient and clean use of coal; - to analyze how renewable energy sources with intermittent availability can be handled; - to understand the performance of the new generation of nuclear facilities with respect to fuel, waste and security; - to explore the best ways of increasing energy efficiency in transport, buildings and industrial production; - to indicate options for low-carbon vehicles; and, - to estimate resource requirements and the environmental impact of different energy sources over their life cycles. All presentations and discussions at the conference are available as documents and videos at the home page. Presentations available: Kjell Aleklett: Fossil motor fuels around 2050; Lennart Bengtsson: The status of climate change research; Peter Cox: Geoengineering the Climate: the findings of the Royal Society study; Mujid Kazimi: The future of nuclear energy; Julia King: Low carbon vehicles; Klaus Lackner: Managing the build-up of carbon dioxide from fossil fuel consumption; George A. Olah: Beyond fossil fuels; Robert Pitz-Paal: Concentrating solar power: a roadmap from research to market; Carlo Rubbia: Innovation: the key to a successful development of renewable energies; Subcritical thorium reactors; Jean-Marie Tarascon: Batteries for transportation now and in the future; Sergio Ulgiati: A systems ecology view on bioenergy/biofuels; Alfred Voss: Life cycle analyses for different energy sources; Friedrich Wagner: Fusion energy - ready for use by 2050?; and, Hermann-Josef Wagner: Energy from wind.

  15. Nuclear energy

    International Nuclear Information System (INIS)

    With simple and accessible explanations, this book presents the physical principles, the history and industrial developments of nuclear energy. More than 25 years after the Chernobyl accidents and few months only after the Fukushima one, it discusses the pros and cons of this energy source with its assets and its risks. (J.S.)

  16. Energy sources

    International Nuclear Information System (INIS)

    A study carried out around 1970 on the world energy future is described. One method is based on world energy evaluations extrapolated to 1985 and 2000. The other one is prospective and tries to account for changes in life style and technology and relations with the developing countries

  17. Energy openly

    International Nuclear Information System (INIS)

    Abstract of a book containing more than hundred articles written by scientists of various disciplines (physics, chemistry, biology, geophysics, environment, geography, economy) and which addresses the main challenges for energy in the 21. century, its definition, its governing physical laws, its means of production, transport and storage, the shares solar, biomass, wind and hydraulic energy may have in the future

  18. Geothermal Energy

    International Nuclear Information System (INIS)

    A general overview of geothermal energy is given that includes a short description of the active and stable areas in the world. The possibilities of geothermal development in Argentina are analyzed taking into account the geothermal fields of the country. The environmental benefits of geothermal energy are outlined

  19. Energy Monitoring

    DEFF Research Database (Denmark)

    Hansen, Claus T.; Madsen, Dines; Christiensen, Thomas;

    Energy measurement has become an important aspect of our daily lives since we have learned that energy consumption, is one of the main source of global warming. Measuring instruments varies from a simple watt-meter to more sophisticated microprocessor control devices. The negative effects...... that fossil fuels induce on our environment has forced us to research renewable energy such as sunlight, wind etc. This new environmental awareness has also helped us to realize the importance of monitoring and controlling our energy use. The main purpose in this research is to introduce a more sophisticated...... but affordable way to monitor energy consumption of individuals or groups of home appliances. By knowing their consumption the utilization can be regulated for more efficient use. A prototype system has been constructed to demonstrate our idea....

  20. Energy alternatives

    International Nuclear Information System (INIS)

    English. A special committe of the Canadian House of Commons was established on 23 May 1980 to investigate the use of alternative energy sources such as 'gasohol', liquified coal, solar energy, methanol, wind and tidal power, biomass, and propane. In its final report, the committee envisions an energy system for Canada based on hydrogen and electricity, using solar and geothermal energy for low-grade heat. The committe was not able to say which method of generating electricty would dominate in the next century, although it recommends that fossil fuels should not be used. The fission process is not specifically discussed, but the outlook for fusion was investigated, and continued governmental support of fusion research is recommended. The report proposes some improvements in governmental energy organizations and programs

  1. Energy Magazine

    International Nuclear Information System (INIS)

    The present issue of the Energy Magazine is including a summary of the six years of implementation of the energy and sustainable development project, which also includes the participation of the Economic Commission for Latin America and the Caribbean (ECLAC). The substantially parameters and indicators defined by this project have been applied in case studies for Bolivia, Brazil, Colombia, Chile and El Salvador and have yielded sound results. A few pages are dedicated to highlight the preliminary results stemming from the initiative aimed at promoting hydropower projects that OLADE started with the Government of Quebec last year. The main themes included are: Energy efficiency in OLADE-GTZ cooperation. Liberalization and energy development, Energy statistics

  2. Ocean energies

    International Nuclear Information System (INIS)

    This timely volume provides a comprehensive review of current technology for all ocean energies. It opens with an analysis of ocean thermal energy conversion (OTEC), with and without the use of an intermediate fluid. The historical and economic background is reviewed, and the geographical areas in which this energy could be utilized are pinpointed. The production of hydrogen as a side product, and environmental consequences of OTEC plants are considered. The competitiveness of OTEC with conventional sources of energy is analysed. Optimisation, current research and development potential are also examined. Separate chapters provide a detailed examination of other ocean energy sources. The possible harnessing of solar ponds, ocean currents, and power derived from salinity differences is considered. There is a fascinating study of marine winds, and the question of using the ocean tides as a source of energy is examined, focussing on a number of tidal power plant projects, including data gathered from China, Australia, Great Britain, Korea and the USSR. Wave energy extraction has excited recent interest and activity, with a number of experimental pilot plants being built in northern Europe. This topic is discussed at length in view of its greater chance of implementation. Finally, geothermal and biomass energy are considered, and an assessment of their future is given. The authors also distinguished between energy schemes which might be valuable in less-industrialized regions of the world, but uneconomical in the developed countries. A large number of illustrations support the text. This book will be of particular interest to energy economists, engineers, geologists and oceanographers, and to environmentalists and environmental engineers

  3. Energy release

    International Nuclear Information System (INIS)

    Full text: Small island developing states (SIDS) are particularly vulnerable to the vagaries of the world's energy markets. Most depend almost entirely on oil for their needs, but few have any oil of their own. So they must rely on importing it and are enormously exposed to the volatility of its price, and to the uncertainty of supplies. As most SIDS are remote, the fuel has to be transported for long distances, greatly increasing its cost. This dependence entails a major threat to their economies. Importing the fuel absorbs a large proportion of their foreign exchange earnings, constraining investment in economic and social development. Additionally, the high price of energy slows down development even further, and makes it hard for the poor to get energy for the lighting and services they need. Yet, while most SIDS are poor in fossil fuels, they are usually rich in renewable sources of energy such as the sun and the wind and could do much to improve their energy efficiency. They are therefore well placed to benefit from sustainable energy policies, which would cut back their expensive fuel imports and make modern forms of energy much more widely available to their people. There is also a moral reason for taking this approach. Many SIDS are among the countries most vulnerable to the sea-level rise and extremes of climate brought about by climate change - yet they emit only a tiny proportion of the greenhouse gases that cause global warming. Setting an example by cutting back their use of fossil fuels would strengthen their moral position even further. So far, however, little renewable energy is exploited in SIDS, and what development has taken place has been largely restricted to international assistance programmes. Now a planned project, initially in three West Indian islands, partially funded by the United Nations Foundation, aims to speed this up. The Global Sustainable Energy Islands Initiative (GSEII) seeks to bring sustainable energy projects, models and

  4. Energy sector

    International Nuclear Information System (INIS)

    Within the framework of assessing the state of the environment in Lebanon, this chapter describes primary energy demand, the electricity generating sector and environmental impacts arising from the energy sector.Apart from hydropower and traditional energy sources, which together represent 1.7% of energy consumption, all energy in Lebanon derives from imported petroleum products and some coal.Tables present the imports of different petroleum products (Gasoil, Kerosene, fuel oil, coal etc...), their use, the energy balance and demand.Energy pricing and pricing policies, formal and informal electricity generations in Lebanon are described emphasized by tables. The main environmental impacts are briefly summarized. Thermal power stations give rise to emissions of Sulphur dioxide (SO2), particulates, oxides of nitrogen (NOx) and CO/CO2 from combustion of primary fuel informally generated power from both industry and domestic consumption produce particulate materials and emissions of NOx and SO2 projected emissions of SO2 from the power sector with the present generating capacity and with the new combined cycle power plants in operation are shown. Other environmental impacts are described. Recommendations for supply and environment policy are presented

  5. Energy perspectives

    International Nuclear Information System (INIS)

    In France and in Europe, the political vision of energy production has not yet been taken to heart as much as its importance merits, despite a certain awareness of the gravity of the phenomena within the population. It would already be very difficult to halve the consumption of fossil fuels in France in 2050, without a swift and profound change in our energy-consumption choices (in particular in transport) and a considerable research effort. To divide it by four seems unrealistic, since France, unlike other countries, has already benefited from the transition from electricity produced from fossil fuels to nuclear electricity which does not emit CO2. A major evolution in energy, in Europe and throughout the World, is inevitable in the course of the century. To prevent this from being too violent and painful, a process of fundamental research and technological development should be launched forthwith, in all fields of energy production, storage and use, with a large effort supported by major research programmes. Some recommendations are given for the main research fields that should be: capture and long term storage of CO2, energy savings in transport, energy supply to large cities and nuclear power plant enhancement, hydrogen storage, wind energy and its unavailability problem, use of forest resources, photovoltaic electricity in rural and isolated regions, temporary storage of electricity

  6. Hydro-energy; Energie hydraulique

    Energy Technology Data Exchange (ETDEWEB)

    Bacher, P. [Electricite de France (EDF), 75 - Paris (France); Tardieu, B. [Coyne et Bellier, 92 - Gennevilliers (France)

    2005-07-01

    The first part of this study concerns the different type of hydraulic works. The second part presents the big hydro-energy, its advantages and disadvantages, the industrial risks, the electric power transport network, the economy and the development perspectives. The third part presents the little hydro-energy, its advantages and disadvantages, the decentralized production and the development perspectives. (A.L.B.)

  7. Clean energy, renewable energies; Energie propre, energies renouvelables

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-09-01

    This document is the compilation of the 4 issues of the 'energie propre - energie renouvelables' newsletter published by the regional energy agency of Provence-Alpes-Cote d'Azur region (ARENE). Each issue is a technical file presenting a particular facility or installation: the pico-hydraulic power plant of the Allos lake (Mercantour, French Alps), the 'Chute de la Guerche' and 'Chute de Chastillon' hydraulic power plant exploited by the Isola town; the pico-hydraulic power plant of the drinkable water network of Hameau des Agnielles village, the direct solar thermal floor. (J.S.)

  8. Energy materials

    CERN Document Server

    Bruce, Duncan W; Walton, Richard I

    2011-01-01

    In an age of global industrialisation and population growth, the area of energy is one that is very much in the public consciousness. Fundamental scientific research is recognised as being crucial to delivering solutions to these issues, particularly to yield novel means of providing efficient, ideally recyclable, ways of converting, transporting and delivering energy. This volume considers a selection of the state-of-the-art materials that are being designed to meet some of the energy challenges we face today. Topics are carefully chosen that show how the skill of the synthetic chemist can

  9. Energy options

    International Nuclear Information System (INIS)

    This chapter focuses on energy options as a means of managing exposure to energy prices. An intuitive approach to energy options is presented, and traditional definitions of call and put options are given. The relationship between options and swaps, option value and option exercises, commodity options, and option pricing are described. An end-user's guide to energy option strategy is outlined, and straight options, collars, participating swaps and collars, bull and bear spreads, and swaption are examined. Panels explaining the defining of basis risk, and discussing option pricing and the Greeks, delta hedging, managing oil options using the Black-Scholes model, caps, floors and collars, and guidelines on hedging versus speculation with options are included in the paper

  10. Energy options

    Energy Technology Data Exchange (ETDEWEB)

    Hampton, Michael [HDS Shipping (United States)

    1999-07-01

    This chapter focuses on energy options as a means of managing exposure to energy prices. An intuitive approach to energy options is presented, and traditional definitions of call and put options are given. The relationship between options and swaps, option value and option exercises, commodity options, and option pricing are described. An end-user's guide to energy option strategy is outlined, and straight options, collars, participating swaps and collars, bull and bear spreads, and swaption are examined. Panels explaining the defining of basis risk, and discussing option pricing and the Greeks, delta hedging, managing oil options using the Black-Scholes model, caps, floors and collars, and guidelines on hedging versus speculation with options are included in the paper.

  11. Tidal Energy.

    Science.gov (United States)

    Impact of Science on Society, 1987

    1987-01-01

    States that tidal power projects are feasible in a relatively limited number of locations around the world. Claims that together they could theoretically produce the energy equivalent to more than one million barrels of oil per year. (TW)

  12. Energy coppice

    International Nuclear Information System (INIS)

    One form of renewable energy production involves the growing of energy coppice on agricultural land. It is important as it can be grown on those areas of agricultural land which are surplus to agricultural production. Hence it can be seen as an alternative farm crop, and as such, a possible solution to the problem of agricultural surpluses as well as providing a source of energy. Studies have indicated that up to one million hectares of land surplus to agricultural production may be suitable for growing energy coppice. However, its development as an agricultural crop will only happen if it can be produced at costs competitive with alternative fuels and there is a reliable and long term market offering good returns. (author)

  13. Geothermal energy

    International Nuclear Information System (INIS)

    A brief article reviews the development of geothermal energy within the OECD countries. Topics covered include power generation, direct use, hot dry rocks and geothermal heat pumps. The limited exploitation in the UK is also described. (UK)

  14. Energy Neighbor

    OpenAIRE

    Marcus Müller, Projektmanager EEBatt

    2015-01-01

    Beschreibung des Energy Neighbor, der im Kirchdorfer Ortsteil Moosham lokal erzeugten Strom für den lokalen Verbrauch speichert. Ziel ist es, die Eigenverbrauchsquote zu erhöhen und das Nierspannungsnetz zu stabilisieren.

  15. Energy efficiency

    International Nuclear Information System (INIS)

    World energy demand is constantly rising. This is a legitimate trend, insofar as access to energy enables enhanced quality of life and sanitation levels for populations. On the other hand, such increased consumption generates effects that may be catastrophic for the future of the planet (climate change, environmental imbalance), should this growth conform to the patterns followed, up to recent times, by most industrialized countries. Reduction of greenhouse gas emissions, development of new energy sources and energy efficiency are seen as the major challenges to be taken up for the world of tomorrow. In France, the National Energy Debate indeed emphasized, in 2003, the requirement to control both demand for, and offer of, energy, through a strategic orientation law for energy. The French position corresponds to a slightly singular situation - and a privileged one, compared to other countries - owing to massive use of nuclear power for electricity generation. This option allows France to be responsible for a mere 2% of worldwide greenhouse gas emissions. Real advances can nonetheless still be achieved as regards improved energy efficiency, particularly in the transportation and residential-tertiary sectors, following the lead, in this respect, shown by industry. These two sectors indeed account for over half of the country CO2 emissions (26% and 25% respectively). With respect to transportation, the work carried out by CEA on the hydrogen pathway, energy converters, and electricity storage has been covered by the preceding chapters. As regards housing, a topic addressed by one of the papers in this chapter, investigations at CEA concern integration of the various devices enabling value-added use of renewable energies. At the same time, the organization is carrying through its activity in the extensive area of heat exchangers, allowing industry to benefit from improved understanding in the modeling of flows. An activity evidenced by advances in energy efficiency for

  16. Energy Storage

    Energy Technology Data Exchange (ETDEWEB)

    Mukundan, Rangachary [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-09-30

    Energy storage technology is critical if the U.S. is to achieve more than 25% penetration of renewable electrical energy, given the intermittency of wind and solar. Energy density is a critical parameter in the economic viability of any energy storage system with liquid fuels being 10 to 100 times better than batteries. However, the economical conversion of electricity to fuel still presents significant technical challenges. This project addressed these challenges by focusing on a specific approach: efficient processes to convert electricity, water and nitrogen to ammonia. Ammonia has many attributes that make it the ideal energy storage compound. The feed stocks are plentiful, ammonia is easily liquefied and routinely stored in large volumes in cheap containers, and it has exceptional energy density for grid scale electrical energy storage. Ammonia can be oxidized efficiently in fuel cells or advanced Carnot cycle engines yielding water and nitrogen as end products. Because of the high energy density and low reactivity of ammonia, the capital cost for grid storage will be lower than any other storage application. This project developed the theoretical foundations of N2 catalysis on specific catalysts and provided for the first time experimental evidence for activation of Mo 2N based catalysts. Theory also revealed that the N atom adsorbed in the bridging position between two metal atoms is the critical step for catalysis. Simple electrochemical ammonia production reactors were designed and built in this project using two novel electrolyte systems. The first one demonstrated the use of ionic liquid electrolytes at room temperature and the second the use of pyrophosphate based electrolytes at intermediate temperatures (200 – 300 ºC). The mechanism of high proton conduction in the pyrophosphate materials was found to be associated with a polyphosphate second phase contrary to literature claims and ammonia production rates as high as 5X 10

  17. Saving Energy

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    More and more Chinese consumers are beginning to think about their energy-saving needs when buying apartments. The energy-saving estate market is huge, which provides great opportunities for companies in the business, especially foreign investors. But just how big is this market and how is it developing? Which fields in this industry are suitable for foreign businesses? With these questions in mind, Beijing Review spoke with Li Shuren, Vice Secretary General of the China Real Estate and Housing Research ...

  18. Wind energy

    International Nuclear Information System (INIS)

    Wind is not only free, it is inexhaustible. Wind energy has come a very long way since the prototypes of just 20 years ago. Today's wind turbines are state-of-the-art technology - modular and quick to install anywhere where there is sufficient wind potential to provide secure, centralised or distributed generation. It is a global phenomenon, the world's fastest growing energy sector, a clean and effective modern technology that completely avoids pollution and thus reducing the 'green house' effect. (Original)

  19. Geothermal energy

    OpenAIRE

    Manzella A.

    2015-01-01

    Geothermal technologies use renewable energy resources to generate electricity and direct use of heat while producing very low levels of greenhouse-gas (GHG) emissions. Geothermal energy is stored in rocks and in fluids circulating in the underground. Electricity generation usually requires geothermal resources temperatures of over 100°C. For heating, geothermal resources spanning a wider range of temperatures can be used in applications such as space and district heating (and cooling, with p...

  20. Energy futures

    International Nuclear Information System (INIS)

    This book provides fifteen of the futures industry's leading authorities with broader background in both theory and practice of energy futures trading in this updated text. The authors review the history of the futures market and the fundamentals of trading, hedging, and technical analysis; then they update you with the newest trends in energy futures trading - natural gas futures, options, regulations, and new information services. The appendices outline examples of possible contracts and their construction

  1. Energy trading

    International Nuclear Information System (INIS)

    This document brings together 18 testimonies of experts about energy trading: 1 - the energy trading experience on European deregulated markets: structure of deregulated energy markets in Europe, case study: a two years experience of a power exchange in western Europe, case study: European energy exchanges (experience of spot and future trading), case study: risk management on energy deregulated markets; 2 - the trading activity environment and realities in France: the French electrical law and the purchase for resale, experience feedback: status after 3 months of trading in France (the first experience of a French producer), the access to the power transportation network, which legal constraints for trading in France, the access of eligible clients to the French power market, conditions of implementation of a power exchange market in France, which real trading possibilities in France for producers and self-producers in the legal frame, case study: the role of trading in the company (main part or link to process), convergence of gas and electricity markets, gas-electricity trading: which pricing models; 3 - risk management and use of new technologies potentiality, the results outside the French borders: case study: what differences between the European and US markets, prices volatility and commodity risk management: towards the on-line trading, role and developments of E-business in energy trading, how to simplify trade in a liberalized market. (J.S.)

  2. Brazilian energy

    International Nuclear Information System (INIS)

    Brazilian Energy provides all the information necessary for energy companies to invest and operate in Brazil, including: a review of Brazil's natural resources; an assessment of privatisation strategies at the federal, state and regional level; an analysis of the electricity industry and the future for Electrobras; an analysis of the oil industry and, in particular, Petrobras; a discussion of the fuel alcohol industry; the discovery of local natural gas, its prospects and the involvement of the auto industry; an assessment of the problems facing the coal industry and its future; a discussion of the regulatory framework for the newly privatised companies; the importance of intra-regional energy links and the booming membership of Mercosur; the difficulties experienced by foreign investors doing business in Brazil; brief profiles of the key energy companies; profiles of key people influencing the privatisation process in Brazil. Brazilian energy is essential reading for those wishing to advise and assist Brazil in this period of change and development, as well as those who wish to invest or become key players in the Brazilian energy sector. (author)

  3. Energy awareness

    Energy Technology Data Exchange (ETDEWEB)

    1977-01-01

    The objective of the Symposium for Public Awareness on Energy was to provide an information exchange among the members of the technical community and the public, civic, fraternal, service, and labor organizations on timely energy-related issues. The 1977 symposium was oriented toward state and local governmental officials in the southeastern states. Since it is these officials who have the responsibility for the development and actualization of local energy strategies, the program was directed toward providing information which would be of help to them in considering energy plans. The symposium presentations featured speakers who are recognized in many facets of the energy field. A variety of views were expressed and a number of policy alternatives were suggested. It is hoped that the presentations provided the motivation for the audience to return to their respective communities with a new and expanded perspective regarding energy issues and policies. The private and public organizations represented at the symposium can continue to provide pertinent information to those who are interested. A separate abstract was prepared for each of the 9 presentations.

  4. Energy resources

    International Nuclear Information System (INIS)

    Cuba, like most island nations, lacks a large energy resource base and satisfies most of its energy needs with imported fossil fuels. The evaluation of the availability of domestic energy reserves and resources, as well as their future extraction potential, is a necessary task in an assessment of sustainable energy development. When estimates of potential availability of fossil fuels are carried out, a distinction is made between reserves and resources. In this study, reserves are known quantities that can be extracted with current technology at current prices. Resources are either less certain as to their existence or known to be technically or economically unfeasible or both. In the case of renewables, the concept of resources needs to be modified. Renewable resources are part of a natural flow that can be regenerated in a time frame that is suitable for human activities. For this reason, it is necessary to refer to renewable energy potential rather than resources. Both resources and reserves change as new technologies become available or due to changes in the market. This is another reason to distinguish between resources, reserves and energy potential

  5. Energy challenges

    International Nuclear Information System (INIS)

    Satisfying the world's insatiable appetite for fuel without destroying the environment is the biggest challenge facing the energy industry. World energy consumption is expected to soar by 50% to a staggering 180 000 GW h per year by 2020, with the developing world demanding an ever-increasing share. Although oil and natural-gas reserves will last for several more decades, environmental concerns are increasingly dominating the agenda. Last year 178 countries agreed to a watered-down version of the original Kyoto protocol, which was designed to reduce the emissions of greenhouse gases from industrialized countries by an average of 5.2% below 1990 levels. Under the new agreement, dubbed 'Kyoto lite' by environmentalists, emissions will be cut by just 2%. The relaxed targets are still not enough to convince the US, the world's biggest polluter, to sign the Kyoto treaty. Renewable technologies still make up less than 1% of the world's commercial energy. Distributed power is also likely to emerge from the development of fuel cells - devices that convert the chemical energy of hydrogen and oxygen directly into electricity, with only water as a by-product. The move away from carbon-based fossil fuels to hydrogen is also driving the hydrogen economy. A longer-term possibility is nuclear fusion. Despite the enormous progress in the performance of experiments over the past 30 years, nuclear fusion is still decades away from generating electricity. Advocates of fusion power claim that it could be a safe and sustainable source of energy that does not produce any greenhouse gases or long-lived nuclear waste. However, physicists have still to demonstrate that the energy produced by the fusion of deuterium and tritium can be sustained. Advances in physics and engineering are making energy from renewable sources increasingly affordable. But political will - as well as scientific progress - is just as crucial for safeguarding the environment for generations to come

  6. Geothermal energy

    Science.gov (United States)

    Manzella, A.

    2015-08-01

    Geothermal technologies use renewable energy resources to generate electricity and direct use of heat while producing very low levels of greenhouse-gas (GHG) emissions. Geothermal energy is stored in rocks and in fluids circulating in the underground. Electricity generation usually requires geothermal resources temperatures of over 100°C. For heating, geothermal resources spanning a wider range of temperatures can be used in applications such as space and district heating (and cooling, with proper technology), spa and swimming pool heating, greenhouse and soil heating, aquaculture pond heating, industrial process heating and snow melting. Geothermal technology, which has focused so far on extracting naturally heated steam or hot water from natural hydrothermal reservoirs, is developing to more advanced techniques to exploit the heat also where underground fluids are scarce and to use the Earth as a potential energy battery, by storing heat. The success of the research will enable energy recovery and utilization from a much larger fraction of the accessible thermal energy in the Earth's crust.

  7. Geothermal energy

    Directory of Open Access Journals (Sweden)

    Manzella A.

    2015-01-01

    Full Text Available Geothermal technologies use renewable energy resources to generate electricity and direct use of heat while producing very low levels of greenhouse-gas (GHG emissions. Geothermal energy is stored in rocks and in fluids circulating in the underground. Electricity generation usually requires geothermal resources temperatures of over 100°C. For heating, geothermal resources spanning a wider range of temperatures can be used in applications such as space and district heating (and cooling, with proper technology, spa and swimming pool heating, greenhouse and soil heating, aquaculture pond heating, industrial process heating and snow melting. Geothermal technology, which has focused so far on extracting naturally heated steam or hot water from natural hydrothermal reservoirs, is developing to more advanced techniques to exploit the heat also where underground fluids are scarce and to use the Earth as a potential energy battery, by storing heat. The success of the research will enable energy recovery and utilization from a much larger fraction of the accessible thermal energy in the Earth’s crust.

  8. Energy Deskbook

    Energy Technology Data Exchange (ETDEWEB)

    Glasstone, S

    1982-06-01

    The purpose of the Energy Deskbook is to serve as a convenient reference to definitions of energy-related terms and descriptions of current and potential energy sources and their utilization. The material is presented at a low technical level with emphasis on general principles, which are not difficult to understand, rather than technology. The entries vary in length from a few lines to several pages, according to circumstances. As a general rule, each topic is defined and outlined in the first paragraph; this may be followed by a more detailed treatment, as required. An important feature of the Deskbook is the use of boldface (heavy) type for cross references. Words in the text set in boldface are the titles of articles where the particular subjects are described.

  9. Nuclear energy

    International Nuclear Information System (INIS)

    This book provides the man in the street with a fair presentation of nuclear energy and can help him to build his own opinion about this much debated question. The first chapter defines what is involved in the hazy term of energy. The second chapter explains how a nuclear power plant operates. The chapters 3 to 6 give a good grounding in basic physics to understand radioactivity and the different processes that occur in a nuclear reactor. The chapters 7 and 8 present the different reactor types and the complete fuel cycle from uranium ore extraction to radioactive waste storage. The last chapter is dedicated to the pros and cons of nuclear energy, this chapter includes a presentation of the organization of nuclear safety in France. (A.C.)

  10. World energy

    International Nuclear Information System (INIS)

    Three major concerns face mankind's future: the impending energy crisis as caused by the depletion of the world's fossil fuel reserves, world atmospheric pollution as caused by the burning of these fuels, and mankind's destruction if the vast energy contained in nuclear weapons stockpiles is released in a global conflict. This paper describes an ambitious, combined solution to these problems by the use of deep underground detonations of thermonuclear devices/bombs to provide a virtually pollution free, world energy source into the far distant future, while achieving a significant increase in mutual trust between the superpowers and all nations. The key is believed to be thermonuclear geothermal stimulation to produce the electrical power needed for a hydrogen economy

  11. Geothermal energy

    International Nuclear Information System (INIS)

    Geothermal energy is the natural heat of the earth. It represents an inexhaustible source of energy. In many countries, which are mostly located within the geothermal belts of the world, geothermal energy is being used since many decades for electricity generation and direct heating applications comprising municipal, industrial and agricultural heating. Outside the geothermal anomalous volcanic regions, hot ground water from deep rock formations at temperatures above 70oC is used for process heat and space heating. Low prices for gas and oil hinder the development of geothermal plants in areas outside positive geothermal anomalies; the cost of drilling to reach depths, where temperatures are above 50oC to 70oC, is high. The necessary total investment per MWth installed capacity is in the order of 5 Mio- DM/MWth (3 Mio $/MWth). Experience shows, that an economic break even with oil is reached at an oil price of 30$ per barrel or if an adequate bonus for the clean, environmentally compatible production of geothermal heat is granted. Worldwide the installed electric capacity of geothermal power plants is approximately 6 000 MWe. About 15 000 MWth of thermal capacity is being extracted for process heat and space heat. The importance of the terrestrial heat as an energy resource would be substantially increased, if the heat, stored in the hot crystalline basement could be extracted at economical production costs. Geothermal energy is a competitive energy source in areas with high geothermal gradients (relative low cost for drilling) and would be competitive in areas with normal geothermal gradients, if a fair compensation for environmental implications from fossil and nuclear power production would be granted. (author) 2 figs., 1 tab., 6 refs

  12. Energy Futures

    DEFF Research Database (Denmark)

    Davies, Sarah Rachael; Selin, Cynthia

    2012-01-01

    foresight and public and stakeholder engagement are used to reflect on?and direct?the impacts of new technology. In this essay we draw on our experience of anticipatory governance, in the shape of the ?NanoFutures? project on energy futures, to present a reflexive analysis of engagement and deliberation. We...... draw out five tensions of the practice of deliberation on energy technologies. Through tracing the lineages of these dilemmas, we discuss some of the implications of these tensions for the practice of civic engagement and deliberation in a set of questions for this community of practitioner-scholars....

  13. Biomass energy

    International Nuclear Information System (INIS)

    Bioenergy systems can provide an energy supply that is environmentally sound and sustainable, although, like all energy systems, they have an environmental impact. The impact often depends more on the way the whole system is managed than on the fuel or on the conversion technology. The authors first describe traditional biomass systems: combustion and deforestation; health impact; charcoal conversion; and agricultural residues. A discussion of modern biomass systems follows: biogas; producer gas; alcohol fuels; modern wood fuel resources; and modern biomass combustion. The issue of bioenergy and the environment (land use; air pollution; water; socioeconomic impacts) and a discussion of sustainable bioenergy use complete the paper. 53 refs., 9 figs., 14 tabs

  14. Energy randomness

    OpenAIRE

    Miller, Joseph S.; Rute, Jason

    2015-01-01

    Energy randomness is a notion of partial randomness introduced by Diamondstone and Kjos-Hanssen to characterize the sequences that can be elements of a Martin-L\\"of random closed set (in the sense of Barmpalias, Brodhead, Cenzer, Dashti, and Weber). It has also been applied by Allen, Bienvenu, and Slaman to the characterization of the possible zero times of a Martin-L\\"of random Brownian motion. In this paper, we show that $X \\in 2^\\omega$ is $s$-energy random if and only if $\\sum_{n\\in\\omega...

  15. The Energy Crisis and Solar Energy

    Science.gov (United States)

    Bockris, J. O'M.

    1974-01-01

    Examines the status of the energy crisis in Australia. Outlines energy alternatives for the 1990's and describes the present status of solar energy research and the economics of solar energy systems. (GS)

  16. Critical energy

    International Nuclear Information System (INIS)

    Access to clean energy is essential for alleviating poverty and fulfilling sustainable development goals. Energy is both an engine of development and a source of many of the problems we face. Approximately four fifths of all the energy used worldwide comes from fossil fuels - and they are also the main contributors to environmental and health problems at local, regional and global levels. Meanwhile, much biomass in the form of wood and agricultural waste continues to be used in inefficient cooking stoves in rural areas - a major source of health problems, which mainly affect poor women and children. Providing alternatives to substitute for wood fuels and to support new opportunities for earning income would address the needs of more than a half billion poor people around the world. Access to clean energy may by no means be sufficient in itself to ensure sustainable development, but it is an essential component of strategies for rural jobs, education, food, security, water supplies, urban and rural public health, local self-sufficiency and a host of other development benefits

  17. Nuclear energy

    International Nuclear Information System (INIS)

    An overview about the evolution of nuclear energy for the next 25 years is presented. Several types of nuclear power reactors are described and the power installed up to year 2000 are discussed. Some processes of nuclear fuel enrichment used in the world are shown. (E.G.)

  18. Energy globalization

    International Nuclear Information System (INIS)

    Toward the future, the petroleum could stop to be the main energy source in the world and the oil companies will only survive if they are adjusted to the new winds that blow in the general energy sector. It will no longer be enough to be the owner of the resource (petroleum or gas) so that a company subsists and be profitable in the long term. The future, it will depend in great measure of the vision with which the oil companies face the globalization concept that begins to experience the world in the energy sector. Concepts like globalization, competition, integration and diversification is something that the companies of the hydrocarbons sector will have very present. Globalization means that it should be been attentive to what happens in the world, beyond of the limits of its territory, or to be caught by competitive surprises that can originate in very distant places. The search of cleaner and friendlier energy sources with the means it is not the only threat that it should fear the petroleum. Their substitution for electricity in the big projects of massive transport, the technology of the communications, the optic fiber and the same relationships with the aboriginal communities are aspects that also compete with the future of the petroleum

  19. Wasted energy?

    NARCIS (Netherlands)

    E.M. Steg

    1999-01-01

    Original title: Verspilde energie? Many environmental problems are increasing primarily due to rising production and consumption, in other words due to the behaviour of consumers. Accordingly, there is a growing realisation that environmental problems must be partly resolved through a change in con

  20. Creative Energy

    Science.gov (United States)

    Dexter, Stephen F., Jr.

    2008-01-01

    In this article, the author shares four strategies that will keep school leaders involved in their schools, connected to their peers, and enthusiastic about it all. Here, the author describes how he has managed to balance the "impossible" with things that give him the energy to face the Mondays and start each new year. So, whether it's finding…

  1. Energy, tourism

    Czech Academy of Sciences Publication Activity Database

    Frantál, Bohumil

    1. Switzerland: Springer International Publishing, 2015 - (Jafar, J.; Honggen, H.) ISBN 978-3-319-01383-1 R&D Projects: GA MŠk EE2.3.20.0025 Institutional support: RVO:68145535 Keywords : energy * tourism * sustainability Subject RIV: DE - Earth Magnetism, Geodesy, Geography http://link.springer.com/referenceworkentry/10.1007/978-3-319-01669-6_441-1

  2. Energy: reproduction

    International Nuclear Information System (INIS)

    The ovulatory activity in the livestock depends on the readiness of nutritious energy with relationship to its use for the nursing. During the early nursing the cup of increment in the production of milk exceeds to the consumption of food, the difference in the energy consumption of the diet with relationship to the energy used for production is a negative energy balance. During the first weeks of nursing this reaches their maximum and it diminishes slowly with the increment in the consumption of dry matter. This first metabolic sign is in an increment in the pulses of hormone luteinizant that acts as and stimulate for the ovary and that with a great readiness of insulin, it takes to the ovarian follicles to respond to the stimulus. The sub-alimentation seems to affect the hypothalamic function and ovarian. The return to the positive energy balance in cows highly producers can be accelerated by the consumption of protected fat. The functions of the lipids are to provide energy for normal maintenance and production, to serve as source of essential fatty acids and eat payee of liposoluble vitamins. The importance of the addition of vegetable fat is that this is not degraded in the rumen but rather it is digested in its entirety in abomasa and absorbed in intestine. The addition of a source of Ca to diets with fats promotes the formation of insoluble soaps achieving that the fat doesn't inhibit the fiber fermentation; the chloride of Ca to be of high solubility in water it is completely ionized in rumen and it is more efficient in the formation of insoluble soaps of Ca. The addition of fat in the diet bears increase in the production of N microbial, inhibition of methane formation, increase and change in population of bacteria and mushrooms. The efficiency of the fat is superior when sources of fatty acids of long chain are used, the employment of these, in its protected form, in a diet, stimulates the number of follicles and it increases its size. The linolic acid is

  3. Renewable energy sources: Energy Efficiency Agency

    International Nuclear Information System (INIS)

    The paper presents the activities of the Energy Efficiency Agency, its main functions, as well as the new legislation stimulating the use of RES, stipulated in the new Energy Law of Bulgaria. The second part of the paper describes the potential of renewable energy in i.e. wind energy; solar energy; biomass energy; hydro energy; geothermal energy; draft of a National Program on RES 2005-2015. The third part describes the main issues of the new ENERGY EFFICIENCY LAW and the established Energy efficiency fund. (Author)

  4. Annual Energy Review, 2008

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-06-01

    The Annual Energy Review (AER) is the Energy Information Administration's (EIA) primary report of annual historical energy statistics. For many series, data begin with the year 1949. Included are statistics on total energy production, consumption, trade, and energy prices; overviews of petroleum, natural gas, coal, electricity, nuclear energy, renewable energy, and international energy; financial and environment indicators; and data unit conversions.

  5. Energy exchange

    International Nuclear Information System (INIS)

    The article discusses the identification of efficiencies that can minimise transaction costs in energy trading and marketing. The article describes what is meant by 'trade management'. It is argued that a trade management system should be able to dovetail with existing or future ERP, advanced risk management, and financial management systems, to provide total enterprise integration. With the right trade management systems, traders have all the necessary information to help them manage exposure to financial risks in a world where energy trading companies are forced to accept very small margins. A trade management system can cover many aspects of a business including the winning of contracts for transportation deals, including rail, car, truck, barge and pipeline. There appears to be unprecedented opportunities for companies specialising in development and provision of trade management systems

  6. Venezuelan energy

    International Nuclear Information System (INIS)

    This paper reports that because military and political instability in the Persian Gulf makes the United States vulnerable to oil supply disruptions, a 1991 Department of Energy report encourages diversification of U.S. oil sources and greater reliance on imports from countries outside the Gulf, such as Venezuela. GAO's report, also published in Spanish, discusses recent increases in Venezuelan oil production and the main factors affecting continued increases through 1996, assesses recent investment reforms in the Venezuelan petroleum industry and U.S. petroleum companies' response to these reforms, identifies the major impediments and inducements to U.S. investment in Venezuela's petroleum industry, and reviews U.S. government efforts to support Venezuela's energy sector

  7. Wasted energy?

    OpenAIRE

    E.M. Steg

    1999-01-01

    Original title: Verspilde energie? Many environmental problems are increasing primarily due to rising production and consumption, in other words due to the behaviour of consumers. Accordingly, there is a growing realisation that environmental problems must be partly resolved through a change in consumer behaviour. However, consumers are a target group that is difficult to reach with environmental policy. This study seeks to answer the question of what consumers do and avoid doing to help the ...

  8. Fusion energy

    International Nuclear Information System (INIS)

    The efforts of the Chemical Technology Division in fusion energy include the areas of fuel handling, processing, and containment. Current studies are concerned largely with the development of vacuum pumps for fusion reactors and experiments and with development and evaluation of techniques for recovering tritium from solid or liquid breeding blankets. In addition, a small effort is devoted to support of the ORNL design of a major Tokamak experiment, The Next Step (TNS)

  9. Energy alternative

    International Nuclear Information System (INIS)

    The present work is about primary sources the conventional fossil fuels (petroleum, coal and natural gas) and not conventional (nuclear fuels), as well as the solar light that reaches the floor, the winds, the rivers, the oceanic currents including the seas, and the biomass, among others. In the present technological era the primary sources are used for the most part to transform their energy into electric power.

  10. Energy management

    OpenAIRE

    Mohd, Alaa

    2013-01-01

    Our present and future power network situation requires extra flexibility in the integration of distributed generation more than ever. Mainly for the small and medium energy converting systems including intelligent control and advanced power electronics conversion systems. This research study showed the visibility of various methods of forming an electric power supply system by paralleling power electronic inverters. These methods foundation is based on the conventional grid control methodolo...

  11. Cold energy

    International Nuclear Information System (INIS)

    Deviations in Q for resonant superconducting radio frequency niobium accelerator cavities are generally correlated with resistivity loss mechanisms. Field dependent Qs are not well modeled by these classical loss mechanisms, but rather can represent a form of precision cavity surface thermometry. When the field dependent Q variation shows improvement with increasing B field level the classical treatment of this problem is inadequate. To justify this behavior hydrogen as a ubiquitous impurity in niobium, which creates measurable property changes, even at very low concentrations is typically considered the cause of such anomalous behavior. This maybe the case in some instances, but more importantly any system operating with a highly coherent field with a significant time dependent magnetic component at near 2° K will have the ability to organize the remaining free spins within the London penetration depth to form a coupled energy reservoir in the form of low mass spin waves. The niobium resonant cavities are composed of a single isotope with a large nuclear spin. When the other loss mechanisms are stripped away this may be the gain medium activated by the low level residual magnetic fields. It was found that one resonant cavity heat treatment produced optimum surface properties and then functioned as a MASER extracting energy from the 2° K thermal bath while cooling the cavity walls. The cavity operating in this mode is a simulator of what can take place in the wider but not colder universe using the cosmic microwave background (CMB) as a thermal source. The low mass, long lifetimes, and the scale of the magnetic spin waves on the weakly magnetized interstellar medium allows energy to be stored that is many orders of magnitude colder than the cosmic microwave background. A linear accelerator cavity becomes a tool to explore the properties of the long wave length magnetic spin waves that populate this cold low energy regime

  12. Cold energy

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, John P., E-mail: jpw@castinganalysis.com [Casting Analysis Corp., PO Box 52, Weyers Cave, VA 24486 (United States)

    2015-12-04

    Deviations in Q for resonant superconducting radio frequency niobium accelerator cavities are generally correlated with resistivity loss mechanisms. Field dependent Qs are not well modeled by these classical loss mechanisms, but rather can represent a form of precision cavity surface thermometry. When the field dependent Q variation shows improvement with increasing B field level the classical treatment of this problem is inadequate. To justify this behavior hydrogen as a ubiquitous impurity in niobium, which creates measurable property changes, even at very low concentrations is typically considered the cause of such anomalous behavior. This maybe the case in some instances, but more importantly any system operating with a highly coherent field with a significant time dependent magnetic component at near 2° K will have the ability to organize the remaining free spins within the London penetration depth to form a coupled energy reservoir in the form of low mass spin waves. The niobium resonant cavities are composed of a single isotope with a large nuclear spin. When the other loss mechanisms are stripped away this may be the gain medium activated by the low level residual magnetic fields. It was found that one resonant cavity heat treatment produced optimum surface properties and then functioned as a MASER extracting energy from the 2° K thermal bath while cooling the cavity walls. The cavity operating in this mode is a simulator of what can take place in the wider but not colder universe using the cosmic microwave background (CMB) as a thermal source. The low mass, long lifetimes, and the scale of the magnetic spin waves on the weakly magnetized interstellar medium allows energy to be stored that is many orders of magnitude colder than the cosmic microwave background. A linear accelerator cavity becomes a tool to explore the properties of the long wave length magnetic spin waves that populate this cold low energy regime.

  13. Geothermal energy

    International Nuclear Information System (INIS)

    To put it simply, geothermal power is the utilization of the earth's natural heat. At many locations around the world, heat from the earth's mantle approaches close to the surface, chiefly in volcanically and or seismically active zones. Magnificent examples include the Big Island of Hawaii, Mount Pinatubo in the Philippines, Yellowstone, and Mt. St. Helens. Commercially viable sources of geothermal energy exist when the heat is close to the surface, a source of water can act as a heat transfer medium, and a geologic setting exists that contains the heat so it concentrates and doesn't dissipate. In addition, the heat must be adequate to provide temperatures at least above 290 degrees F to take advantage of currently available energy conversion technologies. This paper is directed toward the utilization of geothermal energy for power generation. It describes the industry today, the author's view of the benefits of geothermal power, and some measures that could increase the beneficial use of this power source

  14. ТРАНСКРИПЦИОННЫЕ ФАКТОРЫ GATA-3, FOXP3 И ИХ КООПЕРАТИВНЫЕ ВЗАИМОДЕЙСТВИЯ ПРИ БРОНХИАЛЬНОЙ АСТМЕ

    OpenAIRE

    Минеев, Валерий; Сорокина, Лада; Еремеева, Анна

    2012-01-01

    В обзоре рассматривается функциональная роль транскрипционных факторов GATA-3, FOXP3 и их кооперативных взаимодействий. Преобладание одного из данных факторов приводит с дифференцировке наивного Т-лимфоцита в соответствующий Т-хелпер, что обуславливает развитие определенного типа воспаления. Изучение GATA-3 и FOXP3 важно для понимания патогенетических механизмов воспалительных заболеваний легких, в частности бронхиальной астмы, поиска и разработки новых методов лечения этих патологий....

  15. ПАТОГЕНЕТИЧЕСКАЯ РОЛЬ КООПЕРАТИВНЫХ ВЗАИМОДЕЙСТВИЙ ТРАНСКРИПЦИОННЫХ ФАКТОРОВ FOXP3, GATA-3, РАХ-5 ПРИ БРОНХИАЛЬНОЙ АСТМЕ

    OpenAIRE

    Минеев, В.; Сорокина, Л.; Еремеева, А.; Нёма, М.; Беденко, А.

    2013-01-01

    В настоящем обзоре подробно рассматривается функциональная роль транскрипционных факторов лимфоцитов Foxp3, GATA-3, РАХ-5 и их кооперативных взаимодействий. Преобладание одного из данных факторов приводит к выработке соответствующих цитокинов Ти В-лимфоцитами и последующему изменению их функций, что приводит к развитию определенного типа воспаления и характерной симптоматики. Изучение FохP3, GATA-3 и РАХ-5 важно для понимания патогенетических механизмов различных патологических процессов, в ч...

  16. Man, energy, society

    Energy Technology Data Exchange (ETDEWEB)

    Cook, E.F.

    1976-01-01

    The use of energy is examined considering technical, social, economic, and political factors. From a geographical viewpoint, the history of energy consumption is reviewed, current energy problems are delineated, and possible solutions to the energy dilemma are discussed. The following chapters are included: Energy, Environment, and Evolution; Man and Other Engines; Renewable Energy Resources; Non-Renewable Energy Resources; the Physical Economy of Energy Use; the Conservation of Free Energy; Social Evolution and Energy; Life Styles, Government, and Energy; the Geography of Energy; the Social Economy of Energy Use; Energy and the United States; Decisions About Energy; Depletion of Geologic Resources; Ethical and Moral Aspects of Energy Use; and Alternative Energy Futures. It is concluded that man must ultimately rely on renewable energy forms, but there is no promise that these energy sources can be made available at costs low enough to ensure man's survival. (165 references) (BYB)

  17. Hydrogen energy

    International Nuclear Information System (INIS)

    This book consists of seven chapters, which deals with hydrogen energy with discover and using of hydrogen, Korean plan for hydrogen economy and background, manufacturing technique on hydrogen like classification and hydrogen manufacture by water splitting, hydrogen storage technique with need and method, hydrogen using technique like fuel cell, hydrogen engine, international trend on involving hydrogen economy, technical current for infrastructure such as hydrogen station and price, regulation, standard, prospect and education for hydrogen safety and system. It has an appendix on related organization with hydrogen and fuel cell.

  18. Developments in energy supply

    International Nuclear Information System (INIS)

    After an explanation of the fundamentals (measuring units, energy sources, energy comsumption, energy demand, energy reserves), nuclear and renewable energy sources are investigated with a view to their possible contribution to energy supply in the future. There is a final chapter on problems of energy supply in West Germany. (UA)

  19. The Energy Problem

    OpenAIRE

    Giacomelli, Giorgio

    2009-01-01

    A brief general picture of the world, european and italian energy situations is made, analyzing several different energy sources and paying attention to the relations energy-quality of life, energy-environment and energy-health. Then will be discussed fossil fuels, renewable energies, the role of electric energy, nuclear energy, energy savings, the greenhouse effect, a possible sustainable development, the hydrogen economy and the risk and its perception. Then follow the conclusions and persp...

  20. Are renewable marine energies tomorrow's energies?

    International Nuclear Information System (INIS)

    Written by the main involved actors (DCNS, IFPEN and others within the French 'Mer Bretagne' pole), this article indicates the various technologies used to produce marine energy at sea (offshore wind energy, wave energy, current energy, tide energy, thermal energy, marine biomass, and salinity gradient power). It discusses the development status of each of these technologies. It outlines that they are still very expensive, but have an interesting economic and energetic potential