Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in Yarrowia lipolytica

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Pomraning, Kyle R.; Bredeweg, Erin L.; Baker, Scott E.

2017-02-15

Fungi accumulate lipids in a manner dependent on the quantity and quality of the nitrogen source on which they are growing. In the oleaginous yeastYarrowia lipolytica, growth on a complex source of nitrogen enables rapid growth and limited accumulation of neutral lipids, while growth on a simple nitrogen source promotes lipid accumulation in large lipid droplets. Here we examined the roles of nitrogen catabolite repression and its regulation by GATA zinc finger transcription factors on lipid metabolism inY. lipolytica. Deletion of the GATA transcription factor genesgzf3andgzf2resulted in nitrogen source-specific growth defects and greater accumulation of lipids when the cells were growing on a simple nitrogen source. Deletion ofgzf1, which is most similar to activators of genes repressed by nitrogen catabolite repression in filamentous ascomycetes, did not affect growth on the nitrogen sources tested. We examined gene expression of wild-type and GATA transcription factor mutants on simple and complex nitrogen sources and found that expression of enzymes involved in malate metabolism, beta-oxidation, and ammonia utilization are strongly upregulated on a simple nitrogen source. Deletion ofgzf3results in overexpression of genes with GATAA sites in their promoters, suggesting that it acts as a repressor, whilegzf2is required for expression of ammonia utilization genes but does not grossly affect the transcription level of genes predicted to be controlled by nitrogen catabolite repression. Both GATA transcription factor mutants exhibit decreased expression of genes controlled by carbon catabolite repression via the repressormig1, including genes for beta-oxidation, highlighting the complex interplay between regulation of carbon, nitrogen, and lipid metabolism.

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Dynamics of GATA1 binding and expression response in a GATA1-induced erythroid differentiation system

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Deepti Jain

2015-06-01

Full Text Available During the maturation phase of mammalian erythroid differentiation, highly proliferative cells committed to the erythroid lineage undergo dramatic changes in morphology and function to produce circulating, enucleated erythrocytes. These changes are caused by equally dramatic alterations in gene expression, which in turn are driven by changes in the abundance and binding patterns of transcription factors such as GATA1. We have studied the dynamics of GATA1 binding by ChIP-seq and the global expression responses by RNA-seq in a GATA1-dependent mouse cell line model for erythroid maturation, in both cases examining seven progressive stages during differentiation. Analyses of these data should provide insights both into mechanisms of regulation (early versus late targets and the consequences in cell physiology (e.g., distinctive categories of genes regulated at progressive stages of differentiation. The data are deposited in the Gene Expression Omnibus, series GSE36029, GSE40522, GSE49847, and GSE51338.

Combinatorial regulation of tissue specification by GATA and FOG factors

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Chlon, Timothy M.; Crispino, John D.

2012-01-01

The development of complex organisms requires the formation of diverse cell types from common stem and progenitor cells. GATA family transcriptional regulators and their dedicated co-factors, termed Friend of GATA (FOG) proteins, control cell fate and differentiation in multiple tissue types from Drosophila to man. FOGs can both facilitate and antagonize GATA factor transcriptional regulation depending on the factor, cell, and even the specific gene target. In this review, we highlight recent studies that have elucidated mechanisms by which FOGs regulate GATA factor function and discuss how these factors use these diverse modes of gene regulation to control cell lineage specification throughout metazoans. PMID:23048181

B-GATA transcription factors - insights into their structure, regulation and role in plant development

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Claus eSchwechheimer

2015-02-01

Full Text Available GATA transcription factors are evolutionarily conserved transcriptional regulators that recognize promoter elements with a G-A-T-A core sequence. In comparison to animal genomes, the GATA transcription factor family in plants is comparatively large with approximately 30 members. In spite of a long-standing interest of plant molecular biologists in GATA factors, only research conducted in the last years has led to reliable insights into their functions during plant development. Here, we review the current knowledge on B-GATAs, one of four GATA factor subfamilies from Arabidopsis thaliana. We show that B-GATAs can be subdivided based on structural features and their biological function into family members with a C-terminal LLM- (leucine-leucine-methionine domain or an N-terminal HAN- (HANABA TARANU domain. The paralogous GNC (GATA, NITRATE-INDUCIBLE, CARBON-METABOLISM INVOLVED and CGA1/GNL (CYTOKININ-INDUCED GATA1/GNC-LIKE are introduced as LLM-domain containing B-GATAs from Arabidopsis that control germination, greening, senescence and flowering time downstream from several growth regulatory signals including light and the hormones gibberellin, auxin, and cytokinin. Arabidopsis HAN and its monocot-specific paralogs from rice (NECK LEAF1, maize (TASSEL SHEATH1, and barley (THIRD OUTER GLUME are HAN-domain-containing B-GATAs with a predominant role in embryo development and floral development. We also review GATA23, a regulator of lateral root initiation from Arabidopsis, that is closely related to GNC and GNL but has a degenerate LLM-domain that is seemingly specific for the Brassicaceae family. The Brassicaceae-specific GATA23 together with the above-mentioned monocot-specific HAN-domain GATAs provide evidence that neofunctionalization of the B-GATAs was used during plant evolution to expand the functional repertoire of these transcription factors.

Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

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Salonen, Jonna; Rajpert-De Meyts, E; Mannisto, Susanna

2010-01-01

Testicular germ cell cancer is the most common malignancy among young males. The pre-invasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular deve...... development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms....

GATA2 Deficiency and Epstein–Barr Virus Disease

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Jeffrey I. Cohen

2017-12-01

Full Text Available GATA2 is a transcription factor that binds to the promoter of hematopoietic genes. Mutations in one copy of the gene are associated with haploinsufficiency and reduced levels of protein. This results in reduced numbers of several cell types important for immune surveillance including dendritic cells, monocytes, CD4, and NK cells, as well as impaired NK cell function. Recently, GATA2 has been associated with several different presentations of severe Epstein–Barr virus (EBV disease including primary infection requiring repeated hospitalizations, chronic active EBV disease, EBV-associated hydroa vacciniforme with hemophagocytosis, and EBV-positive smooth muscle tumors. EBV was found predominantly in B cells in each of the cases in which it was studied, unlike most cases of chronic active EBV disease in which the virus is usually present in T or NK cells. The variety of EBV-associated diseases seen in patients with GATA2 deficiency suggest that additional forms of severe EBV disease may be found in patients with GATA2 deficiency in the future.

GATA2 Deficiency and Epstein-Barr Virus Disease.

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Cohen, Jeffrey I

2017-01-01

GATA2 is a transcription factor that binds to the promoter of hematopoietic genes. Mutations in one copy of the gene are associated with haploinsufficiency and reduced levels of protein. This results in reduced numbers of several cell types important for immune surveillance including dendritic cells, monocytes, CD4, and NK cells, as well as impaired NK cell function. Recently, GATA2 has been associated with several different presentations of severe Epstein-Barr virus (EBV) disease including primary infection requiring repeated hospitalizations, chronic active EBV disease, EBV-associated hydroa vacciniforme with hemophagocytosis, and EBV-positive smooth muscle tumors. EBV was found predominantly in B cells in each of the cases in which it was studied, unlike most cases of chronic active EBV disease in which the virus is usually present in T or NK cells. The variety of EBV-associated diseases seen in patients with GATA2 deficiency suggest that additional forms of severe EBV disease may be found in patients with GATA2 deficiency in the future.

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

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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.

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

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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

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

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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.

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

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

2014-08-01

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. Polymerase chain reaction and DNA sequencing was performed to detect the exons of the GATA3 gene for mutation analysis. 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 finger domains. We identified a novel nonsense mutation which will expand the spectrum of HDR-associated GATA3 mutations.

Regulation of Nitrogen Metabolism by GATA Zinc Finger Transcription Factors in Yarrowia lipolytica

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Pomraning, Kyle R.; Bredeweg, Erin L.; Baker, Scott E.

2017-01-01

ABSTRACT Fungi accumulate lipids in a manner dependent on the quantity and quality of the nitrogen source on which they are growing. In the oleaginous yeast Yarrowia lipolytica, growth on a complex source of nitrogen enables rapid growth and limited accumulation of neutral lipids, while growth on a simple nitrogen source promotes lipid accumulation in large lipid droplets. Here we examined the roles of nitrogen catabolite repression and its regulation by GATA zinc finger transcription factors...

Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve

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Yang, Bo; Zhou, Wei-Wu; Jiao, Jiao

2017-01-01

. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4...

GATA3 expression in advanced breast cancer: prognostic value and organ-specific relapse.

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McCleskey, Brandi C; Penedo, Thuy L; Zhang, Kui; Hameed, Omar; Siegal, Gene P; Wei, Shi

2015-11-01

GATA3 is a transcription factor regulating luminal cell differentiation in the mammary glands and has been implicated in the luminal types of breast carcinoma. The prognostic significance of GATA3 in breast cancer remains controversial. In this study, we assessed the prognostic value of the molecule in a subset of 62 advanced breast cancers and 10 control breast cancers (no metastasis after follow-up). GATA3 expression levels in luminal tumors of advanced stage were significantly higher than that of the human epidermal growth factor receptor 2 (HER2) subtype and triple-negative carcinomas, as expected, but were similar to those of the luminal controls. Furthermore, 88% of nonluminal tumors showed variable GATA3 expression, for which the HER2 subtype had significantly higher GATA3 expression than that of the triple-negative carcinomas. Interestingly, GATA3 levels were significantly lower in carcinomas with lung relapse compared to those with metastatic recurrence to other organs, thus reflecting the findings in animal models. No significant difference was observed between tumors with bone relapse and those metastasized to nonskeletal sites. Moreover, high GATA3 expression was significantly associated with favorable relapse-free survival and overall survival. These findings suggest that GATA3 may not act solely as a luminal differentiation marker, and further uncovering the molecular pathways by which GATA3 regulates the downstream targets will be crucial to our understanding of breast cancer dissemination. Copyright© by the American Society for Clinical Pathology.

Estrogen promotes megakaryocyte polyploidization via estrogen receptor beta-mediated transcription of GATA1.

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Du, C; Xu, Y; Yang, K; Chen, S; Wang, X; Wang, S; Wang, C; Shen, M; Chen, F; Chen, M; Zeng, D; Li, F; Wang, T; Wang, F; Zhao, J; Ai, G; Cheng, T; Su, Y; Wang, J

2017-04-01

Estrogen is reported to be involved in thrombopoiesis and the disruption of its signaling may cause myeloproliferative disease, yet the underlying mechanisms remain largely unknown. GATA-binding factor 1 (GATA1) is a key regulator of megakaryocyte (MK) differentiation and its deficiency will lead to megakaryoblastic leukemia. Here we show that estrogen can dose-dependently promote MK polyploidization and maturation via activation of estrogen receptor beta (ERβ), accompanied by a significant upregulation of GATA1. Chromatin immunoprecipitation and a dual luciferase assay demonstrate that ERβ can directly bind the promoter region of GATA1 and activate its transcription. Steroid receptor coactivator 3 (SRC3) is involved in ERβ-mediated GATA1 transcription. The deficiency of ERβ or SRC3, similar to the inhibition of GATA1, leads to the impediment of estrogen-induced MK polyploidization and platelet production. Further investigations reveal that signal transducer and activator of transcription 1 signaling pathway downstream of GATA1 has a crucial role in estrogen-induced MK polyploidization, and ERβ-mediated GATA1 upregulation subsequently enhances nuclear factor erythroid-derived 2 expression, thereby promoting proplatelet formation and platelet release. Our study provides a deep insight into the molecular mechanisms of estrogen signaling in regulating thrombopoiesis and the pathogenesis of ER deficiency-related leukemia.

A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function

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Cory A. Rubel

2016-10-01

Full Text Available Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2 are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR. Additionally, Gata2 knockout uteri exhibit abnormal luminal epithelia with ectopic TRP63 expressing squamous cells and a cancer-related molecular profile in a progesterone-independent manner. Lastly, we found a conserved GATA2-PGR regulatory network in both human and mice based on gene signature and path analyses using gene expression profiles of human endometrial tissues. In conclusion, uterine Gata2 regulates a key regulatory network of gene expression for progesterone signaling at the early pregnancy stage.

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

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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.

VEGF and IHH rescue definitive hematopoiesis in Gata-4 and Gata-6-deficient murine embryoid bodies.

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Pierre, Monique; Yoshimoto, Momoko; Huang, Lan; Richardson, Matthew; Yoder, Mervin C

2009-09-01

Murine embryonic stem cells can be differentiated into embryoid bodies (EBs), which serve as an in vitro model recapitulating many aspects of embryonic yolk sac hematopoiesis. Differentiation of embryonic stem cells deficient in either Gata-4 or Gata-6 results in EBs with disrupted visceral endoderm (VE). While lack of VE has detrimental effects on hematopoiesis in vivo, it is unclear whether lack of VE affects hematopoiesis in EBs. Therefore, we compared Gata-4 null (G4N) and Gata-6 null (G6N) EBs with wild-type EBs to assess their ability to commit to hematopoietic cells. EB VE formation was examined using cell-sorting techniques and analysis visceral endoderm gene expression. Hematopoietic progenitor potential of EBs cultured under various conditions was assessed using colony-forming assays. Definitive erythroid, granulocyte-macrophage, and mixed colonies were significantly reduced in G4N and G6N EBs compared to wild-type EBs. Vascular endothelial growth factor (VEGF) expression and secretion were also reduced in both G4N and G6N EBs, consistent with VE serving as a site of VEGF production. Addition of exogenous VEGF(165), to EB cultures completely rescued definitive colony-forming cells in G4N and G6N EBs. This rescue response could be blocked by addition of soluble Flk-1 Fc to EB cultures. Similarly, addition of exogenous Indian hedgehog to EB cultures also recovers the diminishment in definitive hematopoiesis in a reversible manner. These results suggest that the absence of VE in G4N and G6N EBs does not prevent emergence of definitive progenitors from EBs. However, the decreased level of VEGF and Indian hedgehog production in VE devoid G4N and G6N EBs attenuates definitive hematopoietic progenitor cell expansion.

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

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

2006-01-01

stenosis. We have screened 99 unrelated Danish patients with different CHD phenotypes to evaluate the prevalence of GATA4 mutations in CHD. No pathogenic mutations were found among the patients, suggesting that GATA4 mutations are relatively rare among CHD patients. Thus, the diagnostic importance of GATA4...

GATA4 Regulates Epithelial Cell Proliferation to Control Intestinal Growth and Development in MiceSummary

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Bridget M. Kohlnhofer

2016-03-01

Full Text Available Background & Aims: The embryonic small intestinal epithelium is highly proliferative, and although much is known about mechanisms regulating proliferation in the adult intestine, the mechanisms controlling epithelial cell proliferation in the developing intestine are less clear. GATA4, a transcription factor that regulates proliferation in other developing tissues, is first expressed early in the developing gut in midgut endoderm. GATA4 function within midgut endoderm and the early intestinal epithelium is unknown. Methods: By using Sonic Hedgehog Cre to eliminate GATA4 in the midgut endoderm of mouse embryos, we determined the impact of loss of GATA4 on intestinal development, including epithelial cell proliferation, between embryonic day (E9.5 and E18.5. Results: We found that intestinal length and width were decreased in GATA4 mutants compared with controls. GATA4-deficient intestinal epithelium contained fewer cells, and epithelial girth was decreased. We further observed a decreased proportion of proliferating epithelial cells at E10.5 and E11.5 in GATA4 mutants. We showed that GATA4 binds to chromatin containing GATA4 consensus binding sites within cyclin D2 (Ccnd2, cyclin-dependent kinase 6 (Cdk6, and frizzled 5 (Fzd5. Moreover, Ccnd2, Cdk6, and Fzd5 transcripts were reduced at E11.5 in GATA4 mutant tissue. Villus morphogenesis was delayed, and villus structure was abnormal in GATA4 mutant intestine. Conclusions: Our data identify GATA4 as an essential regulator of early intestinal epithelial cell proliferation. We propose that GATA4 controls proliferation in part by directly regulating transcription of cell-cycle mediators. Our data further suggest that GATA4 affects proliferation through transcriptional regulation of Fzd5, perhaps by influencing the response of the epithelium to WNT signaling. Keywords: Transcriptional Regulation, WNT Signaling, Villus Morphogenesis

Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation.

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Chennupati, Vijaykumar; Veiga, Diogo Ft; Maslowski, Kendle M; Andina, Nicola; Tardivel, Aubry; Yu, Eric Chi-Wang; Stilinovic, Martina; Simillion, Cedric; Duchosal, Michel A; Quadroni, Manfredo; Roberts, Irene; Sankaran, Vijay G; MacDonald, H Robson; Fasel, Nicolas; Angelillo-Scherrer, Anne; Schneider, Pascal; Hoang, Trang; Allam, Ramanjaneyulu

2018-04-02

Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anemia and 5q- syndrome, mutations in RP genes lead to a specific defect in erythroid gene translation and cause anemia. Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. Ribonuclease inhibitor 1 (RNH1) is a ubiquitously expressed protein that binds to and inhibits pancreatic-type ribonucleases. Here, we report that RNH1 binds to ribosomes and regulates erythropoiesis by controlling translation of the erythroid transcription factor GATA1. Rnh1-deficient mice die between embryonic days E8.5 and E10 due to impaired production of mature erythroid cells from progenitor cells. In Rnh1-deficient embryos, mRNA levels of Gata1 are normal, but GATA1 protein levels are decreased. At the molecular level, we found that RNH1 binds to the 40S subunit of ribosomes and facilitates polysome formation on Gata1 mRNA to confer transcript-specific translation. Further, RNH1 knockdown in human CD34+ progenitor cells decreased erythroid differentiation without affecting myelopoiesis. Our results reveal an unsuspected role for RNH1 in the control of GATA1 mRNA translation and erythropoiesis.

Genomic profiling identifies GATA6 as a candidate oncogene amplified in pancreatobiliary cancer.

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Kevin A Kwei

2008-05-01

Full Text Available Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46% primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies.

GATA2 is associated with familial early-onset coronary artery disease.

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Jessica J Connelly

2006-08-01

Full Text Available The transcription factor GATA2 plays an essential role in the establishment and maintenance of adult hematopoiesis. It is expressed in hematopoietic stem cells, as well as the cells that make up the aortic vasculature, namely aortic endothelial cells and smooth muscle cells. We have shown that GATA2 expression is predictive of location within the thoracic aorta; location is suggested to be a surrogate for disease susceptibility. The GATA2 gene maps beneath the Chromosome 3q linkage peak from our family-based sample set (GENECARD study of early-onset coronary artery disease. Given these observations, we investigated the relationship of several known and novel polymorphisms within GATA2 to coronary artery disease. We identified five single nucleotide polymorphisms that were significantly associated with early-onset coronary artery disease in GENECARD. These results were validated by identifying significant association of two of these single nucleotide polymorphisms in an independent case-control sample set that was phenotypically similar to the GENECARD families. These observations identify GATA2 as a novel susceptibility gene for coronary artery disease and suggest that the study of this transcription factor and its downstream targets may uncover a regulatory network important for coronary artery disease inheritance.

GATA4 Is Sufficient to Establish Jejunal Versus Ileal Identity in the Small IntestineSummary

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Cayla A. Thompson

2017-05-01

Full Text Available Background & Aims: Patterning of the small intestinal epithelium along its cephalocaudal axis establishes three functionally distinct regions: duodenum, jejunum, and ileum. Efficient nutrient assimilation and growth depend on the proper spatial patterning of specialized digestive and absorptive functions performed by duodenal, jejunal, and ileal enterocytes. When enterocyte function is disrupted by disease or injury, intestinal failure can occur. One approach to alleviate intestinal failure would be to restore lost enterocyte functions. The molecular mechanisms determining regionally defined enterocyte functions, however, are poorly delineated. We previously showed that GATA binding protein 4 (GATA4 is essential to define jejunal enterocytes. The goal of this study was to test the hypothesis that GATA4 is sufficient to confer jejunal identity within the intestinal epithelium. Methods: To test this hypothesis, we generated a novel Gata4 conditional knock-in mouse line and expressed GATA4 in the ileum, where it is absent. Results: We found that GATA4-expressing ileum lost ileal identity. The global gene expression profile of GATA4-expressing ileal epithelium aligned more closely with jejunum and duodenum rather than ileum. Focusing on jejunal vs ileal identity, we defined sets of jejunal and ileal genes likely to be regulated directly by GATA4 to suppress ileal identity and promote jejunal identity. Furthermore, our study implicates GATA4 as a transcriptional repressor of fibroblast growth factor 15 (Fgf15, which encodes an enterokine that has been implicated in an increasing number of human diseases. Conclusions: Overall, this study refines our understanding of an important GATA4-dependent molecular mechanism to pattern the intestinal epithelium along its cephalocaudal axis by elaborating on GATA4’s function as a crucial dominant molecular determinant of jejunal enterocyte identity. Microarray data from this study have been deposited into

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

International Nuclear Information System (INIS)

Wada, Hiromichi; Abe, Mitsuru; Ono, Koh; Morimoto, Tatsuya; Kawamura, Teruhisa; Takaya, Tomohide; Satoh, Noriko; Fujita, Masatoshi; Kita, Toru; Shimatsu, Akira; Hasegawa, Koji

2008-01-01

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

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

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Wada, Hiromichi [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan); Abe, Mitsuru; Ono, Koh [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Morimoto, Tatsuya; Kawamura, Teruhisa; Takaya, Tomohide [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan); Satoh, Noriko [Division of Metabolic Research, National Hospital Organization Kyoto Medical Center, Kyoto (Japan); Fujita, Masatoshi [Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Kita, Toru [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Shimatsu, Akira [Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto (Japan); Hasegawa, Koji [Division of Translational Research, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555 (Japan)

2008-10-03

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 {mu}M of Sm or 100 nM of At. Stimulating proliferative VSMCs with Sm or At induced the expression of SM-{alpha}-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 {mu}M), 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.

Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.

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Tanimura, Nobuyuki; Miller, Eli; Igarashi, Kazuhiko; Yang, David; Burstyn, Judith N; Dewey, Colin N; Bresnick, Emery H

2016-02-01

Metal ion-containing macromolecules have fundamental roles in essentially all biological processes throughout the evolutionary tree. For example, iron-containing heme is a cofactor in enzyme catalysis and electron transfer and an essential hemoglobin constituent. To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2). Using genetic editing to unravel mechanisms governing heme biosynthesis, we discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis elements strongly reduces GATA-1-induced Alas2 transcription, heme biosynthesis, and surprisingly, GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network. Heme amplifies GATA-1 function by downregulating the heme-sensing transcriptional repressor Bach1 and via a Bach1-insensitive mechanism. Through this dual mechanism, heme and a master regulator collaborate to orchestrate a cell type-specific transcriptional program that promotes cellular differentiation. © 2015 The Authors.

Hypoxia-inducible factor 1-mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions.

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Zhang, Feng-Lin; Shen, Guo-Min; Liu, Xiao-Ling; Wang, Fang; Zhao, Ying-Ze; Zhang, Jun-Wu

2012-08-01

Hypoxia-inducible factor promotes erythropoiesis through coordinated cell type-specific hypoxia responses. GATA1 is essential to normal erythropoiesis and plays a crucial role in erythroid differentiation. In this study, we show that hypoxia-induced GATA1 expression is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased GATA1 mRNA and protein levels were detected in K562 cells and erythroid induction cultures of CD34(+) haematopoietic stem/progenitor cells. Enforced HIF1α expression increased GATA1 expression, while HIF1α knockdown by RNA interference decreased GATA1 expression. In silico analysis revealed one potential hypoxia response element (HRE). The results from reporter gene and mutation analysis suggested that this element is necessary for hypoxic response. Chromatin immunoprecipitation (ChIP)-PCR showed that the putative HRE was recognized and bound by HIF1 in vivo. These results demonstrate that the up-regulation of GATA1 during hypoxia is directly mediated by HIF1.The mRNA expression of some erythroid differentiation markers was increased under hypoxic conditions, but decreased with RNA interference of HIF1α or GATA1. Flow cytometry analysis also indicated that hypoxia, desferrioxamine or CoCl(2) induced expression of erythroid surface markers CD71 and CD235a, while expression repression of HIF1α or GATA1 by RNA interference led to a decreased expression of CD235a. These results suggested that HIF1-mediated GATA1 up-regulation promotes erythropoiesis in order to satisfy the needs of an organism under hypoxic conditions. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

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

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Perdomo, José; Jiang, Xing-Mai; Carter, Daniel R; Khachigian, Levon M; Chong, Beng H

2012-01-01

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.

Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 reduces cardiac fibroblast proliferation by suppressing GATA Binding Protein 4

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Liu, Bin; Liu, Ning-Ning; Liu, Wei-Hua; Zhang, Shuang-Wei; Zhang, Jing-Zhi; Li, Ai-Qun [Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Guangzhou Institute of Cardiovascular Disease, Guangzhou (China); Liu, Shi-Ming, E-mail: gzliushiming@126.com [Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Guangzhou Institute of Cardiovascular Disease, Guangzhou (China)

2016-07-08

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and GATA Binding Protein 4 (GATA4) are important for the growth of cardiac fibroblasts (CFs). When deregulated, LOX-1 and GATA4 can cause cardiac remodeling. In the present study, we found novel evidence that GATA4 was required for the LOX-1 regulation of CF proliferation. The inhibition of LOX-1 by RNA interference LOX-1 lentivirus resulted in the loss of PI3K/Akt activation and GATA4 protein expression. The overexpression of LOX-1 by lentivirus rescued CF proliferation, PI3K/Akt activation, and GATA4 protein expression. Moreover, GATA4 overexpression enhanced CF proliferation with LOX-1 inhibition. We also found that the inhibition of PI3K/Akt activation by LY294002, a PI3K inhibitor, reduced cell proliferation and protein level of GATA4. In summary, GATA4 may play an important role in the LOX-1 and PI3K/Akt regulation of CF proliferation. -- Highlights: •GATA4 is regulated by LOX-1 signaling in CFs. •GATA4 is involved in LOX-1 regulating CF proliferation. •GATA4 is regulated by PI3K/Akt signaling in CFs.

GATA-dependent regulation of TPO-induced c-mpl gene expression during megakaryopoiesis.

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Sunohara, Masataka; Morikawa, Shigeru; Fuse, Akira; Sato, Iwao

2014-01-01

Thrombopoietin (TPO) and its receptor, c-Mpl, play the crucial role during megakaryocytopoiesis. Previously, we have shown that the promoter activity of c-mpl induced by TPO is modulated by transcription through a PKC-dependent pathway and that GATA(-77) is involved as a positive regulatory element in TPO-induced c-mpl gene expression in the megakaryoblastic CMK cells. In this research, to examine participating possibility of GATA promoter element in TPO- induced c-mpl gene expression through a PKC-independent pathway, the promoter activity of site-directed mutagenesis and the effect of potein kinase C modulator were measured by a transient transfection assay system. Together with our previous results on the TPO-induced c-mpl promoter, this study indicates destruction of -77GATA in c-mpl promoter decreased the activity by 47.3% under existence of GF109203. These results suggest that GATA promoter element plays significant role in TPO-induced c-mpl gene expression through a PKC-independent pathway.

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

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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.

Transcription factor GATA-4 is a marker of anaplasia in adrenocortical neoplasms of the domestic ferret (Mustela putorius furo).

Science.gov (United States)

Peterson, R A; Kiupel, M; Bielinska, M; Kiiveri, S; Heikinheimo, M; Capen, C C; Wilson, D B

2004-07-01

Adrenocortical neoplasms are a common cause of morbidity in neutered ferrets. Recently we showed that gonadectomized DBA/2J mice develop adrenocortical tumors that express transcription factor GATA-4. Therefore, we screened archival specimens of adrenocortical neoplasms from neutered ferrets to determine whether GATA-4 could be used as a tumor marker in this species. Nuclear immunoreactivity for GATA-4 was evident in 19/22 (86%) of ferret adrenocortical carcinomas and was prominent in areas exhibiting myxoid differentiation. Normal adrenocortical cells lacked GATA-4 expression. Two other markers of adrenocortical tumors in gonadectomized mice, inhibin-alpha and luteinizing hormone receptor, were coexpressed with GATA-4 in some of the ferret tumors. No GATA-4 expression was observed in three cases of nodular hyperplasia, but patches of anaplastic cells expressing GATA-4 were evident in 7/14 (50%) of tumors classified as adenomas. We conclude that GATA-4 can function as a marker of anaplasia in ferret adrenocortical tumors.

Electrostatic study of Alanine mutational effects on transcription: application to GATA-3:DNA interaction complex.

Science.gov (United States)

El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges

2015-01-01

Protein-DNA interaction is of fundamental importance in molecular biology, playing roles in functions as diverse as DNA transcription, DNA structure formation, and DNA repair. Protein-DNA association is also important in medicine; understanding Protein-DNA binding kinetics can assist in identifying disease root causes which can contribute to drug development. In this perspective, this work focuses on the transcription process by the GATA Transcription Factor (TF). GATA TF binds to DNA promoter region represented by `G,A,T,A' nucleotides sequence, and initiates transcription of target genes. When proper regulation fails due to some mutations on the GATA TF protein sequence or on the DNA promoter sequence (weak promoter), deregulation of the target genes might lead to various disorders. In this study, we aim to understand the electrostatic mechanism behind GATA TF and DNA promoter interactions, in order to predict Protein-DNA binding in the presence of mutations, while elaborating on non-covalent binding kinetics. To generate a family of mutants for the GATA:DNA complex, we replaced every charged amino acid, one at a time, with a neutral amino acid like Alanine (Ala). We then applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations, for each mutation. These calculations delineate the contribution to binding from each Ala-replaced amino acid in the GATA:DNA interaction. After analyzing the obtained data in view of a two-step model, we are able to identify potential key amino acids in binding. Finally, we applied the model to GATA-3:DNA (crystal structure with PDB-ID: 3DFV) binding complex and validated it against experimental results from the literature.

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

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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

Esrrb directly binds to Gata6 promoter and regulates its expression with Dax1 and Ncoa3

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Uranishi, Kousuke; Akagi, Tadayuki; Koide, Hiroshi; Yokota, Takashi

2016-01-01

Estrogen-related receptor beta (Esrrb) is expressed in embryonic stem (ES) cells and is involved in self-renewal ability and pluripotency. Previously, we found that Dax1 is associated with Esrrb and represses its transcriptional activity. Further, the disruption of the Dax1–Esrrb interaction increases the expression of the extra-embryonic endoderm marker Gata6 in ES cells. Here, we investigated the influences of Esrrb and Dax1 on Gata6 expression. Esrrb overexpression in ES cells induced endogenous Gata6 mRNA and Gata6 promoter activity. In addition, the Gata6 promoter was found to contain the Esrrb recognition motifs ERRE1 and ERRE2, and the latter was the responsive element of Esrrb. Associations between ERRE2 and Esrrb were then confirmed by biotin DNA pulldown and chromatin immunoprecipitation assays. Subsequently, we showed that Esrrb activity at the Gata6 promoter was repressed by Dax1, and although Dax1 did not bind to ERRE2, it was associated with Esrrb, which directly binds to ERRE2. In addition, the transcriptional activity of Esrrb was enhanced by nuclear receptor co-activator 3 (Ncoa3), which has recently been shown to be a binding partner of Esrrb. Finally, we showed that Dax1 was associated with Ncoa3 and repressed its transcriptional activity. Taken together, the present study indicates that the Gata6 promoter is activated by Esrrb in association with Ncoa3, and Dax1 inhibited activities of Esrrb and Ncoa3, resulting maintenance of the undifferentiated status of ES cells. - Highlights: • Esrrb induced Gata6 expression in ES cells. • Gata6 promoter activity was enhanced by Esrrb, which was repressed by Dax1. • Dax1 associated with the Gata6 promoter via Esrrb. • Dax1 associated with Ncoa3 and repressed its transcriptional activity.

A single cis element maintains repression of the key developmental regulator Gata2.

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Jonathan W Snow

2010-09-01

Full Text Available In development, lineage-restricted transcription factors simultaneously promote differentiation while repressing alternative fates. Molecular dissection of this process has been challenging as transcription factor loci are regulated by many trans-acting factors functioning through dispersed cis elements. It is not understood whether these elements function collectively to confer transcriptional regulation, or individually to control specific aspects of activation or repression, such as initiation versus maintenance. Here, we have analyzed cis element regulation of the critical hematopoietic factor Gata2, which is expressed in early precursors and repressed as GATA-1 levels rise during terminal differentiation. We engineered mice lacking a single cis element -1.8 kb upstream of the Gata2 transcriptional start site. Although Gata2 is normally repressed in late-stage erythroblasts, the -1.8 kb mutation unexpectedly resulted in reactivated Gata2 transcription, blocked differentiation, and an aberrant lineage-specific gene expression pattern. Our findings demonstrate that the -1.8 kb site selectively maintains repression, confers a specific histone modification pattern and expels RNA Polymerase II from the locus. These studies reveal how an individual cis element establishes a normal developmental program via regulating specific steps in the mechanism by which a critical transcription factor is repressed.

Efficient production of platelets from mouse embryonic stem cells by enforced expression of Gata2 in late hemogenic endothelial cells

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Kawaguchi, Manami [Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506 (Japan); Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510 (Japan); Kitajima, Kenji [Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506 (Japan); Kanokoda, Mai [Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506 (Japan); Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510 (Japan); Suzuki, Hidenori [Division of Morphological and Biomolecular Research, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602 (Japan); Miyashita, Kazuya; Nakajima, Marino [Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506 (Japan); Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510 (Japan); Nuriya, Hideko [Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506 (Japan); Kasahara, Kohji [Laboratory of Biomembrane, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506 (Japan); Hara, Takahiko, E-mail: hara-tk@igakuken.or.jp [Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506 (Japan); Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510 (Japan)

2016-06-03

Platelets are essential for blood circulation and coagulation. Previous study indicated that overexpression of Gata2 in differentiated mouse embryonic stem cells (ESCs) resulted in robust induction of megakaryocytes (Mks). To evaluate platelet production capacity of the Gata2-induced ESC-derived Mks, we generated iGata2-ESC line carrying the doxycycline-inducible Gata2 expression cassette. When doxycycline was added to day 5 hemogenic endothelial cells in the in vitro differentiation culture of iGata2-ESCs, c-Kit{sup −}Tie2{sup −}CD41{sup +} Mks were predominantly generated. These iGata2-ESC-derived Mks efficiently produced CD41{sup +}CD42b{sup +}CD61{sup +} platelets and adhered to fibrinogen-coated glass coverslips in response to thrombin stimulation. Transmission electron microscopy analysis demonstrated that the iGata2-ESC-derived platelets were discoid-shaped with α-granules and an open canalicular system, but were larger than peripheral blood platelets in size. These results demonstrated that an enforced expression of Gata2 in late HECs of differentiated ESCs efficiently promotes megakaryopoiesis followed by platelet production. This study provides valuable information for ex vivo platelet production from human pluripotent stem cells in future. -- Highlights: •Megakaryocytes are efficiently induced by Gata2 from ESC-derived day 5 HECs. •Gata2-induced ESC-derived megakaryocytes are c-Kit{sup −}Tie2{sup −}CD41{sup +}. •Gata2-induced ESC-derived megakaryocytes produce larger discoid-shaped platelets. •Gata2-induced ESC-derived platelets bind fibrinogen upon thrombin stimulation.

Efficient production of platelets from mouse embryonic stem cells by enforced expression of Gata2 in late hemogenic endothelial cells

International Nuclear Information System (INIS)

Kawaguchi, Manami; Kitajima, Kenji; Kanokoda, Mai; Suzuki, Hidenori; Miyashita, Kazuya; Nakajima, Marino; Nuriya, Hideko; Kasahara, Kohji; Hara, Takahiko

2016-01-01

Platelets are essential for blood circulation and coagulation. Previous study indicated that overexpression of Gata2 in differentiated mouse embryonic stem cells (ESCs) resulted in robust induction of megakaryocytes (Mks). To evaluate platelet production capacity of the Gata2-induced ESC-derived Mks, we generated iGata2-ESC line carrying the doxycycline-inducible Gata2 expression cassette. When doxycycline was added to day 5 hemogenic endothelial cells in the in vitro differentiation culture of iGata2-ESCs, c-Kit − Tie2 − CD41 + Mks were predominantly generated. These iGata2-ESC-derived Mks efficiently produced CD41 + CD42b + CD61 + platelets and adhered to fibrinogen-coated glass coverslips in response to thrombin stimulation. Transmission electron microscopy analysis demonstrated that the iGata2-ESC-derived platelets were discoid-shaped with α-granules and an open canalicular system, but were larger than peripheral blood platelets in size. These results demonstrated that an enforced expression of Gata2 in late HECs of differentiated ESCs efficiently promotes megakaryopoiesis followed by platelet production. This study provides valuable information for ex vivo platelet production from human pluripotent stem cells in future. -- Highlights: •Megakaryocytes are efficiently induced by Gata2 from ESC-derived day 5 HECs. •Gata2-induced ESC-derived megakaryocytes are c-Kit − Tie2 − CD41 + . •Gata2-induced ESC-derived megakaryocytes produce larger discoid-shaped platelets. •Gata2-induced ESC-derived platelets bind fibrinogen upon thrombin stimulation.

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

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Ushijima, Hironori; Horyozaki, Akiko; Maeda, Masatomo, E-mail: mmaeda@nupals.ac.jp

2016-09-09

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. - Highlights: • Anisomycin induces proteolysis of GATA-6 in DLD-1 cells. • Anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest. • Anisomycin suppresses the growth of spheroids of DLD-1, and enhances the effect of 5-FU.

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

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...... of the GATA-1-PU.1 interaction. A combination of NMR titration data and extensive mutagenesis revealed that the PU.1-Ets domain and the GATA-1 C-terminal zinc finger (CF) form a low affinity interaction in which specific regions of each protein are implicated. Surprisingly, the interaction cannot be disrupted...

Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.

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Tohru Fujiwara

Full Text Available Aplastic anemia is characterized by a reduced hematopoietic stem cell number. Although GATA-2 expression was reported to be decreased in CD34-positive cells in aplastic anemia, many questions remain regarding the intrinsic characteristics of hematopoietic stem cells in this disease. In this study, we identified HOXB4 as a downstream target of GATA-2 based on expression profiling with human cord blood-derived CD34-positive cells infected with control or GATA-2 lentiviral shRNA. To confirm the functional link between GATA-2 and HOXB4, we conducted GATA-2 gain-of-function and loss-of-function experiments, and HOXB4 promoter analysis, including luciferase assay, in vitro DNA binding analysis and quantitative ChIP analysis, using K562 and CD34-positive cells. The analyses suggested that GATA-2 directly regulates HOXB4 expression through the GATA sequence in the promoter region. Furthermore, we assessed GATA-2 and HOXB4 expression in CD34-positive cells from patients with aplastic anemia (n = 10 and idiopathic thrombocytopenic purpura (n = 13, and demonstrated that the expression levels of HOXB4 and GATA-2 were correlated in these populations (r = 0.6573, p<0.01. Our results suggested that GATA-2 directly regulates HOXB4 expression in hematopoietic stem cells, which may play an important role in the development and/or progression of aplastic anemia.

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

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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)

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

International Nuclear Information System (INIS)

Bonin, F.; Molina, M.; Berthier-Vergnes, O.; Lamartine, J.; Malet, C.; Ginestet, C.; Martin, M.T.

2009-01-01

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, 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)

ASSOCIATION BETWEEN SPECIFIC FEATURES OF GATA3 TRANSCRIPTION FACTOR EXPRESSION AND LYMPH NODE METASTASIS IN LUMINAL BREAST CANCER

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S. V. Vtorushin

2017-01-01

Full Text Available Currently, the study of the markers of cell differentiation, proliferative regulators, and molecules involved in the development of drug resistance mechanisms in breast cancer is extremely important. The transcription factor GATA3 plays an essential role in the differentiation and proliferative activity of luminal breast cancer cells, being a tumor suppressor. The GATA3 positive expression is most frequently observed in invasive carcinoma of no special type. High expression of GATA3 is associated with low-grade ER-positive cancer with a favorable prognosis. Low GATA3 expression is observed in patients with high-grade and hormone receptor-negative cancer. The study of GATA3 expression is necessary for understanding the development of drug resistance mechanisms and developing approaches to overcome them as well as for determining the response to hormone therapy. Aim. The present study was undertaken to study the expression characteristics of the transcription factor GATA3 in patients with luminal breast cancer and to evaluate their relationship with the parameters of lymphogenous metastasis. Material and methods. The study included 64 patients with stage T1–4N1–3M0 invasive breast cancer. The primary tumor tissue and all removed lymph nodes were morphologically examined. The diagnosis was established according to the WHO criteria (2012. Results. Low GATA3 expression was associated with a high risk of lymph node metastases, while high GATA3 expression was associated with the absence of lymph node metastases. Heterogeneous GATA3 expression was associated with high risk of lymph node metastasis, and as a consequence, with poor prognosis. Conclusion. The relationship between the expression of GATA3 protein and lymphogenic metastasis in patients with luminal breast cancer was found.

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

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Nanako Kawaguchi

2010-12-01

Full Text Available 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.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.c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway.

Displasia cística mamária em uma gata

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Cartagna Lúcia Maria

2005-01-01

Full Text Available 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.

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

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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.

Chemical Inhibition of Histone Deacetylases 1 and 2 Induces Fetal Hemoglobin through Activation of GATA2.

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Jeffrey R Shearstone

Full Text Available Therapeutic intervention aimed at reactivation of fetal hemoglobin protein (HbF is a promising approach for ameliorating sickle cell disease (SCD and β-thalassemia. Previous studies showed genetic knockdown of histone deacetylase (HDAC 1 or 2 is sufficient to induce HbF. Here we show that ACY-957, a selective chemical inhibitor of HDAC1 and 2 (HDAC1/2, elicits a dose and time dependent induction of γ-globin mRNA (HBG and HbF in cultured primary cells derived from healthy individuals and sickle cell patients. Gene expression profiling of erythroid progenitors treated with ACY-957 identified global changes in gene expression that were significantly enriched in genes previously shown to be affected by HDAC1 or 2 knockdown. These genes included GATA2, which was induced greater than 3-fold. Lentiviral overexpression of GATA2 in primary erythroid progenitors increased HBG, and reduced adult β-globin mRNA (HBB. Furthermore, knockdown of GATA2 attenuated HBG induction by ACY-957. Chromatin immunoprecipitation and sequencing (ChIP-Seq of primary erythroid progenitors demonstrated that HDAC1 and 2 occupancy was highly correlated throughout the GATA2 locus and that HDAC1/2 inhibition led to elevated histone acetylation at well-known GATA2 autoregulatory regions. The GATA2 protein itself also showed increased binding at these regions in response to ACY-957 treatment. These data show that chemical inhibition of HDAC1/2 induces HBG and suggest that this effect is mediated, at least in part, by histone acetylation-induced activation of the GATA2 gene.

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

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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

GATA transcription factors associate with a novel class of nuclear bodies in erythroblasts and megakaryocytes.

NARCIS (Netherlands)

A.G. Elefanty (Andrew); M. Antoniou (Michael); N. Custodio; M. Carmo-Fonseca; F.G. Grosveld (Frank)

1996-01-01

textabstractThe nuclear distribution of GATA transcription factors in murine haemopoietic cells was examined by indirect immunofluorescence. Specific bright foci of GATA-1 fluorescence were observed in erythroleukaemia cells and primary murine erythroblasts and megakaryocytes, in addition to diffuse

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

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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. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

hHO-1 combined with GATA-4 transduction promotes myocardial transdifferentiation and anti- apoptosis of rat mesenchymal stem cells

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Ning-bo DENG

2017-06-01

Full Text Available Objectives To explore if the rat bone marrow mesenchymal stem cells (BMSCs modified by human heme oxygenase 1 (hHO-1 gene combined with GATA-4 gene may promote the ability of anti-apoptosis and myocardial transdifferentiation in vitro in hypoxia ischemic environment. Methods The rat BMSCs were isolated and cultured by whole bone marrow adherence and identified in vitro, and then were transfected with recombinant adenovirus; Western blotting was used to determinate the optimal time of gene expression; the genetically modified BMSCs were taken to hypoxia serum-free conditions simulating ischemia hypoxia microenvironment in vivo; CCK-8 kit and trypan blue staining were performed to detect the 12, 24, 48 and 72h survival rates in hypoxia ischemia respectively; flow cytometry was used to detect the apoptosis of BMSCs in hypoxia ischemia for 24h. The cardiomyocyte-specific cardiac troponin I (cTnI was detected by Western blotting and cellular immunofluorescence. Results The 12, 24, 48 and 72h survival rates were higher in hHO-1+GATA-4 group cultured in ischemia and hypoxia condition than in hHO-1 group (P<0.05 and GATA-4 group (P<0.05. After 24h cultivation in ischemia hypoxia condition, the apoptotic rates were lower in hHO-1+GATA-4 group than in hHO-1 group (P<0.05 and GATA-4 group (P<0.05. No significant difference existed in cTnI expressions between GATA-4 group and hHO-1+GATA-4 group. Conclusion Compared with transfection of hHO-1 or GATA-4 single gene, hHO-1 combined with GATA-4 transduction can significantly increase the survival rate of BMSCs in hypoxia ischemic condition, but myocardial transdifferentiation does not increase significantly. DOI: 10.11855/j.issn.0577-7402.2017.04.08

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

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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.

GATA-3 is involved in the development of serotonergic neurons in the caudal raphe nuclei

NARCIS (Netherlands)

J. van der Wees (Jacqueline); A. Karis (Alar); E. Goedknegt; M. Rutteman; F.G. Grosveld (Frank); J.H. van Doorninck (Hikke); C.I. de Zeeuw (Chris)

1999-01-01

textabstractAbstract The GATA-3 transcription factor shows a specific and restricted expression pattern in the developing and adult mouse brain. In the present study we investigated the role of GATA-3 in the caudal raphe system, which is known to operate as a modulator of motor activity. We

Dew contribution to the water balance in a semiarid coastal steppe ecosystem (Cabo de Gata, SE Spain)

International Nuclear Information System (INIS)

Moro, M. J.; Were, A.; Morillas, L.; Villagarcia, L.; Canton, Y.; Lazaro, R.; Serrano-Ortiz, P.; Kowalski, A. S.; Domingo, F.

2009-01-01

Dewfall deposition can be a significant source of moisture in arid and semiarid ecosystems, thus contribution to improve daily and annual water balances. Occurrence, frequency and amount of dewfall were measured in the Balsa Blanca site (Cabo de Gata, Almeria, Spain) from January 2007 to May 2008. this area has a sparse vegetation cover dominated by Stipa tenacissima combined with bare soil and biological soil crusts. (Author) 3 refs.

GATA-4 and FOG-2 expression in pediatric ovarian sex cord-stromal tumors replicates embryonal gonadal phenotype: results from the TREP project.

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Virgone, Calogero; Cecchetto, Giovanni; Ferrari, Andrea; Bisogno, Gianni; Donofrio, Vittoria; Boldrini, Renata; Collini, Paola; Dall'Igna, Patrizia; Alaggio, Rita

2012-01-01

GATA proteins are a family of zinc finger transcription factors regulating gene expression, differentiation and proliferation in various tissues. The expression of GATA-4 and FOG-2, one of its modulators, was studied in pediatric Sex Cord-Stromal tumors of the ovary, in order to evaluate their potential role as diagnostic markers and prognostic factors. Clinical and histological data of 15 patients, enrolled into the TREP Project since 2000 were evaluated. When available, immunostaines for FOG-2, GATA-4, α-Inhibin, Vimentin and Pancytokeratin were also analyzed. In our series there were 6 Juvenile Granulosa Cell Tumors (JGCT), 6 Sertoli-Leydig Cell Tumors (SLCT), 1 Cellular Fibroma, 1 Theca Cell Tumor and 1 Stromal Sclerosing Tumor (SST). Thirteen patients obtained a complete remission (CR), 1 reached a second CR after the removal of a metachronous tumor and 1 died of disease. Inhibin was detectable in 11/15, Vimentin in 13/15, Pancytokeratin in 6/15, GATA-4 in 5/13 and FOG-2 in 11/15. FOG-2 was highly expressed in 5/6 JGCT, while GATA-4 was weakly detectable only in 1 of the cases. SLCT expressed diffusely FOG-2 (4/6) and GATA-4 (3/5). GATA-4 and FOG-2 were detected in fibroma and thecoma but not in the SST. Pediatric granulosa tumors appear to express a FOG-2/GATA-4 phenotype in keeping with primordial ovarian follicles. High expression of GATA-4 does not correlate with aggressive behaviour as seen in adults, but it is probably involved in cell proliferation its absence can be associated with the better outcome of JGCT. SLCTs replicate the phenotype of Sertoli cells during embryogenesis in normal testis. In this group, the lack of expression of FOG-2 in tumors in advanced stages might reveal a hypothetical role in inhibiting GATA-4 cell proliferation pathway. In fibroma/thecoma group GATA-4 and FOG-2 point out the abnormal activation of GATA pathway and might be involved in the onset of these tumors.

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

[Study of allelic polymorphism of (GATA)n-containing loci in parthenogenetic lizards Darevskia unisexualis (Lacertidae)].

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Korchagin, V I; Martirosian, I A; Omel'chenko, A V; Darevskiĭ, I S; Ryskov, A P; Tokarskaia, O N

2004-10-01

The genesis of mini- and microsatellite loci, which is under extensive study in humans and some other bisexual species, have been virtually overlooked in species with clonal mode of reproduction. Earlier, using multilocus DNA fingerprinting, we have examined variability of some mini- and microsatellite DNA markers in parthenogenetic lizards from the genus Darevskia. In particular, mutant (GATA)n-restrictive DNA fragments were found in Darevskia unisexualis. In the present study, we examined intraspecific polymorphism of three cloned loci of D. unisexualis--Du323, Du215, and Du281--containing (GATA)7GAT(GATA)2, GAT(GATA)9, and (GATA)10TA(GATA) microsatellite clusters, respectively. Different levels of intrapopulation and interpopulation variability of these loci were found. Locus Du281 showed the highest polymorphism--six allelic variants (in the sample of 68 DNA specimens). Three alleles were found for locus Du215. The Du325 locus was electrophoretically invariant. The primers chosen for loci Du323, Du215, and Du281 were also used for PCR analysis of homologous loci in two presumptive parental bisexual species, D. valentini and D. nairensis. The PCR products of the corresponding loci of the parental species had approximately the same size (approximately 200 bp) as their counterparts in D. unisexualis, but the polymorphism levels of the paternal, maternal, and hybrid species were shown to be somewhat different. These data on the structure of the D. unisexualis loci provide a possibility to study genetic diversity in the parthenogenetic species D. unisexualis and other related unisexual and bisexual species of this genus, which can provide new information on the origin of parthenogenetic species and on the phylogenetic relationships in the genus Darevskia. These data can also be used for resolving problems of marking the lizard genome, which is still poorly studied.

Angiotensin II induces apoptosis in intestinal epithelial cells through the AT2 receptor, GATA-6 and the Bax pathway

International Nuclear Information System (INIS)

Sun, Lihua; Wang, Wensheng; Xiao, Weidong; Liang, Hongyin; Yang, Yang; Yang, Hua

2012-01-01

Highlights: ► Ang II-induced apoptosis in intestinal epithelial cell through AT2 receptor. ► The apoptosis process involves in the Bax/Bcl-2 intrinsic pathway. ► GATA-6 short hairpin RNA reduced Bax expression, but not Bcl-2. ► GATA-6 may play a critical role in apoptosis in response to the Ang II challenge. -- Abstract: Angiotensin II (Ang II) has been shown to play an important role in cell apoptosis. However, the mechanisms of Ang-II-induced apoptosis in intestinal epithelial cells are not fully understood. GATA-6 is a zinc finger transcription factor expressed in the colorectal epithelium, which directs cell proliferation, differentiation and apoptosis. In the present study we investigated the underlying mechanism of which GATA-6 affects Ang-II induced apoptosis in intestinal epithelial cells. The in vitro intestinal epithelial cell apoptosis model was established by co-culturing Caco-2 cells with Ang II. Pretreatment with Angiotensin type 2 (AT2) receptor antagonist, PD123319, significantly reduced the expression of Bax and prevented the Caco-2 cells apoptosis induced by Ang II. In addition, Ang II up-regulated the expression of GATA-6. Interestingly, GATA-6 short hairpin RNA prevented Ang II-induced intestinal epithelial cells apoptosis and reduced the expression of Bax, but not Bcl-2. Taken together, the present study suggests that Angiotensin II promotes apoptosis in intestinal epithelial cells through GATA-6 and the Bax pathway in an AT2 receptor-dependent manner.

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

All-trans retinoic acid directs urothelial specification of murine embryonic stem cells via GATA4/6 signaling mechanisms.

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Joshua R Mauney

2010-07-01

Full Text Available The urinary bladder and associated tract are lined by the urothelium, a transitional epithelium that acts as a specialized permeability barrier that protects the underlying tissue from urine via expression of a highly specific group of proteins known as the uroplakins (UP. To date, our understanding of the developmental processes responsible for urothelial differentiation has been hampered due to the lack of suitable models. In this study, we describe a novel in vitro cell culture system for derivation of urothelial cells from murine embryonic stem cells (ESCs following cultivation on collagen matrices in the presence all trans retinoic acid (RA. Upon stimulation with micromolar concentrations of RA, ESCs significantly downregulated the pluripotency factor OCT-4 but markedly upregulated UP1A, UP1B, UP2, UP3A, and UP3B mRNA levels in comparison to naïve ESCs and spontaneously differentiating controls. Pan-UP protein expression was associated with both p63- and cytokeratin 20-positive cells in discrete aggregating populations of ESCs following 9 and 14 days of RA stimulation. Analysis of endodermal transcription factors such as GATA4 and GATA6 revealed significant upregulation and nuclear enrichment in RA-treated UP2-GFP+ populations. GATA4-/- and GATA6-/- transgenic ESC lines revealed substantial attenuation of RA-mediated UP expression in comparison to wild type controls. In addition, EMSA analysis revealed that RA treatment induced formation of transcriptional complexes containing GATA4/6 on both UP1B and UP2 promoter fragments containing putative GATA factor binding sites. Collectively, these data suggest that RA mediates ESC specification toward a urothelial lineage via GATA4/6-dependent processes.

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

International Nuclear Information System (INIS)

Wong, R.; Newton, A.; Crossley, M.; Mackay, J.

2001-01-01

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

Preferential expression of NY-BR-1 and GATA-3 in male breast cancer.

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Biserni, Giovanni Battista; Di Oto, Enrico; Moskovszky, Linda Eszter; Foschini, Maria Pia; Varga, Zsuzsanna

2018-02-01

Male breast cancer is an uncommon disease often discovered in advanced stage; thus, in the setting of metastatic adenocarcinoma, breast origin must be taken to account. Breast markers as NY-BR-1, GATA-3, mammaglobin, and BRST-2 are established tools for labelling primary and metastatic female breast cancer; however, none of them has been sufficiently studied in male breast cancer. The aim of this study was to analyze the expression of these markers in male breast cancer. Thirty consecutive cases of male breast cancer and eight loco-regional metastases were re-revaluated, assembled in tissue micro array (TMA), and stained with immunohistochemistry (IHC) for NY-BR-1, GATA-3, mammaglobin, and BRST-2. The IHC stains were scored either positive or negative. In addition, concordant expression patterns of primary tumors and matched metastasis were noted. 30 of 30 (100%) primary tumors and 8 of 8 (100%) metastases were positive for NY-BR-1. 30 of 30 (100%) primary tumors and 6 of 8 (75%) metastases were positive for GATA-3. 22 of 30 (73.3%) primary tumors and 6 of 8 (75%) metastases were positive for Mammaglobin. 18 of 30 (60%) primary tumors and 5 of 8 (62.5%) metastases were positive for BRST-2. Differences in staining percentage were not significant with Fisher's exact test. We found a high sensitivity for all the markers analyzed. Moreover, the expression of NY-BR-1 and GATA-3 seemed the most effective for labelling male breast cancer in primary and metastatic setting.

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

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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.

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

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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. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel mutation of GATA4 gene in Kurdish population of Iran with nonsyndromic congenital heart septals defects.

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Soheili, Fariborz; Jalili, Zahra; Rahbar, Mahtab; Khatooni, Zahed; Mashayekhi, Amir; Jafari, Hossein

2018-03-01

The mutations in GATA4 gene induce inherited atrial and ventricular septation defects, which is the most frequent forms of congenital heart defects (CHDs) constituting about half of all cases. We have performed High resolution melting (HRM) mutation scanning of GATA4 coding exons of nonsyndrome 100 patients as a case group including 39 atrial septal defects (ASD), 57 ventricular septal defects (VSD) and four patients with both above defects and 50 healthy individuals as a control group. Our samples are categorized according to their HRM graph. The genome sequencing has been done for 15 control samples and 25 samples of patients whose HRM analysis were similar to healthy subjects for each exon. The PolyPhen-2 and MUpro have been used to determine the causative possibility and structural stability prediction of GATA4 sequence variation. The HRM curve analysis exhibit that 21 patients and 3 normal samples have deviated curves for GATA4 coding exons. Sequencing analysis has revealed 12 nonsynonymous mutations while all of them resulted in stability structure of protein 10 of them are pathogenic and 2 of them are benign. Also we found two nucleotide deletions which one of them was novel and one new indel mutation resulting in frame shift mutation, and 4 synonymous variations or polymorphism in 6 of patients and 3 of normal individuals. Six or about 50% of these nonsynonymous mutations have not been previously reported. Our results show that there is a spectrum of GATA4 mutations resulting in septal defects. © 2018 Wiley Periodicals, Inc.

Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers.

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Cohen, Jeffrey I; Dropulic, Lesia; Hsu, Amy P; Zerbe, Christa S; Krogmann, Tammy; Dowdell, Kennichi; Hornung, Ronald L; Lovell, Jana; Hardy, Nancy; Hickstein, Dennis; Cowen, Edward W; Calvo, Katherine R; Pittaluga, Stefania; Holland, Steven M

2016-07-01

Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer. We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings. Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme-like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls. GATA2 is the first gene associated with EBV hydroa vacciniforme-like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization.

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Muntean, Andrew G; Pang, Liyan; Poncz, Mortimer; Dowdy, Steven F; Blobel, Gerd A; Crispino, John D

2007-06-15

Endomitosis is a unique form of cell cycle used by megakaryocytes, in which the latter stages of mitosis are bypassed so that the cell can increase its DNA content and size. Although several transcription factors, including GATA-1 and RUNX-1, have been implicated in this process, the link between transcription factors and polyploidization remains undefined. Here we show that GATA-1-deficient megakaryocytes, which display reduced size and polyploidization, express nearly 10-fold less cyclin D1 and 10-fold increased levels of p16 compared with their wild-type counterparts. We further demonstrate that cyclin D1 is a direct GATA-1 target in megakaryocytes, but not erythroid cells. Restoration of cyclin D1 expression, when accompanied by ectopic overexpression of its partner Cdk4, resulted in a dramatic increase in megakaryocyte size and DNA content. However, terminal differentiation was not rescued. Of note, polyploidization was only modestly reduced in cyclin D1-deficient mice, likely due to compensation by elevated cyclin D3 expression. Finally, consistent with an additional defect conferred by increased levels of p16, inhibition of cyclin D-Cdk4 complexes with a TAT-p16 fusion peptide significantly blocked polyploidization of wild-type megakaryocytes. Together, these data show that GATA-1 controls growth and polyploidization by regulating cyclin D-Cdk4 kinase activity.

Cyclin D–Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization

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Muntean, Andrew G.; Pang, Liyan; Poncz, Mortimer; Dowdy, Steven F.; Blobel, Gerd A.

2007-01-01

Endomitosis is a unique form of cell cycle used by megakaryocytes, in which the latter stages of mitosis are bypassed so that the cell can increase its DNA content and size. Although several transcription factors, including GATA-1 and RUNX-1, have been implicated in this process, the link between transcription factors and polyploidization remains undefined. Here we show that GATA-1–deficient megakaryocytes, which display reduced size and polyploidization, express nearly 10-fold less cyclin D1 and 10-fold increased levels of p16 compared with their wild-type counterparts. We further demonstrate that cyclin D1 is a direct GATA-1 target in megakaryocytes, but not erythroid cells. Restoration of cyclin D1 expression, when accompanied by ectopic overexpression of its partner Cdk4, resulted in a dramatic increase in megakaryocyte size and DNA content. However, terminal differentiation was not rescued. Of note, polyploidization was only modestly reduced in cyclin D1–deficient mice, likely due to compensation by elevated cyclin D3 expression. Finally, consistent with an additional defect conferred by increased levels of p16, inhibition of cyclin D-Cdk4 complexes with a TAT-p16 fusion peptide significantly blocked polyploidization of wild-type megakaryocytes. Together, these data show that GATA-1 controls growth and polyploidization by regulating cyclin D-Cdk4 kinase activity. PMID:17317855

Fisiología reproductiva y control de los ciclos estrales en la gata doméstica

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Giménez, F.; Stornelli, María Cecilia; Savignone, César A.; Tittarelli, Claudia Marcela; Sota, Rodolfo Luzbel de la; Stornelli, María Alejandra

2006-01-01

La gata doméstica es poliéstrica estacional, con ovulación inducida por el coito. Sin embargo, la ovulación espontánea puede ocurrir en algunas hembras. El celo ocurre con un intervalo de 14 a 19 días en aquellas gatas expuestas a un fotoperíodo largo (14 horas luz diarias). El ciclo estral felino se divide en cuatro períodos: proestro, estro, interestro y anestro. Cada etapa presenta ciertas particularidades que diferencian una de otra. Existen diferentes métodos para prevenir tanto la ocurr...

Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts.

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Anna L Mitchell

Full Text Available Gene variants known to contribute to Autoimmune Addison's disease (AAD susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls. In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls. In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity.We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007. In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively.Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.

GATA4-mediated cardiac hypertrophy induced by D-myo-inositol 1,4,5-tris-phosphate

International Nuclear Information System (INIS)

Zhu Zhiming; Zhu Shanjun; Liu Daoyan; Yu Zengping; Yang Yongjian; Giet, Markus van der; Tepel, Martin

2005-01-01

We evaluated the effects of D-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. D-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, β-myosin heavy chain, and α-actin. The administration of D-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that D-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of D-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that D-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia.

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Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; Larochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean; Delabesse, Eric

2013-01-31

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. Mutations of key transcription factor in myeloid malignancies.

A novel GATA3 nonsense mutation in a newly diagnosed adult patient of hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome.

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Nanba, Kazutaka; Usui, Takeshi; Nakamura, Michikazu; Toyota, Yuko; Hirota, Keisho; Tamanaha, Tamiko; Kawashima, Sachiko-Tsukamoto; Nakao, Kanako; Yuno, Akiko; Tagami, Tetsuya; Naruse, Mitsuhide; Shimatsu, Akira

2013-01-01

Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by a GATA3 gene mutation. Here we report a novel mutation of GATA3 in a patient diagnosed with HDR syndrome at the age of 58 with extensive intracranial calcification. A 58-year-old Japanese man showed severe hypocalcemia and marked calcification in the basal ganglia, cerebellum, deep white matter, and gray-white junction on computed tomography (CT). The serum intact parathyroid hormone level was relatively low against low serum calcium concentration. The patient had been diagnosed with bilateral sensorineural deafness in childhood and had a family history of hearing disorders. Imaging studies revealed no renal anomalies. The patient was diagnosed with HDR syndrome, and genetic testing was performed. Genetic analysis of GATA3 showed a novel nonsense mutation at codon 198 (S198X) in exon 3. The S198X mutation leads to a loss of two zinc finger deoxyribonucleic acid (DNA) binding domains and is considered to be responsible for HDR syndrome. We identified a novel nonsense mutation of GATA3 in an adult patient with HDR syndrome who showed extensive intracranial calcification.

Anagrelide represses GATA-1 and FOG-1 expression without interfering with thrombopoietin receptor signal transduction.

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Ahluwalia, M; Donovan, H; Singh, N; Butcher, L; Erusalimsky, J D

2010-10-01

 Anagrelide is a selective inhibitor of megakaryocytopoiesis used to treat thrombocytosis in patients with chronic myeloproliferative disorders. The effectiveness of anagrelide in lowering platelet counts is firmly established, but its primary mechanism of action remains elusive.  Here, we have evaluated whether anagrelide interferes with the major signal transduction cascades stimulated by thrombopoietin in the hematopoietic cell line UT-7/mpl and in cultured CD34(+) -derived human hematopoietic cells. In addition, we have used quantitative mRNA expression analysis to assess whether the drug affects the levels of known transcription factors that control megakaryocytopoiesis.  In UT-7/mpl cells, anagrelide (1μm) did not interfere with MPL-mediated signaling as monitored by its lack of effect on JAK2 phosphorylation. Similarly, the drug did not affect the phosphorylation of STAT3, ERK1/2 or AKT in either UT-7/mpl cells or primary hematopoietic cells. In contrast, during thrombopoietin-induced megakaryocytic differentiation of normal hematopoietic cultures, anagrelide (0.3μm) reduced the rise in the mRNA levels of the transcription factors GATA-1 and FOG-1 as well as those of the downstream genes encoding FLI-1, NF-E2, glycoprotein IIb and MPL. However, the drug showed no effect on GATA-2 or RUNX-1 mRNA expression. Furthermore, anagrelide did not diminish the rise in GATA-1 and FOG-1 expression during erythropoietin-stimulated erythroid differentiation. Cilostamide, an exclusive and equipotent phosphodiesterase III (PDEIII) inhibitor, did not alter the expression of these genes.  Anagrelide suppresses megakaryocytopoiesis by reducing the expression levels of GATA-1 and FOG-1 via a PDEIII-independent mechanism that is differentiation context-specific and does not involve inhibition of MPL-mediated early signal transduction events. © 2010 International Society on Thrombosis and Haemostasis.

HER2 and GATA4 are new prognostic factors for early-stage ovarian granulosa cell tumor—a long-term follow-up study

International Nuclear Information System (INIS)

Färkkilä, Anniina; Andersson, Noora; Bützow, Ralf; Leminen, Arto; Heikinheimo, Markku; Anttonen, Mikko; Unkila-Kallio, Leila

2014-01-01

Granulosa cell tumors (GCTs) carry a risk of recurrence also at an early stage, but reliable prognostic factors are lacking. We assessed clinicopathological prognostic factors and the prognostic roles of the human epidermal growth factor receptors (HER 2–4) and the transcription factor GATA4 in GCTs. We conducted a long-term follow-up study of 80 GCT patients with a mean follow-up time of 16.8 years. A tumor-tissue microarray was immunohistochemically stained for HER2–4 and GATA4. Expression of HER2–4 mRNA was studied by means of real time polymerase chain reaction and HER2 gene amplification was analyzed by means of silver in situ hybridization. The results were correlated to clinical data on recurrences and survival. We found that GCTs have an indolent prognosis, with 5-year disease-specific survival (DSS) being 97.5%. Tumor recurrence was detected in 24% of the patients at a median of 7.0 years (range 2.6–18 years) after diagnosis. Tumor stage was not prognostic of disease-free survival (DFS). Of the molecular prognostic factors, high-level expression of HER2, and GATA4, and high nuclear atypia were prognostic of shorter DFS. In multivariate analyses, high-level coexpression of HER2 and GATA4 independently predicted DFS (hazard ratio [HR] 8.75, 95% CI 2.20–39.48, P = 0.002). High-level expression of GATA4 also predicted shorter DSS (HR 3.96, 95% CI 1.45–12.57, P = 0.006). In multivariate analyses, however, tumor stage (II–III) and nuclear atypia were independent prognostic factors of DSS. In conclusion HER2 and GATA4 are new molecular prognostic markers of GCT recurrence, which could be utilized to optimize the management and follow-up of patients with early-stage GCTs

Art27 interacts with GATA4, FOG2 and NKX2.5 and is a novel co-repressor of cardiac genes.

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Daniel R Carter

Full Text Available Transcription factors play a crucial role in regulation of cardiac biology. FOG-2 is indispensable in this setting, predominantly functioning through a physical interaction with GATA-4. This study aimed to identify novel co-regulators of FOG-2 to further elaborate on its inhibitory activity on GATA-4. The Art27 transcription factor was identified by a yeast-2-hybrid library screen to be a novel FOG-2 protein partner. Characterisation revealed that Art27 is co-expressed with FOG-2 and GATA-4 throughout cardiac myocyte differentiation and in multiple structures of the adult heart. Art27 physically interacts with GATA-4, FOG-2 and other cardiac transcription factors and by this means, down-regulates their activity on cardiac specific promoters α-myosin heavy chain, atrial natriuretic peptide and B-type natriuretic peptide. Regulation of endogenous cardiac genes by Art27 was shown using microarray analysis of P19CL6-Mlc2v-GFP cardiomyocytes. Together these results suggest that Art27 is a novel transcription factor that is involved in downregulation of cardiac specific genes by physically interacting and inhibiting the activity of crucial transcriptions factors involved in cardiac biology.

Nicotine promotes initiation and progression of KRAS-induced pancreatic cancer via Gata6-dependent dedifferentiation of acinar cells in mice.

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Hermann, Patrick C; Sancho, Patricia; Cañamero, Marta; Martinelli, Paola; Madriles, Francesc; Michl, Patrick; Gress, Thomas; de Pascual, Ricardo; Gandia, Luis; Guerra, Carmen; Barbacid, Mariano; Wagner, Martin; Vieira, Catarina R; Aicher, Alexandra; Real, Francisco X; Sainz, Bruno; Heeschen, Christopher

2014-11-01

Although smoking is a leading risk factor for pancreatic ductal adenocarcinoma (PDAC), little is known about the mechanisms by which smoking promotes initiation or progression of PDAC. We studied the effects of nicotine administration on pancreatic cancer development in Kras(+/LSLG12Vgeo);Elas-tTA/tetO-Cre (Ela-KRAS) mice, Kras(+/LSLG12D);Trp53+/LSLR172H;Pdx-1-Cre (KPC) mice (which express constitutively active forms of KRAS), and C57/B6 mice. Mice were given nicotine for up to 86 weeks to produce blood levels comparable with those of intermediate smokers. Pancreatic tissues were collected and analyzed by immunohistochemistry and reverse transcriptase polymerase chain reaction; cells were isolated and assayed for colony and sphere formation and gene expression. The effects of nicotine were also evaluated in primary pancreatic acinar cells isolated from wild-type, nAChR7a(-/-), Trp53(-/-), and Gata6(-/-);Trp53(-/-) mice. We also analyzed primary PDAC cells that overexpressed GATA6 from lentiviral expression vectors. Administration of nicotine accelerated transformation of pancreatic cells and tumor formation in Ela-KRAS and KPC mice. Nicotine induced dedifferentiation of acinar cells by activating AKT-ERK-MYC signaling; this led to inhibition of Gata6 promoter activity, loss of GATA6 protein, and subsequent loss of acinar differentiation and hyperactivation of oncogenic KRAS. Nicotine also promoted aggressiveness of established tumors as well as the epithelial-mesenchymal transition, increasing numbers of circulating cancer cells and their dissemination to the liver, compared with mice not exposed to nicotine. Nicotine induced pancreatic cells to acquire gene expression patterns and functional characteristics of cancer stem cells. These effects were markedly attenuated in K-Ras(+/LSL-G12D);Trp53(+/LSLR172H);Pdx-1-Cre mice given metformin. Metformin prevented nicotine-induced pancreatic carcinogenesis and tumor growth by up-regulating GATA6 and promoting

Wnt3 and Gata4 regulate axon regeneration in adult mouse DRG neurons.

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Duan, Run-Shan; Liu, Pei-Pei; Xi, Feng; Wang, Wei-Hua; Tang, Gang-Bin; Wang, Rui-Ying; Saijilafu; Liu, Chang-Mei

2018-05-05

Neurons in the adult central nervous system (CNS) have a poor intrinsic axon growth potential after injury, but the underlying mechanisms are largely unknown. Wingless-related mouse mammary tumor virus integration site (WNT) family members regulate neural stem cell proliferation, axon tract and forebrain development in the nervous system. Here we report that Wnt3 is an important modulator of axon regeneration. Downregulation or overexpression of Wnt3 in adult dorsal root ganglion (DRG) neurons enhances or inhibits their axon regeneration ability respectively in vitro and in vivo. Especially, we show that Wnt3 modulates axon regeneration by repressing mRNA translation of the important transcription factor Gata4 via binding to the three prime untranslated region (3'UTR). Downregulation of Gata4 could restore the phenotype exhibited by Wnt3 downregulation in DRG neurons. Taken together, these data indicate that Wnt3 is a key intrinsic regulator of axon growth ability of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

[Effect of Acupuncture on the Expression of Transcription Factor T-bet/GATA-3 in Plasma of Rats with Chronic Fatigue Syndrome].

Science.gov (United States)

Wang, Xiang-Yi; Liu, Chang-Zheng; Lei, Bo

2017-06-25

To observe the effect of acupuncture on the expression of T-box expressed in T cell (T-bet)/GATA binding factor-3 (GATA-3) in plasma of rats with chronic fatigue syndrome (CFS) and explore the mechanism of acupuncture treatment for CFS. Forty-eight healthy male SD rats were randomly divided into blank control group, CFS model group, acupuncture group, and ginsenoside group (12 rats in each group). CFS rat model was established by combining restriction and cold water swimming. Acupuncture was applied to "Baihui"(GV 20), "Guanyuan" (CV 4) and "Zusanli" (ST 36, bilate-ral) acupoints, once a day for two weeks. The ginsenoside group was gavage administrated with ginsenoside, once a day for two weeks. After 14 days, behavioural changes were observed, and the expression levels of T-bet/GATA-3 genes in plasma were detected by RT-PCR. Compared with the blank control group, the time for immobility of forced suspensory test was signi-ficantly longer ( P <0.05) and the time for exhaustive swimming was significantly shortened ( P <0.05) in the CFS model group. Compared with the model group, the two indexes above-mentioned were reversed ( P <0.05) both in the acupuncture group and the ginsenoside group, and the effects in the acupuncture group were more significant than those in the ginsenoside group ( P <0.05). Compared with the blank control group, the expression level of T-cell transcription factor T-bet gene in plasma was higher in the CFS model group ( P <0.05), companied with lower GATA-3 gene expression ( P <0.05). The ratio of T-bet/GATA-3 was higher in the model group than in the blank control group( P <0.05). Compared with the CFS model group, all the indexes above-mentioned were reversed ( P <0.05) in the two treatment groups. Acupuncture group showed a better effect on reducing T-bet gene expression than the ginsenoside group ( P <0.05). Acupuncture can decrease the expression level of T-bet gene while increase the expression of GATA-3 gene, which may be associated

The GATA transcription factor egl-27 delays aging by promoting stress resistance in Caenorhabditis elegans.

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Xiao Xu

Full Text Available Stress is a fundamental aspect of aging, as accumulated damage from a lifetime of stress can limit lifespan and protective responses to stress can extend lifespan. In this study, we identify a conserved Caenorhabditis elegans GATA transcription factor, egl-27, that is involved in several stress responses and aging. We found that overexpression of egl-27 extends the lifespan of wild-type animals. Furthermore, egl-27 is required for the pro-longevity effects from impaired insulin/IGF-1 like signaling (IIS, as reduced egl-27 activity fully suppresses the longevity of worms that are mutant for the IIS receptor, daf-2. egl-27 expression is inhibited by daf-2 and activated by pro-longevity factors daf-16/FOXO and elt-3/GATA, suggesting that egl-27 acts at the intersection of IIS and GATA pathways to extend lifespan. Consistent with its role in IIS signaling, we found that egl-27 is involved in stress response pathways. egl-27 expression is induced in the presence of multiple stresses, its targets are significantly enriched for many types of stress genes, and altering levels of egl-27 itself affects survival to heat and oxidative stress. Finally, we found that egl-27 expression increases between young and old animals, suggesting that increased levels of egl-27 in aged animals may act to promote stress resistance. These results identify egl-27 as a novel factor that links stress and aging pathways.

Endoglin expression in blood and endothelium is differentially regulated by modular assembly of the Ets/Gata hemangioblast code.

Science.gov (United States)

Pimanda, John E; Chan, Wan Y I; Wilson, Nicola K; Smith, Aileen M; Kinston, Sarah; Knezevic, Kathy; Janes, Mary E; Landry, Josette-Renée; Kolb-Kokocinski, Anja; Frampton, Jonathan; Tannahill, David; Ottersbach, Katrin; Follows, George A; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold

2008-12-01

Endoglin is an accessory receptor for TGF-beta signaling and is required for normal hemangioblast, early hematopoietic, and vascular development. We have previously shown that an upstream enhancer, Eng -8, together with the promoter region, mediates robust endothelial expression yet is inactive in blood. To identify hematopoietic regulatory elements, we used array-based methods to determine chromatin accessibility across the entire locus. Subsequent transgenic analysis of candidate elements showed that an endothelial enhancer at Eng +9 when combined with an element at Eng +7 functions as a strong hemato-endothelial enhancer. Chromatin immunoprecipitation (ChIP)-chip analysis demonstrated specific binding of Ets factors to the promoter as well as to the -8, +7+9 enhancers in both blood and endothelial cells. By contrast Pu.1, an Ets factor specific to the blood lineage, and Gata2 binding was only detected in blood. Gata2 was bound only at +7 and GATA motifs were required for hematopoietic activity. This modular assembly of regulators gives blood and endothelial cells the regulatory freedom to independently fine-tune gene expression and emphasizes the role of regulatory divergence in driving functional divergence.

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

OpenAIRE

Mir, Muhammad A; Kochuparambil, Samith T; Abraham, Roshini S; Rodriguez, Vilmarie; Howard, Matthew; Hsu, Amy P; Jackson, Amie E; Holland, Steven M; Patnaik, Mrinal M

2015-01-01

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 c...

Tumor de células da granulosa com metástases numa gata

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Márcia Regina Giacóia

1999-01-01

Full Text Available As características clínicas, macroscópicas e microscópicas de um tumor de células da granulosa no ovário de uma gata de 2 anos de idade são descritas neste trabalho. Essa neoplasia é rara em gatos, principalmente devido à idade apresentada pelo animal. O diagnóstico foi feito clinicamente através de exame ultra-sonográfico. O tumor, uma massa cística na região do ovário esquerdo, metastatizou para o epíploo e para os pulmões. As células tumorais expressaram vimentina e arranjavam-se num padrão sarcomatoso e difuso, sustentado por fino estroma fibrovascular. A presença de sinais clínicos, como perda de pêlos e repetição de estros, é indicativa de síndrome paraneoplásica ortoendócrina, devido à excessiva estimulação estrogênica. A existência desse tipo de tumor deve ser considerada no diagnóstico diferencial de distúrbios comportamentais em gatas.

The solution structure of the N-terminal zinc finger of GATA-1 reveals a specific binding face for the transcriptional co-factor FOG

International Nuclear Information System (INIS)

Kowalski, K.; Czolij, R.; King, G.F.; Crossley, M.; Mackay, J.P.

1999-01-01

Zinc fingers (ZnFs) are generally regarded as DNA-binding motifs. However, a number of recent reports have implicated particular ZnFs in the mediation of protein-protein interactions. The N-terminal ZnF of GATA-1 (NF) is one such finger, having been shown to interact with a number of other proteins, including the recently discovered transcriptional co-factor FOG. Here we solve the three-dimensional structure of the NF in solution using multidimensional 1H/15N NMR spectroscopy, and we use 1H/15N spin relaxation measurements to investigate its backbone dynamics. The structure consists of two distorted β-hairpins and a single α-helix, and is similar to that of the C-terminal ZnF of chicken GATA-1. Comparisons of the NF structure with those of other C4-type zinc binding motifs, including hormone receptor and LIM domains, also reveal substantial structural homology. Finally, we use the structure to map the spatial locations of NF residues shown by mutagenesis to be essential for FOG binding, and demonstrate that these residues all lie on a single face of the NF. Notably, this face is well removed from the putative DNA- binding face of the NF, an observation which is suggestive of simultaneous roles for the NF; that is, stabilisation of GATA-1 DNA complexes and recruitment of FOG to GATA-1-controlled promoter regions

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

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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

Nitrogen-responsive Regulation of GATA Protein Family Activators Gln3 and Gat1 Occurs by Two Distinct Pathways, One Inhibited by Rapamycin and the Other by Methionine Sulfoximine*

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Georis, Isabelle; Tate, Jennifer J.; Cooper, Terrance G.; Dubois, Evelyne

2011-01-01

Nitrogen availability regulates the transcription of genes required to degrade non-preferentially utilized nitrogen sources by governing the localization and function of transcription activators, Gln3 and Gat1. TorC1 inhibitor, rapamycin (Rap), and glutamine synthetase inhibitor, methionine sulfoximine (Msx), elicit responses grossly similar to those of limiting nitrogen, implicating both glutamine synthesis and TorC1 in the regulation of Gln3 and Gat1. To better understand this regulation, we compared Msx- versus Rap-elicited Gln3 and Gat1 localization, their DNA binding, nitrogen catabolite repression-sensitive gene expression, and the TorC1 pathway phosphatase requirements for these responses. Using this information we queried whether Rap and Msx inhibit sequential steps in a single, linear cascade connecting glutamine availability to Gln3 and Gat1 control as currently accepted or alternatively inhibit steps in two distinct parallel pathways. We find that Rap most strongly elicits nuclear Gat1 localization and expression of genes whose transcription is most Gat1-dependent. Msx, on the other hand, elicits nuclear Gln3 but not Gat1 localization and expression of genes that are most Gln3-dependent. Importantly, Rap-elicited nuclear Gln3 localization is absolutely Sit4-dependent, but that elicited by Msx is not. PP2A, although not always required for nuclear GATA factor localization, is highly required for GATA factor binding to nitrogen-responsive promoters and subsequent transcription irrespective of the gene GATA factor specificities. Collectively, our data support the existence of two different nitrogen-responsive regulatory pathways, one inhibited by Msx and the other by rapamycin. PMID:22039046

Nitrogen-responsive regulation of GATA protein family activators Gln3 and Gat1 occurs by two distinct pathways, one inhibited by rapamycin and the other by methionine sulfoximine.

Science.gov (United States)

Georis, Isabelle; Tate, Jennifer J; Cooper, Terrance G; Dubois, Evelyne

2011-12-30

Nitrogen availability regulates the transcription of genes required to degrade non-preferentially utilized nitrogen sources by governing the localization and function of transcription activators, Gln3 and Gat1. TorC1 inhibitor, rapamycin (Rap), and glutamine synthetase inhibitor, methionine sulfoximine (Msx), elicit responses grossly similar to those of limiting nitrogen, implicating both glutamine synthesis and TorC1 in the regulation of Gln3 and Gat1. To better understand this regulation, we compared Msx- versus Rap-elicited Gln3 and Gat1 localization, their DNA binding, nitrogen catabolite repression-sensitive gene expression, and the TorC1 pathway phosphatase requirements for these responses. Using this information we queried whether Rap and Msx inhibit sequential steps in a single, linear cascade connecting glutamine availability to Gln3 and Gat1 control as currently accepted or alternatively inhibit steps in two distinct parallel pathways. We find that Rap most strongly elicits nuclear Gat1 localization and expression of genes whose transcription is most Gat1-dependent. Msx, on the other hand, elicits nuclear Gln3 but not Gat1 localization and expression of genes that are most Gln3-dependent. Importantly, Rap-elicited nuclear Gln3 localization is absolutely Sit4-dependent, but that elicited by Msx is not. PP2A, although not always required for nuclear GATA factor localization, is highly required for GATA factor binding to nitrogen-responsive promoters and subsequent transcription irrespective of the gene GATA factor specificities. Collectively, our data support the existence of two different nitrogen-responsive regulatory pathways, one inhibited by Msx and the other by rapamycin.

DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.

Science.gov (United States)

Mueller, Michael M; Castells-Roca, Laia; Babu, Vipin; Ermolaeva, Maria A; Müller, Roman-Ulrich; Frommolt, Peter; Williams, Ashley B; Greiss, Sebastian; Schneider, Jennifer I; Benzing, Thomas; Schermer, Bernhard; Schumacher, Björn

2014-12-01

Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.

Caracterização química e física de batatas ágata e monalisa minimamente processadas Chemical and physical characterization of fresh-cut potatoes

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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

GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes

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Idoia Martinez de LaPiscina

2018-04-01

Full Text Available Disorders of sex development (DSD consist of a wide range of conditions involving numerous genes. Nevertheless, about half of 46,XY individuals remain genetically unsolved. GATA4 gene variants, mainly related to congenital heart defects (CHD, have also been recently associated with 46,XY DSD. In this study, we characterized three individuals presenting with 46,XY DSD with or without CHD and GATA4 variants in order to understand the phenotypical variability. We studied one patient presenting CHD and 46,XY gonadal dysgenesis, and two patients with a history of genetically unsolved 46,XY DSD, also known as male primary hypogonadism. Mutation analysis was carried out by candidate gene approach or targeted gene panel sequencing. Functional activity of GATA4 variants was tested in vitro on the CYP17 promoter involved in sex development using JEG3 cells. We found two novel and one previously described GATA4 variants located in the N-terminal zinc finger domain of the protein. Cys238Arg variant lost transcriptional activity on the CYP17 promoter reporter, while Trp228Cys and Pro226Leu behaved similar to wild type. These results were in line with bioinformatics simulation studies. Additional DSD variations, in the LRP4 and LHCGR genes, respectively, were identified in the two 46,XY individuals without CHD. Overall, our study shows that human GATA4 mutations identified in patients with 46,XY DSD may or may not be associated with CHD. Possible explanations for phenotypical variability may comprise incomplete penetrance, variable sensitivity of partner genes, and oligogenic mechanisms.

Reciprocal patterns of allergen-induced GATA-3 expression in peripheral blood mononuclear cells from atopics vs. non-atopics.

Science.gov (United States)

Macaubas, C; Lee, P T; Smallacombe, T B; Holt, B J; Wee, C; Sly, P D; Holt, P G

2002-01-01

T helper (Th)2 cytokines are considered to play a central role in the induction and expression of allergic disease. However, the relative importance of individual cytokines is unclear, and overall disease pathogenesis appears to involve the coordinate activities of a range of Th2 cytokines acting in sequence or in parallel. The present study examines an alternative approach to the study of cytokine gene function in atopy, focusing instead upon T cell transcription factors (TFs) which play a role in the regulation of multiple cytokine genes. To investigate the allergen-induced expression of the TF GATA-3 and c-Maf in peripheral blood mononuclear cells (PBMCs) and in cytokine-driven Th polarization. PBMC from house dust mite (HDM)-atopic and non-atopics were stimulated in vitro with allergen or anti-CD3/IL-2. TF expression was analysed by semiquantitative RT-PCR and major findings were validated by real-time PCR. Cell separations were performed to analyse the contribution of CD45RO+ cells. CD4+ cord blood cells were Th1 or Th2 polarized in vitro by exogenous cytokines and TF expression analysed by Northern blot and real-time PCR. Results We demonstrate for the first time that during differentiation of CD4+ CD45RA+ naïve human T cells towards Th2 commitment, and during allergen-specific reactivation of peripheral CD4+ CD45RO+ Th2 memory cells in established atopics, expression of the Th2-associated TF GATA-3 is rapidly up-regulated, whereas T cells from non-atopics display equally rapid GATA-3 down-regulation under identical conditions of allergen stimulation. These findings identify Th2-associated TFs as key determinants of the atopic phenotype, suggesting their unique potential as therapeutic targets for disease control.

In Vivo Interplay between p27Kip1, GATA3, ATOH1, and POU4F3 Converts Non-sensory Cells to Hair Cells in Adult Mice

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Bradley J. Walters

2017-04-01

Full Text Available Summary: Hearing loss is widespread and persistent because mature mammalian auditory hair cells (HCs are nonregenerative. In mice, the ability to regenerate HCs from surrounding supporting cells (SCs declines abruptly after postnatal maturation. We find that combining p27Kip1 deletion with ectopic ATOH1 expression surmounts this age-related decline, leading to conversion of SCs to HCs in mature mouse cochleae and after noise damage. p27Kip1 deletion, independent of canonical effects on Rb-family proteins, upregulated GATA3, a co-factor for ATOH1 that is lost from SCs with age. Co-activation of GATA3 or POU4F3 and ATOH1 promoted conversion of SCs to HCs in adult mice. Activation of POU4F3 alone also converted mature SCs to HCs in vivo. These data illuminate a genetic pathway that initiates auditory HC regeneration and suggest p27Kip1, GATA3, and POU4F3 as additional therapeutic targets for ATOH1-mediated HC regeneration. : Auditory hair cells are nonregenerative, resulting in persistent hearing loss upon damage. Walters et al. find that manipulating two genes, p27Kip1 and Atoh1, induces the conversion of nonsensory cells to hair cells in adult mice. This effect is mediated by GATA3 and POU4F3, where POU4F3 alone was found to convert nonsensory cells. Keywords: regeneration, aging, differentiation, proliferation, development, cancer, sensory, cochlea, hearing

Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in prenatally androgenized rats.

Science.gov (United States)

Jahromi, Marziyeh Salehi; Tehrani, Fahimeh Ramezani; Noroozzadeh, Mahsa; Zarkesh, Maryam; Ghasemi, Asghar; Zadeh-Vakili, Azita

2016-11-15

It is believed that excess androgen exposure of the fetus, via altered gene expression, causes hyperandrogenism a key feature of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate expression of Cytochrome P450-17 (CYP17), GATA-binding protein (GAGT6) and Steroidogenic acute regulatory protein (StAR), genes of adult female rats prenatally exposed to androgen excess, closely reflect endocrine and ovarian disturbances of PCOS in women, by comparing them during different phases of estrus cycle with those of non-treated rats. Both the adult prenatally testosterone exposed and control rats (n=23, each) were divided into four groups based on their observed vaginal smear (proestrus, estrus, metestrus and diestrus) and the relative expression of CYP17, GATA6 and StAR genes was measured in ovarian theca cells using Cyber-green Real-Time PCR. Serum sex steroid hormones and gonadotropins levels were measured using the ELISA method; a comparison of these two groups showed that there was an overall increase in the studied genes (CYP17; 2.39 fold change, 95% CI: 1.23-3.55; PPCOS. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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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.

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)

Si, Lina; Shi, Jin; Gao, Wenqun; Zheng, Min; Liu, Lingjuan; Zhu, Jing; Tian, Jie

2014-01-01

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

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

Importância do binômio design e engenharia no beneficiamento de rejeito mineral de opala e ágata na produção de camafeus por usinagem CNC

OpenAIRE

Camila Sieburger Tessmann

2009-01-01

No estado do Rio Grande do Sul, os garimpos de pedras preciosas estão distribuídos em duas regiões principais: no Distrito Mineiro de Ametista do Sul (maior produtor de ametista) e no Distrito Mineiro de Salto do Jacuí (maior produtor de ágata). Nestes dois distritos mineiros são explorados geodos, parcial ou totalmente preenchidos por camadas intercaladas de ágata, quartzo incolor, ametista, calcita e opala. O processo de extração desses geodos gera grande quantidade de rejeito, composto tan...

Symbolic Representation and Protection of the Marine Landscape in the Natural Park of Cabo de Gata-Níjar (Almería- Spain

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Carmen Gaona Pisonero

2017-09-01

Full Text Available This case study article centered on the Natural Park of Cabo de Gata-Níjar (Almería-España on the correspondence or mismatch between the virtual landscape representations and the socio-cultural reality of the protected natural space. Therefore, the purpose of this article is to analyze the reconstruction of the natural market of Cabo de Gata Níjar in some sectors of the Spanish public sphere. The reflection focuses on the visibility of the virtual symbolic representative plains of space. The analysis of the results detects the virtual emic representations a reframing of the Park characterized by an on-line spectacular landscape. A dreamy exaltation in the emic representations virtual which practically invisibilizan real problems attacking against the coasts and reserve marine of this area. On the contrary, the media representation reflects with greater correspondence the dialectical reality of the landscape.

Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma.

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Jin Choi

Full Text Available Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF, the levels of total immunoglobulin (Ig E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues. ELISA analysis showed that picroside II down-regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13 and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNγ in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes and the transcription factor GATA3 in the lung tissues of HDM-induced mice. Finally, we demonstrated that picroside II significantly decreased the expression of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo results. Taken together, these results indicate that picroside II has protective effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias.

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

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

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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

Predictive mapping using GIS to locate epithermal gold deposits at Cabo de Gata (Prov. of Almeria, Spain); Cartografia predictiva mediante SIG de depositos epitermales de oro en Cabo de Gata, Almeria, Espana

Energy Technology Data Exchange (ETDEWEB)

Rogol-Sanchez, J. P.; Chica-Olmo, M.; Rodriguez-Galiano, V.; Pardo-Iguzquiza, E.

2011-07-01

The main aim of mineral potential mapping is to generate predictive maps showing the spatial distribution of a numerical index of favour ability for the presence of a mineral deposit of the type sought. We have studied the mineral favorability for epithermal gold deposits in the Cabo de Gata volcanic field in the Province of Almeria in Spain. Predictive maps deriving from the models suggest the presence of several potentially favourable zones. The performance of predictive maps is similar in most cases. Nevertheless, data-driven methods are able to capture more readily the spatial distribution of known gold occurrences in the area. (Author) 32 refs.

The +37 kb Cebpa Enhancer Is Critical for Cebpa Myeloid Gene Expression and Contains Functional Sites that Bind SCL, GATA2, C/EBPα, PU.1, and Additional Ets Factors

Science.gov (United States)

Cooper, Stacy; Guo, Hong; Friedman, Alan D.

2015-01-01

The murine Cebpa gene contains an evolutionarily conserved 453 bp enhancer located at +37 kb that, together with its promoter, directs expression to myeloid progenitors and to long-term hematopoietic stem cells in transgenic mice. In human acute myeloid leukemia cases, the enhancer lacks point mutations but binds the RUNX1-ETO oncoprotein. The enhancer contains the H3K4me1 and H3K27Ac histone modifications, denoting an active enhancer, at progressively increasing levels as long-term hematopoietic stem cells transition to granulocyte-monocyte progenitors. We previously identified four enhancer sites that bind RUNX1 and demonstrated that their integrity is required for maximal enhancer activity in 32Dcl3 myeloid cells. The +37 kb Cebpa enhancer also contains C/EBP, Ets factor, Myb, GATA, and E-box consensus sites conserved in the human +42 kb CEBPA enhancer. Mutation of the two C/EBP, seven Ets, one Myb, two GATA, or two E-box sites reduces activity of an enhancer-promoter reporter in 32Dcl3 cells. In 293T gel shift assays, exogenous C/EBPα binds both C/EBP sites, c-Myb binds the Myb site, PU.1 binds the second Ets site, PU.1, Fli-1, ERG, and Ets1 bind the sixth Ets site, GATA2 binds both GATA sites, and SCL binds the second E-box. Endogenous hematopoietic RUNX1, PU.1, Fli-1, ERG, C/EBPα, GATA2, and SCL were previously shown to bind the enhancer, and we find that endogenous PU.1 binds the second Ets site in 32Dcl3 cells. Using CRISPR/Cas9, we developed 32Dcl3 lines in which the wild-type enhancer alleles are replaced with a variant mutant in the seven Ets sites. These lines have 20-fold reduced Cebpa mRNA when cultured in IL-3 or G-CSF, demonstrating a critical requirement for enhancer integrity for optimal Cebpa expression. In addition, these results indicate that the +37 kb Cebpa enhancer is the focus of multiple regulatory transcriptional pathways that impact its expression during normal hematopoiesis and potentially during myeloid transformation. PMID:25938608

Epigenetic subgroups of esophageal and gastric adenocarcinoma with differential GATA5 DNA methylation associated with clinical and lifestyle factors.

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Xinhui Wang

Full Text Available BACKGROUND: Adenocarcinomas located near the gastroesophageal junction have unclear etiology and are difficult to classify. We used DNA methylation analysis to identify subtype-specific markers and new subgroups of gastroesophageal adenocarcinomas, and studied their association with epidemiological risk factors and clinical outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We used logistic regression models and unsupervised hierarchical cluster analysis of 74 DNA methylation markers on 45 tumor samples (44 patients of esophageal and gastric adenocarcinomas obtained from a population-based case-control study to uncover epigenetic markers and cluster groups of gastroesophageal adenocarcinomas. No distinct epigenetic differences were evident between subtypes of gastric and esophageal cancers. However, we identified two gastroesophageal adenocarcinoma subclusters based on DNA methylation profiles. Group membership was best predicted by GATA5 DNA methylation status. We analyzed the associations between these two epigenetic groups and exposure using logistic regression, and the associations with survival time using Cox regression in a larger set of 317 tumor samples (278 patients. There were more males with esophageal and gastric cardia cancers in Cluster Group 1 characterized by higher GATA5 DNA methylation values (all p<0.05. This group also showed associations of borderline statistical significance with having ever smoked (p-value = 0.07, high body mass index (p-value = 0.06, and symptoms of gastroesophageal reflux (p-value = 0.07. Subjects in cluster Group 1 showed better survival than those in Group 2 after adjusting for tumor differentiation grade, but this was not found to be independent of tumor stage. CONCLUSIONS/SIGNIFICANCE: DNA methylation profiling can be used in population-based studies to identify epigenetic subclasses of gastroesophageal adenocarcinomas and class-specific DNA methylation markers that can be linked to

Sr isotope zoning in plagioclase from andesites at Cabo De Gata, Spai

DEFF Research Database (Denmark)

Waight, Tod Earle; Tørnqvist, Jakob

2018-01-01

Plagioclase crystals in andesites from the Cabo De Gata region show generally radiogenic Sr isotope compositions and consistent core to rim increases in 87Sr/86Sr that are indicative of open system processes in the lithosphere and crustal contamination during crystallization. High-grade metamorphic...... rocks of the Alpujárride and Nevado-Filábride complexes represent the most likely crustal contaminants. The plagioclases are characterized by subtly zoned and resorbed calcic cores (An73-86). These cores also have radiogenic 87Sr/86Sr (0.7127-0.7129), although less radiogenic than plagioclase rims......, groundmass plagioclase and whole rock compositions (up to 87Sr/86Sr = 0.7135). These cores are interpreted to represent early crystallization of plagioclase from hydrous melts emplaced into the lower crust. The parental melts to these andesites must therefore have already inherited their radiogenic Sr...

Identification of GATA2 and AP-1 activator elements within the enhancer VNTR occurring in intron 5 of the human SIRT3 gene

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Human SIRT3 gene contains an intronic VNTR enhancer. A T > C transition occurring in the second repeat of each VNTR allele implies the presence/absence of a putative GATA binding motif. A partially overlapping AP-1 site, not affected by the transition, was also identified. Aims of the present study ...

Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge's disease.

Science.gov (United States)

Azad, Priti; Zhao, Huiwen W; Cabrales, Pedro J; Ronen, Roy; Zhou, Dan; Poulsen, Orit; Appenzeller, Otto; Hsiao, Yu Hsin; Bafna, Vineet; Haddad, Gabriel G

2016-11-14

In this study, because excessive polycythemia is a predominant trait in some high-altitude dwellers (chronic mountain sickness [CMS] or Monge's disease) but not others living at the same altitude in the Andes, we took advantage of this human experiment of nature and used a combination of induced pluripotent stem cell technology, genomics, and molecular biology in this unique population to understand the molecular basis for hypoxia-induced excessive polycythemia. As compared with sea-level controls and non-CMS subjects who responded to hypoxia by increasing their RBCs modestly or not at all, respectively, CMS cells increased theirs remarkably (up to 60-fold). Although there was a switch from fetal to adult HgbA0 in all populations and a concomitant shift in oxygen binding, we found that CMS cells matured faster and had a higher efficiency and proliferative potential than non-CMS cells. We also established that SENP1 plays a critical role in the differential erythropoietic response of CMS and non-CMS subjects: we can convert the CMS phenotype into that of non-CMS and vice versa by altering SENP1 levels. We also demonstrated that GATA1 is an essential downstream target of SENP1 and that the differential expression and response of GATA1 and Bcl-xL are a key mechanism underlying CMS pathology. © 2016 Azad et al.

En tránsito a ningún lugar. Sobre Diario de una pasajera de Ágata Gligo

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Alberto Giordano

2014-06-01

This essay presents a reading of Ágata Gligo’s Diario de una pasajera heedful to the ways in which her writing responds to the experiences of unhappiness and frustration related to the autobiographical circumstances that are in their origin: the disease (cancer and the literary block. The present workdiscusses how the act of understanding the disease and its social consequences reduce the diary’s writing performative power great thanksand how the distrust of the language dynamics and the novelist idealization obstruct the diary’s possibility of becoming a literary and existential immanent search.

Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA-3.

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Arundhoti Das

Full Text Available Naïve CD4 T (NCD4T cells post-activation undergo programming for inducible production of cytokines leading to generation of memory cells with various functions. Based on cytokine based polarization of NCD4T cells in vitro, programming for either 'Th1' (interferon-gamma [IFNg] or 'Th2' (interleukin [IL]-4/5/13 cytokines is thought to occur via mutually exclusive expression and functioning of T-bet or GATA-3 transcription factors (TFs. However, we show that a high proportion of mouse and human memory-phenotype CD4 T (MCD4T cells generated in vivo which expressed either Th1 or Th2 cytokines commonly co-expressed T-bet and GATA-3. While T-bet levels did not differ between IFNg-expressing and IL-4/5/13-expressing MCD4T cells, GATA-3 levels were higher in the latter. These observations were also confirmed in MCD4T cells from FVB/NJ or aged C57BL/6 or IFNg-deficient mice. While MCD4T cells from these strains showed greater Th2 commitment than those from young C57BL/6 mice, pattern of co-expression of TF was similar. Effector T cells generated in vivo following immunization also showed TF co-expression in Th1 or Th2 cytokine producing cells. We speculated that the difference in TF expression pattern of MCD4T cells generated in vivo and those generated in cytokine polarized cultures in vitro could be due to relative absence of polarizing conditions during activation in vivo. We tested this by NCD4T cell activation in non-polarizing conditions in vitro. Anti-CD3 and anti-CD28-mediated priming of polyclonal NCD4T cells in vitro without polarizing milieu generated cells that expressed either IFNg or IL-4/5/13 but not both, yet both IFNg- and IL-4/5/13-expressing cells showed upregulation of both TFs. We also tested monoclonal T cell populations activated in non-polarizing conditions. TCR-transgenic NCD4T cells primed in vitro by cognate peptide in non-polarizing conditions which expressed either IFNg or IL-4/5/13 also showed a high proportion of cells co

Vasohibin 2 promotes epithelial-mesenchymal transition in human breast cancer via activation of transforming growth factor β 1 and hypoxia dependent repression of GATA-binding factor 3.

Science.gov (United States)

Tu, Min; Li, Zhanjun; Liu, Xian; Lv, Nan; Xi, Chunhua; Lu, Zipeng; Wei, Jishu; Song, Guoxin; Chen, Jianmin; Guo, Feng; Jiang, Kuirong; Wang, Shui; Gao, Wentao; Miao, Yi

2017-03-01

Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2, and expression of a dominant negative TGFβ type II receptor could block VASH2-mediated EMT. In clinical breast cancer tissues VASH2 positively correlated with TGFβ1 expression, but negatively correlated with E-cadherin (a marker of EMT) expression. Under hypoxic conditions in vitro or in vivo, we found that down-regulation of estrogen receptor 1 (ESR1) in VASH2 overexpressing ESR1 positive cells suppressed E-cadherin. Correlation coefficient analysis indicated that VASH2 and ESR1 expression were negatively correlated in clinical human breast cancer tissues. Further study revealed that a transcription factor of ESR1, GATA-binding factor 3 (GATA3), was down-regulated by VASH2 under hypoxia or in vivo. These findings suggest that VASH2 drives breast cancer cells to undergo EMT by activation of the TGFβ1 pathway and hypoxia dependent repression GATA3-ESR1 pathway, leading to cancer metastasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Plasmacytoid Urothelial Carcinoma of the Urinary Bladder Metastatic to the Duodenum: A Case Report—Diagnostic Relevance of GATA3 Immunohistochemistry

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Hermann Brustmann

2017-01-01

Full Text Available Plasmacytoid urothelial carcinoma (PUC of the urinary bladder is a rare and aggressive subtype of urothelial carcinoma. Its deceptive morphology is characterized by a discohesive growth of cells with plasmacytoid morphology. Since this tumor might be confused with plasmacytoma, lymphoma, or carcinoma variants, appropriate diagnosis in small biopsy samples could be challenging. This study reports the case of a 53-year-old man who presented with frequent nocturnal urgency, without hematuria. A transurethral bladder and a prostate resection specimen displayed infiltration of neoplastic cells in a spray-like discohesive pattern with occasional formation of small irregular nests and cord-like arrangements. The basic morphology of the tumor cells was plasmacytoid, with eccentric nuclei and eosinophilic cytoplasm. Tumor cells grew through the lamina muscularis mucosae, with splintering of the bladder wall musculature and infiltration of prostatic tissue. They displayed strong and diffuse nuclear reactivity for p53 and GATA3. Eight months after surgery, the patient experienced upper abdominal discomfort. A duodenal biopsy showed infiltration of plasmacytoid atypical cells strongly immunoreactive for GATA3, consistent with the previously diagnosed PUC. The patient died eleven months after the primary diagnosis of his PUC of tumor cachexia losing about 50% of his original body weight, furthermore, with ascites and intraperitoneal tumor spread.

Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge’s disease

Science.gov (United States)

Azad, Priti; Zhao, Huiwen W.; Ronen, Roy; Zhou, Dan; Poulsen, Orit; Hsiao, Yu Hsin; Bafna, Vineet

2016-01-01

In this study, because excessive polycythemia is a predominant trait in some high-altitude dwellers (chronic mountain sickness [CMS] or Monge’s disease) but not others living at the same altitude in the Andes, we took advantage of this human experiment of nature and used a combination of induced pluripotent stem cell technology, genomics, and molecular biology in this unique population to understand the molecular basis for hypoxia-induced excessive polycythemia. As compared with sea-level controls and non-CMS subjects who responded to hypoxia by increasing their RBCs modestly or not at all, respectively, CMS cells increased theirs remarkably (up to 60-fold). Although there was a switch from fetal to adult HgbA0 in all populations and a concomitant shift in oxygen binding, we found that CMS cells matured faster and had a higher efficiency and proliferative potential than non-CMS cells. We also established that SENP1 plays a critical role in the differential erythropoietic response of CMS and non-CMS subjects: we can convert the CMS phenotype into that of non-CMS and vice versa by altering SENP1 levels. We also demonstrated that GATA1 is an essential downstream target of SENP1 and that the differential expression and response of GATA1 and Bcl-xL are a key mechanism underlying CMS pathology. PMID:27821551

Expression Analysis of Gata4, Tbx5 and Nkx2.5 Genes Involved in Congenital Heart Disease

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Mahta Mazaheri-Naeeini

2016-04-01

Full Text Available Background Congenital heart disease (CHD is the most widespread congenital disease in newborn babies and is one of the main causes of death worldwide. The causal agent of heart congenital diseases is unknown but genetic factors have an important role in prevalence of disease. Objectives The main objective of this research is comparison of the gene expression level of three Gata4, Tbx5 and Nkx2.5 genes in three groups of children between 6 months and 13 year old with congenital heart disease. Patients and Methods In this case-control study, 30 samples from each cyanotic and acyanotic patients and 30 samples from healthy children as control were used. RNA extraction was done using commercial kit and gene expression analysis was performed by qRT-PCR approach in three replication using Gata4, Tbx5 and Nkx2.5 genes. Data analysis was done by REST software. Results The results of RNA extraction and cDNA synthesis of all sample showed high quantity and quality of genetic materials. Expression level of tested genes was reduced in two patients group. In cyanotic group reduction was more than acyanotic samples. All tested gene were reduced in both group. Tbx5 gene was suppressed more than other genes. Conclusions Based on our results we could conclude that a gene family play an important role in cardiogenesis process and heart formation. These genes are closely related together. So a genetic consultation for such diseases on parents of these patients to determine the probable genetic mutations is recommended.

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

International Nuclear Information System (INIS)

Mir, Muhammad A; Kochuparambil, Samith T; Abraham, Roshini S; Rodriguez, Vilmarie; Howard, Matthew; Hsu, Amy P; Jackson, Amie E; Holland, Steven M; Patnaik, Mrinal M

2015-01-01

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

PEER REVIEW (Correlation between GATA-3, Ki67 and p53 expressions to Histopathology grading of Breast Cancer bin Makassar, Indonesia)

OpenAIRE

Islam, Andi Asadul

2016-01-01

- PEER REVIEW Judul karya Ilmiah (artikel): Correlation between GATA-3, Ki67 and p53 expressions to Histopathology grading of Breast Cancer bin Makassar, Indonesia : 9 Orang : Penulis Ketiga : a. Nama Jurnal : Cancer Research Journal b. Nomor ISSN : 2330-8192, E: 2330-8214 c. Volume,nomor, bulan, tahun : Volume 4, No. 3 Tahun 2016 d. Penerbit : Science PG e. DOI artikel (Jika ada) : 10.11648/j.crj .20160403.11 f. Alamat web Jurnal : www.sciencepublishingg...

A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS).

Science.gov (United States)

Na, Rong; Helfand, Brian T; Chen, Haitao; Conran, Carly A; Crawford, Susan E; Hayward, Simon W; Tammela, Teuvo L J; Hoffman-Bolton, Judy; Zheng, Siqun L; Walsh, Patrick C; Schleutker, Johanna; Platz, Elizabeth A; Isaacs, William B; Xu, Jianfeng

2017-08-01

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common conditions. Little is known about their etiologies except that studies have suggested a substantial heritable component. Our objective is to provide a comprehensive, genome-wide evaluation of inherited risks and possible mechanisms of etiology in BPH. We performed a three-stage, genome-wide association study (GWAS) of men from three independent populations, the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, the CLUE II cohort, and a Finnish hospital-based population. DNA samples were genotyped using the Illumina HumanOmniExpress BeadChip in REDUCE and CLUE II, and using the Sequenom iPLEX system for the confirmation stage in the Finnish population. A logistic regression model was used to evaluate the association between each SNP and BPH/LUTS. Fourteen SNPs reached P BPH pathogenesis and progression. Rs17144046 located near GATA3 was significantly associated with BPH/LUTS in three independent populations, but did not reach a stringent GWAS significance level. Genetic variants of GATA3 may play a role in the inherited susceptibility and etiology of BPH/LUTS. Further research in this area is needed. © 2017 Wiley Periodicals, Inc.

Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 undergo the stochastic cardiomyogenic fate and behave like transient amplifying cells

International Nuclear Information System (INIS)

Yamada, Yoji; Sakurada, Kazuhiro; Takeda, Yukiji; Gojo, Satoshi; Umezawa, Akihiro

2007-01-01

Bone marrow-derived stromal cells can give rise to cardiomyocytes as well as adipocytes, osteocytes, and chondrocytes in vitro. The existence of mesenchymal stem cells has been proposed, but it remains unclear if a single-cell-derived stem cell stochastically commits toward a cardiac lineage. By single-cell marking, we performed a follow-up study of individual cells during the differentiation of 9-15c mesenchymal stromal cells derived from bone marrow cells. Three types of cells, i.e., cardiac myoblasts, cardiac progenitors and multipotent stem cells were differentiated from a single cell, implying that cardiomyocytes are generated stochastically from a single-cell-derived stem cell. We also demonstrated that overexpression of Csx/Nkx2.5 and GATA4, precardiac mesodermal transcription factors, enhanced cardiomyogenic differentiation of 9-15c cells, and the frequency of cardiomyogenic differentiation was increased by co-culturing with fetal cardiomyocytes. Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4 behaved like cardiac transient amplifying cells, and still retained their plasticity in vivo

Braçadeira de poliamida e fio de náilon na ovário-histerectomia em gatas

OpenAIRE

PRADO, Tales Dias do

2012-01-01

A ovário-histerectomia representa um dos procedimentos mais realizados pela clínica de pequenos animais, tendo por finalidade o controle da natalidade, prevenção de cio e pseudogestação, como também, tratar afecções do trato reprodutor feminino. Foram descritas muitas variações de técnicas de ovário-histerectomia, incluindo, além da tradicional abordagem pela linha média, abordagem pelo flanco e diversas abordagens laparoscópicas. Participaram, no presente estudo, 24 gatas hígidas, sem raça d...

Constraining controls on carbonate sequences with high-resolution chronostratigraphy: Upper Miocene, Cabo de Gata region, SE Spain

Science.gov (United States)

Montgomery, P.; Farr, M.R.; Franseen, E.K.; Goldstein, R.H.

2001-01-01

A high-resolution chronostratigraphy has been developed for Miocene shallow-water carbonate strata in the Cabo de Gata region of SE Spain for evaluation of local, regional and global factors that controlled platform architecture prior to and during the Messinian salinity crisis. Paleomagnetic data were collected from strata at three localities. Mean natural remanent magnetization (NRM) ranges between 1.53 ?? 10-8 and 5.2 ?? 10-3 Am2/kg. Incremental thermal and alternating field demagnetization isolated the characteristic remanent magnetization (ChRM). Rock magnetic studies show that the dominant magnetic mineral is magnetite, but mixtures of magnetite and hematite occur. A composite chronostratigraphy was derived from five stratigraphic sections. Regional stratigraphic data, biostratigraphic data, and an 40Ar/39Ar date of 8.5 ?? 0.1 Ma, for an interbedded volcanic flow, place the strata in geomagnetic polarity Chrons C4r to C3r. Sequence-stratigraphic and diagenetic evidence indicate a major unconformity at the base of depositional sequence (DS)3 that contains a prograding reef complex, suggesting that approximately 250 000 yr of record (Subchrons C3Br.2r to 3Br.1r) are missing near the Messinian-Tortonian boundary. Correlation to the GPTS shows that the studied strata represent five third- to fourth-order DSs. Basal units are temperate to subtropical ramps (DS1A, DS1B, DS2); these are overlain by subtropical to tropical reefal platforms (DS3), which are capped by subtropical to tropical cyclic carbonates (Terminal Carbonate Complex, TCC). Correlation of the Cabo de Gata record to the Melilla area of Morocco, and the Sorbas basin of Spain indicate that early - Late Tortonian ramp strata from these areas are partially time-equivalent. Similar strata are extensively developed in the Western Mediterranean and likely were influenced by a cool climate or influx of nutrients during an overall rise in global sea-level. After ramp deposition, a sequence boundary (SB3) in

PTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3β/GATA-6 signaling pathways in TNF-α-activated human endothelial cells.

Science.gov (United States)

Tsoyi, Konstantin; Jang, Hwa Jin; Nizamutdinova, Irina Tsoy; Park, Kyungok; Kim, Young Min; Kim, Hye Jung; Seo, Han Geuk; Lee, Jae Heun; Chang, Ki Churl

2010-11-01

Phosphotase and tensin homolog deleted on chromosome 10 (PTEN) is a potent negative regulator of PI3K/Akt pathway. Here, we tried to elucidate the role of PTEN in the regulation of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1, induced by TNF-α in human endothelial cells (ECs). Transfection with PTEN overexpressing vector resulted in the significant decrease in phosphorylation of Akt in TNF-α-treated ECs. PTEN strongly inhibited VCAM-1 but not ICAM-1, however this inhibitory effect was reversed by co-transfection with constitutively active-Akt (CA-Akt-HA) in TNF-α-stimulated ECs. Additionally, silencing of PTEN with specific siRNA showed significant increase of phosphor-Akt compared with TNF-α alone treated ECs. siPTEN significantly upregulated VCAM-1 but was indifferent to ICAM-1 in TNF-α-treated cells. Further, chromatin immunoprecipitation (ChIP) assay showed that PTEN targets GATA-6 but not IRF-1 binding to VCAM-1 promoter. In addition, GATA-6 is associated with glycogen synthesis kinase-3beta (GSK-3β) which is in turn regulated by PTEN-dependent Akt activity. Finally, PTEN significantly prevented monocyte adhesion to TNF-α-induced ECs probably through VCAM-1 regulation. It is concluded that PTEN selectively inhibits expression of VCAM-1 but not ICAM-1 through modulation of PI3K/Akt/GSK-3β/GATA-6 signaling cascade in TNF-α-treated ECs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Sr isotope zoning in plagioclase from andesites at Cabo De Gata, Spain: Evidence for shallow and deep contamination

Science.gov (United States)

Waight, Tod E.; Tørnqvist, Jakob B.

2018-05-01

Plagioclase crystals in andesites from the Cabo De Gata region show generally radiogenic Sr isotope compositions and consistent core to rim increases in 87Sr/86Sr that are indicative of open system processes in the lithosphere and crustal contamination during crystallization. High-grade metamorphic rocks of the Alpujárride and Nevado-Filábride complexes represent the most likely crustal contaminants. The plagioclases are characterized by subtly zoned and resorbed calcic cores (An73-86). These cores also have radiogenic 87Sr/86Sr (0.7127-0.7129), although typically less radiogenic than plagioclase rims, groundmass plagioclase and whole rock compositions (up to 87Sr/86Sr = 0.7135). These cores are interpreted to represent early crystallization of plagioclase from hydrous melts emplaced into the lower crust. The parental melts to these andesites must therefore have already inherited their radiogenic Sr isotope compositions prior to entering the lower crust and before the onset of crystallization of plagioclase, which is inconsistent with previous models suggesting that the generally radiogenic nature of Sr in these volcanics reflects large amounts of crustal contamination. Instead, the isotope systematics are consistent with models invoked significant addition of a subducted sediment component to the mantle source. The high-An% plagioclase cores are characterized by resorption textures, which are consistent with dissolution during rapid decompression and/or devolatisation during magma migration from the lower crust into upper crustal magma chambers.

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

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

International Nuclear Information System (INIS)

Turowska, Agnieszka; Librizzi, Damiano; Baumgartl, Nadja; Kuhlmann, Jens; Dicke, Tanja; Merkel, Olivia; Homburg, Ursula; Höffken, Helmut; Renz, Harald; Garn, Holger

2013-01-01

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

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

Drosophila C-terminal binding protein, dCtBP is required for sensory organ prepattern and sharpens proneural transcriptional activity of the GATA factor Pnr.

Science.gov (United States)

Biryukova, Inna; Heitzler, Pascal

2008-11-01

The peripheral nervous system is required for animals to detect and to relay environmental stimuli to central nervous system for the information processing. In Drosophila, the precise spatial and temporal expression of two proneural genes achaete (ac) and scute (sc), is necessary for development of the sensory organs. Here we present an evidence that the transcription co-repressor, dCtBP acts as a negative regulator of sensory organ prepattern. Loss of dCtBP function mutant exhibits ectopic sensory organs, while overexpression of dCtBP results in a dramatic loss of sensory organs. These phenotypes are correlated with mis-emerging of sensory organ precursors and perturbated expression of proneural transcription activator Ac. Mammalian CtBP-1 was identified via interaction with the consensus motif PXDLSX(K/R) of adenovirus E1A oncoprotein. We demonstrated that dCtBP binds directly to PLDLS motif of Drosophila Friend of GATA-1 protein, U-shaped and sharpens the adult sensory organ development. Moreover, we found that dCtBP mediates multivalent interaction with the GATA transcriptional activator Pannier and acts as a direct co-repressor of the Pannier-mediated activation of proneural genes. We demonstrated that Pannier genetically interacts with dCtBP-interacting protein HDAC1, suggesting that the dCtBP-dependent regulation of Pannier activity could utilize a repressive mechanism involving alteration of local chromatine structure.

INDUÇÃO DE OVULAÇÃO COM SWAB VAGINAL EM GATAS DOMÉSTICAS E SEUS EFEITOS SOBRE A MORFOLOGIA UTERINA

OpenAIRE

Silva, Sandra Cristina Becker; Silva, Maíra Corona da; Silva, Fabiana Lessa; Snoeck, Paola Pereira das Neves

2017-01-01

Resumo A ovulação em gatas é induzida por um reflexo neuroendócrino atribuído à estimulação mecânica dos receptores sensoriais durante o coito. Esta estimulação pode ser simulada com auxílio do swab vaginal, desencadeando a pseudogestação. Objetivou-se verificar a eficiência da indução de ovulação com swab, a fim de estabelecer um tratamento contraceptivo natural para felinos domésticos, bem como os efeitos sobre o útero do uso repetido dessa técnica. Na primeira fase do trabalho, foram avali...

Gonadectomia em gatas impúberes: técnica anestésica

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Sandra Mastrocinque

2006-12-01

Full Text Available O objetivo deste estudo foi descrever e avaliar um protocolo anestésico em filhotes de gatas submetidas a gonadectomia. Foram estudadas 40 fêmeas, com 2 a 4 meses de idade, sem raça definida, encaminhadas para ovariohisterectomia. O protocolo anestésico empregado consistiu de pré-medicação com acepromazina e meperidina e a indução e manutenção anestésicas realizadas com tiletamina-zolazepam. Foram avaliadas freqüências cardíaca e respiratória, saturação periférica da oxihemoglobina, temperatura corpórea, qualidade do relaxamento de coto uterino e pedículos ovarianos, tempo cirúrgico e de recuperação anestésica, bem como qualidade da recuperação anestésica e outros efeitos adversos. Houve redução da freqüência respiratória e manutenção da cardíaca no período trans-operatório. Apenas dois animais necessitaram de suplementação com oxigênio e a qualidade da recuperação foi satisfatoriamente tranqüila. O relaxamento dos pedículos ovarianos e coto uterino foi adequado e não foram observados demais efeitos adversos. Diante dos resultados obtidos pode-se concluir que a técnica anestésica empregada foi segura e efetiva nos animais estudados.

Xenotransplante ovariano de gatas domésticas em camundongas C57BL/6 SCID e sua resposta á gonadotrofina coriõnica equina

OpenAIRE

Santos, Fernanda Araujo dos

2015-01-01

Xenotransplante ovariano é uma técnica reprodutiva auxiliar que permite a conservação do germoplasma de espécies de alto valor zootécnico ou em perigo de extinção. O uso de gonadotrofinas exógenas auxilia no desenvolvimento desses tecidos xenotransplantados e na obtenção de folículos viáveis para produção in vitro de embriões (PIVE), entretanto esse uso não foi relatado em xenotransplante de ovários de gatas com fêmeas C57BL/6 SCID como receptora. Dessa forma, o objetivo desse trabalho ...

Respostas cardiorrespiratória e metabólica do propofol nas formulações em emulsão lipídica ou microemulsão em gatas

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Renato Batista Tamanho

2013-08-01

Full Text Available O presente estudo objetiva avaliar os efeitos cardiorrespiratórios e metabólicos do propofol em emulsão lipídica e microemulsão em gatas. Foram utilizadas 12 gatas, hígidas, adultas, alocadas em dois grupos: microemulsão (MICRO, n=6 e emulsão lipídica (EMU, n=6, os quais receberam propofol, na respectiva formulação, em dose suficiente para intubação. Em seguida, foram intubados, fornecendo-se oxigênio 100%, em sistema sem reinalação de gases. Ato contínuo, iniciou-se a infusão de propofol na dose de 0,3mg kg-1 min-1 durante 90 minutos. A dose necessária para indução foi de 9,5±1,3mg kg-1 e 10±1mg kg-1 para MICRO e EMU, respectivamente. Os valores de pressão arterial sistólica (PAS, pressão arterial média (PAM, pressão arterial diastólica (PAD e pH foram menores, em todos os momentos, no EMU em relação ao MICRO; a f do EMU foi menor de T30 até T75 em relação ao MICRO. A PaCO2 do EMU foi maior de T15 até T90. Os tempos de extubação, decúbito esternal, deambulação e recuperação total foram de 40,6±30,7; 91±37,5; 134,5±54,5 e 169,1±55,4 minutos no MICRO e de 68,8±37,3; 133,3±85,3; 171,3±77,1 e 233,1±60,6 minutos no EMU, respectivamente. Houve aumento da enzima Alanina Aminotransferase de 12 às 72h no EMU e de 48 às 72h no MICRO. O propofol em microemulsão apresentou características clínicas de indução e manutenção, bem como efeitos metabólicos semelhantes à formulação em emulsão lipídica. A formulação em microemulsão proporcionou maior estabilidade cardiovascular e respiratória para indução e infusão contínua em gatas hígidas.

Stable T-bet+GATA-3+ Th1/Th2 Hybrid Cells Arise In Vivo, Can Develop Directly from Naive Precursors, and Limit Immunopathologic Inflammation

Science.gov (United States)

Peine, Michael; Fröhlich, Anja; Hegazy, Ahmed N.; Kühl, Anja A.; Grevelding, Christoph G.; Höfer, Thomas; Hartmann, Susanne; Löhning, Max

2013-01-01

Differentiated T helper (Th) cell lineages are thought to emerge from alternative cell fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show that natural primary immune responses against parasites generate bifunctional Th1 and Th2 hybrid cells that co-express the lineage-specifying transcription factors T-bet and GATA-3 and co-produce Th1 and Th2 cytokines. The integration of Th1-promoting interferon (IFN)-γ and interleukin (IL)-12 signals together with Th2-favoring IL-4 signals commits naive Th cells directly and homogeneously to the hybrid Th1/2 phenotype. Specifically, IFN-γ signals are essential for T-bet+GATA-3+ cells to develop in vitro and in vivo by breaking the dominance of IL-4 over IL-12 signals. The hybrid Th1/2 phenotype is stably maintained in memory cells in vivo for months. It resists reprogramming into classic Th1 or Th2 cells by Th1- or Th2-promoting stimuli, which rather induce quantitative modulations of the combined Th1 and Th2 programs without abolishing either. The hybrid phenotype is associated with intermediate manifestations of both Th1 and Th2 cell properties. Consistently, hybrid Th1/2 cells support inflammatory type-1 and type-2 immune responses but cause less immunopathology than Th1 and Th2 cells, respectively. Thus, we propose the self-limitation of effector T cells based on the stable cell-intrinsic balance of two opposing differentiation programs as a novel concept of how the immune system can prevent excessive inflammation. PMID:23976880

Stable T-bet(+GATA-3(+ Th1/Th2 hybrid cells arise in vivo, can develop directly from naive precursors, and limit immunopathologic inflammation.

Directory of Open Access Journals (Sweden)

Michael Peine

Full Text Available Differentiated T helper (Th cell lineages are thought to emerge from alternative cell fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show that natural primary immune responses against parasites generate bifunctional Th1 and Th2 hybrid cells that co-express the lineage-specifying transcription factors T-bet and GATA-3 and co-produce Th1 and Th2 cytokines. The integration of Th1-promoting interferon (IFN-γ and interleukin (IL-12 signals together with Th2-favoring IL-4 signals commits naive Th cells directly and homogeneously to the hybrid Th1/2 phenotype. Specifically, IFN-γ signals are essential for T-bet(+GATA-3(+ cells to develop in vitro and in vivo by breaking the dominance of IL-4 over IL-12 signals. The hybrid Th1/2 phenotype is stably maintained in memory cells in vivo for months. It resists reprogramming into classic Th1 or Th2 cells by Th1- or Th2-promoting stimuli, which rather induce quantitative modulations of the combined Th1 and Th2 programs without abolishing either. The hybrid phenotype is associated with intermediate manifestations of both Th1 and Th2 cell properties. Consistently, hybrid Th1/2 cells support inflammatory type-1 and type-2 immune responses but cause less immunopathology than Th1 and Th2 cells, respectively. Thus, we propose the self-limitation of effector T cells based on the stable cell-intrinsic balance of two opposing differentiation programs as a novel concept of how the immune system can prevent excessive inflammation.

Effects of β-D-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients

Directory of Open Access Journals (Sweden)

Barati A

2017-03-01

Full Text Available Anis Barati,1 Ahmad Reza Jamshidi,2,* Hossein Ahmadi,1 Zahra Aghazadeh,1 Abbas Mirshafiey1,* 1Department of Immunology, School of Public Health, 2Iranian Institute for Health Sciences Research, Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Abstract: Rheumatoid arthritis (RA is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs and biological drugs can interfere with the disease process. In this study, the effect of β-D-mannuronic acid (M2000 as a novel non-steroidal anti-inflammatory drug (NSAID with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4 has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier

The evolutionary duplication and probable demise of an endodermal GATA factor in Caenorhabditis elegans.

Science.gov (United States)

Fukushige, Tetsunari; Goszczynski, Barbara; Tian, Helen; McGhee, James D

2003-10-01

We describe the elt-4 gene from the nematode Caenorhabditis elegans. elt-4 is predicted to encode a very small (72 residues, 8.1 kD) GATA-type zinc finger transcription factor. The elt-4 gene is located approximately 5 kb upstream of the C. elegans elt-2 gene, which also encodes a GATA-type transcription factor; the zinc finger DNA-binding domains are highly conserved (24/25 residues) between the two proteins. The elt-2 gene is expressed only in the intestine and is essential for normal intestinal development. This article explores whether elt-4 also has a role in intestinal development. Reporter fusions to the elt-4 promoter or reporter insertions into the elt-4 coding regions show that elt-4 is indeed expressed in the intestine, beginning at the 1.5-fold stage of embryogenesis and continuing into adulthood. elt-4 reporter fusions are also expressed in nine cells of the posterior pharynx. Ectopic expression of elt-4 cDNA within the embryo does not cause detectable ectopic expression of biochemical markers of gut differentiation; furthermore, ectopic elt-4 expression neither inhibits nor enhances the ectopic marker expression caused by ectopic elt-2 expression. A deletion allele of elt-4 was isolated but no obvious phenotype could be detected, either in the gut or elsewhere; brood sizes, hatching efficiencies, and growth rates were indistinguishable from wild type. We found no evidence that elt-4 provided backup functions for elt-2. We used microarray analysis to search for genes that might be differentially expressed between L1 larvae of the elt-4 deletion strain and wild-type worms. Paired hybridizations were repeated seven times, allowing us to conclude, with some confidence, that no candidate target transcript could be identified as significantly up- or downregulated by loss of elt-4 function. In vitro binding experiments could not detect specific binding of ELT-4 protein to candidate binding sites (double-stranded oligonucleotides containing single or multiple

C. elegans GATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells.

Science.gov (United States)

Gorrepati, Lakshmi; Thompson, Kenneth W; Eisenmann, David M

2013-05-01

The C. elegans seam cells are lateral epithelial cells arrayed in a single line from anterior to posterior that divide in an asymmetric, stem cell-like manner during larval development. These asymmetric divisions are regulated by Wnt signaling; in most divisions, the posterior daughter in which the Wnt pathway is activated maintains the progenitor seam fate, while the anterior daughter in which the Wnt pathway is not activated adopts a differentiated hypodermal fate. Using mRNA tagging and microarray analysis, we identified the functionally redundant GATA factor genes egl-18 and elt-6 as Wnt pathway targets in the larval seam cells. EGL-18 and ELT-6 have previously been shown to be required for initial seam cell specification in the embryo. We show that in larval seam cell asymmetric divisions, EGL-18 is expressed strongly in the posterior seam-fated daughter. egl-18 and elt-6 are necessary for larval seam cell specification, and for hypodermal to seam cell fate transformations induced by ectopic Wnt pathway overactivation. The TCF homolog POP-1 binds a site in the egl-18 promoter in vitro, and this site is necessary for robust seam cell expression in vivo. Finally, larval overexpression of EGL-18 is sufficient to drive expression of a seam marker in other hypodermal cells in wild-type animals, and in anterior hypodermal-fated daughters in a Wnt pathway-sensitized background. These data suggest that two GATA factors that are required for seam cell specification in the embryo independently of Wnt signaling are reused downstream of Wnt signaling to maintain the progenitor fate during stem cell-like divisions in larval development.

The nT1 translocation separates vulval regulatory elements from the egl-18 and elt-6 GATA factor genes.

Science.gov (United States)

Koh, Kyunghee; Bernstein, Yelena; Sundaram, Meera V

2004-03-01

egl-18 and elt-6 are partially redundant, adjacent genes encoding GATA factors essential for viability, seam cell development, and vulval development in Caenorhabditis elegans. The nT1 reciprocal translocation causes a strong Vulvaless phenotype, and an nT1 breakpoint was previously mapped to the left arm of LGIV, where egl-18/elt-6 are located. Here we present evidence that the nT1 vulval phenotype is due to a disruption of egl-18/elt-6 function specifically in the vulva. egl-18 mutations do not complement nT1 for vulval defects, and the nT1 breakpoint on LGIV is located within approximately 800 bp upstream of a potential transcriptional start site of egl-18. In addition, we have identified a approximately 350-bp cis-regulatory region sufficient for vulval expression just upstream of the nT1 breakpoint. By examining the fusion state and division patterns of the cells in the developing vulva of nT1 mutants, we demonstrate that egl-18/elt-6 prevent fusion and promote cell proliferation at multiple steps of vulval development.

UTERINE PROLAPSE IN QUEEN AND UTERINE PROLAPSO UTERINO EM GATA E RETROFLEXÃO UTERINA EM CADELA

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Giuliano Queiroz Mostachio

2008-10-01

Full Text Available

Obstetrical emergencies are problem in veterinary clinics and hospital. So, the aim of this report is to describe the clinical-surgical aspect of one of them, the uterine prolapse. Complete protrusion and retroflexion of uterus had been diagnosed in a queen and female dog, respectively. After the stabilization of the animals and reduction of the prolapses followed by ovary-hysterectomy, one of the animals came to death due to septicemia and hypovolemic shock. Rapid assessment and intensive treatments are required to sustain the life of the animal.

KEY WORDS: Cat, dog, uterine prolapse, uterine retroflexion.

Johne's disease in cattle is associated with enhanced expression of genes encoding IL-5, GATA-3, tissue inhibitors of matrix metalloproteinases 1 and 2, and factors promoting apoptosis in peripheral blood mononuclear cells

DEFF Research Database (Denmark)

Coussens, P.M.; Pudrith, C.B.; Skovgaard, Kerstin

2005-01-01

remodeling deficiencies through higher expression of tissue inhibitor of matrix metalloproteinase (TIMP) 1 and TIMP2 RNA and lower expression of matrix metalloproteinase (MMP) 14 RNA than similar cells from healthy controls, and that cells within the PBMC population of M. paratuberculosis-infected cows...... upon by quantitative real-time PCR (Q-RT-PCR). Our results indicate that T cells within PBMCs from M. paratuberculosis-infected cows have adopted a predominant Th 2-like phenotype (enhanced expression of IL-5, GATA 3, and possibly IL-4 mRNA), that cells within infected cow PBMCs may exhibit tissue...

Fungal Morphology, Iron Homeostasis, and Lipid Metabolism Regulated by a GATA Transcription Factor in Blastomyces dermatitidis.

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Amber J Marty

2015-06-01

Full Text Available In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0-48 hours, gene expression microarrays were used to compare SREB∆ to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C and during the phase transition to mold (22°C. This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.

Cooperative action of multiple cis-acting elements is required for N-myc expression in branchial arches: specific contribution of GATA3.

Science.gov (United States)

Potvin, Eric; Beuret, Laurent; Cadrin-Girard, Jean-François; Carter, Marcelle; Roy, Sophie; Tremblay, Michel; Charron, Jean

2010-11-01

The precise expression of the N-myc proto-oncogene is essential for normal mammalian development, whereas altered N-myc gene regulation is known to be a determinant factor in tumor formation. Using transgenic mouse embryos, we show that N-myc sequences from kb -8.7 to kb +7.2 are sufficient to reproduce the N-myc embryonic expression profile in developing branchial arches and limb buds. These sequences encompass several regulatory elements dispersed throughout the N-myc locus, including an upstream limb bud enhancer, a downstream somite enhancer, a branchial arch enhancer in the second intron, and a negative regulatory element in the first intron. N-myc expression in the limb buds is under the dominant control of the limb bud enhancer. The expression in the branchial arches necessitates the interplay of three regulatory domains. The branchial arch enhancer cooperates with the somite enhancer region to prevent an inhibitory activity contained in the first intron. The characterization of the branchial arch enhancer has revealed a specific role of the transcription factor GATA3 in the regulation of N-myc expression. Together, these data demonstrate that correct N-myc developmental expression is achieved via cooperation of multiple positive and negative regulatory elements.

Cultural Resources Investigations in the Vicinity of Fort Jackson, Plaquemines Parish, Louisiana: The Proposed Solari Borrow Area

Science.gov (United States)

1989-08-01

tory of flora. Trees such as Virginia live oak (Quercus virginiana), black willow (Salix nigra), hackberry (Celtislaevi- gata), and persimmon ( Diospyros ...bullfrog, is a human food source today and may have been prehistorically as well. The toad, however, of the genus Bufo is not normally consumed

Minocycline Blocks Asthma-associated Inflammation in Part by Interfering with the T Cell Receptor-Nuclear Factor κB-GATA-3-IL-4 Axis without a Prominent Effect on Poly(ADP-ribose) Polymerase*

Science.gov (United States)

Naura, Amarjit S.; Kim, Hogyoung; Ju, Jihang; Rodriguez, Paulo C.; Jordan, Joaquin; Catling, Andrew D.; Rezk, Bashir M.; Elmageed, Zakaria Y. Abd; Pyakurel, Kusma; Tarhuni, Abdelmetalab F.; Abughazleh, Mohammad Q.; Errami, Youssef; Zerfaoui, Mourad; Ochoa, Augusto C.; Boulares, A. Hamid

2013-01-01

Minocycline protects against asthma independently of its antibiotic function and was recently reported as a potent poly(ADP-ribose) polymerase (PARP) inhibitor. In an animal model of asthma, a single administration of minocycline conferred excellent protection against ovalbumin-induced airway eosinophilia, mucus hypersecretion, and Th2 cytokine production (IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF) and a partial protection against airway hyperresponsiveness. These effects correlated with pronounced reduction in lung and sera allergen-specific IgE. A reduction in poly(ADP-ribose) immunoreactivity in the lungs of minocycline-treated/ovalbumin-challenged mice correlated with decreased oxidative DNA damage. The effect of minocycline on PARP may be indirect, as the drug failed to efficiently block direct PARP activation in lungs of N-methyl-N′-nitro-N-nitroso-guanidine-treated mice or H2O2-treated cells. Minocycline blocked allergen-specific IgE production in B cells potentially by modulating T cell receptor (TCR)-linked IL-4 production at the mRNA level but not through a modulation of the IL-4-JAK-STAT-6 axis, IL-2 production, or NFAT1 activation. Restoration of IL-4, ex vivo, rescued IgE production by minocycline-treated/ovalbumin-stimulated B cells. IL-4 blockade correlated with a preferential inhibition of the NF-κB activation arm of TCR but not GSK3, Src, p38 MAPK, or ERK1/2. Interestingly, the drug promoted a slightly higher Src and ERK1/2 phosphorylation. Inhibition of NF-κB was linked to a complete blockade of TCR-stimulated GATA-3 expression, a pivotal transcription factor for IL-4 expression. Minocycline also reduced TNF-α-mediated NF-κB activation and expression of dependent genes. These results show a potentially broad effect of minocycline but that it may block IgE production in part by modulating TCR function, particularly by inhibiting the signaling pathway, leading to NF-κB activation, GATA-3 expression, and subsequent IL-4 production. PMID:23184953

Minocycline blocks asthma-associated inflammation in part by interfering with the T cell receptor-nuclear factor κB-GATA-3-IL-4 axis without a prominent effect on poly(ADP-ribose) polymerase.

Science.gov (United States)

Naura, Amarjit S; Kim, Hogyoung; Ju, Jihang; Rodriguez, Paulo C; Jordan, Joaquin; Catling, Andrew D; Rezk, Bashir M; Abd Elmageed, Zakaria Y; Pyakurel, Kusma; Tarhuni, Abdelmetalab F; Abughazleh, Mohammad Q; Errami, Youssef; Zerfaoui, Mourad; Ochoa, Augusto C; Boulares, A Hamid

2013-01-18

Minocycline protects against asthma independently of its antibiotic function and was recently reported as a potent poly(ADP-ribose) polymerase (PARP) inhibitor. In an animal model of asthma, a single administration of minocycline conferred excellent protection against ovalbumin-induced airway eosinophilia, mucus hypersecretion, and Th2 cytokine production (IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF) and a partial protection against airway hyperresponsiveness. These effects correlated with pronounced reduction in lung and sera allergen-specific IgE. A reduction in poly(ADP-ribose) immunoreactivity in the lungs of minocycline-treated/ovalbumin-challenged mice correlated with decreased oxidative DNA damage. The effect of minocycline on PARP may be indirect, as the drug failed to efficiently block direct PARP activation in lungs of N-methyl-N'-nitro-N-nitroso-guanidine-treated mice or H(2)O(2)-treated cells. Minocycline blocked allergen-specific IgE production in B cells potentially by modulating T cell receptor (TCR)-linked IL-4 production at the mRNA level but not through a modulation of the IL-4-JAK-STAT-6 axis, IL-2 production, or NFAT1 activation. Restoration of IL-4, ex vivo, rescued IgE production by minocycline-treated/ovalbumin-stimulated B cells. IL-4 blockade correlated with a preferential inhibition of the NF-κB activation arm of TCR but not GSK3, Src, p38 MAPK, or ERK1/2. Interestingly, the drug promoted a slightly higher Src and ERK1/2 phosphorylation. Inhibition of NF-κB was linked to a complete blockade of TCR-stimulated GATA-3 expression, a pivotal transcription factor for IL-4 expression. Minocycline also reduced TNF-α-mediated NF-κB activation and expression of dependent genes. These results show a potentially broad effect of minocycline but that it may block IgE production in part by modulating TCR function, particularly by inhibiting the signaling pathway, leading to NF-κB activation, GATA-3 expression, and subsequent IL-4 production.

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

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 ...

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

Science.gov (United States)

Marroquin-Guzman, Margarita; Wilson, Richard A

2015-04-01

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.

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

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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.

The LXCXE Retinoblastoma Protein-Binding Motif of FOG-2 Regulates Adipogenesis.

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Goupille, Olivier; Penglong, Tipparat; Kadri, Zahra; Granger-Locatelli, Marine; Denis, Raphaël; Luquet, Serge; Badoual, Cécile; Fucharoen, Suthat; Maouche-Chrétien, Leila; Leboulch, Philippe; Chrétien, Stany

2017-12-19

GATA transcription factors and their FOG cofactors play a key role in tissue-specific development and differentiation, from worms to humans. Mammals have six GATA and two FOG factors. We recently demonstrated that interactions between retinoblastoma protein (pRb) and GATA-1 are crucial for erythroid proliferation and differentiation. We show here that the LXCXE pRb-binding site of FOG-2 is involved in adipogenesis. Unlike GATA-1, which inhibits cell division, FOG-2 promotes proliferation. Mice with a knockin of a Fog2 gene bearing a mutated LXCXE pRb-binding site are resistant to obesity and display higher rates of white-to-brown fat conversion. Thus, each component of the GATA/FOG complex (GATA-1 and FOG-2) is involved in pRb/E2F regulation, but these molecules have markedly different roles in the control of tissue homeostasis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A novel in vivo adjuvant activity of kaempferol: enhanced Tbx-21, GATA-3 expression and peritoneal CD11c+MHCII+ dendritic cell infiltration.

Science.gov (United States)

Singh, Divya; Tanwar, Himanshi; Das, Sudeshna; Ganju, Lilly; Singh, Shashi Bala

2018-02-28

Kaempferol, a natural flavonol present in various traditional medicinal plants, is known to possess potent anti-inflammatory properties. This study was designed to study the adjuvant effect of kaempferol administration along with ovalbumin antigen (K + O) in balb/c mice. Mice were immunized with kaempferol (100 and 50 mg/kg body weight) without or with ovalbumin (20 µg/mouse). After priming, booster was administered on day 21. Antigen specific IgG titers and its subtypes, on day 28, were estimated by indirect ELISA. Effect of kaempferol administration on CD11c + MHCII + peritoneal dendritic cells was studied by flow cytometry. Expression levels of proteins Tbx21, GATA-3, BLIMP-1, Caspase-1 and Oct-2 were studied by western blotting. LPS activated IL-1β production by peritoneal cells of immunized mice was estimated by sandwich ELISA. Ovalbumin specific IgG, IgG1 and IgG2a antibody titers in sera samples of K + O immunized mice increased significantly (p Kaempferol increased the infiltration of peritoneal CD11c + MHCII + dendritic cells but failed to enhance LPS activated IL-1β by peritoneal macrophages and suppressed caspase-1 protein expression as compared to that in ovalbumin immunized mice. Present study strongly demonstrates the novel adjuvant activity of kaempferol in vivo and its potential as an immunostimulatory agent.

Friend of GATA (FOG) interacts with the nucleosome remodeling and deacetylase complex (NuRD) to support primitive erythropoiesis in Xenopus laevis.

Science.gov (United States)

Mimoto, Mizuho S; Christian, Jan L

2012-01-01

Friend of GATA (FOG) plays many diverse roles in adult and embryonic hematopoiesis, however the mechanisms by which it functions and the roles of potential interaction partners are not completely understood. Previous work has shown that overexpression of FOG in Xenopus laevis causes loss of blood suggesting that in contrast to its role in mammals, FOG might normally function to repress erythropoiesis in this species. Using loss-of-function analysis, we demonstrate that FOG is essential to support primitive red blood cell (RBC) development in Xenopus. Moreover, we show that it is specifically required to prevent excess apoptosis of circulating primitive RBCs and that in the absence of FOG, the pro-apoptotic gene Bim-1 is strongly upregulated. To identify domains of FOG that are essential for blood development and, conversely, to begin to understand the mechanism by which overexpressed FOG represses primitive erythropoiesis, we asked whether FOG mutants that are unable to interact with known co-factors retain their ability to rescue blood formation in FOG morphants and whether they repress erythropoiesis when overexpressed in wild type embryos. We find that interaction of FOG with the Nucleosome Remodeling and Deacetylase complex (NuRD), but not with C-terminal Binding Protein, is essential for normal primitive RBC development. In contrast, overexpression of all mutant and wild type constructs causes a comparable repression of primitive erythropoiesis. Together, our data suggest that a requirement for FOG and its interaction with NuRD during primitive erythropoiesis are conserved in Xenopus and that loss of blood upon FOG overexpression is due to a dominant-interfering effect.

The C. elegans embryonic fate specification factor EGL-18 (GATA) is reutilized downstream of Wnt signaling to maintain a population of larval progenitor cells.

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Gorrepati, Lakshmi; Eisenmann, David M

2015-01-01

In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further. Wnt signaling pathway is known to regulate the asymmetry of these divisions and maintain the progenitor cell fate in one daughter, but how activation of the Wnt pathway accomplished this was unknown. We describe here our recent work that identified the GATA transcription factor EGL-18 as a downstream target of Wnt signaling necessary for maintenance of a progenitor population of larval seam cells. EGL-18 was previously shown to act in the initial specification of the seam cells in the embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an embryonic fate specification factor to be reutilized later in life downstream of a different regulator (Wnt signaling) to maintain a progenitor cell population. These results support the use of seam cell development in C. elegans as a simple model system for studying stem and progenitor cell biology.

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

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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.

Friend of GATA (FOG interacts with the nucleosome remodeling and deacetylase complex (NuRD to support primitive erythropoiesis in Xenopus laevis.

Directory of Open Access Journals (Sweden)

Mizuho S Mimoto

Full Text Available Friend of GATA (FOG plays many diverse roles in adult and embryonic hematopoiesis, however the mechanisms by which it functions and the roles of potential interaction partners are not completely understood. Previous work has shown that overexpression of FOG in Xenopus laevis causes loss of blood suggesting that in contrast to its role in mammals, FOG might normally function to repress erythropoiesis in this species. Using loss-of-function analysis, we demonstrate that FOG is essential to support primitive red blood cell (RBC development in Xenopus. Moreover, we show that it is specifically required to prevent excess apoptosis of circulating primitive RBCs and that in the absence of FOG, the pro-apoptotic gene Bim-1 is strongly upregulated. To identify domains of FOG that are essential for blood development and, conversely, to begin to understand the mechanism by which overexpressed FOG represses primitive erythropoiesis, we asked whether FOG mutants that are unable to interact with known co-factors retain their ability to rescue blood formation in FOG morphants and whether they repress erythropoiesis when overexpressed in wild type embryos. We find that interaction of FOG with the Nucleosome Remodeling and Deacetylase complex (NuRD, but not with C-terminal Binding Protein, is essential for normal primitive RBC development. In contrast, overexpression of all mutant and wild type constructs causes a comparable repression of primitive erythropoiesis. Together, our data suggest that a requirement for FOG and its interaction with NuRD during primitive erythropoiesis are conserved in Xenopus and that loss of blood upon FOG overexpression is due to a dominant-interfering effect.

Vascularização arterial dos cornos uterinos em gatas gestantes sem raça definida (Felis catus Linnaeus, 1758

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Rosana Marques Silva

2004-02-01

Full Text Available Utilizaram-se 24 gatas gestantes, sem raça definida, doadas para o estudo da vascularização arterial dos cornos uterinos. Em 20 animais, com o intervalo gestacional entre 7 e 9 semanas, a aorta abdominal foi injetada com Látex-Neoprene 650 corado, associado ao Sulfato de Bário 1004. Os animais foram então radiografados, fixados em solução aquosa de formol 10% e dissecados para estudo da distribuição dos vasos arteriais destinados às regiões paraplacentárias e de cintas placentárias. Em 4 animais realizou-se o exame por Ecografia Power Doppler, onde se observou que nas regiões das cintas placentárias o índice de resistência dos vasos apresenta-se menor do que o encontrado ao longo da artéria uterina. Em todas as observações, a artéria uterina é o principal vaso a irrigar os cornos uterinos, emitindo de 2 a 17 ramos, com maior freqüência de 5 a 12 ramos, os quais se distribuem nas regiões paraplacentárias e/ou das cintas placentárias, formando arcadas anastomósticas. Não houve diferenças estatísticas significativas do número de ramos para cada região individualmente, porém a análise das radiografias contrastadas demonstrou haver uma concentração maior de contraste nas regiões das cintas placentárias. A artéria ovárica participa da vascularização arterial da extremidade cranial dos cornos uterinos, onde se anastomosa com ramos da artéria uterina.

A Novel Differentiation Therapy Approach to Reduce the Metastatic Potential of Basal, Highly Metastatic, Triple-Negative Breast Cancers

Science.gov (United States)

2012-05-01

metastatic process (Condeelis and Pollard 2006), we quantitated macrophage recruitment in the lungs of mice injected with 231-Empty or 231-GATA3 cells by...image quantitation of Ki-67 expression and H&E staining of metastatic lung lesions using Apirio Image Analysis software (Figure 9) which demonstrated...expression in MD A-MB-231 and in another triple negative breast cancer cell line, Hs578T Transient knock down of GATA3 in the lum inal GATA3 positiv

Ubiquitin specific protease 21 is dispensable for normal development, hematopoiesis and lymphocyte differentiation.

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Jaspreet Pannu

Full Text Available USP21 is a ubiquitin specific protease that catalyzes protein deubiquitination, however the identification of its physiological substrates remains challenging. USP21 is known to deubiquitinate transcription factor GATA3 and death-domain kinase RIPK1 in vitro, however the in vivo settings where this regulation plays a biologically significant role remain unknown. In order to determine whether USP21 is an essential and non-redundant regulator of GATA3 or RIPK1 activity in vivo, we characterized Usp21-deficient mice, focusing on mouse viability and development, hematopoietic stem cell function, and lymphocyte differentiation. The Usp21-knockout mice were found to be viable and fertile, with no significant dysmorphology, in contrast to the GATA3 and RIPK1 knockout lines that exhibit embryonic or perinatal lethality. Loss of USP21 also had no effect on hematopoietic stem cell function, lymphocyte development, or the responses of antigen presenting cells to TLR and TNFR stimulation. GATA3 levels in hematopoietic stem cells or T lymphocytes remained unchanged. We observed that aged Usp21-knockout mice exhibited spontaneous T cell activation, however this was not linked to altered GATA3 levels in the affected cells. The contrast in the phenotype of the Usp21-knockout line with the previously characterized GATA3 and RIPK1 knockout mice strongly indicates that USP21 is redundant for the regulation of GATA3 and RIPK1 activity during mouse development, in hematopoietic stem cells, and in lymphocyte differentiation. The Usp21-deficient mouse line characterized in this study may serve as a useful tool for the future characterization of USP21 physiological functions.

Experiment list: SRX092303 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available trol description=This data represents a control being compared to experiments usi...ng antibody eGFP-GATA2 || control=Control_eGFP-GATA2 || control description=This data represents a control being

Conserved regulatory modules in the Sox9 testis-specific enhancer predict roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination.

Science.gov (United States)

Bagheri-Fam, Stefan; Sinclair, Andrew H; Koopman, Peter; Harley, Vincent R

2010-03-01

While the primary sex determining switch varies between vertebrate species, a key downstream event in testicular development, namely the male-specific up-regulation of Sox9, is conserved. To date, only two sex determining switch genes have been identified, Sry in mammals and the Dmrt1-related gene Dmy (Dmrt1bY) in the medaka fish Oryzias latipes. In mice, Sox9 expression is evidently up-regulated by SRY and maintained by SOX9 both of which directly activate the core 1.3 kb testis-specific enhancer of Sox9 (TESCO). How Sox9 expression is up-regulated and maintained in species without Sry (i.e. non-mammalian species) is not understood. In this study, we have undertaken an in-depth comparative genomics approach and show that TESCO contains an evolutionarily conserved region (ECR) of 180 bp which is present in marsupials, monotremes, birds, reptiles and amphibians. The ECR contains highly conserved modules that predict regulatory roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination/differentiation. Our data suggest that tetrapods share common aspects of Sox9 regulation in the testis, despite having different sex determining switch mechanisms. They also suggest that Sox9 autoregulation is an ancient mechanism shared by all tetrapods, raising the possibility that in mammals, SRY evolved by mimicking this regulation. The validation of ECR regulatory sequences conserved from human to frogs will provide new insights into vertebrate sex determination. Copyright 2009 Elsevier Ltd. All rights reserved.

Prenatal diagnosis of two fetuses with deletions of 8p23.1, critical region for congenital diaphragmatic hernia and heart defects.

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Keitges, Elisabeth A; Pasion, Romela; Burnside, Rachel D; Mason, Carla; Gonzalez-Ruiz, Antonio; Dunn, Teresa; Masiello, Meredith; Gebbia, Joseph A; Fernandez, Carlos O; Risheg, Hiba

2013-07-01

Microdeletions of 8p23.1 are mediated by low copy repeats and can cause congenital diaphragmatic hernia (CDH) and cardiac defects. Within this region, point mutations of the GATA4 gene have been shown to cause cardiac defects. However, the cause of CDH in these deletions has been difficult to determine due to the paucity of mutations that result in CDH, the lack of smaller deletions to refine the region and the reduced penetrance of CDH in these large deletions. Mice deficient for one copy of the Gata4 gene have been described with CDH and heart defects suggesting mutations in Gata4 can cause the phenotype in mice. We report on the SNP microarray analysis on two fetuses with deletions of 8p23.1. The first had CDH and a ventricular septal defect (VSD) on ultrasonography and a family history of a maternal VSD. Microarray analysis detected a 127-kb deletion which included the GATA4 and NEIL2 genes which was inherited from the mother. The second fetus had an incomplete atrioventricular canal defect on ultrasonography. Microarray analysis showed a 315-kb deletion that included seven genes, GATA4, NEIL2, FDFT1, CTSB, DEFB136, DEFB135, and DEFB134. These results suggest that haploinsufficiency of the two genes in common within 8p23.1; GATA4 and NEIL2 can cause CDH and cardiac defects in humans. Copyright © 2013 Wiley Periodicals, Inc.

Hypoparathyroidism, sensorineural deafness, and renal dysgenesis syndrome with a mutation

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Yong Suk Shim

2015-03-01

Full Text Available Hypoparathyroidism, sensorineural deafness, and renal dysgenesis syndrome is an autosomal dominant disease caused by mutations in the GATA3 gene on chromosome 10p15. We identified a patient diagnosed with hypoparathyroidism who also had a family history of hypoparathyroidism and sensorineural deafness, present in the father. The patient was subsequently diagnosed and found to be a heterozygote for an insertion mutation c.255_256ins4 (GTGC in exon 2 of GATA3. His father was also confirmed to have the same mutation in GATA3.

Experiment list: SRX092310 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available aw signal before peaks are called. || control=Control_eGFP-GATA2 || control description=This data represents a control being...trol_eGFP-GATA2 || control description=This data represents a control being compared to experiments using an

Eletroacupuntura e morfina sobre parâmetros cardiorrespiratórios em gatas submetidas à ovariosalpingohisterectomia eletiva Electroacupuncture and morphine on cardiorespiratory parameters on cat elective ovariohysterectomy

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Marilda Onghero Taffarel

2011-12-01

Full Text Available Objetivou-se avaliar os efeitos da morfina e da eletroacupuntura sobre parâmetros cardiorrespiratórios e consumo do anestésico isofluorano em gatas submetidas à ovariosalpingohisterectomia eletiva. Foram utilizadas 18 gatas hígidas, adultas, distribuídas em três grupos: Eletroacupuntura, Morfina e Controle, as quais receberam acepromazina, propofol e isoflurano. Nos animais dos grupos Controle e Morfina foram introduzidas agulhas em acupontos falsos, e nos do grupo Eletroacupuntura nos pontos Zusanli e Yanglingquan. A eletroestimulação no grupo submetido a Eletroacupuntura foi realizada na frequência de 2 e 100Hz. Nos animais do grupo Morfina, administrou-se a dose de 0,3mg/kg por via intramuscular e no grupo Controle não foi realizado tratamento. O registro das variáveis foi obtido anteriormente à administração da acepromazina; 10 minutos após a aplicação desse fármaco; após indução e estabilização anestésica; decorridos 30 minutos do início da eletroestimulação ou aplicação da morfina; e a cada 10 minutos, durante 60 minutos. Foram estudadas temperatura retal, frequência respiratória e cardíaca, saturação parcial de oxiemoglobina, pressão arterial média, volume total de isoflurano consumido e volume inspirado de isoflurano. Os dados foram submetidos a Análise de Perfil. Somente os animais do grupo Eletroacupuntura (GE não apresentaram diferença significativa entre os momentos para a pressão arterial média, e observou-se melhor estabilidade cardíaca nos animais do grupo Eletroacupuntura e Morfina. O volume inspirado de isoflurano foi 58,33% menor no grupo Eletroacupuntura e 22,02% no grupo Morfina quando comparados ao grupo Controle. Pode-se concluir que eletroestimulação dos acupontos Zusanli e Yanglingquan, diminui o volume inspirado de isoflurano e promove estabilidade cardiorrespiratória, sendo superior ao uso da morfina.The aim of this work was to evaluate the morphine and electroacupuncture

associated with fecundity in goats

African Journals Online (AJOL)

USER

2010-02-08

Feb 8, 2010 ... ... PCR method was used. The ovary and uterus were selected for the detection of expression ..... during postnatal development and pregnancy. Mol. Cell. ... (2008). GATA-4 and GATA-6 expression in human ovarian surface epithelial ... (2004). The premammillary hypothalamic area of the ewe: anatomical.

Retinoic acid signaling plays a restrictive role in zebrafish primitive myelopoiesis.

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Dong Liang

Full Text Available Retinoic acid (RA is known to regulate definitive myelopoiesis but its role in vertebrate primitive myelopoiesis remains unclear. Here we report that zebrafish primitive myelopoiesis is restricted by RA in a dose dependent manner mainly before 11 hpf (hours post fertilization when anterior hemangioblasts are initiated to form. RA treatment significantly reduces expressions of anterior hemangioblast markers scl, lmo2, gata2 and etsrp in the rostral end of ALPM (anterior lateral plate mesoderm of the embryos. The result indicates that RA restricts primitive myelopoiesis by suppressing formation of anterior hemangioblasts. Analyses of ALPM formation suggest that the defective primitive myelopoiesis resulting from RA treatment before late gastrulation may be secondary to global loss of cells for ALPM fate whereas the developmental defect resulting from RA treatment during 10-11 hpf should be due to ALPM patterning shift. Overexpressions of scl and lmo2 partially rescue the block of primitive myelopoiesis in the embryos treated with 250 nM RA during 10-11 hpf, suggesting RA acts upstream of scl to control primitive myelopoiesis. However, the RA treatment blocks the increased primitive myelopoiesis caused by overexpressing gata4/6 whereas the abolished primitive myelopoiesis in gata4/5/6 depleted embryos is well rescued by 4-diethylamino-benzaldehyde, a retinal dehydrogenase inhibitor, or partially rescued by knocking down aldh1a2, the major retinal dehydrogenase gene that is responsible for RA synthesis during early development. Consistently, overexpressing gata4/6 inhibits aldh1a2 expression whereas depleting gata4/5/6 increases aldh1a2 expression. The results reveal that RA signaling acts downstream of gata4/5/6 to control primitive myelopoiesis. But, 4-diethylamino-benzaldehyde fails to rescue the defective primitive myelopoiesis in either cloche embryos or lycat morphants. Taken together, our results demonstrate that RA signaling restricts

Population data for 15 Y-chromosome STRs in a population sample from Quito (Ecuador).

Science.gov (United States)

Baeza, Carlos; Guzmán, Rodrigo; Tirado, Miriam; López-Parra, Ana María; Rodríguez, Tatiana; Mesa, María Soledad; Fernández, Eva; Arroyo-Pardo, Eduardo

2007-12-20

Population frequencies for the 9 Y-STR loci included in the "minimal haplotype" from Y-STR Haplotype Reference Database (YHRD), plus other 6 Y-STRs (DYS437, DYS438, DYS439, GATA A7.2, GATA H4 and GATA A10) were obtained for a sample of 120 males from Quito (Ecuador). One hundred and sixteen unique haplotypes were identified within the sample. Haplotype diversity (0.9994) was among the highest in comparison to other populations from Iberia and South-America. Genetic distances were calculated and our sample presented significative differences with all other samples, the lowest values being with a Guinean sample.

The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro

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Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to 'nd out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast can...

Cell and genetic predictors of human blastocyst hatching success in assisted reproduction.

Science.gov (United States)

Syrkasheva, Anastasiya G; Dolgushina, Nataliya V; Romanov, Andrey Yu; Burmenskaya, Olga V; Makarova, Nataliya P; Ibragimova, Espet O; Kalinina, Elena A; Sukhikh, Gennady T

2017-10-01

The aim was to identify cell and genetic predictors of human blastocyst hatching success in assisted reproduction programmes via a prospective case-control study. Blastocysts, donated by couples in assisted reproduction programmes were used. Hatching success assessment was performed after 144-146 h post-fertilization. The mRNA expression levels of cathepsin V (CTSV), GATA-binding protein 3 (GATA3) and human chorionic gonadotropin beta subunit 3, 5, 7 and 8 (CGB) genes were detected by quantitative real-time polymerase chain reaction. The odds ratio (OR) of hatching due to zona pellucida (ZP) thickness, oocyte and sperm quality, embryo quality and mRNA expression of CTSV, GATA3 and CGB genes in blastocysts was determined. From 62 blastocysts included in the study, 47 (75.8%) were unable to hatch spontaneously. The ZP thickening, and oocyte and sperm quality did not affect human blastocyst ability to hatch, except the combination of cytoplasmic and extracytoplasmic oocyte dysmorphisms (OR = 1.25; 95% confidence interval = 1.08, 1.45). Hatching-capable blastocysts had higher Gardner scale grade and mRNA expression of CTSV, GATA3 and CGB genes than hatching-incapable blastocysts. The human blastocyst hatching success depends on the blastocyst Gardner grade, but not on ZP and gamete quality. Blastocyst development was regulated by CTSV, GATA3 and CGB gene expression.

Reconstruction of the gene regulatory network involved in the sonic hedgehog pathway with a potential role in early development of the mouse brain.

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Jinhua Liu

2014-10-01

Full Text Available The Sonic hedgehog (Shh signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1- and Shh-Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh-Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1- domain and down-regulates the genes characteristic of the Shh-Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain.

Linking patient outcome to high throughput protein expression data identifies novel regulators of colorectal adenocarcinoma aggressiveness [v1; ref status: indexed, http://f1000r.es/5ad

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Christi L. French

2015-04-01

Full Text Available A key question in cancer systems biology is how to use molecular data to predict the biological behavior of tumors from individual patients. While genomics data have been heavily used, protein signaling data are more directly connected to biological phenotype and might predict cancer phenotypes such as invasion, metastasis, and patient survival. In this study, we mined publicly available data for colorectal adenocarcinoma from the Cancer Genome Atlas and identified protein expression and signaling changes that are statistically associated with patient outcome. Our analysis identified a number of known and potentially new regulators of colorectal cancer. High levels of insulin growth factor binding protein 2 (IGFBP2 were associated with both recurrence and death, and this was validated by immunohistochemical staining of a tissue microarray for a secondary patient dataset. Interestingly, GATA binding protein 3 (GATA3 was the protein most frequently associated with death in our analysis, and GATA3 expression was significantly decreased in tumor samples from stage I-II deceased patients. Experimental studies using engineered colon cancer cell lines show that exogenous expression of GATA3 decreases three-dimensional colony growth and invasiveness of colon cancer cells but does not affect two-dimensional proliferation. These findings suggest that protein data are useful for biomarker discovery and identify GATA3 as a regulator of colorectal cancer  aggressiveness.

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

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 ...

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

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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.

Synergistic role of 5-azacytidine and ascorbic acid in directing cardiosphere derived cells to cardiomyocytes in vitro by downregulating Wnt signaling pathway via phosphorylation of β-catenin.

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Reddy Sailaja Mundre

Full Text Available Cardiosphere derived cells (CDCs represent a valuable source in stem cell based therapy for cardiovascular diseases, yet poor differentiation rate hinders the transplantation efficiency. The aim of this study is to check the ability of 5-Azacytidine (Aza alone and in combination with ascorbic acid (Aza+AA in delineating CDCs to cardiomyogenesis and the underlying Wnt signaling mechanism in induced differentiation.CDCs were treated with Aza and Aza+AA for a period of 14 days to examine the expression of cardiac specific markers and Wnt downstream regulators by immunofluorescence, real time PCR and western blot.Results revealed that Aza+AA induced efficient commitment of CDCs to cardiomyogenic lineage. Immunofluorescence analysis showed significant augment for Nkx 2.5, GATA 4 and α-Sarcomeric actinin markers in Aza+AA group than control group (p = 0.0118, p = 0.009 and p = 0.0091, respectively. Relative upregulation of cardiac markers, Nkx 2.5 (p = 0.0156, GATA 4 (p = 0.0087 and down regulation of Wnt markers, β-catenin (p = 0.0107 and Cyclin D1 (p = 0. 0116 in Aza+AA group was revealed by RNA expression analysis. Moreover, the Aza+AA induced prominent expression of GATA 4, α-Sarcomeric actinin and phospho β-catenin while non phospho β-catenin and Cyclin D1 expression was significantly suppressed as displayed in protein expression analysis. Generation of spontaneous beating in Aza+AA treated CDCs further reinforced that Aza+AA accelerates the cardiomyogenic potential of CDCs.Combined treatment of Aza along with AA implicit in inducing cardiomyogenic potential of CDCs and is associated with down regulating Wnt signaling pathway. Altogether, CDCs represent a valuable tool for the treatment of cardiovascular disorders.

Plasmodium Apicoplast Gln-tRNA Gln Biosynthesis Utilizes a Unique GatAB Amidotransferase Essential for Erythrocytic Stage Parasites

KAUST Repository

Mailu, Boniface M.; Li, Ling; Arthur, Jen; Nelson, Todd M.; Ramasamy, Gowthaman; Fritz-Wolf, Karin; Becker, Katja; Gardner, Malcolm J.

2015-01-01

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. The malaria parasite Plasmodium falciparum apicoplast indirect aminoacylation pathway utilizes a non-discriminating glutamyl-tRNA synthetase to synthesize Glu-tRNAGln and a glutaminyl-tRNA amidotransferase to convert Glu-tRNAGln to Gln-tRNAGln. Here, we show that Plasmodium falciparum and other apicomplexans possess a unique heterodimeric glutamyltRNA amidotransferase consisting of GatA and GatB subunits (GatAB). We localized the P. falciparum GatA and GatB subunits to the apicoplast in blood stage parasites and demonstrated that recombinant GatAB converts Glu-tRNAGln to Gln-tRNAGln in vitro. We demonstrate that the apicoplast GatAB-catalyzed reaction is essential to the parasite blood stages because we could not delete the Plasmodium berghei gene encoding GatA in blood stage parasites in vivo. A phylogenetic analysis placed the split between Plasmodium GatB, archaeal GatE, and bacterial GatB prior to the phylogenetic divide between bacteria and archaea. Moreover, Plasmodium GatA also appears to have emerged prior to the bacterial-archaeal phylogenetic divide. Thus, although GatAB is found in Plasmodium, it emerged prior to the phylogenetic separation of archaea and bacteria.

Plasmodium Apicoplast Gln-tRNA Gln Biosynthesis Utilizes a Unique GatAB Amidotransferase Essential for Erythrocytic Stage Parasites

KAUST Repository

Mailu, Boniface M.

2015-08-28

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. The malaria parasite Plasmodium falciparum apicoplast indirect aminoacylation pathway utilizes a non-discriminating glutamyl-tRNA synthetase to synthesize Glu-tRNAGln and a glutaminyl-tRNA amidotransferase to convert Glu-tRNAGln to Gln-tRNAGln. Here, we show that Plasmodium falciparum and other apicomplexans possess a unique heterodimeric glutamyltRNA amidotransferase consisting of GatA and GatB subunits (GatAB). We localized the P. falciparum GatA and GatB subunits to the apicoplast in blood stage parasites and demonstrated that recombinant GatAB converts Glu-tRNAGln to Gln-tRNAGln in vitro. We demonstrate that the apicoplast GatAB-catalyzed reaction is essential to the parasite blood stages because we could not delete the Plasmodium berghei gene encoding GatA in blood stage parasites in vivo. A phylogenetic analysis placed the split between Plasmodium GatB, archaeal GatE, and bacterial GatB prior to the phylogenetic divide between bacteria and archaea. Moreover, Plasmodium GatA also appears to have emerged prior to the bacterial-archaeal phylogenetic divide. Thus, although GatAB is found in Plasmodium, it emerged prior to the phylogenetic separation of archaea and bacteria.

Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome

OpenAIRE

Alford, Kate A.; Slender, Amy; Vanes, Lesley; Li, Zhe; Fisher, Elizabeth M. C.; Nizetic, Dean; Orkin, Stuart H.; Roberts, Irene; Tybulewicz, Victor L. J.

2010-01-01

Trisomy of human chromosome 21 (Hsa21) results in Down syndrome (DS), a disorder that affects many aspects of physiology, including hematopoiesis. DS children have greatly increased rates of acute lymphoblastic leukemia and acute megakaryoblastic leukemia (AMKL); DS newborns present with transient myeloproliferative disorder (TMD), a preleukemic form of AMKL. TMD and DS-AMKL almost always carry an acquired mutation in GATA1 resulting in exclusive synthesis of a truncated protein (GATA1s), sug...

Nitrogen Metabolite Repression of Metabolism and Virulence in the Human Fungal Pathogen Cryptococcus neoformans

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Lee, I. Russel; Chow, Eve W. L.; Morrow, Carl A.; Djordjevic, Julianne T.; Fraser, James A.

2011-01-01

Proper regulation of metabolism is essential to maximizing fitness of organisms in their chosen environmental niche. Nitrogen metabolite repression is an example of a regulatory mechanism in fungi that enables preferential utilization of easily assimilated nitrogen sources, such as ammonium, to conserve resources. Here we provide genetic, transcriptional, and phenotypic evidence of nitrogen metabolite repression in the human pathogen Cryptococcus neoformans. In addition to loss of transcriptional activation of catabolic enzyme-encoding genes of the uric acid and proline assimilation pathways in the presence of ammonium, nitrogen metabolite repression also regulates the production of the virulence determinants capsule and melanin. Since GATA transcription factors are known to play a key role in nitrogen metabolite repression, bioinformatic analyses of the C. neoformans genome were undertaken and seven predicted GATA-type genes were identified. A screen of these deletion mutants revealed GAT1, encoding the only global transcription factor essential for utilization of a wide range of nitrogen sources, including uric acid, urea, and creatinine—three predominant nitrogen constituents found in the C. neoformans ecological niche. In addition to its evolutionarily conserved role in mediating nitrogen metabolite repression and controlling the expression of catabolic enzyme and permease-encoding genes, Gat1 also negatively regulates virulence traits, including infectious basidiospore production, melanin formation, and growth at high body temperature (39°–40°). Conversely, Gat1 positively regulates capsule production. A murine inhalation model of cryptococcosis revealed that the gat1Δ mutant is slightly more virulent than wild type, indicating that Gat1 plays a complex regulatory role during infection. PMID:21441208

Helicase-like transcription factor (Hltf regulates G2/M transition, Wt1/Gata4/Hif-1a cardiac transcription networks, and collagen biogenesis.

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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

A functional (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase exhibits diurnal regulation of expression in Stevia rebaudiana (Bertoni).

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Kumar, Hitesh; Kumar, Sanjay

2013-09-15

The leaves of stevia [Stevia rebaudiana (Bertoni)] are a rich source of steviol glycosides that are used as non-calorific sweetener in many countries around the world. Steviol moiety of steviol glycosides is synthesized via plastidial 2C-methyl-D-erythritol 4-phosphate pathway, where (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR) is the key enzyme. HDR catalyzes the simultaneous conversion of (E)-4-hydroxy-3-methylbut-2-enyl diphosphate into five carbon isoprenoid units, isopentenyl diphosphate and dimethylallyl diphosphate. Stevia HDR (SrHDR) successfully rescued HDR lethal mutant strain MG1655 araispH upon genetic complementation, suggesting SrHDR to encode a functional protein. The gene exhibited diurnal variation in expression. To identify the possible regulatory elements, upstream region of the gene was cloned and putative cis-acting elements were detected by in silico analysis. Electrophoretic mobility shift assay, using a putative light responsive element GATA showed the binding of nuclear proteins (NP) isolated from leaves during light period of the day, but not with the NP from leaves during the dark period. Data suggested the involvement of GATA box in light mediated gene regulation of SrHDR in stevia. Copyright © 2013 Elsevier B.V. All rights reserved.

Disruption of the nitrogen regulatory gene AcareA in Acremonium chrysogenum leads to reduction of cephalosporin production and repression of nitrogen metabolism.

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Li, Jinyang; Pan, Yuanyuan; Liu, Gang

2013-12-01

AcareA, encoding a homologue of the fungal nitrogen regulatory GATA zinc-finger proteins, was cloned from Acremonium chrysogenum. Gene disruption and genetic complementation revealed that AcareA was required for nitrogen metabolism and cephalosporin production. Disruption of AcareA resulted in growth defect in the medium using nitrate, uric acid and low concentration of ammonium, glutamine or urea as sole nitrogen source. Transcriptional analysis showed that the transcription of niaD/niiA was increased drastically when induced with nitrate in the wild-type and AcareA complemented strains but not in AcareA disruption mutant. Consistent with the reduction of cephalosporin production, the transcription of pcbAB, cefD2, cefEF and cefG encoding the enzymes for cephalosporin production was reduced in AcareA disruption mutant. Band shift assays showed that AcAREA bound to the promoter regions of niaD, niiA and the bidirectional promoter region of pcbAB-pcbC. Sequence analysis showed that all the AcAREA binding sites contain the consensus GATA elements. These results indicated that AcAREA plays an important role both in the regulation of nitrogen metabolism and cephalosporin production in A. chrysogenum. Copyright © 2013 Elsevier Inc. All rights reserved.

Resveratrol Ameliorates Dysregulation of Th1, Th2, Th17, and T Regulatory Cell-Related Transcription Factor Signaling in a BTBR T + tf/J Mouse Model of Autism.

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Bakheet, Saleh A; Alzahrani, Mohammad Zeed; Ansari, Mushtaq Ahmad; Nadeem, Ahmed; Zoheir, Khairy M A; Attia, Sabry M; Al-Ayadhi, Laila Yousef; Ahmad, Sheikh Fayaz

2017-09-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. It is characterized by impaired social communication, abnormal social interactions, and repetitive behaviors and/or restricted interests. BTBR T + tf/J (BTBR) inbred mice are commonly used as a model for ASD. Resveratrol is used widely as a beneficial therapeutic in the treatment of an extensive array of pathologies, including neurodegenerative diseases. In the present study, the effect of resveratrol administration (20 and 40 mg/kg) was evaluated in both BTBR and C57BL/6 (B6) mice. Behavioral (self-grooming), Foxp3, T-bet, GATA-3, RORγt, and IL-17A in CD4 + T cells were assessed. Our study showed that BTBR control mice exhibited a distinct immune profile from that of the B6 control mice. BTBR mice were characterized by lower levels of Foxp3 + and higher levels of RORγt + , T-bet + , and GATA-3 + production in CD4 + T cells when compared with B6 control. Resveratrol (20 and 40 mg/kg) treatment to B6 and BTBR mice showed substantial induction of Foxp3 + and reduction of T-bet + , GATA-3 + , and IL-17A + expression in CD4 + cells when compared with the respective control groups. Moreover, resveratrol treatment resulted in upregulated expression of Foxp3 mRNA and decreased expression levels of T-bet, GATA-3, RORγt, and IL-17A in the spleen and brain tissues. Western blot analysis confirmed that resveratrol treatment decreased the protein expression of T-bet, GATA-3, RORγ, and IL-17 and that it increased Foxp3 in B6 and BTBR mice. Our results suggest that autism is associated with dysregulation of transcription factor signaling that can be corrected by resveratrol treatment.

Surface geothermal indication, Halo, from thermal historical standpoint. Netsushi teki ni mita chihyo chinetsu choko Halo

Energy Technology Data Exchange (ETDEWEB)

Nagatani, H

1977-01-01

Surficial effects of geothermal activity may, in certain cases, be detected by means of observing the distribution of vegetation in a given area. Zones of high temperature anomalies may be characterized by a lack of vegetation at their centers, surrounded by concentric belts of recessive dwarf plants, grasses, shrubs, and trees. The vegetation distribution boundary thereby delimits the scale of geothermal activity. Very high temperature portions of these anomalous zones can be detected by infrared imaging, and zones of distinctively patterned vegetation can be distinguished on conventional aerial photographs.

Expression of alpha V integrin is modulated by Epstein-Barr virus nuclear antigen 3C and the metastasis suppressor Nm23-H1 through interaction with the GATA-1 and Sp1 transcription factors

International Nuclear Information System (INIS)

Choudhuri, Tathagata; Verma, Subhash C.; Lan, Ke; Robertson, Erle S.

2006-01-01

Epstein-Barr virus (EBV) is a lymphotrophic herpesvirus infecting most of the world's population. It is associated with a number of human lymphoid and epithelial tumors and lymphoproliferative diseases in immunocompromised patients. A subset of latent EBV antigens is required for immortalization of primary B-lymphocytes. The metastatic suppressor Nm23-H1 which is downregulated in human invasive breast carcinoma reduces the migration and metastatic activity of breast carcinoma cells when expressed from a heterologous promoter. Interestingly, the EBV nuclear antigen 3C (EBNA3C) reverses these activities of Nm23-H1. The alpha V integrins recognize a variety of ligands for signaling and are involved in cell migration and proliferation and also serve as major receptors for extracellular-matrix-mediated cell adhesion and migration. The goal of this study was to determine if Nm23-H1 and EBNA3C can modulate alpha V integrin expression and downstream activities. The results of our studies indicate that Nm23-H1 downregulates alpha V intregrin expression in a dose responsive manner. In contrast, EBNA3C can upregulate alpha V integrin expression. Furthermore, the study showed that the association of the Sp1 and GATA transcription factors with Nm23-H1 is required for modulation of the alpha V integrin activity. Thus, these results suggest a direct correlation between the alpha V integrin expression and the interaction of Nm23-H1 with EBNA3C

Expressional and functional analyses of transcription factors activated by BMP-4s signaling in early xenopus embryo; BMP-4 shigunaru dentatsu kiko to sono hyoteki kakunai tensha inshi ni kansuru kenkyu

Energy Technology Data Exchange (ETDEWEB)

Maeno, Mitsugu [Niigata University, Niigata (Japan). Faculty of Science

1998-12-16

The expression and physiological function of two transcription factors, GATA-2 and Xmsx-1, in amphibian embryos has been analyzed. The expression of these mRNAs in embryonic cells were firmly regulated by the BMP-4 signaling, that plays a central role in the formation of ventral tissues. The microinjection studies of GATA-2 RNA into embryonic cells suggested that this factor functions in two adjacent germ layers, mesoderm and ectoderm, to participate in blood cell formation in ventral area of embryo. Embryos injected with Xmsx-1 RNA, but not with GATA-2, in dorsal blastomeres exhibited a ventralized phenotype, with microcephaly and swollen abdomen. Thus, Xmsx-1 is a ventralizing agent. However, on the basis of molecular marker analyses, Xmsx-1 did not promote erythropoietic differentiation, but promoted muscle tissue formation. It has been concluded that Xmsx-1 si a target transcription factor of the BMP-4 signaling, but possesses a distinct activity on dorso-ventral patterning of mesodermal tissues. (author)

Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia

OpenAIRE

Sanda, Takaomi; Lawton, Lee N.; Barrasa, M. Inmaculada; Fan, Zi Peng; Kohlhammer, Holger; Gutierrez, Alejandro; Ma, Wenxue; Tatarek, Jessica; Ahn, Yebin; Kelliher, Michelle A.; Jamieson, Catriona H.M.; Staudt, Louis M.; Young, Richard A.; Look, A. Thomas

2012-01-01

The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T-cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3 and RUNX1. We show that TAL1 forms a positive interconnected auto-regulatory loop with GATA3 and RUNX1, and that the TAL1 complex directly activates the MY...

Caudal brain infarctions in a kitten – case reportInfartos em região encefálica caudal em gata filhote – relato de caso

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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

Genotyping of Kell, Duffy, Kidd and RHD in patients with b Thalassemia

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Castilho Lilian

2000-01-01

Full Text Available Determination of Rh, Kell, Duffy and Kidd phenotypes in addition to ABO is used to prevent the alloimmunization to red blood cells (RBCs antigens and as part of the antibody identification process in patients with beta Thalassemia. However, phenotyping in these patients can be time consuming and difficult to interpret. In these situations, it would be valuable to have an alternative to hemagglutination tests to determine the patient's antigen profile. We used PCR-RFLP to genotype such patients. DNA was prepared from 50 patients with beta Thalassemia who had been phenotyped by routine hemagglutination, and tested for Kell, Kidd, Duffy/GATA mutation by PCR-RFLP. RHD/non-D was analysed by PCR product size associated to RHD gene sequence in intron 4 and exon 10/3'UTR. The genotyping assays were performed without knowledge of phenotype results. For RHD/non-D, 47 were RhD+ and RHD+/RHCE+, and 3 were RhD- and RHD-/RHCE+. For Kell, 48 kk were K2K2 and 2 Kk were K1K2. For Duffy, of 44 samples that had normal GATA box, 8 Fy(a+b- were FYA/FYA, 15 Fy(a+b+ were FYB/FYB, and 19 Fy(a+b+ were FYA/FYB; of the other 4 samples 3 were FYA/FYB and heterozygous GATA mutation, and 1 Fy(a-b- was FYB/FYB, homozygous GATA mutation. Two samples phenotyped as Fy(a+b- that had normal GATA , presented the 265T/298A mutations and two samples phenotyped as Fy(a-b+ were genotyped was FYA/FYB.. For Kidd , 15 Jk(a+b were JKA/JKA, 12 Jk(a-b+ were JKB/JKB, and 20 Jk(a+b+ were JKA/JKB. Three samples phenotyped as JK(a+b+ were genotyped as JKB/JKB. Genotype is more accurate than phenotype for determination of blood groups in polytransfused patients with betaThalassemia. Genotyping in these patients can be helpful to select antigen-negative RBCs for transfusion.

Desempenho de cultivares nacionais de batata para produtividade de tubérculos

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Giovani Olegario da Silva

2014-10-01

Full Text Available O objetivo deste trabalho foi verificar o desempenho dos cultivares de batata nacionais BRS Ana e BRS Clara, em comparação com os cultivares importados Ágata e Asterix, em relação à produtividade de tubérculos. Os experimentos foram realizados no município de Canoinhas, SC. Foram avaliados quatro cultivares de batata: BRS Ana, BRS Clara, Asterix e Ágata. O delineamento experimental foi em blocos casualizados, com quatro repetições. As parcelas continham quatro linhas com 20 plantas em cada linha. Cento e dez dias após o plantio foi realizada a colheita e, os tubérculos de cada parcela, avaliados para caracteres relacionados com a produtividade de tubérculos. Os dados foram submetidos à análise de variância e agrupamento de médias, por Skott & Knott, a 5% de probabilidade. Os cultivares de batata nacionais BRS Ana e BRS Clara foram mais produtivos do que os importados Asterix e Ágata; no entanto, são mais tardios, quanto ao ciclo vegetativo.

Supplymentary type semiconductor device and manufacturing method. Soho gata handotai sochi oyobi sono seizo hoho

Energy Technology Data Exchange (ETDEWEB)

Uno, Masaaki

1990-01-08

As a supplementary type semiconductor device has a complicated structure, it is extremely difficult to construct it in a three dimensional structure. This invention aims to reduce its occupying area by forming p-channel and n-channel transistors in a solid structure; moreover in an easy method of production. In other words, an opening is made in the element-forming region of a semiconductor substrate, forming a gate-insulation film on each of the p-type and n-type semiconductors which are exposed on the two facing surfaces; on it formed a gate electrode; p-type semiconductor surface is used as a channel domain; a drain region of n-channel transistor on one surface and a source region on another surface; the n-type semiconductor surface corresponding to the gate electrode is used as a channel region; a source region of the n-channel transistor is formed on the same surface and the drain region on the substrate surface. Occupied area is thus made less and the production gets easier. 20 figs.

NF-Y recruits both transcription activator and repressor to modulate tissue- and developmental stage-specific expression of human γ-globin gene.

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Xingguo Zhu

Full Text Available The human embryonic, fetal and adult β-like globin genes provide a paradigm for tissue- and developmental stage-specific gene regulation. The fetal γ-globin gene is expressed in fetal erythroid cells but is repressed in adult erythroid cells. The molecular mechanism underlying this transcriptional switch during erythroid development is not completely understood. Here, we used a combination of in vitro and in vivo assays to dissect the molecular assemblies of the active and the repressed proximal γ-globin promoter complexes in K562 human erythroleukemia cell line and primary human fetal and adult erythroid cells. We found that the proximal γ-globin promoter complex is assembled by a developmentally regulated, general transcription activator NF-Y bound strongly at the tandem CCAAT motifs near the TATA box. NF-Y recruits to neighboring DNA motifs the developmentally regulated, erythroid transcription activator GATA-2 and general repressor BCL11A, which in turn recruit erythroid repressor GATA-1 and general repressor COUP-TFII to form respectively the NF-Y/GATA-2 transcription activator hub and the BCL11A/COUP-TFII/GATA-1 transcription repressor hub. Both the activator and the repressor hubs are present in both the active and the repressed γ-globin promoter complexes in fetal and adult erythroid cells. Through changes in their levels and respective interactions with the co-activators and co-repressors during erythroid development, the activator and the repressor hubs modulate erythroid- and developmental stage-specific transcription of γ-globin gene.

DESCOLORIMENTO DE EFLUENTE ASSOCIADO AO TINGIMENTO DE ÁGATAS CONTENDO RODAMINA B COM DIFERENTES COMBINAÇÕES FOTOCATALÍTICAS VIA PROCESSOS OXIDATIVOS AVANÇADOS (POA´s

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Tiago Bender Wermuth

2013-12-01

Full Text Available O tingimento é um dos processos de acabamento das pedras semi-preciosas até a sua comercialização. Este é muito usado na indústria da ágata utilizando elevada demanda de água o que gera uma grande quantidade de águas residuárias, contendo moléculas corantes complexas, como a Rodamina B, que apresenta características de poluente orgânico com ecotoxicidade e genotoxicidade elevadas. Neste trabalho objetivou-se buscar o desenvolvimento de POA’s capazes de degradar os efluentes sintéticos provenientes do tingimento de pedras semi-preciosas contendo o corante Rodamina B (C.I 45170. Para uma melhor eficiência de remoção da Rodamina B, utilizou-se dois métodos distintos de fixação do catalisador utilizado. Primeiramente se trabalho com sílica-gel branca (1-3 mm, Tyvek e posteriormente com o Polietileno de baixa densidade (PEBD. Realizada a preparação dos materiais, investigou-se algumas combinações de métodos como UV/TiO2/SiO2/O3, UV/TiO2/PEBD/O3 bem como, o monitoramento de alguns parâmetros, como pH e a absorbância de amostras sintéticas. Os testes foram realizados em um reator em acrílico composto de lâmpada germicida (SCT – G13/T8/15W, onde se trabalhou com um volume útil de 1 L.Compondo ainda o reator, utilizou-se uma proveta de 1 litro e uma bomba peristáltica. A concentração de Rodamina B utilizada foi de 20 mg L-1. A partir dos resultados obtidos foi possível verificar que a combinação do UV/TiO2/PEBD/O3 mostrou-se ser mais eficiente. Essa combinação proporcionou um valor de constante cinética na ordem de 28,6 x 10-3 min-1. Se comparado aos demais processos investigados, pode-se observar que se teve um aumento do valor de k.

The Chandra Source Catalog : Automated Source Correlation

Science.gov (United States)

Hain, Roger; Evans, I. N.; Evans, J. D.; Glotfelty, K. J.; Anderson, C. S.; Bonaventura, N. R.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Fabbiano, G.; Galle, E.; Gibbs, D. G.; Grier, J. D.; Hall, D. M.; Harbo, P. N.; He, X.; Houck, J. C.; Karovska, M.; Lauer, J.; McCollough, M. L.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Nowak, M. A.; Plummer, D. A.; Primini, F. A.; Refsdal, B. L.; Rots, A. H.; Siemiginowska, A. L.; Sundheim, B. A.; Tibbetts, M. S.; Van Stone, D. W.; Winkelman, S. L.; Zografou, P.

2009-01-01

Chandra Source Catalog (CSC) master source pipeline processing seeks to automatically detect sources and compute their properties. Since Chandra is a pointed mission and not a sky survey, different sky regions are observed for a different number of times at varying orientations, resolutions, and other heterogeneous conditions. While this provides an opportunity to collect data from a potentially large number of observing passes, it also creates challenges in determining the best way to combine different detection results for the most accurate characterization of the detected sources. The CSC master source pipeline correlates data from multiple observations by updating existing cataloged source information with new data from the same sky region as they become available. This process sometimes leads to relatively straightforward conclusions, such as when single sources from two observations are similar in size and position. Other observation results require more logic to combine, such as one observation finding a single, large source and another identifying multiple, smaller sources at the same position. We present examples of different overlapping source detections processed in the current version of the CSC master source pipeline. We explain how they are resolved into entries in the master source database, and examine the challenges of computing source properties for the same source detected multiple times. Future enhancements are also discussed. This work is supported by NASA contract NAS8-03060 (CXC).

Global regulator SATB1 recruits beta-catenin and regulates T(H2 differentiation in Wnt-dependent manner.

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Dimple Notani

2010-01-01

Full Text Available In vertebrates, the conserved Wnt signalling cascade promotes the stabilization and nuclear accumulation of beta-catenin, which then associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs to activate target genes. Wnt/beta -catenin signalling is essential for T cell development and differentiation. Here we show that special AT-rich binding protein 1 (SATB1, the T lineage-enriched chromatin organizer and global regulator, interacts with beta-catenin and recruits it to SATB1's genomic binding sites. Gene expression profiling revealed that the genes repressed by SATB1 are upregulated upon Wnt signalling. Competition between SATB1 and TCF affects the transcription of TCF-regulated genes upon beta-catenin signalling. GATA-3 is a T helper type 2 (T(H2 specific transcription factor that regulates production of T(H2 cytokines and functions as T(H2 lineage determinant. SATB1 positively regulated GATA-3 and siRNA-mediated knockdown of SATB1 downregulated GATA-3 expression in differentiating human CD4(+ T cells, suggesting that SATB1 influences T(H2 lineage commitment by reprogramming gene expression. In the presence of Dickkopf 1 (Dkk1, an inhibitor of Wnt signalling, GATA-3 is downregulated and the expression of signature T(H2 cytokines such as IL-4, IL-10, and IL-13 is reduced, indicating that Wnt signalling is essential for T(H2 differentiation. Knockdown of beta-catenin also produced similar results, confirming the role of Wnt/beta-catenin signalling in T(H2 differentiation. Furthermore, chromatin immunoprecipitation analysis revealed that SATB1 recruits beta-catenin and p300 acetyltransferase on GATA-3 promoter in differentiating T(H2 cells in a Wnt-dependent manner. SATB1 coordinates T(H2 lineage commitment by reprogramming gene expression. The SATB1:beta-catenin complex activates a number of SATB1 regulated genes, and hence this study has potential to find novel Wnt responsive genes. These results demonstrate that SATB1

Clinical and mutational spectrum of hypoparathyroidism, deafness and renal dysplasia syndrome.

Science.gov (United States)

Belge, Hendrica; Dahan, Karin; Cambier, Jean-François; Benoit, Valérie; Morelle, Johann; Bloch, Julie; Vanhille, Philippe; Pirson, Yves; Demoulin, Nathalie

2017-05-01

Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder, secondary to mutations in the GATA-3 gene. Due to its wide range of penetrance and expressivity, the disease may not always be recognized. We herein describe clinical and genetic features of patients with HDR syndrome, highlighting diagnostic clues. Medical records of eight patients from five unrelated families exhibiting GATA-3 mutations were reviewed retrospectively, in conjunction with all previously reported cases. HDR syndrome was diagnosed in eight patients between the ages of 18 and 60 years. Sensorineural deafness was consistently diagnosed, ranging from clinical hearing loss since infancy in seven patients to deafness detected only by audiometry in adulthood in one single patient. Hypoparathyroidism was present in six patients (with hypocalcaemia and inaugural seizures in two out of six). Renal abnormalities observed in six patients were diverse and of dysplastic nature. Three patients displayed nephrotic-range proteinuria and reached end-stage renal disease (ESRD) between the ages of 19 and 61 years, whilst lesions of focal and segmental glomerulosclerosis were histologically demonstrated in one of them. Interestingly, phenotype severity differed significantly between a mother and son within one family. Five new mutations of GATA-3 were identified, including three missense mutations affecting zinc finger motifs [NM_001002295.1: c.856A>G (p.N286D) and c.1017C>G (p.C339W)] or the conserved linker region [c.896G>A (p.R299G)], and two splicing mutations (c.924+4_924+19del and c.1051-2A>G). Review of 115 previously reported cases of GATA-3 mutations showed hypoparathyroidism and deafness in 95% of patients, and renal abnormalities in only 60%. Overall, 10% of patients had reached ESRD. We herein expand the clinical and mutational spectrum of HDR syndrome, illustrating considerable inter- and intrafamilial phenotypic variability. Diagnosis of HDR should be

The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells.

Science.gov (United States)

Matsumura, I; Kanakura, Y; Kato, T; Ikeda, H; Horikawa, Y; Ishikawa, J; Kitayama, H; Nishiura, T; Tomiyama, Y; Miyazaki, H; Matsuzawa, Y

1996-10-15

Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic level in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2.

A gene regulatory network armature for T-lymphocyte specification

Energy Technology Data Exchange (ETDEWEB)

Fung, Elizabeth-sharon [Los Alamos National Laboratory

2008-01-01

Choice of a T-lymphoid fate by hematopoietic progenitor cells depends on sustained Notch-Delta signaling combined with tightly-regulated activities of multiple transcription factors. To dissect the regulatory network connections that mediate this process, we have used high-resolution analysis of regulatory gene expression trajectories from the beginning to the end of specification; tests of the short-term Notchdependence of these gene expression changes; and perturbation analyses of the effects of overexpression of two essential transcription factors, namely PU.l and GATA-3. Quantitative expression measurements of >50 transcription factor and marker genes have been used to derive the principal components of regulatory change through which T-cell precursors progress from primitive multipotency to T-lineage commitment. Distinct parts of the path reveal separate contributions of Notch signaling, GATA-3 activity, and downregulation of PU.l. Using BioTapestry, the results have been assembled into a draft gene regulatory network for the specification of T-cell precursors and the choice of T as opposed to myeloid dendritic or mast-cell fates. This network also accommodates effects of E proteins and mutual repression circuits of Gfil against Egr-2 and of TCF-l against PU.l as proposed elsewhere, but requires additional functions that remain unidentified. Distinctive features of this network structure include the intense dose-dependence of GATA-3 effects; the gene-specific modulation of PU.l activity based on Notch activity; the lack of direct opposition between PU.l and GATA-3; and the need for a distinct, late-acting repressive function or functions to extinguish stem and progenitor-derived regulatory gene expression.

Source-space ICA for MEG source imaging.

Science.gov (United States)

Jonmohamadi, Yaqub; Jones, Richard D

2016-02-01

One of the most widely used approaches in electroencephalography/magnetoencephalography (MEG) source imaging is application of an inverse technique (such as dipole modelling or sLORETA) on the component extracted by independent component analysis (ICA) (sensor-space ICA + inverse technique). The advantage of this approach over an inverse technique alone is that it can identify and localize multiple concurrent sources. Among inverse techniques, the minimum-variance beamformers offer a high spatial resolution. However, in order to have both high spatial resolution of beamformer and be able to take on multiple concurrent sources, sensor-space ICA + beamformer is not an ideal combination. We propose source-space ICA for MEG as a powerful alternative approach which can provide the high spatial resolution of the beamformer and handle multiple concurrent sources. The concept of source-space ICA for MEG is to apply the beamformer first and then singular value decomposition + ICA. In this paper we have compared source-space ICA with sensor-space ICA both in simulation and real MEG. The simulations included two challenging scenarios of correlated/concurrent cluster sources. Source-space ICA provided superior performance in spatial reconstruction of source maps, even though both techniques performed equally from a temporal perspective. Real MEG from two healthy subjects with visual stimuli were also used to compare performance of sensor-space ICA and source-space ICA. We have also proposed a new variant of minimum-variance beamformer called weight-normalized linearly-constrained minimum-variance with orthonormal lead-field. As sensor-space ICA-based source reconstruction is popular in EEG and MEG imaging, and given that source-space ICA has superior spatial performance, it is expected that source-space ICA will supersede its predecessor in many applications.

Generation of electrophysiologically functional cardiomyocytes from mouse induced pluripotent stem cells

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Hongran Wang

2016-03-01

Full Text Available Induced pluripotent stem (iPS cells can efficiently differentiate into the three germ layers similar to those formed by differentiated embryonic stem (ES cells. This provides a new source of cells in which to establish preclinical allogeneic transplantation models. Our iPS cells were generated from mouse embryonic fibroblasts (MEFs transfected with the Yamanaka factors, the four transcription factors (Oct4, Sox2, Klf4 and c-Myc, without antibiotic selection or MEF feeders. After the formation of embryoid bodies (EBs, iPS cells spontaneously differentiated into Flk1-positive cardiac progenitors and cardiomyocytes expressing cardiac-specific markers such as alpha sarcomeric actinin (α-actinin, cardiac alpha myosin heavy chain (α-MHC, cardiac troponin T (cTnT, and connexin 43 (CX43, as well as cardiac transcription factors Nk2 homebox 5 (Nkx2.5 and gata binding protein 4 (gata4. The electrophysiological activity of iPS cell-derived cardiomyocytes (iPS-CMs was detected in beating cell clusters with optical mapping and RH237 a voltage-sensitive dye, and in single contracting cells with patch-clamp technology. Incompletely differentiated iPS cells formed teratomas when transplanted into a severe combined immunodeficiency (SCID mouse model of myocardial infarction. Our results show that somatic cells can be reprogrammed into pluripotent stem cells, which in turn spontaneously differentiate into electrophysiologically functional mature cardiomyocytes expressing cardiac-specific makers, and that these cells can potentially be used to repair myocardial infarction (MI in the future.

The epigenetic modifiers 5-aza-2'-deoxycytidine and trichostatin A influence adipocyte differentiation in human mesenchymal stem cells

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J. Zych

2013-05-01

Full Text Available Epigenetic mechanisms such as DNA methylation and histone modification are important in stem cell differentiation. Methylation is principally associated with transcriptional repression, and histone acetylation is correlated with an active chromatin state. We determined the effects of these epigenetic mechanisms on adipocyte differentiation in mesenchymal stem cells (MSCs derived from bone marrow (BM-MSCs and adipose tissue (ADSCs using the chromatin-modifying agents trichostatin A (TSA, a histone deacetylase inhibitor, and 5-aza-2′-deoxycytidine (5azadC, a demethylating agent. Subconfluent MSC cultures were treated with 5, 50, or 500 nM TSA or with 1, 10, or 100 µM 5azadC for 2 days before the initiation of adipogenesis. The differentiation was quantified and expression of the adipocyte genes PPARG and FABP4 and of the anti-adipocyte gene GATA2 was evaluated. TSA decreased adipogenesis, except in BM-MSCs treated with 5 nM TSA. Only treatment with 500 nM TSA decreased cell proliferation. 5azadC treatment decreased proliferation and adipocyte differentiation in all conditions evaluated, resulting in the downregulation of PPARG and FABP4 and the upregulation of GATA2. The response to treatment was stronger in ADSCs than in BM-MSCs, suggesting that epigenetic memories may differ between cells of different origins. As epigenetic signatures affect differentiation, it should be possible to direct the use of MSCs in cell therapies to improve process efficiency by considering the various sources available.

Sources

International Nuclear Information System (INIS)

Duffy, L.P.

1991-01-01

This paper discusses the sources of radiation in the narrow perspective of radioactivity and the even narrow perspective of those sources that concern environmental management and restoration activities at DOE facilities, as well as a few related sources. Sources of irritation, Sources of inflammatory jingoism, and Sources of information. First, the sources of irritation fall into three categories: No reliable scientific ombudsman to speak without bias and prejudice for the public good, Technical jargon with unclear definitions exists within the radioactive nomenclature, and Scientific community keeps a low-profile with regard to public information. The next area of personal concern are the sources of inflammation. This include such things as: Plutonium being described as the most dangerous substance known to man, The amount of plutonium required to make a bomb, Talk of transuranic waste containing plutonium and its health affects, TMI-2 and Chernobyl being described as Siamese twins, Inadequate information on low-level disposal sites and current regulatory requirements under 10 CFR 61, Enhanced engineered waste disposal not being presented to the public accurately. Numerous sources of disinformation regarding low level radiation high-level radiation, Elusive nature of the scientific community, The Federal and State Health Agencies resources to address comparative risk, and Regulatory agencies speaking out without the support of the scientific community

The Chandra Source Catalog: Source Variability

Science.gov (United States)

Nowak, Michael; Rots, A. H.; McCollough, M. L.; Primini, F. A.; Glotfelty, K. J.; Bonaventura, N. R.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Evans, J. D.; Evans, I.; Fabbiano, G.; Galle, E. C.; Gibbs, D. G., II; Grier, J. D.; Hain, R.; Hall, D. M.; Harbo, P. N.; He, X.; Houck, J. C.; Karovska, M.; Lauer, J.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Plummer, D. A.; Refsdal, B. L.; Siemiginowska, A. L.; Sundheim, B. A.; Tibbetts, M. S.; van Stone, D. W.; Winkelman, S. L.; Zografou, P.

2009-09-01

The Chandra Source Catalog (CSC) contains fields of view that have been studied with individual, uninterrupted observations that span integration times ranging from 1 ksec to 160 ksec, and a large number of which have received (multiple) repeat observations days to years later. The CSC thus offers an unprecedented look at the variability of the X-ray sky over a broad range of time scales, and across a wide diversity of variable X-ray sources: stars in the local galactic neighborhood, galactic and extragalactic X-ray binaries, Active Galactic Nuclei, etc. Here we describe the methods used to identify and quantify source variability within a single observation, and the methods used to assess the variability of a source when detected in multiple, individual observations. Three tests are used to detect source variability within a single observation: the Kolmogorov-Smirnov test and its variant, the Kuiper test, and a Bayesian approach originally suggested by Gregory and Loredo. The latter test not only provides an indicator of variability, but is also used to create a best estimate of the variable lightcurve shape. We assess the performance of these tests via simulation of statistically stationary, variable processes with arbitrary input power spectral densities (here we concentrate on results of red noise simulations) at variety of mean count rates and fractional root mean square variabilities relevant to CSC sources. We also assess the false positive rate via simulations of constant sources whose sole source of fluctuation is Poisson noise. We compare these simulations to an assessment of the variability found in real CSC sources, and estimate the variability sensitivities of the CSC.

Sources management; La gestion des sources

Energy Technology Data Exchange (ETDEWEB)

Mansoux, H.; Gourmelon; Scanff, P.; Fournet, F. [Institut de Radioprotection et de Surete Nucleaire, 92 - Fontenay-aux-Roses (France); Murith, Ch. [Office Federal de la SantePublique (Switzerland); Saint-Paul, N. [NOVAR, 75 - Paris (France); Colson, P. [Electricite de France (EDF/DPN), 93 - Saint-Denis (France); Jouve, A.; Feron, F. [Direction Generale de al Surete Nucleaire et de la Radioprotection, 75 - Paris (France); Haranger, D. [Electricite de France (EDF), 75 - Paris (France); Mathieu, P. [Institut Pasteur, 75 - Paris (France); Paycha, F. [CHU Louis Mourier, Unitede Medecine Nucleaire Assistance Publique-Hopitaux de Paris, 92 - Colombes (France); Israel, S. [CEGELEC NDT et la gestion des sources radioactives (France); Auboiroux, B. [APAVE (France); Chartier, P. [DRIRE de Basse-Normandie, Div. Surete Nucleaire et Radioprotection, 14 - Caen (France)

2005-07-01

Organized by the section of technical protection of the French society of radiation protection ( S.F.R.P.), these two days had for objective to review the evolution of the rule relative to the sources of ionising radiations 'sealed and unsealed radioactive sources, electric generators'. They addressed all the actors concerned by the implementation of the new regulatory system in the different sectors of activities ( research, medicine and industry): Authorities, manufacturers, and suppliers of sources, holders and users, bodies involved in the approval of sources, carriers. (N.C.)

Source Water Protection Contaminant Sources

Data.gov (United States)

Iowa State University GIS Support and Research Facility — Simplified aggregation of potential contaminant sources used for Source Water Assessment and Protection. The data is derived from IDNR, IDALS, and US EPA program...

Down-regulation of Notch signaling pathway reverses the Th1/Th2 imbalance in tuberculosis patients.

Science.gov (United States)

Li, Qifeng; Zhang, Hui; Yu, Liang; Wu, Chao; Luo, Xinhui; Sun, He; Ding, Jianbing

2018-01-01

Th1/Th2 imbalance to Th2 is of significance in the peripheral immune responses in Tuberculosis (TB) development. However, the mechanisms for Th1/Th2 imbalance are still not well determined. Notch signaling pathway is involved in the peripheral T cell activation and effector cell differentiation. However, whether it affects Th1/Th2 imbalance in TB patients is still not known. Here, we used γ-secretase inhibitor (DAPT) to treat the peripheral blood mononuclear cells (PBMCs) from healthy people or individuals with latent or active TB infection in vitro, respectively. Then, the Th1/Th2 ratios were determined by flow cytometry, and cytokines of IFN-γ, IL-4, IL-10 in the culture supernatant were measured by CBA method. The Notch signal pathway associated proteins Hes1, GATA3 and T-bet were quantitated by real-time PCR or immunoblotting. Our results showed that DAPT effectively inhibited the protein level of Hes1. In TB patients, the Th2 ratio increased in the PBMCs, alone with the high expression of GATA3 and IL-4, resulting in the high ratios of Th2/Th1 and GATA3/T-bet in TB patients. However, Th2 cells ratio decreased after blocking the Notch signaling pathway by DAPT and the Th2/Th1 ratio in TB patients were DAPT dose-dependent, accompanied by the decrease of IL-4 and GATA3. But, its influence on Th1 ratio and Th1 related T-bet and IFN-γ levels were not significant. In conclusion, our results suggest that blocking Notch signaling by DAPT could inhibit Th2 responses and restore Th1/Th2 imbalance in TB patients. Copyright © 2017. Published by Elsevier B.V.

Altered AKT1 and MAPK1 Gene Expression on Peripheral Blood Mononuclear Cells and Correlation with T-Helper-Transcription Factors in Systemic Lupus Erythematosus Patients

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Sonia Garcia-Rodriguez

2012-01-01

Full Text Available Kinases have been implicated in the immunopathological mechanisms of Systemic Lupus Erythematosus (SLE. v-akt murine-thymoma viral-oncogene-homolog 1 (AKT1 and mitogen-activated-protein-kinase 1 (MAPK1 gene expressions in peripheral mononuclear cells from thirteen SLE patients with inactive or mild disease were evaluated using quantitative real-time reverse-transcription polymerase-chain-reaction and analyzed whether there was any correlation with T-helper (Th transcription factors (TF gene expression, cytokines, and S100A8/S100A9-(Calprotectin. Age- and gender-matched thirteen healthy controls were examined. AKT1 and MAPK1 expressions were upregulated in SLE patients and correlated with Th17-(Retinoic acid-related orphan receptor (ROR-C, T-regulatory-(Treg-(Transforming Growth Factor Beta (TGFB-2, and Th2-(interleukin (IL-5-related genes. MAPK1 expression correlated with Th1-(IL-12A, T-box TF-(T-bet, Th2-(GATA binding protein-(GATA-3, and IL-10 expressions. IL-10 expression was increased and correlated with plasma Tumor Necrosis Factor (TNF-α and Th0-(IL-2, Th1-(IL-12A, T-bet, GATA3, Treg-(Forkhead/winged-helix transcription factor- (FOXP-3, and IL-6 expressions. FOXP3 expression, FOXP3/RORC, and FOXP3/GATA3 expression ratios were increased. Plasma IL-1β, IL-12(p70, Interferon-(IFN-γ, and IL-6 cytokines were augmented. Plasma IL-1β, IL-6, IL-2, IFN-γ, TNF-α, IL-10, and IL-13 correlated with C-reactive protein, respectively. Increased Calprotectin correlated with neutrophils. Conclusion, SLE patients presented a systemic immunoinflammatory activity, augmented AKT1 and MAPK1 expressions, proinflammatory cytokines, and Calprotectin, together with increased expression of Treg-related genes, suggesting a regulatory feedback opposing the inflammatory activity.

Microscopic Colitis Evolved Into Inflammatory Bowel Diseases Is Characterized by Increased Th1/Tc1 Cells in Colonic Mucosal Lamina Propria.

Science.gov (United States)

Li, Ji; Yan, Yuchu; Meng, Ziran; Liu, Shuhong; Beck, Paul L; Ghosh, Subrata; Qian, Jiaming; Gui, Xianyong

2017-10-01

An association between microscopic colitis (MC), i.e., lymphocytic colitis (LC) and collagenous colitis (CC), and inflammatory bowel diseases (IBD) has been noticed. A subset of MC cases may evolve into IBD, and IBD in remission may present as MC in a histologic pattern. Moreover, MC and IBD may coexist in different regions of the bowel. A link between MC and IBD in their pathogenesis is, therefore, suggested. Abnormal mucosal immunity is likely the key. We reviewed 2324 MC cases in Calgary over 14 years and identified 20 cases evolved into IBD (IBD transformers). 13 of them were further investigated for colonic mucosal lamina propria mononuclear cells (LPMNCs), as opposed to 22 cases whose MC resolved. On their index colonic biopsy immunohistochemistry was performed to detect major T cell subsets characterized by key cytokines and master transcription factors (IFNγ and T-bet for Th1/Tc1, GATA-3 for Th2/Tc2, IL-17 and RORc for Th17/Tc17, FoxP3 for Treg/Tcreg) as well as TNFα + cells (partly representing Th1). LPMNCs positive for each marker were counted (average number per high-power field). IBD transformers had increased IFNγ + , T-bet + , TNF-α + , and GATA-3 + LPMNCs compared to the MC-resolved cases. The LC-to-IBD subgroup had increased IFNγ + and GATA-3 + cells compared to the LC-resolved subgroup. The CC-to-IBD subgroup had increased T-bet + , TNF-α + , and GATA-3 + cells compared to the CC-resolved subgroup. Among MC-resolved patients, more TNF-α + and RORc + cells were seen in LC than in CC. Th1/Tc1- and TNFα-producing cells, and likely a subset of Th2/Tc2 cells as well, may be involved in the MC-to-IBD transformation.

Inducible nitric oxide synthase (iNOS) regulatory region variation in non-human primates.

Science.gov (United States)

Roodgar, Morteza; Ross, Cody T; Kenyon, Nicholas J; Marcelino, Gretchen; Smith, David Glenn

2015-04-01

Inducible nitric oxide synthase (iNOS) is an enzyme that plays a key role in intracellular immune response against respiratory infections. Since various species of nonhuman primates exhibit different levels of susceptibility to infectious respiratory diseases, and since variation in regulatory regions of genes is thought to play a key role in expression levels of genes, two candidate regulatory regions of iNOS were mapped, sequenced, and compared across five species of nonhuman primates: African green monkeys (Chlorocebus sabaeus), pig-tailed macaques (Macaca nemestrina), cynomolgus macaques (Macaca fascicularis), Indian rhesus macaques (Macaca mulatta), and Chinese rhesus macaques (M. mulatta). In addition, we conducted an in silico analysis of the transcription factor binding sites associated with genetic variation in these two candidate regulatory regions across species. We found that only one of the two candidate regions showed strong evidence of involvement in iNOS regulation. Specifically, we found evidence of 13 conserved binding site candidates linked to iNOS regulation: AP-1, C/EBPB, CREB, GATA-1, GATA-3, NF-AT, NF-AT5, NF-κB, KLF4, Oct-1, PEA3, SMAD3, and TCF11. Additionally, we found evidence of interspecies variation in binding sites for several regulatory elements linked to iNOS (GATA-3, GATA-4, KLF6, SRF, STAT-1, STAT-3, OLF-1 and HIF-1) across species, especially in African green monkeys relative to other species. Given the key role of iNOS in respiratory immune response, the findings of this study might help guide the direction of future studies aimed to uncover the molecular mechanisms underlying the increased susceptibility of African green monkeys to several viral and bacterial respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular functions of the LIM-homeobox transcription factor Lhx2 in hematopoietic progenitor cells derived from mouse embryonic stem cells.

Science.gov (United States)

Kitajima, Kenji; Kawaguchi, Manami; Iacovino, Michelina; Kyba, Michael; Hara, Takahiko

2013-12-01

We previously demonstrated that hematopoietic stem cell (HSC)-like cells are robustly expanded from mouse embryonic stem cells (ESCs) by enforced expression of Lhx2, a LIM-homeobox domain (LIM-HD) transcription factor. In this study, we analyzed the functions of Lhx2 in that process using an ESC line harboring an inducible Lhx2 gene cassette. When ESCs are cultured on OP9 stromal cells, hematopoietic progenitor cells (HPCs) are differentiated and these HPCs are prone to undergo rapid differentiation into mature hematopoietic cells. Lhx2 inhibited differentiation of HPCs into mature hematopoietic cells and this effect would lead to accumulation of HSC-like cells. LIM-HD factors interact with LIM domain binding (Ldb) protein and this interaction abrogates binding of LIM-only (Lmo) protein to Ldb. We found that one of Lmo protein, Lmo2, was unstable due to dissociation of Lmo2 from Ldb1 in the presence of Lhx2. This effect of Lhx2 on the amount of Lmo2 contributed into accumulation of HSC-like cells, since enforced expression of Lmo2 into HSC-like cells inhibited their self-renewal. Expression of Gata3 and Tal1/Scl was increased in HSC-like cells and enforced expression of Lmo2 reduced expression of Gata3 but not Tal1/Scl. Enforced expression of Gata3 into HPCs inhibited mature hematopoietic cell differentiation, whereas Gata3-knockdown abrogated the Lhx2-mediated expansion of HPCs. We propose that multiple transcription factors/cofactors are involved in the Lhx2-mediated expansion of HSC-like cells from ESCs. Lhx2 appears to fine-tune the balance between self-renewal and differentiation of HSC-like cells. © AlphaMed Press.

Bone Metastasis in Advanced Breast Cancer: Analysis of Gene Expression Microarray.

Science.gov (United States)

Cosphiadi, Irawan; Atmakusumah, Tubagus D; Siregar, Nurjati C; Muthalib, Abdul; Harahap, Alida; Mansyur, Muchtarruddin

2018-03-08

Approximately 30% to 40% of breast cancer recurrences involve bone metastasis (BM). Certain genes have been linked to BM; however, none have been able to predict bone involvement. In this study, we analyzed gene expression profiles in advanced breast cancer patients to elucidate genes that can be used to predict BM. A total of 92 advanced breast cancer patients, including 46 patients with BM and 46 patients without BM, were identified for this study. Immunohistochemistry and gene expression analysis was performed on 81 formalin-fixed paraffin-embedded samples. Data were collected through medical records, and gene expression of 200 selected genes compiled from 6 previous studies was performed using NanoString nCounter. Genetic expression profiles showed that 22 genes were significantly differentially expressed between breast cancer patients with metastasis in bone and other organs (BM+) and non-BM, whereas subjects with only BM showed 17 significantly differentially expressed genes. The following genes were associated with an increasing incidence of BM in the BM+ group: estrogen receptor 1 (ESR1), GATA binding protein 3 (GATA3), and melanophilin with an area under the curve (AUC) of 0.804. In the BM group, the following genes were associated with an increasing incidence of BM: ESR1, progesterone receptor, B-cell lymphoma 2, Rab escort protein, N-acetyltransferase 1, GATA3, annexin A9, and chromosome 9 open reading frame 116. ESR1 and GATA3 showed an increased strength of association with an AUC of 0.928. A combination of the identified 3 genes in BM+ and 8 genes in BM showed better prediction than did each individual gene, and this combination can be used as a training set. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Clonal selection in xenografted TAM recapitulates the evolutionary process of myeloid leukemia in Down syndrome.

Science.gov (United States)

Saida, Satoshi; Watanabe, Ken-ichiro; Sato-Otsubo, Aiko; Terui, Kiminori; Yoshida, Kenichi; Okuno, Yusuke; Toki, Tsutomu; Wang, RuNan; Shiraishi, Yuichi; Miyano, Satoru; Kato, Itaru; Morishima, Tatsuya; Fujino, Hisanori; Umeda, Katsutsugu; Hiramatsu, Hidefumi; Adachi, Souichi; Ito, Etsuro; Ogawa, Seishi; Ito, Mamoru; Nakahata, Tatsutoshi; Heike, Toshio

2013-05-23

Transient abnormal myelopoiesis (TAM) is a clonal preleukemic disorder that progresses to myeloid leukemia of Down syndrome (ML-DS) through the accumulation of genetic alterations. To investigate the mechanism of leukemogenesis in this disorder, a xenograft model of TAM was established using NOD/Shi-scid, interleukin (IL)-2Rγ(null) mice. Serial engraftment after transplantation of cells from a TAM patient who developed ML-DS a year later demonstrated their self-renewal capacity. A GATA1 mutation and no copy number alterations (CNAs) were detected in the primary patient sample by conventional genomic sequencing and CNA profiling. However, in serial transplantations, engrafted TAM-derived cells showed the emergence of divergent subclones with another GATA1 mutation and various CNAs, including a 16q deletion and 1q gain, which are clinically associated with ML-DS. Detailed genomic analysis identified minor subclones with a 16q deletion or this distinct GATA1 mutation in the primary patient sample. These results suggest that genetically heterogeneous subclones with varying leukemia-initiating potential already exist in the neonatal TAM phase, and ML-DS may develop from a pool of such minor clones through clonal selection. Our xenograft model of TAM may provide unique insight into the evolutionary process of leukemia.

Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome

Directory of Open Access Journals (Sweden)

Marianna P.R. Porto

2010-01-01

Full Text Available The Holt-Oram syndrome (HOS is an autosomal dominant condition characterized by upper limb and cardiac malformations. Mutations in the TBX5 gene cause HOS and have also been associated with isolated heart and arm defects. Interactions between the TBX5, GATA4 and NKX2.5 proteins have been reported in humans. We screened the TBX5, GATA4, and NKX2.5 genes for mutations, by direct sequencing, in 32 unrelated patients presenting classical (8 or atypical HOS (1, isolated congenital heart defects (16 or isolated upper-limb malformations (7. Pathogenic mutations in the TBX5 gene were found in four HOS patients, including two new mutations (c.374delG; c.678G > T in typical patients, and the hotspot mutation c.835C > T in two patients, one of them with an atypical HOS phenotype involving lower-limb malformations. Two new mutations in the GATA4 gene were found in association with isolated upper-limb malformations, but their clinical significance remains to be established. A previously described possibly pathogenic mutation in the NKX2.5 gene (c.73C > 7 was detected in a patient with isolated heart malformations and also in his clinically normal father.

Large source test stand for H-(D-) ion source

International Nuclear Information System (INIS)

Larson, R.; McKenzie-Wilson, R.

1981-01-01

The Brookhaven National Laboratory Neutral Beam Group has constructed a large source test stand for testing of the various source modules under development. The first objective of the BNL program is to develop a source module capable of delivering 10A of H - (D - ) at 25 kV operating in the steady state mode with satisfactory gas and power efficiency. The large source test stand contains gas supply and vacuum pumping systems, source cooling systems, magnet power supplies and magnet cooling systems, two arc power supplies rated at 25 kW and 50 kW, a large battery driven power supply and an extractor electrode power supply. Figure 1 is a front view of the vacuum vessel showing the control racks with the 36'' vacuum valves and refrigerated baffles mounted behind. Figure 2 shows the rear view of the vessel with a BNL Mk V magnetron source mounted in the source aperture and also shows the cooled magnet coils. Currently two types of sources are under test: a large magnetron source and a hollow cathode discharge source

Radioactive source recovery program responses to neutron source emergencies

International Nuclear Information System (INIS)

Dinehart, S.M.; Hatler, V.A.; Gray, D.W.; Guillen, A.D.

1997-01-01

Recovery of neutron sources containing Pu 239 and Be is currently taking place at Los Alamos National Laboratory. The program was initiated in 1979 by the Department of Energy (DOE) to dismantle and recover sources owned primarily by universities and the Department of Defense. Since the inception of this program, Los Alamos has dismantled and recovered more than 1000 sources. The dismantlement and recovery process involves the removal of source cladding and the chemical separation of the source materials to eliminate neutron emissions. While this program continues for the disposal of 239 Pu/Be sources, there is currently no avenue for the disposition of any sources other than those containing Pu 239 . Increasingly, there have been demands from agencies both inside and outside the Federal Government and from the public to dispose of unwanted sources containing 238 Pu/Be and 241 Am/Be. DOE is attempting to establish a formal program to recover these sources and is working closely with the Nuclear Regulatory Commission (NRC) on a proposed Memorandum of Understanding to formalize an Acceptance Program. In the absence of a formal program to handle 238 Pu/Be and 241 Am/Be neutron sources, Los Alamos has responded to several emergency requests to receive and recover sources that have been determined to be a threat to public health and safety. This presentation will: (1) review the established 239 Pu neutron source recovery program at Los Alamos, (2) detail plans for a more extensive neutron source disposal program, and (3) focus on recent emergency responses

Mäletamine, aeglus ja kontrollimatu kapitalism / Eugen Ruge ; intervjueerinud Dieter Neidlinger ; saksa keelest eesti keelde vahendanud Aija Sakova

Index Scriptorium Estoniae

Ruge, Eugen, 1954-

2016-01-01

Intervjuu kirjandusfestivalil "Prima vista" esineva saksa kirjaniku Eugen Rugega tema romaanides "Kahaneva valguse aegu" ("In Zeiten des abnehmenden Lichts") ja "Cabo de Gata" ning käsil olevast teosest

Gln3p and Nil1p regulation of invertase activity and SUC2 expression in Saccharomyces cerevisiae.

Science.gov (United States)

Oliveira, Edna Maria Morais; Mansure, José João; Bon, Elba Pinto da Silva

2005-04-01

In Saccharomyces cerevisiae, sensing and signalling pathways regulate gene expression in response to quality of carbon and nitrogen sources. One such system, the target of rapamycin (Tor) proteins, senses nutrients and uses the GATA activators Gln3p and Nil1p to regulate translation in response to low-quality carbon and nitrogen. The signal transduction, triggered in response to nitrogen nutrition that is sensed by the Tor proteins, operates via a regulatory pathway involving the cytoplasmic factor Ure2p. When carbon and nitrogen are abundant, the phosphorylated Ure2p anchors the also phosphorylated Gln3p and Nil1p in the cytoplasm. Upon a shift from high- to low-quality nitrogen or treatment with rapamycin all three proteins are dephosphorylated, causing Gln3p and Nil1p to enter the nucleus and promote transcription. The genes that code for yeast periplasmic enzymes with nutritional roles would be obvious targets for regulation by the sensing and signalling pathways that respond to quality of carbon and nitrogen sources. Indeed, previous results from our laboratory had shown that the GATA factors Gln3p, Nil1p, Dal80p, Nil2p and also the protein Ure2 regulate the expression of asparaginase II, coded by ASP3. We also had observed that the activity levels of the also periplasmic invertase, coded by SUC2, were 6-fold lower in ure2 mutant cells in comparison to wild-type cells collected at stationary phase. These results suggested similarities between the signalling pathways regulating the expression of ASP3 and SUC2. In the present work we showed that invertase levels displayed by the single nil1 and gln3 and by the double gln3nil1 mutant cells, cultivated in a sucrose-ammonium medium and collected at the exponential phase, were 6-, 10- and 60-fold higher, respectively, in comparison to their wild-type counterparts. RT-PCR data of SUC2 expression in the double-mutant cells indicated a 10-fold increase in the mRNA(SUC2) levels.

Industrial ion sources broadbeam gridless ion source technology

CERN Document Server

Zhurin, Viacheslav V

2012-01-01

Due to the large number of uses of ion sources in academia and industry, those who utilize these sources need up to date and coherent information to keep themselves abreast of developments and options, and to chose ideal solutions for quality and cost-effectiveness. This book, written by an author with a strong industrial background and excellent standing, is the comprehensive guide users and developers of ion sources have been waiting for. Providing a thorough refresher on the physics involved, this resource systematically covers the source types, components, and the operational parameters.

Ion source requirements for pulsed spallation neutron sources

International Nuclear Information System (INIS)

Alonso, J.R.

1995-10-01

The neutron scattering community has endorsed the need for a high- power (1 to 5 MW) accelerator-driven source of neutrons for materials research. Properly configured, the accelerator could produce very short (sub-microsecond) bursts of cold neutrons, said time structure offering advantages over the continuous flux from a reactor for a large class of experiments. The recent cancellation of the ANS reactor project has increased the urgency to develop a comprehensive strategy based on the best technological scenarios. Studies to date have built on the experience from ISIS (the 160 KW source in the UK), and call for a high-current (approx. 100 mA peak) H - source-linac combination injecting into one or more accumulator rings in which beam may be further accelerated. The 1 to 5 GeV proton beam is extracted in a single turn and brought to the target-moderator stations. The high current, high duty-factor, high brightness and high reliability required of the ion source present a very large challenge to the ion source community. A workshop held in Berkeley in October 1994, analyzed in detail the source requirements for proposed accelerator scenarios, the present performance capabilities of different H - source technologies, and identified necessary R ampersand D efforts to bridge the gap

Haplotype diversity of 16 Y-chromosomal STRs in three main ethnic populations (Malays, Chinese and Indians) in Malaysia.

Science.gov (United States)

Chang, Yuet Meng; Perumal, Revathi; Keat, Phoon Yoong; Kuehn, Daniel L C

2007-03-22

We have analyzed 16 Y-STR loci (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635 or Y-GATA C4, DYS392, Y-GATA H4, DYS437, DYS438 and DYS448) from the non-recombining region of the human Y-chromosome in 980 male individuals from three main ethnic populations in Malaysia (Malay, Chinese, Indian) using the AmpFlSTR((R)) Y-filertrade mark (Applied Biosystems, Foster City, CA). The observed 17-loci haplotypes and the individual allele frequencies for each locus were estimated, whilst the locus diversity, haplotype diversity and discrimination capacity were calculated in the three ethnic populations. Analysis of molecular variance indicated that 88.7% of the haplotypic variation is found within population and 11.3% is between populations (fixation index F(ST)=0.113, p=0.000). This study has revealed Y-chromosomes with null alleles at several Y-loci, namely DYS458, DYS392, DYS389I, DYS389II, DYS439, DYS448 and Y-GATA H4; and several occurrences of duplications at the highly polymorphic DYS385 loci. Some of these deleted loci were in regions of the Y(q) arm that have been implicated in the occurrence of male infertility.

Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate.

Directory of Open Access Journals (Sweden)

Jatin Narula

2010-05-01

Full Text Available Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad-a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models.

Mouse models for the study of postnatal cardiac hypertrophy

Directory of Open Access Journals (Sweden)

A. Del Olmo-Turrubiarte

2015-06-01

Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

The Chandra Source Catalog 2.0: Estimating Source Fluxes

Science.gov (United States)

Primini, Francis Anthony; Allen, Christopher E.; Miller, Joseph; Anderson, Craig S.; Budynkiewicz, Jamie A.; Burke, Douglas; Chen, Judy C.; Civano, Francesca Maria; D'Abrusco, Raffaele; Doe, Stephen M.; Evans, Ian N.; Evans, Janet D.; Fabbiano, Giuseppina; Gibbs, Danny G., II; Glotfelty, Kenny J.; Graessle, Dale E.; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; Houck, John C.; Lauer, Jennifer L.; Laurino, Omar; Lee, Nicholas P.; Martínez-Galarza, Juan Rafael; McCollough, Michael L.; McDowell, Jonathan C.; McLaughlin, Warren; Morgan, Douglas L.; Mossman, Amy E.; Nguyen, Dan T.; Nichols, Joy S.; Nowak, Michael A.; Paxson, Charles; Plummer, David A.; Rots, Arnold H.; Siemiginowska, Aneta; Sundheim, Beth A.; Tibbetts, Michael; Van Stone, David W.; Zografou, Panagoula

2018-01-01

The Second Chandra Source Catalog (CSC2.0) will provide information on approximately 316,000 point or compact extended x-ray sources, derived from over 10,000 ACIS and HRC-I imaging observations available in the public archive at the end of 2014. As in the previous catalog release (CSC1.1), fluxes for these sources will be determined separately from source detection, using a Bayesian formalism that accounts for background, spatial resolution effects, and contamination from nearby sources. However, the CSC2.0 procedure differs from that used in CSC1.1 in three important aspects. First, for sources in crowded regions in which photometric apertures overlap, fluxes are determined jointly, using an extension of the CSC1.1 algorithm, as discussed in Primini & Kashyap (2014ApJ...796…24P). Second, an MCMC procedure is used to estimate marginalized posterior probability distributions for source fluxes. Finally, for sources observed in multiple observations, a Bayesian Blocks algorithm (Scargle, et al. 2013ApJ...764..167S) is used to group observations into blocks of constant source flux.In this poster we present details of the CSC2.0 photometry algorithms and illustrate their performance in actual CSC2.0 datasets.This work has been supported by NASA under contract NAS 8-03060 to the Smithsonian Astrophysical Observatory for operation of the Chandra X-ray Center.

Positron sources

International Nuclear Information System (INIS)

Chehab, R.

1994-01-01

A tentative survey of positron sources is given. Physical processes on which positron generation is based are indicated and analyzed. Explanation of the general features of electromagnetic interactions and nuclear β + decay makes it possible to predict the yield and emittance for a given optical matching system between the positron source and the accelerator. Some kinds of matching systems commonly used - mainly working with solenoidal field - are studied and the acceptance volume calculated. Such knowledge is helpful in comparing different matching systems. Since for large machines, a significant distance exists between the positron source and the experimental facility, positron emittance has to be preserved during beam transfer over large distances and methods used for that purpose are indicated. Comparison of existing positron sources leads to extrapolation to sources for future linear colliders. Some new ideas associated with these sources are also presented. (orig.)

Sources for charged particles; Les sources de particules chargees

Energy Technology Data Exchange (ETDEWEB)

Arianer, J.

1997-09-01

This document is a basic course on charged particle sources for post-graduate students and thematic schools on large facilities and accelerator physics. A simple but precise description of the creation and the emission of charged particles is presented. This course relies on every year upgraded reference documents. Following relevant topics are considered: electronic emission processes, technological and practical considerations on electron guns, positron sources, production of neutral atoms, ionization, plasma and discharge, different types of positive and negative ion sources, polarized particle sources, materials for the construction of ion sources, low energy beam production and transport. (N.T.).

GANIL Workshop on Ion Sources; Journees Sources d'Ions

Energy Technology Data Exchange (ETDEWEB)

Leroy, Renan [Grand Accelerateur National d' Ions Lourds (GANIL), 14 - Caen (France)

1999-07-01

The proceedings of the GANIL Workshop on Ion Sources held at GANIL - Caen on 18-19 March 1999 contains 13 papers aiming at improving the old source operation and developing new types of sources for nuclear research and studies of ion physics. A number of reports are devoted to applications like surface treatment, ion implantation or fusion injection. The 1+{yields}n+ transformation, charged particle transport in ECR sources, addition of cesium and xenon in negative ion sources and other basic issues in ion sources are also addressed.

Ion source requirements for pulsed spallation neutron sources

International Nuclear Information System (INIS)

Alonso, J.R.

1996-01-01

The neutron scattering community has endorsed the need for a high-power (1 to 5 MW) accelerator-driven source of neutrons for materials research. Properly configured, the accelerator could produce very short (sub-microsecond) bursts of cold neutrons, said time structure offering advantages over the continuous flux from a reactor for a large class of experiments. The recent cancellation of the ANS reactor project has increased the urgency to develop a comprehensive strategy based on the best technological scenarios. Studies to date have built on the experience from ISIS (the 160 kW source in the UK), and call for a high-current (approx. 100 mA peak) H - source-linac combination injecting into one or more accumulator rings in which beam may be further accelerated. The 1 to 5 GeV proton beam is extracted in a single turn and brought to the target-moderator stations. The high current, high duty-factor, high brightness and high reliability required of the ion source present a very large challenge to the ion source community. A workshop held in Berkeley in October 1994, analyzed in detail the source requirements for proposed accelerator scenarios, the present performance capabilities of different H - source technologies, and identified necessary R ampersand D efforts to bridge the gap. copyright 1996 American Institute of Physics

Chandra Source Catalog: Background Determination and Source Detection

Science.gov (United States)

McCollough, Michael L.; Rots, A. H.; Primini, F. A.; Evans, I. N.; Glotfelty, K. J.; Hain, R.; Anderson, C. S.; Bonaventura, N. R.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Evans, J. D.; Fabbiano, G.; Galle, E.; Gibbs, D. G.; Grier, J. D.; Hall, D. M.; Harbo, P. N.; He, X.; Houck, J. C.; Karovska, M.; Lauer, J.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Nowak, M. A.; Plummer, D. A.; Refsdal, B. L.; Siemiginowska, A. L.; Sundheim, B. A.; Tibbetts, M. S.; Van Stone, D. W.; Winkelman, S. L.; Zografou, P.

2009-01-01

The Chandra Source Catalog (CSC) is a major project in which all of the pointed imaging observations taken by the Chandra X-Ray Observatory will used to generate the most extensive X-ray source catalog produced to date. Early in the development of the CSC it was recognized that the ability to estimate local background levels in an automated fashion would be critical for essential CSC tasks such as source detection, photometry, sensitivity estimates, and source characterization. We present a discussion of how such background maps are created directly from the Chandra data and how they are used in source detection. The general background for Chandra observations is rather smoothly varying, containing only low spatial frequency components. However, in the case of ACIS data, a high spatial frequency component is added that is due to the readout streaks of the CCD chips. We discuss how these components can be estimated reliably using the Chandra data and what limitations and caveats should be considered in their use. We will discuss the source detection algorithm used for the CSC and the effects of the background images on the detection results. We will also touch on some the Catalog Inclusion and Quality Assurance criteria applied to the source detection results. This work is supported by NASA contract NAS8-03060 (CXC).

Analysis of the 19 Y-STR and 16 X-STR loci system in the Han population of Shandong province, China.

Science.gov (United States)

Gao, H M; Wang, C; Han, S Y; Sun, S H; Xiao, D J; Wang, Y S; Li, C T; Zhang, M X

2017-03-30

The sex-linked short tandem repeats (STR), Y-STR and X-STR, are important for autosomal STRs in forensic paternity testing. We evaluated the forensic parameters of 19 Y-STRs and 16 X-STRs in the Han population of Shandong province, China. A Goldeneye 20Y kit (DYS391, DYS389I, DYS390, DYS389II, DYS348, DYS456, Y-GATA-H4, DYS447, DYS19, DYS392, DYS393, DYS388, DYS439, DYS635, DYS448, DYS460, DYS458, DYS437, DYS385 a/b) was used to analyze the forensic parameters of 534 unrelated males. A Goldeneye17X system (DXS6795, DXS9902, DXS8378, HPRTB, GATA165B12, DXS7132, DXS7424, DXS6807, DXS6803, GATA172D05, DXS6800, DXS10134, GATA31E08, DXS10159, DXS6789, DXS6810, amelogenin) was used to analyze 97 unrelated males and 214 females. In addition, we used the kits to examine 5 cases with abnormal amelogenin test results, as well as a male child with agenosomia typed by autosomal STR. We found 203 Y-STR haplotypes with allele frequencies ranging from 0.0019 to 0.7959, and GD ranging from 0.3429 to 0.9667. Expect in DXS6803, the allele frequencies of the other 15 X-STR loci showed no differences between females and males. PD F ranged from 0.5504 to 0.9638, while PD M ranged from 0.3176 to 0.8377. With the exception of DXS6803 and DXS6810, the allele frequencies of other X-STR loci were in accordance with Hardy-Weinberg equilibrium in females. One amelogenin negative case was characterized as a deletion of Y-DYS458. This paper provided data regarding the genetic polymorphism of Y-STRs and X-STRs in the Han population, and demonstrated the importance of Y-STR and X-STR in forensic autosomal STR analysis.

Asthma: T-bet--a master controller?

Science.gov (United States)

Robinson, Douglas S; Lloyd, Clare M

2002-04-30

The transcription factors T-bet and GATA3 are important reciprocal determinants of Th1 and Th2 T helper cell differentiation. Recent evidence suggests that these factors may affect airway immunopathology in asthma.

Asthma: T-bet — A Master Controller?

OpenAIRE

Robinson, Douglas S; Lloyd, Clare M

2002-01-01

The transcription factors T-bet and GATA3 are important reciprocal determinants of Th1 and Th2 T helper cell differentiation. Recent evidence suggests that these factors may affect airway immunopathology in asthma.

A new FACS approach isolates hESC derived endoderm using transcription factors.

Directory of Open Access Journals (Sweden)

Yuqiong Pan

2011-03-01

Full Text Available We show that high quality microarray gene expression profiles can be obtained following FACS sorting of cells using combinations of transcription factors. We use this transcription factor FACS (tfFACS methodology to perform a genomic analysis of hESC-derived endodermal lineages marked by combinations of SOX17, GATA4, and CXCR4, and find that triple positive cells have a much stronger definitive endoderm signature than other combinations of these markers. Additionally, SOX17(+ GATA4(+ cells can be obtained at a much earlier stage of differentiation, prior to expression of CXCR4(+ cells, providing an important new tool to isolate this earlier definitive endoderm subtype. Overall, tfFACS represents an advancement in FACS technology which broadly crosses multiple disciplines, most notably in regenerative medicine to redefine cellular populations.

Regulation of basophil and mast cell development by transcription factors

Directory of Open Access Journals (Sweden)

Haruka Sasaki

2016-04-01

Full Text Available Basophils and mast cells play important roles in host defense against parasitic infections and allergic responses. Several progenitor populations, either shared or specific, for basophils and/or mast cells have been identified, thus elucidating the developmental pathways of these cells. Multiple transcription factors essential for their development and the relationships between them have been also revealed. For example, IRF8 induces GATA2 expression to promote the generation of both basophils and mast cells. The STAT5-GATA2 axis induces C/EBPα and MITF expression, facilitating the differentiation into basophils and mast cells, respectively. In addition, C/EBPα and MITF mutually suppress each other's expression. This review provides an overview of recent advances in our understanding of how transcription factors regulate the development of basophils and mast cells.

Sources management

International Nuclear Information System (INIS)

Mansoux, H.; Gourmelon; Scanff, P.; Fournet, F.; Murith, Ch.; Saint-Paul, N.; Colson, P.; Jouve, A.; Feron, F.; Haranger, D.; Mathieu, P.; Paycha, F.; Israel, S.; Auboiroux, B.; Chartier, P.

2005-01-01

Organized by the section of technical protection of the French society of radiation protection ( S.F.R.P.), these two days had for objective to review the evolution of the rule relative to the sources of ionising radiations 'sealed and unsealed radioactive sources, electric generators'. They addressed all the actors concerned by the implementation of the new regulatory system in the different sectors of activities ( research, medicine and industry): Authorities, manufacturers, and suppliers of sources, holders and users, bodies involved in the approval of sources, carriers. (N.C.)

Cytogenetics of the Javan file snake (Acrochordus javanicus) and the evolution of snake sex chromosomes

Czech Academy of Sciences Publication Activity Database

Rovatsos, M.; Altmanová, Marie; Johnson Pokorná, Martina; Augstenová, B.; Kratochvíl, L.

2018-01-01

Roč. 56, č. 1 (2018), s. 117-125 ISSN 0947-5745 Institutional support: RVO:67985904 Keywords : GATA * genome organization * sex determination Subject RIV: EG - Zoology OBOR OECD: Zoology Impact factor: 2.444, year: 2016

Genetics Home Reference: dyserythropoietic anemia and thrombocytopenia

Science.gov (United States)

... factor. The GATA1 protein is involved in the specialization (differentiation) of immature blood cells. To function properly, ... not be used as a substitute for professional medical care or advice. Users with questions about a ...

Positron sources

International Nuclear Information System (INIS)

Chehab, R.

1989-01-01

A tentative survey of positron sources is given. Physical processes on which positron generation is based are indicated and analyzed. Explanation of the general features of electromagnetic interactions and nuclear β + decay makes it possible to predict the yield and emittance for a given optical matching system between the positron source and the accelerator. Some kinds of matching systems commonly used - mainly working with solenoidal fields - are studied and the acceptance volume calculated. Such knowledge is helpful in comparing different matching systems. Since for large machines, a significant distance exists between the positron source and the experimental facility, positron emittance has to be preserved during beam transfer over large distances and methods used for that purpose are indicated. Comparison of existing positron sources leads to extrapolation to sources for future linear colliders

C-188 cobalt-60 sealed source integrity: source monitoring

International Nuclear Information System (INIS)

Defalco, G.M.; Shah, V.

1995-01-01

The integrity of C-188 cobalt-60 sealed sources used for radiation processing will be a key factor in the continued industrial acceptance and growth of gamma irradiation technology. Given the public's relatively poor understanding of most nuclear topics and the news media's tendency to sensationalize events, it is appropriate for suppliers and users of gamma technology to be vigilant and conservative regarding the application of cobalt-60 sources to industrial purposes. Nordion's recent decision to extend the optional warranty on its C-188 cobalt-60 sealed source from 15 years to 20 years is based on over 30 years of data generated from its on-going SOURCE SURVEILLANCE PROGRAM. This paper presents an overview of the C-188 SOURCE SURVEILLANCE PROGRAM. (author)

The Chandra Source Catalog: Background Determination and Source Detection

Science.gov (United States)

McCollough, Michael; Rots, Arnold; Primini, Francis A.; Evans, Ian N.; Glotfelty, Kenny J.; Hain, Roger; Anderson, Craig S.; Bonaventura, Nina R.; Chen, Judy C.; Davis, John E.; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Galle, Elizabeth C.; Danny G. Gibbs, II; Grier, John D.; Hall, Diane M.; Harbo, Peter N.; He, Xiang Qun (Helen); Houck, John C.; Karovska, Margarita; Kashyap, Vinay L.; Lauer, Jennifer; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph B.; Mitschang, Arik W.; Morgan, Douglas L.; Mossman, Amy E.; Nichols, Joy S.; Nowak, Michael A.; Plummer, David A.; Refsdal, Brian L.; Siemiginowska, Aneta L.; Sundheim, Beth A.; Tibbetts, Michael S.; van Stone, David W.; Winkelman, Sherry L.; Zografou, Panagoula

2009-09-01

The Chandra Source Catalog (CSC) is a major project in which all of the pointed imaging observations taken by the Chandra X-Ray Observatory are used to generate one of the most extensive X-ray source catalog produced to date. Early in the development of the CSC it was recognized that the ability to estimate local background levels in an automated fashion would be critical for essential CSC tasks such as source detection, photometry, sensitivity estimates, and source characterization. We present a discussion of how such background maps are created directly from the Chandra data and how they are used in source detection. The general background for Chandra observations is rather smoothly varying, containing only low spatial frequency components. However, in the case of ACIS data, a high spatial frequency component is added that is due to the readout streaks of the CCD chips. We discuss how these components can be estimated reliably using the Chandra data and what limitations and caveats should be considered in their use. We will discuss the source detection algorithm used for the CSC and the effects of the background images on the detection results. We will also touch on some the Catalog Inclusion and Quality Assurance criteria applied to the source detection results. This work is supported by NASA contract NAS8-03060 (CXC).

Polarized source upgrading

International Nuclear Information System (INIS)

Clegg, T.B.; Rummel, R.L.; Carter, E.P.; Westerfeldt, C.R.; Lovette, A.W.; Edwards, S.E.

1985-01-01

The decision was made this past year to move the Lamb-shift polarized ion source which was first installed in the laboratory in 1970. The motivation was the need to improve the flexibility of spin-axis orientation by installing the ion source with a new Wien-filter spin precessor which is capable of rotating physically about the beam axis. The move of the polarized source was accomplished in approximately two months, with the accelerator being turned off for experiments during approximately four weeks of this time. The occasion of the move provided the opportunity to rewire completely the entire polarized ion source frame and to rebuild approximately half of the electronic chassis on the source. The result is an ion source which is now logically wired and carefully documented. Beams obtained from the source are much more stable than those previously available

5-Lipoxygenase-Dependent Recruitment of Neutrophils and Macrophages by Eotaxin-Stimulated Murine Eosinophils

Directory of Open Access Journals (Sweden)

Ricardo Alves Luz

2014-01-01

Full Text Available The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LTB4, a 5-lipoxygenase (5-LO metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We examined responses to eotaxin in the absence of sensitization and their dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1 were injected i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by much larger numbers of recruited neutrophils and monocytes/macrophages. These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.

Development of the 16 X-STR loci typing system and genetic analysis in a Shanghai Han population from China.

Science.gov (United States)

Sun, Kuan; Zhao, Shumin; Tian, Huaizhou; Zhang, Suhua; Li, Chengtao

2013-11-01

This study developed a new multiplex PCR system that simultaneously amplifies 16 X-STR loci in the same PCR reaction, and the polymorphism and mutation rates of these 16 X-STR loci were explored in a Shanghai Han population from China. These loci included DXS10134, DXS10159, DXS6789, DXS6795, DXS6800, DXS6803, DXS6807, DXS6810, DXS7132, DXS7424, DXS8378, DXS9902, GATA165B12, GATA172D05, GATA31E08, and HPRTB. Samples from 591 unrelated individuals (293 males and 298 females) and 400 two-generation families were successfully analyzed using this multiplex system. Allele frequencies and mutation rates of the 16 loci were investigated, with the comparison of allele frequency distributions among different populations performed. Polymorphism information contents of these loci were all >0.6440 except the locus DXS6800 (0.4706). Nine cases of mutations were detected in the 16 loci from the investigation of 9232 meioses. Pairwise comparisons of allele frequency distributions showed significant differences for most loci among populations from different countries and ethnic groups but not among the Han population living in other areas of China. These results suggest that the 16 X-STR loci system provides highly informative polymorphic data for paternity testing and forensic identification in the Han population in Shanghai, China, as a complementary tool. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Eosinophils are required to suppress Th2 responses in Peyer's patches during intestinal infection by nematodes.

Science.gov (United States)

Strandmark, J; Steinfelder, S; Berek, C; Kühl, A A; Rausch, S; Hartmann, S

2017-05-01

Infections with enteric nematodes result in systemic type 2 helper T (Th2) responses, expansion of immunoglobulin (Ig)G1 antibodies, and eosinophilia. Eosinophils have a supportive role in mucosal Th2 induction during airway hyperreactivity. Whether eosinophils affect the local T-cell and antibody response in the gut-associated lymphoid tissue during enteric infections is unknown. We infected eosinophil-deficient ΔdblGATA-1 mice with the Th2-inducing small intestinal nematode Heligmosomoides polygyrus and found that parasite fecundity was decreased in the absence of eosinophils. A lack of eosinophils resulted in significantly augmented expression of GATA-3 and IL-4 by CD4 + T cells during acute infection, a finding strictly limited to Peyer's patches (PP). The increase in IL-4-producing cells in ΔdblGATA-1 mice was particularly evident within the CXCR5 + PD-1 + T-follicular helper cell population and was associated with a switch of germinal centre B cells to IgG1 production and elevated serum IgG1 levels. In contrast, infected wild-type mice had a modest IgG1 response in the PP, whereas successfully maintaining a population of IgA + germinal center B cells. Our results suggest a novel role for eosinophils during intestinal infection whereby they restrict IL-4 responses by follicular T helper cells and IgG1 class switching in the PP to ensure maintenance of local IgA production.

Polarized electron sources

International Nuclear Information System (INIS)

Clendenin, J.E.

1995-05-01

Polarized electron sources for high energy accelerators took a significant step forward with the introduction of a new laser-driven photocathode source for the SLC in 1992. With an electron beam polarization of >80% and with ∼99% uptime during continuous operation, this source is a key factor in the success of the current SLC high-energy physics program. The SLC source performance is used to illustrate both the capabilities and the limitations of solid-state sources. The beam requirements for future colliders are similar to that of the SLC with the addition in most cases of multiple-bunch operation. A design for the next generation accelerator source that can improve the operational characteristics and at least minimize some of the inherent limitations of present sources is presented. Finally, the possibilities for producing highly polarized electron beams for high-duty-factor accelerators are discussed

Pacemakers lower sources

International Nuclear Information System (INIS)

Greatbatch, W.

1984-01-01

Energy sources for cardiac facing are considered including radioisotope sources, in a broad conceptual and historical framework.The main guidelines for future development of energy sources are assessed

Hiperplasia fibroepitelial mamária em felinos: cinco casos

Directory of Open Access Journals (Sweden)

Souza Tatiana Mello de

2002-01-01

Full Text Available São descritos cinco casos de hiperplasia fibroepitelial mamária em gatas com idades variando entre 10 meses e 11 anos. A principal queixa por ocasião do atendimento era relacionada à tumefação das mamas com evolução clínica entre 3 e 24 semanas. Em duas das gatas, a condição desenvolveu-se após o tratamento com contraceptivos. Macroscopicamente, as tumorações na glândula mamária eram cobertas por pele, ocasionalmente ulceradas, e tinham superfície de corte brancacenta com nódulos multifocais mais pálidos de 2mm de diâmetro. Histologicamente, esses nódulos multifocais consistiam de proliferação ductal cercadas por crescimento abundante de tecido conjuntivo fibroso.

Role of promoter element in c-mpl gene expression induced by TPO.

Science.gov (United States)

Sunohara, Masataka; Morikawa, Shigeru; Fuse, Akira; Sato, Iwao

2013-01-01

Thrombopoietin (TPO) and its receptor, c-Mpl, play the crucial role for the development of megakaryocyte and considered to regulate megakaryocytopoiesis. Previously we reported that TPO increased the c-mpl promoter activity determined by a transient expression system using a vector containing the luciferase gene as a reporter and the expression of the c-mpl gene is modulated by transcription through a protein kinase C (PKC)-dependent pathway in the megakaryoblastic cells. In this research, to elucidate the required elements in c-mpl promoter, the promoter activity of the deletion constructs and site-directed mutagenesis were measured by a transient transfection assay system. Destruction of -77GATA in c-mpl promoter decreased the activity by 22.8%. Our study elucidated that -77GATA involved in TPO-induced c-mpl gene expression in a human megakaryoblastic cell line, CMK.

Global Sourcing Flexibility

DEFF Research Database (Denmark)

Ørberg Jensen, Peter D.; Petersen, Bent

2013-01-01

the higher costs (but decreased risk for value chain disruption) embedded in a more flexible global sourcing model that allows the firm to replicate and/or relocate activities across multiple locations. We develop a model and propositions on facilitating and constraining conditions of global sourcing...... sourcing flexibility. Here we draw on prior research in the fields of organizational flexibility, international business and global sourcing as well as case examples and secondary studies. In the second part of the paper, we discuss the implications of global sourcing flexibility for firm strategy...... and operations against the backdrop of the theory-based definition of the construct. We discuss in particular the importance of global sourcing flexibility for operational performance stability, and the trade-off between specialization benefits, emerging from location and service provider specialization, versus...

Source splitting via the point source method

International Nuclear Information System (INIS)

Potthast, Roland; Fazi, Filippo M; Nelson, Philip A

2010-01-01

We introduce a new algorithm for source identification and field splitting based on the point source method (Potthast 1998 A point-source method for inverse acoustic and electromagnetic obstacle scattering problems IMA J. Appl. Math. 61 119–40, Potthast R 1996 A fast new method to solve inverse scattering problems Inverse Problems 12 731–42). The task is to separate the sound fields u j , j = 1, ..., n of n element of N sound sources supported in different bounded domains G 1 , ..., G n in R 3 from measurements of the field on some microphone array—mathematically speaking from the knowledge of the sum of the fields u = u 1 + ... + u n on some open subset Λ of a plane. The main idea of the scheme is to calculate filter functions g 1 ,…, g n , n element of N, to construct u l for l = 1, ..., n from u| Λ in the form u l (x) = ∫ Λ g l,x (y)u(y)ds(y), l=1,... n. (1) We will provide the complete mathematical theory for the field splitting via the point source method. In particular, we describe uniqueness, solvability of the problem and convergence and stability of the algorithm. In the second part we describe the practical realization of the splitting for real data measurements carried out at the Institute for Sound and Vibration Research at Southampton, UK. A practical demonstration of the original recording and the splitting results for real data is available online

Constraints on equivalent elastic source models from near-source data

International Nuclear Information System (INIS)

Stump, B.

1993-01-01

A phenomenological based seismic source model is important in quantifying the important physical processes that affect the observed seismic radiation in the linear-elastic regime. Representations such as these were used to assess yield effects on seismic waves under a Threshold Test Ban Treaty and to help transport seismic coupling experience at one test site to another. These same characterizations in a non-proliferation environment find applications in understanding the generation of the different types of body and surface waves from nuclear explosions, single chemical explosions, arrays of chemical explosions used in mining, rock bursts and earthquakes. Seismologists typically begin with an equivalent elastic representation of the source which when convolved with the propagation path effects produces a seismogram. The Representation Theorem replaces the true source with an equivalent set of body forces, boundary conditions or initial conditions. An extension of this representation shows the equivalence of the body forces, boundary conditions and initial conditions and replaces the source with a set of force moments, the first degree moment tensor for a point source representation. The difficulty with this formulation, which can completely describe the observed waveforms when the propagation path effects are known, is in the physical interpretation of the actual physical processes acting in the source volume. Observational data from within the source region, where processes are often nonlinear, linked to numerical models of the important physical processes in this region are critical to a unique physical understanding of the equivalent elastic source function

ERP correlates of source memory: unitized source information increases familiarity-based retrieval.

Science.gov (United States)

Diana, Rachel A; Van den Boom, Wijnand; Yonelinas, Andrew P; Ranganath, Charan

2011-01-07

Source memory tests typically require subjects to make decisions about the context in which an item was encoded and are thought to depend on recollection of details from the study episode. Although it is generally believed that familiarity does not contribute to source memory, recent behavioral studies have suggested that familiarity may also support source recognition when item and source information are integrated, or "unitized," during study (Diana, Yonelinas, and Ranganath, 2008). However, an alternative explanation of these behavioral findings is that unitization affects the manner in which recollection contributes to performance, rather than increasing familiarity-based source memory. To discriminate between these possibilities, we conducted an event-related potential (ERP) study testing the hypothesis that unitization increases the contribution of familiarity to source recognition. Participants studied associations between words and background colors using tasks that either encouraged or discouraged unitization. ERPs were recorded during a source memory test for background color. The results revealed two distinct neural correlates of source recognition: a frontally distributed positivity that was associated with familiarity-based source memory in the high-unitization condition only and a parietally distributed positivity that was associated with recollection-based source memory in both the high- and low-unitization conditions. The ERP and behavioral findings provide converging evidence for the idea that familiarity can contribute to source recognition, particularly when source information is encoded as an item detail. Copyright © 2010 Elsevier B.V. All rights reserved.

RF H-minus ion source development in China spallation neutron source

Science.gov (United States)

Chen, W.; Ouyang, H.; Xiao, Y.; Liu, S.; Lü, Y.; Cao, X.; Huang, T.; Xue, K.

2017-08-01

China Spallation Neutron Source (CSNS) phase-I project currently uses a Penning surface plasma H- ion source, which has a life time of several weeks with occasional sparks between high voltage electrodes. To extend the life time of the ion source and prepare for the CSNS phase-II, we are trying to develop a RF negative hydrogen ion source with external antenna. The configuration of the source is similar to the DESY external antenna ion source and SNS ion source. However several changes are made to improve the stability and the life time. Firstly, Si3N4 ceramic with high thermal shock resistance, and high thermal conductivity is used for plasma chamber, which can endure an average power of 2000W. Secondly, the water-cooled antenna is brazed on the chamber to improve the energy efficiency. Thirdly, cesium is injected directly to the plasma chamber if necessary, to simplify the design of the converter and the extraction. Area of stainless steel exposed to plasma is minimized to reduce the sputtering and degassing. Instead Mo, Ta, and Pt coated materials are used to face the plasma, which makes the self-cleaning of the source possible.

Sealed radioactive source management

International Nuclear Information System (INIS)

2005-01-01

Sealed radioactive sources have been used in a wide range of application in medicine, agriculture, geology, industry and other fields. Since its utilization many sources have become out of use and became waste but no proper management. This has lead to many accidents causing deaths and serious radiation injuries worldwide. Spent sources application is expanding but their management has seen little improvements. Sealed radioactive sources have become a security risk calling for prompt action. Source management helps to maintain sources in a good physical status and provide means of source tracking and control. It also provides a well documented process of the sources making any future management options safe, secure and cost effective. Last but not least good source management substantially reduces the risk of accidents and eliminates the risk of malicious use. The International Atomic Energy Agency assists Member States to build the infrastructure to properly manage sealed radioactive sources. The assistance includes training of national experts to handle, condition and properly store the sources. For Member States that do not have proper facilities, we provide the technical assistance to design a proper facility to properly manage the radioactive sources and provide for their proper storage. For Member States that need to condition their sources properly but don't have the required infrastructure we provide direct assistance to physically help them with source recovery and provide an international expert team to properly condition their sources and render them safe and secure. We offer software (Radioactive Waste Management Registry) to properly keep a complete record on the sources and provide for efficient tracking. This also helps with proper planning and decision making for long term management

Experiment list: SRX104409 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available two GATA-type zinc fingers and is a n important regulator of T-cell development and plays an important role in endothelial cell biol...ogy. Defects in this gene are the cause of hypoparathyroidism with sensorineural de

GENETIC DIVERSITY OF TYPHA LATIFOLIA (TYPHACEAE) AND THE IMPACT OF POLLUTANTS EXAMINED WITH TANDEM-REPETITIVE DNA PROBES

Science.gov (United States)

Genetic diversity at variable-number-tandem-repeat (VNTR) loci was examined in the common cattail, Typha latifolia (Typhaceae), using three synthetic DNA probes composed of tandemly repeated "core" sequences (GACA, GATA, and GCAC). The principal objectives of this investigation w...

A Hybrid, Current-Source/Voltage-Source Power Inverter Circuit

DEFF Research Database (Denmark)

Trzynadlowski, Andrzej M.; Patriciu, Niculina; Blaabjerg, Frede

2001-01-01

A combination of a large current-source inverter and a small voltage-source inverter circuits is analyzed. The resultant hybrid inverter inherits certain operating advantages from both the constituent converters. In comparison with the popular voltage-source inverter, these advantages include...... reduced switching losses, improved quality of output current waveforms, and faster dynamic response to current control commands. Description of operating principles and characteristics of the hybrid inverter is illustrated with results of experimental investigation of a laboratory model....

THE CHANDRA SOURCE CATALOG

International Nuclear Information System (INIS)

Evans, Ian N.; Primini, Francis A.; Glotfelty, Kenny J.; Anderson, Craig S.; Bonaventura, Nina R.; Chen, Judy C.; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Galle, Elizabeth C.; Gibbs, Danny G.; Grier, John D.; Hain, Roger M.; Harbo, Peter N.; He Xiangqun; Karovska, Margarita; Kashyap, Vinay L.; Davis, John E.; Houck, John C.; Hall, Diane M.

2010-01-01

The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public Advanced CCD Imaging Spectrometer imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents ∼<30''. The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports scientific analysis using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1σ uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of ∼<1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively, including source images, event lists, light curves, and spectra from each observation in which a

The Chandra Source Catalog

Science.gov (United States)

Evans, Ian N.; Primini, Francis A.; Glotfelty, Kenny J.; Anderson, Craig S.; Bonaventura, Nina R.; Chen, Judy C.; Davis, John E.; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Galle, Elizabeth C.; Gibbs, Danny G., II; Grier, John D.; Hain, Roger M.; Hall, Diane M.; Harbo, Peter N.; He, Xiangqun Helen; Houck, John C.; Karovska, Margarita; Kashyap, Vinay L.; Lauer, Jennifer; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph B.; Mitschang, Arik W.; Morgan, Douglas L.; Mossman, Amy E.; Nichols, Joy S.; Nowak, Michael A.; Plummer, David A.; Refsdal, Brian L.; Rots, Arnold H.; Siemiginowska, Aneta; Sundheim, Beth A.; Tibbetts, Michael S.; Van Stone, David W.; Winkelman, Sherry L.; Zografou, Panagoula

2010-07-01

The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public Advanced CCD Imaging Spectrometer imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents lsim30''. The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports scientific analysis using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1σ uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of lsim1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively, including source images, event lists, light curves, and spectra from each observation in which a

New source review for stationary sources of air pollution

National Research Council Canada - National Science Library

Committee on Changes in New Source Review Programs for Stationary Sources of Air Pollution, National Research Council

2006-01-01

The Clean Air Act established a pair of programsâ€"known as New Source Review (NSR)â€"that regulate large stationary sources of air pollution, such as factories and electricity-generating facilities...

Miniature neutron sources: Thermal neutron sources and their users in the academic field

International Nuclear Information System (INIS)

Egelstaff, P.A.

1992-01-01

The three levels of thermal neutron sources are introduced - University laboratory sources infrastructure sources and world-class sources - and the needs for each kind and their inter-dependence will be emphasized. A description of the possibilities for University sources based on α-Be reactions or spontaneous fission emission is given, and current experience with them is described. A new generation of infrastructure sources is needed to continue the regional programs based on small reactors. Some possibilities for accelerator sources that could meet this need are considered

Negative ion sources

International Nuclear Information System (INIS)

Ishikawa, Junzo; Takagi, Toshinori

1983-01-01

Negative ion sources have been originally developed at the request of tandem electrostatic accelerators, and hundreds of nA to several μA negative ion current has been obtained so far for various elements. Recently, the development of large current hydrogen negative ion sources has been demanded from the standpoint of the heating by neutral particle beam injection in nuclear fusion reactors. On the other hand, the physical properties of negative ions are interesting in the thin film formation using ions. Anyway, it is the present status that the mechanism of negative ion action has not been so fully investigated as positive ions because the history of negative ion sources is short. In this report, the many mechanisms about the generation of negative ions proposed so far are described about negative ion generating mechanism, negative ion source plasma, and negative ion generation on metal surfaces. As a result, negative ion sources are roughly divided into two schemes, plasma extraction and secondary ion extraction, and the former is further classified into the PIG ion source and its variation and Duoplasmatron and its variation; while the latter into reflecting and sputtering types. In the second half of the report, the practical negative ion sources of each scheme are described. If the mechanism of negative ion generation will be investigated more in detail and the development will be continued under the unified know-how as negative ion sources in future, the development of negative ion sources with which large current can be obtained for any element is expected. (Wakatsuki, Y.)

Performance analyses of Z-source and quasi Z-source inverter for photovoltaic applications

Science.gov (United States)

Himabind, S.; Priya, T. Hari; Manjeera, Ch.

2018-04-01

This paper presents the comparative analysis of Z-source and Quasi Z-source converter for renewable energy applications. Due to the dependency of renewable energy sources on external weather conditions the output voltage, current changes accordingly which effects the performance of traditional voltage source and current source inverters connected across it. To overcome the drawbacks of VSI and CSI, Z-source and Quasi Z-source inverter (QZSI) are used, which can perform multiple tasks like ac-to-dc, dc-to-ac, ac-to-ac, dc-to-dc conversion. They can be used for both buck and boost operations, by utilizing the shoot-through zero state. The QZSI is derived from the ZSI topology, with a slight change in the impedance network and it overcomes the drawbacks of ZSI. The QZSI draws a constant current from the source when compared to ZSI. A comparative analysis is performed between Z-source and Quasi Z-source inverter, simulation is performed in MATLAB/Simulink environment.

Orphan sources in Slovenia

International Nuclear Information System (INIS)

Janzekovic, H.; Cesarek, J.

2005-01-01

For decades the international standards and requirements postulate severe control over all lifecycle phases of radioactive sources in order to prevent risks associated with exposure of people and the environment. Despite this fact the orphan sources became a serious problem as a consequence of enlargement of economic transactions in many countries in Europe as well as in the world. The countries as well as international organisations, aware of this emerging problem, are trying to gain control over orphan sources using different approaches. These approaches include control over sources before they could become orphan sources. In addition, countries are also developing action plans in case that an orphan source could be found. The problems related to orphan sources in Slovenia is discussed based on the case studies from the last years. While in the nineties of the last century just a few cases of orphan sources were identified their number has increased substantially since 2003. The paper discusses the general reasons for the phenomena of orphan sources as well as the experience related to regaining control over orphan sources. (author)

CHANDRA ACIS SURVEY OF X-RAY POINT SOURCES: THE SOURCE CATALOG

Energy Technology Data Exchange (ETDEWEB)

Wang, Song; Liu, Jifeng; Qiu, Yanli; Bai, Yu; Yang, Huiqin; Guo, Jincheng; Zhang, Peng, E-mail: jfliu@bao.ac.cn, E-mail: songw@bao.ac.cn [Key Laboratory of Optical Astronomy, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)

2016-06-01

The Chandra archival data is a valuable resource for various studies on different X-ray astronomy topics. In this paper, we utilize this wealth of information and present a uniformly processed data set, which can be used to address a wide range of scientific questions. The data analysis procedures are applied to 10,029 Advanced CCD Imaging Spectrometer observations, which produces 363,530 source detections belonging to 217,828 distinct X-ray sources. This number is twice the size of the Chandra Source Catalog (Version 1.1). The catalogs in this paper provide abundant estimates of the detected X-ray source properties, including source positions, counts, colors, fluxes, luminosities, variability statistics, etc. Cross-correlation of these objects with galaxies shows that 17,828 sources are located within the D {sub 25} isophotes of 1110 galaxies, and 7504 sources are located between the D {sub 25} and 2 D {sub 25} isophotes of 910 galaxies. Contamination analysis with the log N –log S relation indicates that 51.3% of objects within 2 D {sub 25} isophotes are truly relevant to galaxies, and the “net” source fraction increases to 58.9%, 67.3%, and 69.1% for sources with luminosities above 10{sup 37}, 10{sup 38}, and 10{sup 39} erg s{sup −1}, respectively. Among the possible scientific uses of this catalog, we discuss the possibility of studying intra-observation variability, inter-observation variability, and supersoft sources (SSSs). About 17,092 detected sources above 10 counts are classified as variable in individual observation with the Kolmogorov–Smirnov (K–S) criterion ( P {sub K–S} < 0.01). There are 99,647 sources observed more than once and 11,843 sources observed 10 times or more, offering us a wealth of data with which to explore the long-term variability. There are 1638 individual objects (∼2350 detections) classified as SSSs. As a quite interesting subclass, detailed studies on X-ray spectra and optical spectroscopic follow-up are needed to

Source Security Program in the Philippines: a lost source search experience

International Nuclear Information System (INIS)

Romallosa, Kristine M.; Salabit, Maria T.; Caseria, Estrella; Valdezco, Eulinia

2008-01-01

The Philippine Nuclear Research Institute (PNRI), the national agency in the licensing and regulations of radioactive materials in the country, is strengthening its capabilities in the security of radioactive sources. Part of this program is the PNRI's participation in the Regional Security of Radioactive Sources (RSRS) Project of the Australian Nuclear Science and Technology Organization (ANSTO). The project has provided equipment and methods training, assistance in the development of PNRI's own training program and support for actual orphan source search activities. On May 2007, a source search for the two lost Cs-137 level gauges of a steel manufacturing company was conducted by the PNRI and ANSTO. The source search are the: a) Development of instrument and source search training for the team, the National Training Workshop on Orphan Source Searches which was organized and conducted as a result of train-the-trainors fellowship under the RSRS project; and b) Planning and implementation of the lost source search activity. The conduct of the actual search on warehouses, product yard, canals, dust storage, steel making building, scrap yards and nearby junk shops of the steel plant took one week. The week-long search did not find the lost sources. However, naturally occurring radioactive materials identified to be Thorium, were found on sands, bricks and sack piles that are stored and/or generally present in the warehouses, yard and steel making building. The search activity had therefore cleared the facility of the lost source and its corresponding hazards. The NORM found present in the plant's premises on the other hand brought the attention of the management of the needed measures to ensure safety of the staff from possible hazards of these materials. Currently, the course syllabus that was developed is continuously enhanced to accommodate the training needs of the PNRI staff particularly for the emergency response and preparedness. This component of the source

Cold source vessel development for the advanced neutron source

Energy Technology Data Exchange (ETDEWEB)

Williams, P.T.; Lucas, A.T. [Oak Ridge National Lab., TN (United States)

1995-09-01

The Advanced Neutron Source (ANS), in its conceptual design phase at Oak Ridge National Laboratory (ORNL), will be a user-oriented neutron research facility that will produce the most intense flux of neutrons in the world. Among its many scientific applications, the productions of cold neutrons is a significant research mission for the ANS. The cold neutrons come from two independent cold sources positioned near the reactor core. Contained by an aluminum alloy vessel, each cold source is a 410 mm diameter sphere of liquid deuterium that functions both as a neutron moderator and a cryogenic coolant. With nuclear heating of the containment vessel and internal baffling, steady-state operation requires close control of the liquid deuterium flow near the vessel`s inner surface. Preliminary thermal-hydraulic analyses supporting the cold source design are being performed with multi-dimensional computational fluid dynamics simulations of the liquid deuterium flow and heat transfer. This paper presents the starting phase of a challenging program and describes the cold source conceptual design, the thermal-hydraulic feasibility studies of the containment vessel, and the future computational and experimental studies that will be used to verify the final design.

Dual-Source Swept-Source Optical Coherence Tomography Reconstructed on Integrated Spectrum

Directory of Open Access Journals (Sweden)

Shoude Chang

2012-01-01

Full Text Available Dual-source swept-source optical coherence tomography (DS-SSOCT has two individual sources with different central wavelengths, linewidth, and bandwidths. Because of the difference between the two sources, the individually reconstructed tomograms from each source have different aspect ratio, which makes the comparison and integration difficult. We report a method to merge two sets of DS-SSOCT raw data in a common spectrum, on which both data have the same spectrum density and a correct separation. The reconstructed tomographic image can seamlessly integrate the two bands of OCT data together. The final image has higher axial resolution and richer spectroscopic information than any of the individually reconstructed tomography image.

Brighter H- source for the intense pulsed neutron source accelerator system

International Nuclear Information System (INIS)

Stipp, V.; DeWitt, A.; Madsen, J.

1983-01-01

Further increases in the beam intensity of the Intense Pulsed Neutron Source (IPNS) at Argonne National Laboratory required the replacement of the H - source with a higher current source. A magnetron ion source of Fermi National Accelerator Laboratory (FNAL) design was adapted with a grooved cathode to provide a stable 40 to 50 mA of beam operating at 30 Hz for up to a 90 μs pulse duration. Problems of space charge blowup due to the lack of neutralization of the H - beam were solved by injecting additional gs into the 20 keV transport system. The source has recently been installed in the machine and the available input to the accelerator has more than doubled

Sourcing Excellence

DEFF Research Database (Denmark)

Adeyemi, Oluseyi

2011-01-01

Sourcing Excellence is one of the key performance indicators (KPIs) in this world of ever changing sourcing strategies. Manufacturing companies need to access and diagnose the reliability and competencies of existing suppliers in order to coordinate and develop them. This would help in managing...

Comparison of the hypothetical (57)Co brachytherapy source with the (192)Ir source.

Science.gov (United States)

Toossi, Mohammad Taghi Bahreyni; Ghorbani, Mahdi; Rostami, Atefeh; Khosroabadi, Mohsen; Khademi, Sara; Knaup, Courtney

2016-01-01

The (57)Co radioisotope has recently been proposed as a hypothetical brachytherapy source due to its high specific activity, appropriate half-life (272 days) and medium energy photons (114.17 keV on average). In this study, Task Group No. 43 dosimetric parameters were calculated and reported for a hypothetical (57)Co source. A hypothetical (57)Co source was simulated in MCNPX, consisting of an active cylinder with 3.5 mm length and 0.6 mm radius encapsulated in a stainless steel capsule. Three photon energies were utilized (136 keV [10.68%], 122 keV [85.60%], 14 keV [9.16%]) for the (57)Co source. Air kerma strength, dose rate constant, radial dose function, anisotropy function, and isodose curves for the source were calculated and compared to the corresponding data for a (192)Ir source. The results are presented as tables and figures. Air kerma strength per 1 mCi activity for the (57)Co source was 0.46 cGyh(-1) cm 2 mCi(-1). The dose rate constant for the (57)Co source was determined to be 1.215 cGyh(-1)U(-1). The radial dose function for the (57)Co source has an increasing trend due to multiple scattering of low energy photons. The anisotropy function for the (57)Co source at various distances from the source is more isotropic than the (192)Ir source. The (57)Co source has advantages over (192)Ir due to its lower energy photons, longer half-life, higher dose rate constant and more isotropic anisotropic function. However, the (192)Ir source has a higher initial air kerma strength and more uniform radial dose function. These properties make (57)Co a suitable source for use in brachytherapy applications.

Open Source Software: critical review of scientific literature and other sources

OpenAIRE

Querol del Amo, Marc

2007-01-01

This thesis presents the results of a survey of Open Source Licensing literature. It aims to assist the reader in choosing the best license for his/her business. For this reason, the content of this thesis can be divided into: (i) an open source licensing overview, (ii) the explication of the main features of the most popular open source licenses, (iii) the consequences of using one or another and (iv) the critical or controversial issues related to Open Source Licensing. Furthermore, at the ...

Research on point source simulating the γ-ray detection efficiencies of stander source

International Nuclear Information System (INIS)

Tian Zining; Jia Mingyan; Shen Maoquan; Yang Xiaoyan; Cheng Zhiwei

2010-01-01

For φ 75 mm x 25 mm sample, the full energy peak efficiencies on different heights of sample radius were obtained using the point sources, and the function parameters about the full energy peak efficiencies of point sources based on radius was fixed. The 59.54 keV γ-ray, 661.66 keV γ-ray, 1173.2 keV γ-ray, 1332.5 keV γ-ray detection efficiencies on different height of samples were obtained, based on the full energy peak efficiencies of point sources and its height, and the function parameters about the full energy peak efficiencies of surface sources based on sample height was fixed. The detection efficiency of (75 mm x 25 mm calibration source can be obtained by integrality, the detection efficiencies simulated by point sources are consistent with the results of stander source in 10%. Therefore, the calibration method of stander source can be substituted by the point source simulation method, and it tis feasible when there is no stander source.) (authors)

Review of Sealed Source Designs and Manufacturing Techniques Affecting Disused Source Management

International Nuclear Information System (INIS)

2012-10-01

This publication presents an investigation on the influence of the design and technical features of sealed radioactive sources (SRSs) on predisposal and disposal activities when the sources become disused. The publication also addresses whether design modifications could contribute to safer and/or more efficient management of disused sources without compromising the benefits provided by the use of the sealed sources. This technical publication aims to collect information on the most typical design features and manufacturing techniques of sealed radioactive sources and examines how they affect the safe management of disused sealed radioactive sources (DSRS). The publication also aims to assist source designers and manufacturers by discussing design features that are important from the waste management point of view. It has been identified that most SRS manufacturers use similar geometries and materials for their designs and apply improved and reliable manufacturing techniques e.g. double- encapsulation. These designs and manufacturing techniques have been proven over time to reduce contamination levels in fabrication and handling, and improve source integrity and longevity. The current source designs and materials ensure as well as possible that SRSs will maintain their integrity in use and when they become disused. No significant improvement options to current designs have been identified. However, some design considerations were identified as important to facilitate source retrieval, to increase the possibility of re-use and to ensure minimal contamination risk and radioactive waste generation at recycling. It was also concluded that legible identifying markings on a source are critical for DSRS management. The publication emphasizes the need for a common understanding of the radioactive source's recommended working life (RWL) for manufacturers and regulators. The conditions of use (COU) are important for the determination of RWL. A formal system for specification

Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia.

Science.gov (United States)

Sanda, Takaomi; Lawton, Lee N; Barrasa, M Inmaculada; Fan, Zi Peng; Kohlhammer, Holger; Gutierrez, Alejandro; Ma, Wenxue; Tatarek, Jessica; Ahn, Yebin; Kelliher, Michelle A; Jamieson, Catriona H M; Staudt, Louis M; Young, Richard A; Look, A Thomas

2012-08-14

The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3, and RUNX1. We show that TAL1 forms a positive interconnected autoregulatory loop with GATA3 and RUNX1 and that the TAL1 complex directly activates the MYB oncogene, forming a positive feed-forward regulatory loop that reinforces and stabilizes the TAL1-regulated oncogenic program. One of the critical downstream targets in this circuitry is the TRIB2 gene, which is oppositely regulated by TAL1 and E2A/HEB and is essential for the survival of T-ALL cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Tzfp represses the androgen receptor in mouse testis.

Science.gov (United States)

Furu, Kari; Klungland, Arne

2013-01-01

The testis zinc finger protein (Tzfp), also known as Repressor of GATA, belongs to the BTB/POZ zinc finger family of transcription factors and is thought to play a role in spermatogenesis due to its remarkably high expression in testis. Despite many attempts to find the in vivo role of the protein, the molecular function is still largely unknown. Here, we address this issue using a novel mouse model with a disrupted Tzfp gene. Homozygous Tzfp null mice are born at reduced frequency but appear viable and fertile. Sertoli cells in testes lacking Tzfp display an increase in Androgen Receptor (AR) signaling, and several genes in the testis, including Gata1, Aie1 and Fanc, show increased expression. Our results indicate that Tzfp function as a transcriptional regulator and that loss of the protein leads to alterations in AR signaling and reduced number of apoptotic cells in the testicular tubules.

Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells.

Science.gov (United States)

Li, LiQi; Jothi, Raja; Cui, Kairong; Lee, Jan Y; Cohen, Tsadok; Gorivodsky, Marat; Tzchori, Itai; Zhao, Yangu; Hayes, Sandra M; Bresnick, Emery H; Zhao, Keji; Westphal, Heiner; Love, Paul E

2011-02-01

The nuclear adaptor Ldb1 functions as a core component of multiprotein transcription complexes that regulate differentiation in diverse cell types. In the hematopoietic lineage, Ldb1 forms a complex with the non-DNA-binding adaptor Lmo2 and the transcription factors E2A, Scl and GATA-1 (or GATA-2). Here we demonstrate a critical and continuous requirement for Ldb1 in the maintenance of both fetal and adult mouse hematopoietic stem cells (HSCs). Deletion of Ldb1 in hematopoietic progenitors resulted in the downregulation of many transcripts required for HSC maintenance. Genome-wide profiling by chromatin immunoprecipitation followed by sequencing (ChIP-Seq) identified Ldb1 complex-binding sites at highly conserved regions in the promoters of genes involved in HSC maintenance. Our results identify a central role for Ldb1 in regulating the transcriptional program responsible for the maintenance of HSCs.

Wavelength sweepable laser source

DEFF Research Database (Denmark)

2014-01-01

Wavelength sweepable laser source is disclosed, wherein the laser source is a semiconductor laser source adapted for generating laser light at a lasing wavelength. The laser source comprises a substrate, a first reflector, and a second reflector. The first and second reflector together defines...... and having a rest position, the second reflector and suspension together defining a microelectromechanical MEMS oscillator. The MEMS oscillator has a resonance frequency and is adapted for oscillating the second reflector on either side of the rest position.; The laser source further comprises electrical...... connections adapted for applying an electric field to the MEMS oscillator. Furthermore, a laser source system and a method of use of the laser source are disclosed....

Electron backstream to the source plasma region in an ion source

International Nuclear Information System (INIS)

Ohara, Y.; Akiba, M.; Arakawa, Y.; Okumura, Y.; Sakuraba, J.

1980-01-01

The flux of backstream electrons to the source plasma region increases significantly with the acceleration voltage of an ion beam, so that the back plate in the arc chamber should be broken for quasi-dc operation. The flux of backstream electrons is estimated at the acceleration voltage of 50--100 kV for a proton beam with the aid of ion beam simulation code. The power flux of backstream electrons is up to about 7% of the total beam output at the acceleration voltage of 75 kV. It is pointed out that the conventional ion sources such as the duoPIGatron or the bucket source which use a magnetic field for source plasma production are not suitable for quasi-dc and high-energy ion sources, because the surface heat flux of the back plate is increased by the focusing of backstream electrons and the removal of it is quite difficult. A new ion source which has an electron beam dump in the arc chamber is proposed

Identifying Sources of Scientific Knowledge: classifying non-source items in the WoS

Energy Technology Data Exchange (ETDEWEB)

Calero-Medina, C.M.

2016-07-01

The sources of scientific knowledge can be tracked using the references in scientific publications. For instance, the publications from the scientific journals covered by the Web of Science database (WoS) contain references to publications for which an indexed source record exist in the WoS (source items) or to references for which an indexed source record does not exist in the WoS (non-source items). The classification of the non-source items is the main objective of the work in progress presented here. Some other scholars have classified and identified non-source items with different purposes (e.g. Butler & Visser (2006); Liseé, Larivière & Archambault (2008); Nerderhof, van Leeuwen & van Raan (2010); Hicks & Wang (2013); Boyack & Klavans (2014)). But these studies are focused in specific source types, fields or set of papers. The work presented here is much broader in terms of the number of publications, source types and fields. (Author)

Spallation neutron sources

International Nuclear Information System (INIS)

Fraser, J.S.; Bartholomew, G.A.

1983-01-01

The principles and theory of spallation neutron sources are outlined and a comparison is given with other types of neutron source. A summary of the available accelerator types for spallation neutron sources and their advantages and disadvantages is presented. Suitable target materials are discussed for specific applications, and typical target assemblies shown. (U.K.)

The female lower genital tract is a privileged compartment with IL-10 producing dendritic cells and poor Th1 immunity following Chlamydia trachomatis infection.

Directory of Open Access Journals (Sweden)

Ellen Marks

Full Text Available While a primary genital tract infection with C. trachomatis stimulates partial-protection against re-infection, it may also result in severe inflammation and tissue destruction. Here we have dissected whether functional compartments exist in the genital tract that restrict Th1-mediated protective immunity. Apart from the Th1-subset, little is known about the role of other CD4(+ T cell subsets in response to a genital tract chlamydial infection. Therefore, we investigated CD4(+ T cell subset differentiation in the genital tract using RT-PCR for expression of critical transcription factors and cytokines in the upper (UGT and lower genital tract (LGT of female C57BL/6 mice in response to C. trachomatis serovar D infection. We found that the Th1 subset dominated the UGT, as IFN-γ and T-bet mRNA expression were high, while GATA-3 was low following genital infection with C. trachomatis serovar D. By contrast, IL-10 and GATA-3 mRNA dominated the LGT, suggesting the presence of Th2 cells. These functional compartments also attracted regulatory T cells (Tregs differently as increased FoxP3 mRNA expression was seen primarily in the UGT. Although IL-17A mRNA was somewhat up-regulated in the LGT, no significant change in RORγ-t mRNA expression was observed, suggesting no involvement of Th17 cells. The dichotomy between the LGT and UGT was maintained during infection by IL-10 because in IL-10-deficient mice the distinction between the two compartments was completely lost and a dramatic shift to the predominance of Th1 cells in the LGT occurred. Unexpectedly, the major source of IL-10 was CD11c(+ CD11b(+ DC, probably creating an anti-inflammatory privileged site in the LGT.

Maternal exposure to airborne particulate matter causes postnatal immunological dysfunction in mice offspring

International Nuclear Information System (INIS)

Hong, Xinru; Liu, Chaobin; Chen, Xiaoqiu; Song, Yanfeng; Wang, Qin; Wang, Ping; Hu, Dian

2013-01-01

Evidence suggests that prenatal exposure to air pollution affects the ontogeny and development of the fetal immune system. The aim of this study was to investigate the effect of maternal exposure to airborne particulate matter (PM) on immune function in postnatal offspring. Pregnant female ICR mice were intralaryngopharyngeally administered with 30 μl of phosphate buffered solution (the control group) or resuspended PM of Standard Reference Material 1649a at 0.09 (low), 0.28 (medium), 1.85 (high) or 6.92 (overdose) μg/μl once every three days from day 0 to 18 of pregnancy (n = 8–10). Offspring were sacrificed on postnatal day 30. Interleukin-4 and interferon-γ levels in plasma and splenocytes, splenic lymphocyte proliferation, and expressions of GATA-3 and T-bet mRNA in the spleen were tested. The spleen and thymus were histopathologically examined. The offspring of the medium, high and overdose PM-exposed dams showed significantly suppressed splenocyte proliferation. Decreased interferon-γ and increased interleukin-4 levels in the blood and splenocytes, and lowered T-bet and elevated GATA-3 mRNA expressions were found in the spleen in the medium, high and overdose groups when compared with the control or low dose group (P < 0.05). Histopathology revealed prominent tissue damage in the spleen and thymus in the overdose group. These results suggest that exposure of pregnant mice to PM modulates the fetal immune system, resulting in postnatal immune dysfunction by exacerbation of Thl/Th2 deviation. This deviation is associated with altered T-bet and GATA-3 gene expressions

Wnt and Hedgehog Signaling Regulate the Differentiation of F9 Cells into Extraembryonic Endoderm

Directory of Open Access Journals (Sweden)

Gurjoth S. J. Deol

2017-10-01

Full Text Available Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE when treated with retinoic acid (RA, and this is accompanied by an up-regulation of Gata6. The role of the GATA6 network in PrE differentiation is known, and we have shown it directly activates Wnt6. Canonical Wnt/β-catenin signaling is required by F9 cells to differentiate to PrE, and this, like most developmental processes, requires input from one or more additional pathways. We found both RA and Gata6 overexpression, can induce the expression of Indian Hedgehog (Ihh and a subset of its target genes through Gli activation during PrE induction. Chemical activation of the Hh pathway using a Smoothened agonist (SAG also increased Gli reporter activity, and as expected, when Hh signaling was blocked with a Smoothened antagonist, cyclopamine, this RA-induced reporter activity was reduced. Interestingly, SAG alone failed to induce markers of PrE differentiation, and had no effect on Wnt/β-catenin-dependent TCF-LEF reporter activity. The expected increase in Wnt/β-catenin-dependent TCF-LEF reporter activity and PrE markers induced by RA was, however, blocked by cyclopamine. Finally, inhibiting GSK3 activity with BIO increased both TCF-LEF and Gli reporter activities. Together, we demonstrate the involvement of Hh signaling in the RA-induced differentiation of F9 cells into PrE, and while the activation of the Hh pathway itself is not sufficient, it as well as active Wnt/β-catenin are necessary for F9 cell differentiation.

The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord.

Science.gov (United States)

Petracca, Yanina L; Sartoretti, Maria Micaela; Di Bella, Daniela J; Marin-Burgin, Antonia; Carcagno, Abel L; Schinder, Alejandro F; Lanuza, Guillermo M

2016-03-01

Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells. © 2016. Published by The Company of Biologists Ltd.

Discovering transcription factor binding sites in highly repetitive regions of genomes with multi-read analysis of ChIP-Seq data.

Science.gov (United States)

Chung, Dongjun; Kuan, Pei Fen; Li, Bo; Sanalkumar, Rajendran; Liang, Kun; Bresnick, Emery H; Dewey, Colin; Keleş, Sündüz

2011-07-01

Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) is rapidly replacing chromatin immunoprecipitation combined with genome-wide tiling array analysis (ChIP-chip) as the preferred approach for mapping transcription-factor binding sites and chromatin modifications. The state of the art for analyzing ChIP-seq data relies on using only reads that map uniquely to a relevant reference genome (uni-reads). This can lead to the omission of up to 30% of alignable reads. We describe a general approach for utilizing reads that map to multiple locations on the reference genome (multi-reads). Our approach is based on allocating multi-reads as fractional counts using a weighted alignment scheme. Using human STAT1 and mouse GATA1 ChIP-seq datasets, we illustrate that incorporation of multi-reads significantly increases sequencing depths, leads to detection of novel peaks that are not otherwise identifiable with uni-reads, and improves detection of peaks in mappable regions. We investigate various genome-wide characteristics of peaks detected only by utilization of multi-reads via computational experiments. Overall, peaks from multi-read analysis have similar characteristics to peaks that are identified by uni-reads except that the majority of them reside in segmental duplications. We further validate a number of GATA1 multi-read only peaks by independent quantitative real-time ChIP analysis and identify novel target genes of GATA1. These computational and experimental results establish that multi-reads can be of critical importance for studying transcription factor binding in highly repetitive regions of genomes with ChIP-seq experiments.

Discovering transcription factor binding sites in highly repetitive regions of genomes with multi-read analysis of ChIP-Seq data.

Directory of Open Access Journals (Sweden)

Dongjun Chung

2011-07-01

Full Text Available Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq is rapidly replacing chromatin immunoprecipitation combined with genome-wide tiling array analysis (ChIP-chip as the preferred approach for mapping transcription-factor binding sites and chromatin modifications. The state of the art for analyzing ChIP-seq data relies on using only reads that map uniquely to a relevant reference genome (uni-reads. This can lead to the omission of up to 30% of alignable reads. We describe a general approach for utilizing reads that map to multiple locations on the reference genome (multi-reads. Our approach is based on allocating multi-reads as fractional counts using a weighted alignment scheme. Using human STAT1 and mouse GATA1 ChIP-seq datasets, we illustrate that incorporation of multi-reads significantly increases sequencing depths, leads to detection of novel peaks that are not otherwise identifiable with uni-reads, and improves detection of peaks in mappable regions. We investigate various genome-wide characteristics of peaks detected only by utilization of multi-reads via computational experiments. Overall, peaks from multi-read analysis have similar characteristics to peaks that are identified by uni-reads except that the majority of them reside in segmental duplications. We further validate a number of GATA1 multi-read only peaks by independent quantitative real-time ChIP analysis and identify novel target genes of GATA1. These computational and experimental results establish that multi-reads can be of critical importance for studying transcription factor binding in highly repetitive regions of genomes with ChIP-seq experiments.

The Chandra Source Catalog: Source Properties and Data Products

Science.gov (United States)

Rots, Arnold; Evans, Ian N.; Glotfelty, Kenny J.; Primini, Francis A.; Zografou, Panagoula; Anderson, Craig S.; Bonaventura, Nina R.; Chen, Judy C.; Davis, John E.; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Galle, Elizabeth C.; Gibbs, Danny G., II; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; He, Xiang Qun (Helen); Houck, John C.; Karovska, Margarita; Kashyap, Vinay L.; Lauer, Jennifer; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph B.; Mitschang, Arik W.; Morgan, Douglas L.; Mossman, Amy E.; Nichols, Joy S.; Nowak, Michael A.; Plummer, David A.; Refsdal, Brian L.; Siemiginowska, Aneta L.; Sundheim, Beth A.; Tibbetts, Michael S.; van Stone, David W.; Winkelman, Sherry L.

2009-09-01

The Chandra Source Catalog (CSC) is breaking new ground in several areas. There are two aspects that are of particular interest to the users: its evolution and its contents. The CSC will be a living catalog that becomes richer, bigger, and better in time while still remembering its state at each point in time. This means that users will be able to take full advantage of new additions to the catalog, while retaining the ability to back-track and return to what was extracted in the past. The CSC sheds the limitations of flat-table catalogs. Its sources will be characterized by a large number of properties, as usual, but each source will also be associated with its own specific data products, allowing users to perform mini custom analysis on the sources. Source properties fall in the spatial (position, extent), photometric (fluxes, count rates), spectral (hardness ratios, standard spectral fits), and temporal (variability probabilities) domains, and are all accompanied by error estimates. Data products cover the same coordinate space and include event lists, images, spectra, and light curves. In addition, the catalog contains data products covering complete observations: event lists, background images, exposure maps, etc. This work is supported by NASA contract NAS8-03060 (CXC).

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.

EPA's Radioactive Source Program

International Nuclear Information System (INIS)

Kopsick, D.

2004-01-01

The US EPA is the lead Federal agency for emergency responses to unknown radiological materials, not licensed, owned or operated by a Federal agency or an Agreement state (Federal Radiological Emergency Response Plan, 1996). The purpose of EPA's clean materials programme is to keep unwanted and unregulated radioactive material out of the public domain. This is achieved by finding and securing lost sources, maintaining control of existing sources and preventing future losses. The focus is on both, domestic and international fronts. The domestic program concentrates on securing lost sources, preventing future losses, alternative technologies like tagging of radioactive sources in commerce, pilot radioactive source roundup, training programs, scrap metal and metal processing facilities, the demolition industry, product stewardship and alternatives to radioactive devices (fewer radioactive source devices means fewer orphan sources). The international program consists of securing lost sources, preventing future losses, radiation monitoring of scrap metal at ports and the international scrap metal monitoring protocol

Detection and Characterization of Infections and Infection Susceptibility

Science.gov (United States)

2018-03-27

Immune Disorders; Chronic Granulomatous Disease; Genetic Immunological Deficiencies; Hyperimmunoglobulin-E Recurrent Infection Syndrome; Recurrent Infections; Unknown Immune Deficiency; GATA2 Deficiency (MonoMAC); Nontuberculous Mycobacterial Infections; Hyper IgE (Job s) Syndrome; Leukocyte Adhesion Deficiency; Susceptibility to Disseminated Infections; Primary Immune Deficiency Disease (PIDD)

Hubble Source Catalog

Science.gov (United States)

Lubow, S.; Budavári, T.

2013-10-01

We have created an initial catalog of objects observed by the WFPC2 and ACS instruments on the Hubble Space Telescope (HST). The catalog is based on observations taken on more than 6000 visits (telescope pointings) of ACS/WFC and more than 25000 visits of WFPC2. The catalog is obtained by cross matching by position in the sky all Hubble Legacy Archive (HLA) Source Extractor source lists for these instruments. The source lists describe properties of source detections within a visit. The calculations are performed on a SQL Server database system. First we collect overlapping images into groups, e.g., Eta Car, and determine nearby (approximately matching) pairs of sources from different images within each group. We then apply a novel algorithm for improving the cross matching of pairs of sources by adjusting the astrometry of the images. Next, we combine pairwise matches into maximal sets of possible multi-source matches. We apply a greedy Bayesian method to split the maximal matches into more reliable matches. We test the accuracy of the matches by comparing the fluxes of the matched sources. The result is a set of information that ties together multiple observations of the same object. A byproduct of the catalog is greatly improved relative astrometry for many of the HST images. We also provide information on nondetections that can be used to determine dropouts. With the catalog, for the first time, one can carry out time domain, multi-wavelength studies across a large set of HST data. The catalog is publicly available. Much more can be done to expand the catalog capabilities.

Pulsed vapor source for use in ion sources for heavy-ion accelerators

International Nuclear Information System (INIS)

Shiloh, J.; Chupp, W.; Faltens, A.; Keefe, D.; Kim, C.; Rosenblum, S.; Tiefenback, M.

1980-01-01

A pulsed cesium vapor source for use in ion sources for high-current heavy-ion accelerators is described. The source employs a vacuum spark in Cs and its properties are measured with a hot-filament Cs detector

Chandra Source Catalog: User Interface

Science.gov (United States)

Bonaventura, Nina; Evans, Ian N.; Rots, Arnold H.; Tibbetts, Michael S.; van Stone, David W.; Zografou, Panagoula; Primini, Francis A.; Glotfelty, Kenny J.; Anderson, Craig S.; Chen, Judy C.; Davis, John E.; Doe, Stephen M.; Evans, Janet D.; Fabbiano, Giuseppina; Galle, Elizabeth C.; Gibbs, Danny G., II; Grier, John D.; Hain, Roger; Hall, Diane M.; Harbo, Peter N.; He, Helen; Houck, John C.; Karovska, Margarita; Kashyap, Vinay L.; Lauer, Jennifer; McCollough, Michael L.; McDowell, Jonathan C.; Miller, Joseph B.; Mitschang, Arik W.; Morgan, Douglas L.; Mossman, Amy E.; Nichols, Joy S.; Nowak, Michael A.; Plummer, David A.; Refsdal, Brian L.; Siemiginowska, Aneta L.; Sundheim, Beth A.; Winkelman, Sherry L.

2009-09-01

The Chandra Source Catalog (CSC) is intended to be the definitive catalog of all X-ray sources detected by Chandra. For each source, the CSC provides positions and multi-band fluxes, as well as derived spatial, spectral, and temporal source properties. Full-field and source region data products are also available, including images, photon event lists, light curves, and spectra. The Chandra X-ray Center CSC website (http://cxc.harvard.edu/csc/) is the place to visit for high-level descriptions of each source property and data product included in the catalog, along with other useful information, such as step-by-step catalog tutorials, answers to FAQs, and a thorough summary of the catalog statistical characterization. Eight categories of detailed catalog documents may be accessed from the navigation bar on most of the 50+ CSC pages; these categories are: About the Catalog, Creating the Catalog, Using the Catalog, Catalog Columns, Column Descriptions, Documents, Conferences, and Useful Links. There are also prominent links to CSCview, the CSC data access GUI, and related help documentation, as well as a tutorial for using the new CSC/Google Earth interface. Catalog source properties are presented in seven scientific categories, within two table views: the Master Source and Source Observations tables. Each X-ray source has one ``master source'' entry and one or more ``source observation'' entries, the details of which are documented on the CSC ``Catalog Columns'' pages. The master source properties represent the best estimates of the properties of a source; these are extensively described on the following pages of the website: Position and Position Errors, Source Flags, Source Extent and Errors, Source Fluxes, Source Significance, Spectral Properties, and Source Variability. The eight tutorials (``threads'') available on the website serve as a collective guide for accessing, understanding, and manipulating the source properties and data products provided by the catalog.

High current ion sources

International Nuclear Information System (INIS)

Brown, I.G.

1989-06-01

The concept of high current ion source is both relative and evolutionary. Within the domain of one particular kind of ion source technology a current of microamperers might be 'high', while in another area a current of 10 Amperes could 'low'. Even within the domain of a single ion source type, what is considered high current performance today is routinely eclipsed by better performance and higher current output within a short period of time. Within their fields of application, there is a large number of kinds of ion sources that can justifiably be called high current. Thus, as a very limited example only, PIGs, Freemen sources, ECR sources, duoplasmatrons, field emission sources, and a great many more all have their high current variants. High current ion beams of gaseous and metallic species can be generated in a number of different ways. Ion sources of the kind developed at various laboratories around the world for the production of intense neutral beams for controlled fusion experiments are used to form large area proton deuteron beams of may tens of Amperes, and this technology can be used for other applications also. There has been significant progress in recent years in the use of microwave ion sources for high current ion beam generation, and this method is likely to find wide application in various different field application. Finally, high current beams of metal ions can be produced using metal vapor vacuum arc ion source technology. After a brief consideration of high current ion source design concepts, these three particular methods are reviewed in this paper

Source Segregation and Collection of Source-Segregated Waste

DEFF Research Database (Denmark)

Christensen, Thomas Højlund; Matsufuji, Y.

2011-01-01

of optimal handling of the waste. But in a few cases, the waste must also be separated at source, for example removing the protective plastic cover from a commercial advertisement received by mail, prior to putting the advertisement into the waste collection bin for recyclable paper. These issues are often...... in wastes segregation addressing: - Purpose of source segregation. - Segregation criteria and guidance. - Segregation potentials and efficiencies. - Systems for collecting segregated fraction....

ERP correlates of source memory: Unitized source information increases familiarity-based retrieval

OpenAIRE

Diana, Rachel A.; Van den Boom, Wijnand; Yonelinas, Andrew P.; Ranganath, Charan

2010-01-01

Source memory tests typically require subjects to make decisions about the context in which an item was encoded and are thought to depend on recollection of details from the study episode. Although it is generally believed that familiarity does not contribute to source memory, recent behavioral studies have suggested that familiarity may also support source recognition when item and source information are integrated, or “unitized”, during study (Diana, Yonelinas, and Ranganath 2008). However,...

Source signature estimation from multimode surface waves via mode-separated virtual real source method

Science.gov (United States)

Gao, Lingli; Pan, Yudi

2018-05-01

The correct estimation of the seismic source signature is crucial to exploration geophysics. Based on seismic interferometry, the virtual real source (VRS) method provides a model-independent way for source signature estimation. However, when encountering multimode surface waves, which are commonly seen in the shallow seismic survey, strong spurious events appear in seismic interferometric results. These spurious events introduce errors in the virtual-source recordings and reduce the accuracy of the source signature estimated by the VRS method. In order to estimate a correct source signature from multimode surface waves, we propose a mode-separated VRS method. In this method, multimode surface waves are mode separated before seismic interferometry. Virtual-source recordings are then obtained by applying seismic interferometry to each mode individually. Therefore, artefacts caused by cross-mode correlation are excluded in the virtual-source recordings and the estimated source signatures. A synthetic example showed that a correct source signature can be estimated with the proposed method, while strong spurious oscillation occurs in the estimated source signature if we do not apply mode separation first. We also applied the proposed method to a field example, which verified its validity and effectiveness in estimating seismic source signature from shallow seismic shot gathers containing multimode surface waves.

Amateur Sources Breaking the News, Meta Sources Authorizing the News of Gaddafi's Death

DEFF Research Database (Denmark)

Mortensen, Mette; Kristensen, Nete Nørgaard

2013-01-01

access to information from war zones, but are instead brought in to comment on, validate and grant legitimacy to amateur sources as a form of explicit source criticism that we would like to term metasourcing. This new pattern of information gathering and sourcing within war reporting manifests itself......This article takes its point of departure in the thesis that today’s global, digitalized and conver- gent media environment has promoted new patterns of information gathering and dissemina- tion within journalism, and war journalism in particular, which involve changing forms and various degrees...... of interplay between elite and non-elite sources as well as media professionals and amateur sources. On account of their proximity to unfolding events, amateur sources often break the news by means of raw and fragmented bits of visual and verbal information. Elite sources rarely possess the same exclusive...

Compact microwave ion source

International Nuclear Information System (INIS)

Leung, K.N.; Walther, S.; Owren, H.W.

1985-05-01

A small microwave ion source has been fabricated from a quartz tube with one end enclosed by a two grid accelerator. The source is also enclosed by a cavity operated at a frequency of 2.45 GHz. Microwave power as high as 500 W can be coupled to the source plasma. The source has been operated with and without multicusp fields for different gases. In the case of hydrogen, ion current density of 200 mA/cm -2 with atomic ion species concentration as high as 80% has been extracted from the source

Characteristics and locations of sources

International Nuclear Information System (INIS)

Lahtinen, J.; Poellaenen, R.; Toivonen, H.

1997-01-01

Ten artificial radiation sources were placed in the terrain in order to test the capability of airborne measuring teams to detect them. One of the sources was a line source, others were point sources (three of them collimated). The radionuclides used in the sources were 60 Co, 137 Cs, 99m Tc and 192 Ir. The source activities ranged from about 26 MBq (one of the cobalt sources) to 0.56 TBq (iridium). (au)

H- radio frequency source development at the Spallation Neutron Source.

Science.gov (United States)

Welton, R F; Dudnikov, V G; Gawne, K R; Han, B X; Murray, S N; Pennisi, T R; Roseberry, R T; Santana, M; Stockli, M P; Turvey, M W

2012-02-01

The Spallation Neutron Source (SNS) now routinely operates nearly 1 MW of beam power on target with a highly persistent ∼38 mA peak current in the linac and an availability of ∼90%. H(-) beam pulses (∼1 ms, 60 Hz) are produced by a Cs-enhanced, multicusp ion source closely coupled with an electrostatic low energy beam transport (LEBT), which focuses the 65 kV beam into a radio frequency quadrupole accelerator. The source plasma is generated by RF excitation (2 MHz, ∼60 kW) of a copper antenna that has been encased with a thickness of ∼0.7 mm of porcelain enamel and immersed into the plasma chamber. The ion source and LEBT normally have a combined availability of ∼99%. Recent increases in duty-factor and RF power have made antenna failures a leading cause of downtime. This report first identifies the physical mechanism of antenna failure from a statistical inspection of ∼75 antennas which ran at the SNS, scanning electron microscopy studies of antenna surface, and cross sectional cuts and analysis of calorimetric heating measurements. Failure mitigation efforts are then described which include modifying the antenna geometry and our acceptance∕installation criteria. Progress and status of the development of the SNS external antenna source, a long-term solution to the internal antenna problem, are then discussed. Currently, this source is capable of delivering comparable beam currents to the baseline source to the SNS and, an earlier version, has briefly demonstrated unanalyzed currents up to ∼100 mA (1 ms, 60 Hz) on the test stand. In particular, this paper discusses plasma ignition (dc and RF plasma guns), antenna reliability, magnet overheating, and insufficient beam persistence.

Digital intelligence sources transporter

International Nuclear Information System (INIS)

Zhang Zhen; Wang Renbo

2011-01-01

It presents from the collection of particle-ray counting, infrared data communication, real-time monitoring and alarming, GPRS and other issues start to realize the digital management of radioactive sources, complete the real-time monitoring of all aspects, include the storing of radioactive sources, transporting and using, framing intelligent radioactive sources transporter, as a result, achieving reliable security supervision of radioactive sources. (authors)

Guidelines for the calibration of low energy photon sources at beta-ray brachytherapy sources

International Nuclear Information System (INIS)

2000-01-01

With the development of improved methods of implanting brachytherapy sources in a precise manner for treating prostate cancer and other disease processes, there has been a tremendous growth in the use of low energy photon sources, such as 125 I and 103 Pd brachytherapy seeds. Low energy photon sources have the advantage of easier shielding and also lowering the dose to normal tissue. However, the dose distributions around these sources are affected by the details in construction of the source and its encapsulation more than other sources used for brachytherapy treatments, such as 192 Ir. With increasing number of new low energy photon sources on the market, care should be taken with regard to its traceability to primary standards. It cannot be assumed that a calibration factor for an ionization chamber that is valid for one type of low energy photon source, automatically is valid for another source even if both would use the same isotope. Moreover, the method used to calculate the dose must also take into account the structure of the source and the encapsulation. The dose calculation algorithm that is valid for one type of low energy source may not be valid for another source even if in both cases the same radionuclide is used. Simple ''point source'' approximations, i.e. where the source is modeled as a point, should be avoided, as such methods do not account for any details in the source construction. In this document, the dose calculation formalism adopted for low energy photon sources is that recommended by the American Association of Physicists in Medicine (AAPM) as outlined by Task Group-43 (TG-43). This method accounts for the source and capsule geometry. The AAPM recommends brachytherapy photon sources to be specified in terms of 'Air Kerma Strength' that is also used in the formalism mentioned above. On the other hand, the International Commission on Radiation Units and Measurements (ICRU) recommends that the specification be done in terms of Reference Air

Point Pollution Sources Dimensioning

Directory of Open Access Journals (Sweden)

Georgeta CUCULEANU

2011-06-01

Full Text Available In this paper a method for determining the main physical characteristics of the point pollution sources is presented. It can be used to find the main physical characteristics of them. The main physical characteristics of these sources are top inside source diameter and physical height. The top inside source diameter is calculated from gas flow-rate. For reckoning the physical height of the source one takes into account the relation given by the proportionality factor, defined as ratio between the plume rise and physical height of the source. The plume rise depends on the gas exit velocity and gas temperature. That relation is necessary for diminishing the environmental pollution when the production capacity of the plant varies, in comparison with the nominal one.

Specification of brachytherapy sources

Energy Technology Data Exchange (ETDEWEB)

1984-10-01

BCRU recommends that the following specification of gamma-ray brachytherapy sources be adopted. Unless otherwise stated, the output of a cylindrical source should be specified in air kerma rate at a point in free space at a distance of 1 m from the source on the radial plane of symmetry, i.e. the plane bisecting the active length and perpendicular to the cylindrical axis of the source. For a wire source the output should be specified for a 1 cm length. For any other construction of source, the point at which the output is specified should be stated. It is also recommended that the units in which the air kerma rate is expressed should be micrograys per hour (..mu..Gy/h).

Characteristics and locations of sources

Energy Technology Data Exchange (ETDEWEB)

Lahtinen, J.; Poellaenen, R.; Toivonen, H. [Finnish Centre for Radiation and Nuclear Safety, Helsinki (Finland)

1997-12-31

Ten artificial radiation sources were placed in the terrain in order to test the capability of airborne measuring teams to detect them. One of the sources was a line source, others were point sources (three of them collimated). The radionuclides used in the sources were {sup 60}Co, {sup 137}Cs, {sup 99m}Tc and {sup 192}Ir. The source activities ranged from about 26 MBq (one of the cobalt sources) to 0.56 TBq (iridium). (au).

Characteristics and locations of sources

Energy Technology Data Exchange (ETDEWEB)

Lahtinen, J; Poellaenen, R; Toivonen, H [Finnish Centre for Radiation and Nuclear Safety, Helsinki (Finland)

1998-12-31

Ten artificial radiation sources were placed in the terrain in order to test the capability of airborne measuring teams to detect them. One of the sources was a line source, others were point sources (three of them collimated). The radionuclides used in the sources were {sup 60}Co, {sup 137}Cs, {sup 99m}Tc and {sup 192}Ir. The source activities ranged from about 26 MBq (one of the cobalt sources) to 0.56 TBq (iridium). (au).

Characteristics of hearing loss in HDR (hypoparathyroidism, sensorineural deafness, renal dysplasia) syndrome

NARCIS (Netherlands)

van Looij, Marjolein A. J.; Meijers-Heijboer, Hanne; Beetz, Rolf; Thakker, Rajesh V.; Christie, Paul T.; Feenstra, Lou W.; van Zanten, Bert G. A.

2006-01-01

Haploinsufficiency of the zinc finger transcription factor GATA3 causes the triad of hypoparathyroidism, deafness and renal dysplasia, known by its acronym HDR syndrome. The purpose of the current study was to describe in detail the auditory phenotype in human HDR patients and compare these to

Sources of atmospheric acidity

International Nuclear Information System (INIS)

Clarke, A.G.

1992-01-01

The emissions of acid gases from anthropogenic sources and their impact on the environment are the main concern of this book. However, that impact can only be assessed if all the naturally occurring sources of these gases are also known and can be quantified. Given the widely dispersed nature of the natural sources and the problems of measurement of trace species at low concentrations, often in remote regions, the quantification is a very difficult task. Nevertheless, considerable progress has been made over the last decade. In this chapter both man-made and natural sources of atmospheric acidity will be reviewed, but the emphasis will be placed not so much on the global balances as on the scale of the natural sources in relation to the man-made sources. This requires that the very uneven geographical distribution of emissions and the lifetime of individual chemical species be taken into account. The emissions considered are sulphur compounds, nitrogen compounds, chlorine compounds and organic acids. The anthropogenic sources discussed are the combustion of fossil fuels and certain industrial processes. Emissions data for anthropogenic sources are given for the United Kingdom, Europe, USA and globally. A list of 95 references is given. (Author)

Open-Source Colorimeter

OpenAIRE

Anzalone, Gerald C.; Glover, Alexandra G.; Pearce, Joshua M.

2013-01-01

The high cost of what have historically been sophisticated research-related sensors and tools has limited their adoption to a relatively small group of well-funded researchers. This paper provides a methodology for applying an open-source approach to design and development of a colorimeter. A 3-D printable, open-source colorimeter utilizing only open-source hardware and software solutions and readily available discrete components is discussed and its performance compared to a commercial porta...

Source Apportionment of Suspended Sediment Sources using 137Cs and 210Pbxs

Science.gov (United States)

Lamba, J.; Karthikeyan, K.; Thompson, A.

2017-12-01

A study was conducted in the Pleasant Valley Watershed (50 km 2) in South Central Wisconsin to better understand sediment transport processes using sediment fingerprinting technique. Previous studies conducted in this watershed showed that resuspension of fine sediment deposited on the stream bed is an important source of suspended sediment. To better understand the role of fine sediment deposited on the stream bed, fallout radionuclides,137Cs and 210Pbxs were used to determine relative contribution to suspended sediment from in-stream (stream bank and stream bed) and upland sediment sources. Suspended sediment samples were collected during the crop growing season. Potential sources of suspended sediment considered in this study included cropland, pasture and in-stream (stream bed and stream bank). Suspended sediment sources were determined at a subwatershed level. Results of this study showed that in-stream sediment sources are important sources of suspended sediment. Future research should be conducted to better understand the role of legacy sediment in watershed-level sediment transport processes.

Nonpoint source pollution of urban stormwater runoff: a methodology for source analysis.

Science.gov (United States)

Petrucci, Guido; Gromaire, Marie-Christine; Shorshani, Masoud Fallah; Chebbo, Ghassan

2014-09-01

The characterization and control of runoff pollution from nonpoint sources in urban areas are a major issue for the protection of aquatic environments. We propose a methodology to quantify the sources of pollutants in an urban catchment and to analyze the associated uncertainties. After describing the methodology, we illustrate it through an application to the sources of Cu, Pb, Zn, and polycyclic aromatic hydrocarbons (PAH) from a residential catchment (228 ha) in the Paris region. In this application, we suggest several procedures that can be applied for the analysis of other pollutants in different catchments, including an estimation of the total extent of roof accessories (gutters and downspouts, watertight joints and valleys) in a catchment. These accessories result as the major source of Pb and as an important source of Zn in the example catchment, while activity-related sources (traffic, heating) are dominant for Cu (brake pad wear) and PAH (tire wear, atmospheric deposition).

Thermal neutron source study

International Nuclear Information System (INIS)

Holden, T.M.

1983-05-01

The value of intense neutron beams for condensed matter research is discussed with emphasis on the complementary nature of steady state and pulsed neutron sources. A large body of information on neutron sources, both existing and planned, is then summarized under four major headings: fission reactors, electron accelerators with heavy metal targets, pulsed spallation sources and 'steady state' spallation sources. Although the cost of a spallation source is expected to exceed that of a fission reactor of the same flux by a factor of two, there are significant advantages for a spallation device such as the proposed Electronuclear Materials Test Facility (EMTF)

Spallation neutrons pulsed sources

International Nuclear Information System (INIS)

Carpenter, J.

1996-01-01

This article describes the range of scientific applications which can use these pulsed neutrons sources: Studies on super fluids, measures to verify the crawling model for the polymers diffusion; these sources are also useful to study the neutron disintegration, the ultra cold neutrons. In certain applications which were not accessible by neutrons diffusion, for example, radiations damages, radionuclides production and activation analysis, the spallation sources find their use and their improvement will bring new possibilities. Among others contributions, one must notice the place at disposal of pulsed muons sources and neutrinos sources. (N.C.). 3 figs

Sources for charged particles

International Nuclear Information System (INIS)

Arianer, J.

1997-01-01

This document is a basic course on charged particle sources for post-graduate students and thematic schools on large facilities and accelerator physics. A simple but precise description of the creation and the emission of charged particles is presented. This course relies on every year upgraded reference documents. Following relevant topics are considered: electronic emission processes, technological and practical considerations on electron guns, positron sources, production of neutral atoms, ionization, plasma and discharge, different types of positive and negative ion sources, polarized particle sources, materials for the construction of ion sources, low energy beam production and transport. (N.T.)

MiniX-STR multiplex system population study in Japan and application to degraded DNA analysis.

Science.gov (United States)

Asamura, H; Sakai, H; Kobayashi, K; Ota, M; Fukushima, H

2006-05-01

We sought to evaluate a more effective system for analyzing X-chromosomal short tandem repeats (X-STRs) in highly degraded DNA. To generate smaller amplicon lengths, we designed new polymerase chain reaction (PCR) primers for DXS7423, DXS6789, DXS101, GATA31E08, DXS8378, DXS7133, DXS7424, and GATA165B12 at X-linked short tandem repeat (STR) loci, devising two miniX-multiplex PCR systems. Among 333 Japanese individuals, these X-linked loci were detected in amplification products ranging in length from 76 to 169 bp, and statistical analyses of the eight loci indicated a high usefulness for the Japanese forensic practice. Results of tests on highly degraded DNA indicated the miniX-STR multiplex strategies to be an effective system for analyzing degraded DNA. We conclude that analysis by the current miniX-STR multiplex systems offers high effectiveness for personal identification from degraded DNA samples.

Biology and management of transient abnormal myelopoiesis (TAM) in children with Down syndrome.

Science.gov (United States)

Roy, Anindita; Roberts, Irene; Vyas, Paresh

2012-08-01

Children with Down syndrome (DS) have an increased risk of Acute Myeloid Leukaemia (ML-DS), particularly megakaryoblastic leukaemia, which is clonally -related to the neonatal myeloproliferative syndrome, Transient Abnormal Myelopoiesis (TAM) unique to infants with DS. Molecular, biological, and clinical data indicate that TAM is initiated before birth when fetal liver haematopoietic cells trisomic for chromosome 21 acquire mutations in GATA1. TAM usually resolves spontaneously by 6 months; however 20-30% subsequently develop ML-DS harbouring the same GATA1 mutation(s). This review focuses on recent studies describing haematological, clinical and biological features of TAM and discusses approaches to diagnose, treat and monitor minimal residual disease in TAM. An important unanswered question is whether ML-DS is always preceded by TAM as it may be clinically and possibly haematologically 'silent'. We have briefly discussed the role of population-based screening for TAM and development of treatment strategies to eliminate the preleukaemic TAM clone, thereby preventing ML-DS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Circulation-Independent Differentiation Pathway from Extraembryonic Mesoderm toward Hematopoietic Stem Cells via Hemogenic Angioblasts

Directory of Open Access Journals (Sweden)

Yosuke Tanaka

2014-07-01

Full Text Available A large gap exists in our understanding of the course of differentiation from mesoderm to definitive hematopoietic stem cells (HSCs. Previously, we reported that Runx1+ cells in embryonic day 7.5 (E7.5 embryos contribute to the hemogenic endothelium in the E10.5 aorta-gonad-mesonephros (AGM region and HSCs in the adult bone marrow. Here, we show that two Runx1+ populations subdivided by Gata1 expression exist in E7.5 embryos. The hemogenic endothelium and the HSCs are derived only from the Runx1+Gata1− population. A subset of this population moves from the extra- to intraembryonic region during E7.5–E8.0, where it contributes to the hemogenic endothelium of the dorsal aorta (DA. Migration occurs before the heartbeat is initiated, and it is independent of circulation. This suggests a developmental trajectory from Runx1+ cells in the E7.5 extraembryonic region to definitive HSCs via the hemogenic endothelium.

Tzfp represses the androgen receptor in mouse testis.

Directory of Open Access Journals (Sweden)

Kari Furu

Full Text Available The testis zinc finger protein (Tzfp, also known as Repressor of GATA, belongs to the BTB/POZ zinc finger family of transcription factors and is thought to play a role in spermatogenesis due to its remarkably high expression in testis. Despite many attempts to find the in vivo role of the protein, the molecular function is still largely unknown. Here, we address this issue using a novel mouse model with a disrupted Tzfp gene. Homozygous Tzfp null mice are born at reduced frequency but appear viable and fertile. Sertoli cells in testes lacking Tzfp display an increase in Androgen Receptor (AR signaling, and several genes in the testis, including Gata1, Aie1 and Fanc, show increased expression. Our results indicate that Tzfp function as a transcriptional regulator and that loss of the protein leads to alterations in AR signaling and reduced number of apoptotic cells in the testicular tubules.

Single-Cell Network Analysis Identifies DDIT3 as a Nodal Lineage Regulator in Hematopoiesis

Directory of Open Access Journals (Sweden)

Cristina Pina

2015-06-01

Full Text Available We explore cell heterogeneity during spontaneous and transcription-factor-driven commitment for network inference in hematopoiesis. Since individual genes display discrete OFF states or a distribution of ON levels, we compute and combine pairwise gene associations from binary and continuous components of gene expression in single cells. Ddit3 emerges as a regulatory node with positive linkage to erythroid regulators and negative association with myeloid determinants. Ddit3 loss impairs erythroid colony output from multipotent cells, while forcing Ddit3 in granulo-monocytic progenitors (GMPs enhances self-renewal and impedes differentiation. Network analysis of Ddit3-transduced GMPs reveals uncoupling of myeloid networks and strengthening of erythroid linkages. RNA sequencing suggests that Ddit3 acts through development or stabilization of a precursor upstream of GMPs with inherent Meg-E potential. The enrichment of Gata2 target genes in Ddit3-dependent transcriptional responses suggests that Ddit3 functions in an erythroid transcriptional network nucleated by Gata2.

Anomaly metrics to differentiate threat sources from benign sources in primary vehicle screening.

Energy Technology Data Exchange (ETDEWEB)

Cohen, Israel Dov; Mengesha, Wondwosen

2011-09-01

Discrimination of benign sources from threat sources at Port of Entries (POE) is of a great importance in efficient screening of cargo and vehicles using Radiation Portal Monitors (RPM). Currently RPM's ability to distinguish these radiological sources is seriously hampered by the energy resolution of the deployed RPMs. As naturally occurring radioactive materials (NORM) are ubiquitous in commerce, false alarms are problematic as they require additional resources in secondary inspection in addition to impacts on commerce. To increase the sensitivity of such detection systems without increasing false alarm rates, alarm metrics need to incorporate the ability to distinguish benign and threat sources. Principal component analysis (PCA) and clustering technique were implemented in the present study. Such techniques were investigated for their potential to lower false alarm rates and/or increase sensitivity to weaker threat sources without loss of specificity. Results of the investigation demonstrated improved sensitivity and specificity in discriminating benign sources from threat sources.

Rf power sources

International Nuclear Information System (INIS)

Allen, M.A.

1988-05-01

This paper covers RF power sources for accelerator applications. The approach has been with particular customers in mind. These customers are high energy physicists who use accelerators as experimental tools in the study of the nucleus of the atom, and synchrotron light sources derived from electron or positron storage rings. This paper is confined to electron-positron linear accelerators since the RF sources have always defined what is possible to achieve with these accelerators. 11 refs., 13 figs

Biogenic Emission Sources

Science.gov (United States)

Biogenic emissions sources come from natural sources and need to accounted for in photochemical grid models. They are computed using a model which utilizes spatial information on vegetation and land use.

10 years and 20,000 sources: the GTRI offsite source recovery project

International Nuclear Information System (INIS)

Whitworth, Julia; Streeper, Charles; Cuthbertson, Abigail

2009-01-01

Full text: The Global Threat Reduction Initiative's (GTRI) Offsite Source Recovery Project (OSRP) has been recovering excess and unwanted radioactive sealed sources for ten years. In January 2009, GTRI announced that the project had recovered 20,000 sealed radioactive sources. This project grew out of early efforts at Los Alamos National Laboratory (LANL) to recover and disposition excess Plutonium-239 ( 239 Pu) sealed sources that were distributed in the 1960s and 1970s under the Atoms for Peace Program. Decades later, these sources began to exceed their design life or fall out of regular use. Sealed source recovery was initially considered a waste management activity, but after the terrorist attacks of 2001, the interagency community began to recognize the threat posed by excess and unwanted radiological materials, particularly those that could not be disposed at the end of their useful life. After being transferred to the U.S. National Nuclear Security Administration (NNSA) to be part of GTRI, OSRP's mission was expanded to include not only material that would be classified as Greater-than-Class-C (GTCC) when it became waste, but also any other materials that might constitute a 'national security consideration'. This paper discusses OSRP's history, recovery operations, expansion to accept high-activity beta-gamma-emitting sealed sources and devices and foreign-possessed sources, and more recent efforts such as involvement in GTRI's Search and Secure project. Current challenges and future work will also be discussed

Quasi-Y-source inverter

DEFF Research Database (Denmark)

Siwakoti, Yam Prasad; Blaabjerg, Frede; Loh, Poh Chiang

2015-01-01

This paper introduces a new inverter topology called a “quasi-Y-source inverter”. The proposed inverter inherits all the advantages of the original Y-source inverter. In addition, the new topology draws continuous current from the source which is required for many renewable sources. It also has dc......-current-blocking capacitors, which avoids saturation in the transformer core. Simulations and experimental results have proved the validity of the proposed inverter....

Open source posturography.

Science.gov (United States)

Rey-Martinez, Jorge; Pérez-Fernández, Nicolás

2016-12-01

The proposed validation goal of 0.9 in intra-class correlation coefficient was reached with the results of this study. With the obtained results we consider that the developed software (RombergLab) is a validated balance assessment software. The reliability of this software is dependent of the used force platform technical specifications. Develop and validate a posturography software and share its source code in open source terms. Prospective non-randomized validation study: 20 consecutive adults underwent two balance assessment tests, six condition posturography was performed using a clinical approved software and force platform and the same conditions were measured using the new developed open source software using a low cost force platform. Intra-class correlation index of the sway area obtained from the center of pressure variations in both devices for the six conditions was the main variable used for validation. Excellent concordance between RombergLab and clinical approved force platform was obtained (intra-class correlation coefficient =0.94). A Bland and Altman graphic concordance plot was also obtained. The source code used to develop RombergLab was published in open source terms.

10 years and 20,000 sources: the offsite source recovery project

Energy Technology Data Exchange (ETDEWEB)

Whitworth, Julia R [Los Alamos National Laboratory; Abeyta, Cristy L [Los Alamos National Laboratory; Pearson, Michael W [Los Alamos National Laboratory

2009-01-01

The Global Threat Reduction Initiative's (GTRI) Offsite Source Recovery Project (OSRP) has been recovering excess and unwanted sealed sources for ten years. In January 2009, GTRI announced that the project had recovered 20,000 sealed radioactive sources. This project grew out of early efforts at Los Alamos National Laboratory (LANL) to recover and disposition excess Plutonium-239 (Pu-239) sealed sources that were distributed in the 1960s and 1970s under the Atoms for Peace Program. Sealed source recovery was initially considered a waste management activity, as evidenced by its initial organization under the Department of Energy's (DOE's) Environmental Management (EM) program. After the terrorist attacks of 2001, however, the interagency community began to recognize the threat posed by excess and unwanted radiological material, particularly those that could not be disposed at the end of their useful life. After being transferred to the National Nuclear Security Administration (NNSA) to be part of GTRI, OSRP's mission was expanded to include not only material that would be classified as Greater-than-Class-C (GTCC) when it became waste, but also any other materials that might be a 'national security consideration.' This paper discusses OSRP's history, recovery operations, expansion to accept high-activity beta-gamma-emitting sealed sources and devices and foreign-possessed sources, and more recent efforts such as cooperative projects with the Council on Radiation Control Program Directors (CRCPD) and involvement in GTRI's Search and Secure project. Current challenges and future work will also be discussed.

Sources of polarized neutrons

International Nuclear Information System (INIS)

Walter, L.

1983-01-01

Various sources of polarized neutrons are reviewed. Monoenergetic source produced with unpolarized or polarized beams, white sources of polarized neutrons, production by transmissions through polarized hydrogen targets and polarized thermal neutronsare discussed, with appropriate applications included. (U.K.)

SOFTWARE OPEN SOURCE, SOFTWARE GRATIS?

Directory of Open Access Journals (Sweden)

Nur Aini Rakhmawati

2006-01-01

Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Berlakunya Undang – undang Hak Atas Kekayaan Intelektual (HAKI, memunculkan suatu alternatif baru untuk menggunakan software open source. Penggunaan software open source menyebar seiring dengan isu global pada Information Communication Technology (ICT saat ini. Beberapa organisasi dan perusahaan mulai menjadikan software open source sebagai pertimbangan. Banyak konsep mengenai software open source ini. Mulai dari software yang gratis sampai software tidak berlisensi. Tidak sepenuhnya isu software open source benar, untuk itu perlu dikenalkan konsep software open source mulai dari sejarah, lisensi dan bagaimana cara memilih lisensi, serta pertimbangan dalam memilih software open source yang ada. Kata kunci :Lisensi, Open Source, HAKI

Thermal-hydraulic studies of the Advanced Neutron Source cold source

International Nuclear Information System (INIS)

Williams, P.T.; Lucas, A.T.

1995-08-01

The Advanced Neutron Source (ANS), in its conceptual design phase at Oak Ridge National Laboratory, was to be a user-oriented neutron research facility producing the most intense steady-state flux of thermal and cold neutrons in the world. Among its many scientific applications, the production of cold neutrons was a significant research mission for the ANS. The cold neutrons come from two independent cold sources positioned near the reactor core. Contained by an aluminum alloy vessel, each cold source is a 410-mm-diam sphere of liquid deuterium that functions both as a neutron moderator and a cryogenic coolant. With nuclear heating of the containment vessel and internal baffling, steady-state operation requires close control of the liquid deuterium flow near the vessel's inner surface. Preliminary thermal-hydraulic analyses supporting the cold source design were performed with heat conduction simulations of the vessel walls and multidimensional computational fluid dynamics simulations of the liquid deuterium flow and heat transfer. This report presents the starting phase of a challenging program and describes the cold source conceptual design, the thermal-hydraulic feasibility studies of the containment vessel, and the future computational and experimental studies that were planned to verify the final design

Journal of Genetics, Volume 86, 2007

Indian Academy of Sciences (India)

phalipoproteinemia in a Moroccan family (Research note) 159 dog. Isolation, characterization and genetic analysis of canine GATA4 gene in a family of Doberman Pinschers with an atrial septal de- fect. 241. Isolation, characterization and molecular screening of canine. SLC26A2 (sulphate transporter) in German Shepherd ...

Role of Mitochondrial Reactive Oxygen Species in the Activation of Cellular Signals, Molecules, and Function

DEFF Research Database (Denmark)

Indo, Hiroko P.; Hawkins, Clare L; Nakanishi, Ikuo

2017-01-01

-κB) and GATA signaling pathways. We have also reviewed the effects of ROS on the activation of MMP and HIF. There is significant evidence to support the hypothesis that mitochondrial superoxide can initiate signaling pathways following transport into the cytosol. In this study, we provide evidence of TATA...

Chandra Source Catalog: User Interfaces

Science.gov (United States)

Bonaventura, Nina; Evans, I. N.; Harbo, P. N.; Rots, A. H.; Tibbetts, M. S.; Van Stone, D. W.; Zografou, P.; Anderson, C. S.; Chen, J. C.; Davis, J. E.; Doe, S. M.; Evans, J. D.; Fabbiano, G.; Galle, E.; Gibbs, D. G.; Glotfelty, K. J.; Grier, J. D.; Hain, R.; Hall, D. M.; He, X.; Houck, J. C.; Karovska, M.; Lauer, J.; McCollough, M. L.; McDowell, J. C.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Nowak, M. A.; Plummer, D. A.; Primini, F. A.; Refsdal, B. L.; Siemiginowska, A. L.; Sundheim, B. A.; Winkelman, S. L.

2010-03-01

The CSCview data mining interface is available for browsing the Chandra Source Catalog (CSC) and downloading tables of quality-assured source properties and data products. Once the desired source properties and search criteria are entered into the CSCview query form, the resulting source matches are returned in a table along with the values of the requested source properties for each source. (The catalog can be searched on any source property, not just position.) At this point, the table of search results may be saved to a text file, and the available data products for each source may be downloaded. CSCview save files are output in RDB-like and VOTable format. The available CSC data products include event files, spectra, lightcurves, and images, all of which are processed with the CIAO software. CSC data may also be accessed non-interactively with Unix command-line tools such as cURL and Wget, using ADQL 2.0 query syntax. In fact, CSCview features a separate ADQL query form for those who wish to specify this type of query within the GUI. Several interfaces are available for learning if a source is included in the catalog (in addition to CSCview): 1) the CSC interface to Sky in Google Earth shows the footprint of each Chandra observation on the sky, along with the CSC footprint for comparison (CSC source properties are also accessible when a source within a Chandra field-of-view is clicked); 2) the CSC Limiting Sensitivity online tool indicates if a source at an input celestial location was too faint for detection; 3) an IVOA Simple Cone Search interface locates all CSC sources within a specified radius of an R.A. and Dec.; and 4) the CSC-SDSS cross-match service returns the list of sources common to the CSC and SDSS, either all such sources or a subset based on search criteria.

The continued development of the Spallation Neutron Source external antenna H- ion source

International Nuclear Information System (INIS)

Welton, R. F.; Carmichael, J.; Fuga, R.; Goulding, R. H.; Han, B.; Kang, Y.; Lee, S. W.; Murray, S. N.; Pennisi, T.; Potter, K. G.; Santana, M.; Stockli, M. P.; Desai, N. J.

2010-01-01

The U.S. Spallation Neutron Source (SNS) is an accelerator-based, pulsed neutron-scattering facility, currently in the process of ramping up neutron production. In order to ensure that the SNS will meet its operational commitments as well as provide for future facility upgrades with high reliability, we are developing a rf-driven, H - ion source based on a water-cooled, ceramic aluminum nitride (AlN) plasma chamber. To date, early versions of this source have delivered up to 42 mA to the SNS front end and unanalyzed beam currents up to ∼100 mA (60 Hz, 1 ms) to the ion source test stand. This source was operated on the SNS accelerator from February to April 2009 and produced ∼35 mA (beam current required by the ramp up plan) with availability of ∼97%. During this run several ion source failures identified reliability issues, which must be addressed before the source re-enters production: plasma ignition, antenna lifetime, magnet cooling, and cooling jacket integrity. This report discusses these issues, details proposed engineering solutions, and notes progress to date.

Note: Development of ESS Bilbao's proton ion source: Ion Source Hydrogen Positive

International Nuclear Information System (INIS)

Miracoli, R.; Feuchtwanger, J.; Arredondo, I.; Belver, D.; Gonzalez, P. J.; Corres, J.; Djekic, S.; Echevarria, P.; Eguiraun, M.; Garmendia, N.; Muguira, L.

2014-01-01

The Ion Source Hydrogen positive is a 2.7 GHz off-resonance microwave discharge ion source. It uses four coils to generate an axial magnetic field in the plasma chamber around 0.1 T that exceeds the ECR resonance field. A new magnetic system was designed as a combination of the four coils and soft iron in order to increase the reliability of the source. The description of the simulations of the magnetic field and the comparison with the magnetic measurements are presented. Moreover, results of the initial commissioning of the source for extraction voltage until 50 kV will be reported

Gravitation and source theory

International Nuclear Information System (INIS)

Yilmaz, H.

1975-01-01

Schwinger's source theory is applied to the problem of gravitation and its quantization. It is shown that within the framework of a flat-space the source theory implementation leads to a violation of probability. To avoid the difficulty one must introduce a curved space-time hence the source concept may be said to necessitate the transition to a curved-space theory of gravitation. It is further shown that the curved-space theory of gravitation implied by the source theory is not equivalent to the conventional Einstein theory. The source concept leads to a different theory where the gravitational field has a stress-energy tensor t/sup nu//sub mu/ which contributes to geometric curvatures

Global Sourcing of Services

DEFF Research Database (Denmark)

Ørberg Jensen, Peter D.; Petersen, Bent

2013-01-01

The global sourcing of services offers high returns but is also associated with high risks. The extent to which firms engage in ‘transformational’ global sourcing (i.e., global sourcing implying considerable changes in the home organization) chiefly depends on management's comfort zone which...

Crowd Sourcing.

Science.gov (United States)

Baum, Neil

2016-01-01

The Internet has contributed new words and slang to our daily vernacular. A few terms, such as tweeting, texting, sexting, blogging, and googling, have become common in most vocabularies and in many languages, and are now included in the dictionary. A new buzzword making the rounds in industry is crowd sourcing, which involves outsourcing an activity, task, or problem by sending it to people or groups outside a business or a practice. Crowd sourcing allows doctors and practices to tap the wisdom of many instead of relying only on the few members of their close-knit group. This article defines "crowd sourcing," offers examples, and explains how to get started with this approach that can increase your ability to finish a task or solve problems that you don't have the time or expertise to accomplish.

Neutron source

International Nuclear Information System (INIS)

Cason, J.L. Jr.; Shaw, C.B.

1975-01-01

A neutron source which is particularly useful for neutron radiography consists of a vessel containing a moderating media of relatively low moderating ratio, a flux trap including a moderating media of relatively high moderating ratio at the center of the vessel, a shell of depleted uranium dioxide surrounding the moderating media of relatively high moderating ratio, a plurality of guide tubes each containing a movable source of neutrons surrounding the flux trap, a neutron shield surrounding one part of each guide tube, and at least one collimator extending from the flux trap to the exterior of the neutron source. The shell of depleted uranium dioxide has a window provided with depleted uranium dioxide shutters for each collimator. Reflectors are provided above and below the flux trap and on the guide tubes away from the flux trap

A STATISTICAL APPROACH TO RECOGNIZING SOURCE CLASSES FOR UNASSOCIATED SOURCES IN THE FIRST FERMI-LAT CATALOG

Energy Technology Data Exchange (ETDEWEB)

Ackermann, M. [Deutsches Elektronen Synchrotron DESY, D-15738 Zeuthen (Germany); Ajello, M.; Allafort, A.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Borgland, A. W.; Buehler, R. [W. W. Hansen Experimental Physics Laboratory, Kavli Institute for Particle Astrophysics and Cosmology, Department of Physics and SLAC National Accelerator Laboratory, Stanford University, Stanford, CA 94305 (United States); Antolini, E.; Bonamente, E. [Istituto Nazionale di Fisica Nucleare, Sezione di Perugia, I-06123 Perugia (Italy); Baldini, L.; Bellazzini, R.; Bregeon, J. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, I-56127 Pisa (Italy); Ballet, J. [Laboratoire AIM, CEA-IRFU/CNRS/Universite Paris Diderot, Service d' Astrophysique, CEA Saclay, 91191 Gif sur Yvette (France); Barbiellini, G. [Istituto Nazionale di Fisica Nucleare, Sezione di Trieste, I-34127 Trieste (Italy); Bastieri, D. [Istituto Nazionale di Fisica Nucleare, Sezione di Padova, I-35131 Padova (Italy); Bouvier, A. [Santa Cruz Institute for Particle Physics, Department of Physics and Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); Brandt, T. J. [CNRS, IRAP, F-31028 Toulouse Cedex 4 (France); Brigida, M. [Dipartimento di Fisica ' M. Merlin' dell' Universita e del Politecnico di Bari, I-70126 Bari (Italy); Bruel, P., E-mail: monzani@slac.stanford.edu, E-mail: vilchez@cesr.fr, E-mail: salvetti@lambrate.inaf.it, E-mail: elizabeth.c.ferrara@nasa.gov [Laboratoire Leprince-Ringuet, Ecole polytechnique, CNRS/IN2P3, Palaiseau (France); and others

2012-07-01

The Fermi Large Area Telescope (LAT) First Source Catalog (1FGL) provided spatial, spectral, and temporal properties for a large number of {gamma}-ray sources using a uniform analysis method. After correlating with the most-complete catalogs of source types known to emit {gamma} rays, 630 of these sources are 'unassociated' (i.e., have no obvious counterparts at other wavelengths). Here, we employ two statistical analyses of the primary {gamma}-ray characteristics for these unassociated sources in an effort to correlate their {gamma}-ray properties with the active galactic nucleus (AGN) and pulsar populations in 1FGL. Based on the correlation results, we classify 221 AGN-like and 134 pulsar-like sources in the 1FGL unassociated sources. The results of these source 'classifications' appear to match the expected source distributions, especially at high Galactic latitudes. While useful for planning future multiwavelength follow-up observations, these analyses use limited inputs, and their predictions should not be considered equivalent to 'probable source classes' for these sources. We discuss multiwavelength results and catalog cross-correlations to date, and provide new source associations for 229 Fermi-LAT sources that had no association listed in the 1FGL catalog. By validating the source classifications against these new associations, we find that the new association matches the predicted source class in {approx}80% of the sources.

A STATISTICAL APPROACH TO RECOGNIZING SOURCE CLASSES FOR UNASSOCIATED SOURCES IN THE FIRST FERMI-LAT CATALOG

International Nuclear Information System (INIS)

Ackermann, M.; Ajello, M.; Allafort, A.; Berenji, B.; Blandford, R. D.; Bloom, E. D.; Borgland, A. W.; Buehler, R.; Antolini, E.; Bonamente, E.; Baldini, L.; Bellazzini, R.; Bregeon, J.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bouvier, A.; Brandt, T. J.; Brigida, M.; Bruel, P.

2012-01-01

The Fermi Large Area Telescope (LAT) First Source Catalog (1FGL) provided spatial, spectral, and temporal properties for a large number of γ-ray sources using a uniform analysis method. After correlating with the most-complete catalogs of source types known to emit γ rays, 630 of these sources are 'unassociated' (i.e., have no obvious counterparts at other wavelengths). Here, we employ two statistical analyses of the primary γ-ray characteristics for these unassociated sources in an effort to correlate their γ-ray properties with the active galactic nucleus (AGN) and pulsar populations in 1FGL. Based on the correlation results, we classify 221 AGN-like and 134 pulsar-like sources in the 1FGL unassociated sources. The results of these source 'classifications' appear to match the expected source distributions, especially at high Galactic latitudes. While useful for planning future multiwavelength follow-up observations, these analyses use limited inputs, and their predictions should not be considered equivalent to 'probable source classes' for these sources. We discuss multiwavelength results and catalog cross-correlations to date, and provide new source associations for 229 Fermi-LAT sources that had no association listed in the 1FGL catalog. By validating the source classifications against these new associations, we find that the new association matches the predicted source class in ∼80% of the sources.

New developments with H-sources

International Nuclear Information System (INIS)

Sherman, Joseph D.; Rouleau, G.

2002-01-01

Existing spallation neutron source upgrades, planned spallation neutron sources, and high-energy accelerators for particle physics place demanding requirements on the Hsources. These requirements ask for increased beam currents and duty factor (df) while generally maintaining state-of-the art H' source emittance. A variety of H sources are being developed to address these challenges. These include volume sources with and without the addition of cesium for enhanced He production, increased df cesiated H' Penning and magnetron sources, and cesiated surface converter H- sources. Research on surface films of tantalum metal for enhanced volume H- production is also being studied. Innovative plasma production techniques to address the longer df requirement without sacrificing H- source reliability and liktime will be reviewed. The physical bases, the goals, and perceived challenges will be discussed.

Cesium glass irradiation sources

International Nuclear Information System (INIS)

Plodinec, M.J.

1982-01-01

The precipitation process for the decontamination of soluble SRP wastes produces a material whose radioactivity is dominated by 137 Cs. Potentially, this material could be vitrified to produce irradiation sources similar to the Hanford CsCl sources. In this report, process steps necessary for the production of cesium glass irradiation sources (CGS), and the nature of the sources produced, are examined. Three options are considered in detail: direct vitrification of precipitation process waste; direct vitrification of this waste after organic destruction; and vitrification of cesium separated from the precipitation process waste. Direct vitrification is compatible with DWPF equipment, but process rates may be limited by high levels of combustible materials in the off-gas. Organic destruction would allow more rapid processing. In both cases, the source produced has a dose rate of 2 x 10 4 rads/hr at the surface. Cesium separation produces a source with a dose rate of 4 x 10 5 at the surface, which is nearer that of the Hanford sources (2 x 10 6 rads/hr). Additional processing steps would be required, as well as R and D to demonstrate that DWPF equipment is compatible with this intensely radioactive material

Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control.

Science.gov (United States)

Rothenberg, Ellen V; Ungerbäck, Jonas; Champhekar, Ameya

2016-01-01

T-lymphocyte development branches off from other lymphoid developmental programs through its requirement for sustained environmental signals through the Notch pathway. In the thymus, Notch signaling induces a succession of T-lineage regulatory factors that collectively create the T-cell identity through distinct steps. This process involves both the staged activation of T-cell identity genes and the staged repression of progenitor-cell-inherited regulatory genes once their roles in self-renewal and population expansion are no longer needed. With the recent characterization of innate lymphoid cells (ILCs) that share transcriptional regulation programs extensively with T-cell subsets, T-cell identity can increasingly be seen as defined in modular terms, as the processes selecting and actuating effector function are potentially detachable from the processes generating and selecting clonally unique T-cell receptor structures. The developmental pathways of different classes of T cells and ILCs are distinguished by the numbers of prerequisites of gene rearrangement, selection, and antigen contact before the cells gain access to nearly common regulatory mechanisms for choosing effector function. Here, the major classes of transcription factors that interact with Notch signals during T-lineage specification are discussed in terms of their roles in these programs, the evidence for their spectra of target genes at different stages, and their cross-regulatory and cooperative actions with each other. Specific topics include Notch modulation of PU.1 and GATA-3, PU.1-Notch competition, the relationship between PU.1 and GATA-3, and the roles of E proteins, Bcl11b, and GATA-3 in guiding acquisition of T-cell identity while avoiding redirection to an ILC fate. © 2016 Elsevier Inc. All rights reserved.

Molecular blood typing augments serologic testing and allows for enhanced matching of red blood cells for transfusion in patients with sickle cell disease.

Science.gov (United States)

Wilkinson, Katie; Harris, Samantha; Gaur, Prashant; Haile, Askale; Armour, Rosalind; Teramura, Gayle; Delaney, Meghan

2012-02-01

Sickle cell disease (SCD) patients have dissimilar red blood cell (RBC) phenotypes compared to the primarily Caucasian blood donor base due, in part, to underlying complex Rh and silenced Duffy expression. Gene array-based technology offers high-throughput antigen typing of blood donors and can identify patients with altered genotypes. The purpose of the study was to ascertain if RBC components drawn from predominantly Caucasian donors could provide highly antigen-matched products for molecularly typed SCD patients. SCD patients were genotyped by a molecular array (HEA Beadchip, BioArray Solutions). The extended antigen phenotype (C, c, E, e, K, k, Jk(a) , Jk(b) , Fy(a) , Fy(b) , S, s) was used to query the inventory using different matching algorithms; the resulting number of products was recorded. A mean of 96.2 RBC products was available for each patient at basic-level, 34 at mid-level, and 16.3 at high-level stringency. The number of negative antigens correlated negatively with the number of available products. The Duffy silencing mutation in the promoter region (67T>C) (GATA) was found in 96.5% of patients. Allowing Fy(b+) products for patients with GATA increased the number of available products by up to 180%, although it does not ensure prevention of Duffy antibodies in all patients. This feasibility study provides evidence that centers with primarily Caucasian donors may be able to provide highly antigen-matched products. Knowledge of the GATA status expands the inventory of antigen-matched products. Further work is needed to determine the most clinically appropriate match level for SCD patients. © 2012 American Association of Blood Banks.

Fast temperature optimization of multi-source hyperthermia applicators with reduced-order modeling of 'virtual sources'

International Nuclear Information System (INIS)

Cheng, K-S; Stakhursky, Vadim; Craciunescu, Oana I; Stauffer, Paul; Dewhirst, Mark; Das, Shiva K

2008-01-01

The goal of this work is to build the foundation for facilitating real-time magnetic resonance image guided patient treatment for heating systems with a large number of physical sources (e.g. antennas). Achieving this goal requires knowledge of how the temperature distribution will be affected by changing each source individually, which requires time expenditure on the order of the square of the number of sources. To reduce computation time, we propose a model reduction approach that combines a smaller number of predefined source configurations (fewer than the number of actual sources) that are most likely to heat tumor. The source configurations consist of magnitude and phase source excitation values for each actual source and may be computed from a CT scan based plan or a simplified generic model of the corresponding patient anatomy. Each pre-calculated source configuration is considered a 'virtual source'. We assume that the actual best source settings can be represented effectively as weighted combinations of the virtual sources. In the context of optimization, each source configuration is treated equivalently to one physical source. This model reduction approach is tested on a patient upper-leg tumor model (with and without temperature-dependent perfusion), heated using a 140 MHz ten-antenna cylindrical mini-annular phased array. Numerical simulations demonstrate that using only a few pre-defined source configurations can achieve temperature distributions that are comparable to those from full optimizations using all physical sources. The method yields close to optimal temperature distributions when using source configurations determined from a simplified model of the tumor, even when tumor position is erroneously assumed to be ∼2.0 cm away from the actual position as often happens in practical clinical application of pre-treatment planning. The method also appears to be robust under conditions of changing, nonlinear, temperature-dependent perfusion. The

Dosimetry of industrial sources

International Nuclear Information System (INIS)

Vega C, H.R.; Rodriguez J, R.; Manzanares A, E.; Hernandez V, R.; Ramirez G, J.; Rivera M, T.

2007-01-01

The gamma rays are produced during the disintegration of the atomic nuclei, its high energy allows them to cross thick materials. The capacity to attenuate a photons beam allows to determine the density, in line, of industrial interest materials as the mining. By means of two active dosemeters and a TLDs group (passive dosimetry) the dose rates of two sources of Cs-137 used for determining in line the density of mining materials were determined. With the dosemeters the dose levels in diverse points inside the grave that it harbors the sources and by means of calculations the isodoses curves were determined. In the phase of calculations was supposed that both sources were punctual and the isodose curves were calculated for two situations: naked sources and in their Pb packings. The dosimetry was carried out around two sources of 137 Cs. The measured values allowed to develop a calculation procedure to obtain the isodoses curves in the grave where the sources are installed. (Author)

Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation

Science.gov (United States)

White, David J.; Congedo, Marco; Ciorciari, Joseph

2014-01-01

A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID

Consider the source: persuasion of implicit evaluations is moderated by source credibility.

Science.gov (United States)

Smith, Colin Tucker; De Houwer, Jan; Nosek, Brian A

2013-02-01

The long history of persuasion research shows how to change explicit, self-reported evaluations through direct appeals. At the same time, research on how to change implicit evaluations has focused almost entirely on techniques of retraining existing evaluations or manipulating contexts. In five studies, we examined whether direct appeals can change implicit evaluations in the same way as they do explicit evaluations. In five studies, both explicit and implicit evaluations showed greater evidence of persuasion following information presented by a highly credible source than a source low in credibility. Whereas cognitive load did not alter the effect of source credibility on explicit evaluations, source credibility had an effect on the persuasion of implicit evaluations only when participants were encouraged and able to consider information about the source. Our findings reveal the relevance of persuasion research for changing implicit evaluations and provide new ideas about the processes underlying both types of evaluation.

Neutron sources and applications

Energy Technology Data Exchange (ETDEWEB)

Price, D.L. [ed.] [Argonne National Lab., IL (United States); Rush, J.J. [ed.] [National Inst. of Standards and Technology, Gaithersburg, MD (United States)

1994-01-01

Review of Neutron Sources and Applications was held at Oak Brook, Illinois, during September 8--10, 1992. This review involved some 70 national and international experts in different areas of neutron research, sources, and applications. Separate working groups were asked to (1) review the current status of advanced research reactors and spallation sources; and (2) provide an update on scientific, technological, and medical applications, including neutron scattering research in a number of disciplines, isotope production, materials irradiation, and other important uses of neutron sources such as materials analysis and fundamental neutron physics. This report summarizes the findings and conclusions of the different working groups involved in the review, and contains some of the best current expertise on neutron sources and applications.

Neutron sources and applications

International Nuclear Information System (INIS)

Price, D.L.; Rush, J.J.

1994-01-01

Review of Neutron Sources and Applications was held at Oak Brook, Illinois, during September 8--10, 1992. This review involved some 70 national and international experts in different areas of neutron research, sources, and applications. Separate working groups were asked to (1) review the current status of advanced research reactors and spallation sources; and (2) provide an update on scientific, technological, and medical applications, including neutron scattering research in a number of disciplines, isotope production, materials irradiation, and other important uses of neutron sources such as materials analysis and fundamental neutron physics. This report summarizes the findings and conclusions of the different working groups involved in the review, and contains some of the best current expertise on neutron sources and applications

Source inversion in the full-wave tomography; Full wave tomography ni okeru source inversion

Energy Technology Data Exchange (ETDEWEB)

Tsuchiya, T [DIA Consultants Co. Ltd., Tokyo (Japan)

1997-10-22

In order to consider effects of characteristics of a vibration source in the full-wave tomography (FWT), a study has been performed on a method to invert vibration source parameters together with V(p)/V(s) distribution. The study has expanded an analysis method which uses as the basic the gradient method invented by Tarantola and the partial space method invented by Sambridge, and conducted numerical experiments. The experiment No. 1 has performed inversion of only the vibration source parameters, and the experiment No. 2 has executed simultaneous inversion of the V(p)/V(s) distribution and the vibration source parameters. The result of the discussions revealed that and effective analytical procedure would be as follows: in order to predict maximum stress, the average vibration source parameters and the property parameters are first inverted simultaneously; in order to estimate each vibration source parameter at a high accuracy, the property parameters are fixed, and each vibration source parameter is inverted individually; and the derived vibration source parameters are fixed, and the property parameters are again inverted from the initial values. 5 figs., 2 tabs.

GANIL Workshop on Ion Sources

International Nuclear Information System (INIS)

Leroy, Renan

1999-01-01

The proceedings of the GANIL Workshop on Ion Sources held at GANIL - Caen on 18-19 March 1999 contains 13 papers aiming at improving the old source operation and developing new types of sources for nuclear research and studies of ion physics. A number of reports are devoted to applications like surface treatment, ion implantation or fusion injection. The 1+→n+ transformation, charged particle transport in ECR sources, addition of cesium and xenon in negative ion sources and other basic issues in ion sources are also addressed

Characteristics of 6.5 GHz ECR ion source for polarized H- ion source

International Nuclear Information System (INIS)

Ikegami, Kiyoshi; Mori, Yoshiharu; Takagi, Akira; Fukumoto, Sadayoshi.

1983-04-01

A 6.5 GHz ECR (electron cyclotron resonance) ion source has been developed for optically pumped polarized H - ion source at KEK. The properties of this ECR ion source such as beam intensities, proton ratios, plasma electron temperatures and beam emittances were measured. (author)

Molten carbonate fuel cell power generation system. Yoyu tansan prime en gata nenryo denchi hatsuden sochi

Energy Technology Data Exchange (ETDEWEB)

Uematsu, K; Hatori, S [Ishikawajima-Harima Heavy Industries Co. Ltd., Tokyo (Japan)

1991-11-01

In an indirect internal reforming type molten carbonate fuel cell, the reforming temperature is limited less than the operating temperature of the fuel cell, as the heat source for reforming is depended on the reaction heat at about 650 {degree} C of the fuel cell. To improve the reforming rate at the low temperature range, it is considered to increase S/C (ratio of steam to carbon), but this scheme will cause such problems as to increase the voltage drop of the anode, to drop the heat recovery ratio on the cogenerator, to increase the capacity of the heat exchanger, etc. In this invention, in the power generating plant of a molten carbonate fuel cell the inert gas is added to the reforming raw gas, and in addition to the above the gas is mixed with steam and led into the reforming chamber of the plant. When the inert gas which is not directly concerned in the reforming reaction is added to, total mol number increases and the reforming reaction is acceralated. Consequently, the reforming rate can be raised, though the reforming temperature is low. 2 figs.

Intense, broadband, pulsed I-R source at the National Synchrotron Light Source

International Nuclear Information System (INIS)

Williams, G.P.

1984-01-01

We describe a broadband (1 μm to 1 mm) synchrotron radiation infrared source, pulsed each 20 to 180 nseconds and delivering about 10 15 photons/sec/1% bandpass into f10 optics. The source size is diffraction limited. This source is thus 100 to 1000 times brighter than a 2000 0 K black body, very stable and capable of being used for calibration

Open Source Business Solutions

Directory of Open Access Journals (Sweden)

Ion IVAN

2008-01-01

Full Text Available This analyses the Open source movement. Open source development process and management is seen different from the classical point of view. This focuses on characteristics and software market tendencies for the main Open source initiatives. It also points out the labor market future evolution for the software developers.

Investigating Primary Source Literacy

Science.gov (United States)

Archer, Joanne; Hanlon, Ann M.; Levine, Jennie A.

2009-01-01

Primary source research requires students to acquire specialized research skills. This paper presents results from a user study testing the effectiveness of a Web guide designed to convey the concepts behind "primary source literacy". The study also evaluated students' strengths and weaknesses when conducting primary source research. (Contains 3…

H{sup -} radio frequency source development at the Spallation Neutron Source

Energy Technology Data Exchange (ETDEWEB)

Welton, R. F.; Gawne, K. R.; Han, B. X.; Murray, S. N.; Pennisi, T. R.; Roseberry, R. T.; Santana, M.; Stockli, M. P. [Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, Tennessee 37830-6471 (United States); Dudnikov, V. G. [Muons, Inc., 552 N. Batavia Avenue, Batavia, Illinois 60510 (United States); Turvey, M. W. [Villanova University, 800E. Lancaster Ave, Villanova, Pennsylvania 19085 (United States)

2012-02-15

The Spallation Neutron Source (SNS) now routinely operates nearly 1 MW of beam power on target with a highly persistent {approx}38 mA peak current in the linac and an availability of {approx}90%. H{sup -} beam pulses ({approx}1 ms, 60 Hz) are produced by a Cs-enhanced, multicusp ion source closely coupled with an electrostatic low energy beam transport (LEBT), which focuses the 65 kV beam into a radio frequency quadrupole accelerator. The source plasma is generated by RF excitation (2 MHz, {approx}60 kW) of a copper antenna that has been encased with a thickness of {approx}0.7 mm of porcelain enamel and immersed into the plasma chamber. The ion source and LEBT normally have a combined availability of {approx}99%. Recent increases in duty-factor and RF power have made antenna failures a leading cause of downtime. This report first identifies the physical mechanism of antenna failure from a statistical inspection of {approx}75 antennas which ran at the SNS, scanning electron microscopy studies of antenna surface, and cross sectional cuts and analysis of calorimetric heating measurements. Failure mitigation efforts are then described which include modifying the antenna geometry and our acceptance/installation criteria. Progress and status of the development of the SNS external antenna source, a long-term solution to the internal antenna problem, are then discussed. Currently, this source is capable of delivering comparable beam currents to the baseline source to the SNS and, an earlier version, has briefly demonstrated unanalyzed currents up to {approx}100 mA (1 ms, 60 Hz) on the test stand. In particular, this paper discusses plasma ignition (dc and RF plasma guns), antenna reliability, magnet overheating, and insufficient beam persistence.

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Directory of Open Access Journals (Sweden)

Broderick TL

2017-01-01

Full Text Available Tom L Broderick,1 Marek Jankowski,2 Jolanta Gutkowska2 1Department of Physiology, Laboratory of Diabetes and Exercise Metabolism, Midwestern University, Glendale, AZ, USA; 2Department of Medicine, Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de l‘Université de Montréal-Hôtel-Dieu, Montréal, QC, Canada Background: Regular exercise training (ET and caloric restriction (CR are the frontline strategies in the treatment of type 2 diabetes mellitus with the aim at reducing cardiometabolic risk. ET and CR improve body weight and glycemic control, and experimental studies indicate that these paradigms afford cardioprotection. In this study, the effects of combined ET and CR on the cardioprotective oxytocin (OT–natriuretic peptide (NP system were determined in the db/db mouse, a model of type 2 diabetes associated with insulin resistance, hyperglycemia, and obesity. Methods: Five-week-old male db/db mice were assigned to the following groups: sedentary, ET, and ET + CR. Nonobese heterozygote littermates served as controls. ET was performed on a treadmill at moderate intensity, and CR was induced by reducing food intake by 30% of that consumed by sedentary db/db mice for a period of 8 weeks. Results: After 8 weeks, only ET + CR, but not ET, slightly improved body weight compared to sedentary db/db mice. Regardless of the treatment, db/db mice remained hyperglycemic. Hearts from db/db mice demonstrated reduced expression of genes linked to the cardiac OT–NP system. In fact, compared to control mice, mRNA expression of GATA binding protein 4 (GATA4, OT receptor, OT, brain NP, NP receptor type C, and endothelial nitric oxide synthase (eNOS was decreased in hearts from sedentary db/db mice. Both ET alone and ET + CR increased the mRNA expression of GATA4 compared to sedentary db/db mice. Only ET combined with CR produced increased eNOS mRNA and protein expression. Conclusion: Our data indicate that enhancement of eNOS by combined

Emission sources and quantities

International Nuclear Information System (INIS)

Heinen, B.

1991-01-01

The paper examines emission sources and quantities for SO 2 and NO x . Natural SO 2 is released from volcanic sources and to a much lower extent from marsh gases. In nature NO x is mainly produced in the course of the chemical and bacterial denitrification processes going on in the soil. Manmade pollutants are produced in combustion processes. The paper concentrates on manmade pollution. Aspects discussed include: mechanism of pollution development; manmade emission sources (e.g. industry, traffic, power plants and domestic sources); and emission quantities and forecasts. 11 refs., 2 figs., 5 tabs

Fission-product source terms

International Nuclear Information System (INIS)

Lorenz, R.A.

1981-01-01

This presentation consists of a review of fission-product source terms for light water reactor (LWR) fuel. A source term is the quantity of fission products released under specified conditions that can be used to calculate the consequences of the release. The source term usually defines release from breached fuel-rod cladding but could also describe release from the primary coolant system, the reactor containment shell, or the site boundary. The source term would be different for each locality, and the chemical and physical forms of the fission products could also differ

Source Monitoring in Alzheimer's Disease

Science.gov (United States)

El Haj, Mohamad; Fasotti, Luciano; Allain, Philippe

2012-01-01

Source monitoring is the process of making judgments about the origin of memories. There are three categories of source monitoring: reality monitoring (discrimination between self- versus other-generated sources), external monitoring (discrimination between several external sources), and internal monitoring (discrimination between two types of…

Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups

DEFF Research Database (Denmark)

van Kessel, Kim E M; van der Keur, Kirstin A; Dyrskjøt, Lars

2018-01-01

prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3, and ZIC4 methylation and FGFR3, TERT, PIK3CA, and RAS mutation status. Cox regression analyses identified markers that were significantly associated...

Belgrade waterworks groundwater source

International Nuclear Information System (INIS)

Sotic, A.; Dasic, M.; Vukcevic, G.; Vasiljevic, Lj.; Nikolic, S.

2002-01-01

Paper deals with Belgrade Waterworks groundwater source, its characteristics, conception of protection programme, contaminations on source and with parameters of groundwater quality degradation. Groundwaters present natural heritage with their strategic and slow renewable natural resources attributes, and as such they require priority in protection. It is of greatest need that existing source is to be protected and used optimally for producing quality drinkable water. The concept of source protection programme should be based on regular water quality monitoring, identification of contaminators, defining areas of their influences on the source and their permanent control. However, in the last 10 years, but drastically in the last 3, because of the overall situation in the country, it is very characteristic downfall in volume of business, organisation and the level of supply of the technical equipment

Influence of source geometry and materials on the transverse axis dosimetry of 192Ir brachytherapy sources

International Nuclear Information System (INIS)

Wang, Ruqing; Sloboda, Ron S.

1998-01-01

Monte Carlo dose rates on the transverse axis in water and air kerma strengths normalized to unit source activity were calculated for a low dose rate steel-clad 192 Ir source, MicroSelectron high dose rate and pulsed dose rate 192 Ir sources, and a VariSource high dose rate 192 Ir source, as well as five other hypothetical cylindrical 192 Ir source designs. Based on these results, the dependence of dose rate and air kerma strength on source geometry and materials was analysed. Source geometry and attenuation in the core material are the important factors determining basic dosimetric characteristics. Core length, h, only affects the dose rate on the transverse axis at radial distances r 192 Ir sources is suggested, and similarities and differences in the dose rate constant and radial dose function between these sources are explained. (author)

[Source data management in clinical researches].

Science.gov (United States)

Ho, Effie; Yao, Chen; Zhang, Zi-bao; Liu, Yu-xiu

2015-11-01

Source data and its source documents are the foundation of clinical research. Proper source data management plays an essential role for compliance with regulatory and GCP requirements. Both paper and electronic source data co-exist in China. Due to the increasing use of electronic technology in pharmaceutical and health care industry, electronic data source becomes an upcoming trend with clear advantages. To face new opportunities and to ensure data integrity, quality and traceability from source data to regulatory submission, this document demonstrates important concepts, principles and best practices during managing source data. It includes but not limited to: (1) important concepts of source data (e.g., source data originator, source data elements, source data identifier for audit trail, etc.); (2) various modalities of source data collection in paper and electronic methods (e.g., paper CRF, EDC, Patient Report Outcomes/eCOA, etc.); (3) seven main principles recommended in the aspect of data collection, traceability, quality standards, access control, quality control, certified copy and security during source data management; (4) a life cycle from source data creation to obsolete is used as an example to illustrate consideration and implementation of source data management.

Polarized electron sources

Energy Technology Data Exchange (ETDEWEB)

Prepost, R. [Univ. of Wisconsin, Madison, WI (United States)

1994-12-01

The fundamentals of polarized electron sources are described with particular application to the Stanford Linear Accelerator Center. The SLAC polarized electron source is based on the principle of polarized photoemission from Gallium Arsenide. Recent developments using epitaxially grown, strained Gallium Arsenide cathodes have made it possible to obtain electron polarization significantly in excess of the conventional 50% polarization limit. The basic principles for Gallium and Arsenide polarized photoemitters are reviewed, and the extension of the basic technique to strained cathode structures is described. Results from laboratory measurements of strained photocathodes as well as operational results from the SLAC polarized source are presented.

Polarized electron sources

International Nuclear Information System (INIS)

Prepost, R.

1994-01-01

The fundamentals of polarized electron sources are described with particular application to the Stanford Linear Accelerator Center. The SLAC polarized electron source is based on the principle of polarized photoemission from Gallium Arsenide. Recent developments using epitaxially grown, strained Gallium Arsenide cathodes have made it possible to obtain electron polarization significantly in excess of the conventional 50% polarization limit. The basic principles for Gallium and Arsenide polarized photoemitters are reviewed, and the extension of the basic technique to strained cathode structures is described. Results from laboratory measurements of strained photocathodes as well as operational results from the SLAC polarized source are presented

Open source development

DEFF Research Database (Denmark)

Ulhøi, John Parm

2004-01-01

This paper addresses innovations based on open source or non-proprietary knowledge. Viewed through the lens of private property theory, such agency appears to be a true anomaly. However, by a further turn of the theoretical kaleidoscope, we will show that there may be perfectly justifiable reasons...... for not regarding open source innovations as anomalies. The paper is based on three sectorial and generic cases of open source innovation, which is an offspring of contemporary theory made possible by combining elements of the model of private agency with those of the model of collective agency. In closing...

Heavy ion fusion sources

International Nuclear Information System (INIS)

Grote, D.P.; Kwan, J.; Westenskow, G.

2003-01-01

In Heavy-Fusion and in other applications, there is a need for high brightness sources with both high current and low emittance. The traditional design with a single monolithic source, while very successful, has significant constraints on it when going to higher currents. With the Child-Langmuir current-density limit, geometric aberration limits, and voltage breakdown limits, the area of the source becomes a high power of the current, A ∼ I 8/3 . We are examining a multi-beamlet source, avoiding the constraints by having many beamlets each with low current and small area. The beamlets are created and initially accelerated separately and then merged to form a single beam. This design offers a number of potential advantages over a monolithic source, such as a smaller transverse footprint, more control over the shaping and aiming of the beam, and more flexibility in the choice of ion sources. A potential drawback, however, is the emittance that results from the merging of the beamlets. We have designed injectors using simulation that have acceptably low emittance and are beginning to examine them experimentally

Fission product gamma-ray sources as an alternative to cobalt-60 sources for sewage sludge sterilization

International Nuclear Information System (INIS)

Herrnberger, V.R.D.

1975-01-01

The sterilization of sewage sludge is now performed successfully using 60 Co gamma-ray sources. The question arises whether more economic gamma-ray sources exist that could replace the 60 Co source. The following types of sources are considered: Spent fuel elements; mixtures of solidified fission products; and isolated solidified fission products such as 134 / 137 Cs. For a particular irradiation plant the specific source costs (S.Fr./Ci) and their contribution to the irradiation costs for 1 m 3 of sewage irradiated to a dose of 250 krad(S.Fr./m 3 ) are determined and compared with the costs of a plant using a 60 Co source. The encapsulation costs and the effect of the gamma absorption of the source are taken into account. Different encapsulation and source management techniques are reviewed to find the most economic for each source type. A spent fuel element irradiation facility is recommended for use either in combination with a sewage water purification plant or as part of a power reactor station where it replaces the storage water pool for the spent fuel elements. Additional source capsules are not envisaged, as long as double-walled source containers are used. The fission product mixtures are enclosed in double-walled capsules of two different forms: Small cylindrical rods and hollow cylinders. For caesium and cobalt cylindrical rods only are used. The main conclusions of the study are that the highest irradiation costs arise from the use of a fission product mixture source. The costs are, however, only 15% above those of a 60 Co plant. To be competitive the flow-rate has to be adapted to the decreasing activity of the source, resulting in a reduction to 20% within ten years of source utilization. The integrated irradiation plant with a spent fuel element source offers irradiation costs comparable with those of a 60 Co plant, if the flow-rate is constant during one year of source utilization. The irradiation costs are reduced to 25% of those of a 60 Co plant

Accelerator based continuous neutron source.

CERN Document Server

Shapiro, S M; Ruggiero, A G

2003-01-01

Until the last decade, most neutron experiments have been performed at steady-state, reactor-based sources. Recently, however, pulsed spallation sources have been shown to be very useful in a wide range of neutron studies. A major review of neutron sources in the US was conducted by a committee chaired by Nobel laureate Prof. W. Kohn: ''Neutron Sources for America's Future-BESAC Panel on Neutron Sources 1/93''. This distinguished panel concluded that steady state and pulsed sources are complementary and that the nation has need for both to maintain a balanced neutron research program. The report recommended that both a new reactor and a spallation source be built. This complementarity is recognized worldwide. The conclusion of this report is that a new continuous neutron source is needed for the second decade of the 20 year plan to replace aging US research reactors and close the US neutron gap. it is based on spallation production of neutrons using a high power continuous superconducting linac to generate pr...

Equivalent charge source model based iterative maximum neighbor weight for sparse EEG source localization.

Science.gov (United States)

Xu, Peng; Tian, Yin; Lei, Xu; Hu, Xiao; Yao, Dezhong

2008-12-01

How to localize the neural electric activities within brain effectively and precisely from the scalp electroencephalogram (EEG) recordings is a critical issue for current study in clinical neurology and cognitive neuroscience. In this paper, based on the charge source model and the iterative re-weighted strategy, proposed is a new maximum neighbor weight based iterative sparse source imaging method, termed as CMOSS (Charge source model based Maximum neighbOr weight Sparse Solution). Different from the weight used in focal underdetermined system solver (FOCUSS) where the weight for each point in the discrete solution space is independently updated in iterations, the new designed weight for each point in each iteration is determined by the source solution of the last iteration at both the point and its neighbors. Using such a new weight, the next iteration may have a bigger chance to rectify the local source location bias existed in the previous iteration solution. The simulation studies with comparison to FOCUSS and LORETA for various source configurations were conducted on a realistic 3-shell head model, and the results confirmed the validation of CMOSS for sparse EEG source localization. Finally, CMOSS was applied to localize sources elicited in a visual stimuli experiment, and the result was consistent with those source areas involved in visual processing reported in previous studies.

Argonne inverted sputter source

International Nuclear Information System (INIS)

Yntema, J.L.; Billquist, P.J.

1983-01-01

The emittance of the inverted sputter source with immersion lenses was measured to be about 5π mm mrad MeV/sup 1/2/ at the 75% level over a wide range of beam intensities. The use of the source in experiments with radioactive sputter targets and hydrogen loaded targets is described. Self contamination of the source is discussed

H- source developments

International Nuclear Information System (INIS)

Allison, P.W.

1978-01-01

The design and operation of a Penning discharge, cold cathode, surface plasma H - ion source are described. A high current density, about 2 A/cm 2 , is extracted from the source by putting about 20 keV across the 2 to 2 1 / 2 mm gap

Radioactive Sources Service

CERN Document Server

2007-01-01

Please note that the radioactive sources service will be open by appointment only every Monday, Wednesday and Friday during CERN working hours (instead of alternate weeks). In addition, please note that our 2007 schedule is available on our web site: http://cern.ch/service-rp-sources

Online Sources of Competitive Intelligence.

Science.gov (United States)

Wagers, Robert

1986-01-01

Presents an approach to using online sources of information for competitor intelligence (i.e., monitoring industry and tracking activities of competitors); identifies principal sources; and suggests some ways of making use of online databases. Types and sources of information and sources and database charts are appended. Eight references are…

Alternative Energy Sources

CERN Document Server

Michaelides, Efstathios E (Stathis)

2012-01-01

Alternative Energy Sources is designed to give the reader, a clear view of the role each form of alternative energy may play in supplying the energy needs of the human society in the near and intermediate future (20-50 years).   The two first chapters on energy demand and supply and environmental effects, set the tone as to why the widespread use of alternative energy is essential for the future of human society. The third chapter exposes the reader to the laws of energy conversion processes, as well as the limitations of converting one energy form to another. The sections on exergy give a succinct, quantitative background on the capability/potential of each energy source to produce power on a global scale. The fourth, fifth and sixth chapters are expositions of fission and fusion nuclear energy. The following five chapters (seventh to eleventh) include detailed descriptions of the most common renewable energy sources – wind, solar, geothermal, biomass, hydroelectric – and some of the less common sources...

Californium source transfer

International Nuclear Information System (INIS)

Wallace, C.R.

1995-01-01

In early 1995, the receipt of four sealed californium-252 sources from Oak Ridge National Lab was successfully accomplished by a team comprised of Radiological Engineering, Radiological Operations and Health Physics Instrumentation personnel. A procedure was developed and walked-down by the participants during a Dry Run Evolution. Several special tools were developed during the pre-planning phases of the project which reduced individual and job dose to minimal levels. These included a mobile lifting device for attachment of a transfer ball valve assembly to the undercarriage of the Cannonball Carrier, a transfer tube elbow to ensure proper angle of the source transfer tube, and several tools used during emergency response for remote retrieval and handling of an unshielded source. Lessons were learned in the areas of contamination control, emergency preparedness, and benefits of thorough pre-planning, effectiveness of locally creating and designing special tools to reduce worker dose, and methods of successfully accomplishing source receipt evolutions during extreme or inclement weather

Muon sources

International Nuclear Information System (INIS)

Parsa, Z.

2001-01-01

A full high energy muon collider may take considerable time to realize. However, intermediate steps in its direction are possible and could help facilitate the process. Employing an intense muon source to carry out forefront low energy research, such as the search for muon-number non-conservation, represents one interesting possibility. For example, the MECO proposal at BNL aims for 2 x 10 -17 sensitivity in their search for coherent muon-electron conversion in the field of a nucleus. To reach that goal requires the production, capture and stopping of muons at an unprecedented 10 11 μ/sec. If successful, such an effort would significantly advance the state of muon technology. More ambitious ideas for utilizing high intensity muon sources are also being explored. Building a muon storage ring for the purpose of providing intense high energy neutrino beams is particularly exciting.We present an overview of muon sources and example of a muon storage ring based Neutrino Factory at BNL with various detector location possibilities

Equivalency of Buffalo (Bubalus Bubalis) Embryonic Stem Cells Derived From Fertilized, Parthenogenetic, and Hand-Made Cloned Embryos

Science.gov (United States)

Muzaffar, Musharifa; Selokar, Naresh L.; Singh, Karn P.; Zandi, Mohammad; Singh, Manoj K.; Shah, Riaz A.; Chauhan, Manmohan S.; Singla, Suresh K.; Palta, Prabhat

2012-01-01

Abstract This study was aimed at establishing buffalo embryonic stem cells (ESCs) from in vitro fertilized (IVF), parthenogenetic, and hand-made cloned (HMC) embryos and to check their equivalency in terms of stem cell marker expression, longevity, proliferation, and differentiation pattern. ESCs derived from all three sources were found by immunofluorescence to express the pluripotency markers SSEA-4, TRA-1-60, TRA-1-81, OCT4, and SOX2 and were able to form embryoid bodies containing cells expressing genes specific to endoderm (AFP, HNF4, and GATA4), mesoderm (MSX1, BMP4, and ASA), and ectoderm (cytokeratin 8 and NF68). Reverse transcriptase PCR (RT-PCR) showed cells from all sources to be positive for pluripotency markers OCT4, SOX2, NANOG, STAT3, REX1, FOXD3, NUCLEOSTEMIN, and TELOMERASE. Pluripotency markers OCT4, SOX2, NANOG, and c-MYC were also analyzed by real-time PCR. No significant differences were observed among ESCs from all three sources for all these genes except NANOG, whose expression was higher (pcells (1.603±0.315 and 1±0, respectively). Pluripotent, stable buffalo ESC lines derived from IVF, parthenogenesis, and HMC embryos may be genetically manipulated to provide a powerful tool for studies involving embryonic development, genomic imprinting, gene targeting, cloning, chimera formation, and transgenic animal production. PMID:22582863

The Chandra Source Catalog: Algorithms

Science.gov (United States)

McDowell, Jonathan; Evans, I. N.; Primini, F. A.; Glotfelty, K. J.; McCollough, M. L.; Houck, J. C.; Nowak, M. A.; Karovska, M.; Davis, J. E.; Rots, A. H.; Siemiginowska, A. L.; Hain, R.; Evans, J. D.; Anderson, C. S.; Bonaventura, N. R.; Chen, J. C.; Doe, S. M.; Fabbiano, G.; Galle, E. C.; Gibbs, D. G., II; Grier, J. D.; Hall, D. M.; Harbo, P. N.; He, X.; Lauer, J.; Miller, J. B.; Mitschang, A. W.; Morgan, D. L.; Nichols, J. S.; Plummer, D. A.; Refsdal, B. L.; Sundheim, B. A.; Tibbetts, M. S.; van Stone, D. W.; Winkelman, S. L.; Zografou, P.

2009-09-01

Creation of the Chandra Source Catalog (CSC) required adjustment of existing pipeline processing, adaptation of existing interactive analysis software for automated use, and development of entirely new algorithms. Data calibration was based on the existing pipeline, but more rigorous data cleaning was applied and the latest calibration data products were used. For source detection, a local background map was created including the effects of ACIS source readout streaks. The existing wavelet source detection algorithm was modified and a set of post-processing scripts used to correct the results. To analyse the source properties we ran the SAO Traceray trace code for each source to generate a model point spread function, allowing us to find encircled energy correction factors and estimate source extent. Further algorithms were developed to characterize the spectral, spatial and temporal properties of the sources and to estimate the confidence intervals on count rates and fluxes. Finally, sources detected in multiple observations were matched, and best estimates of their merged properties derived. In this paper we present an overview of the algorithms used, with more detailed treatment of some of the newly developed algorithms presented in companion papers.

Physico-chemical and sensory evaluation of potato (Solanum tuberosum L. after irradiation

Directory of Open Access Journals (Sweden)

IVANESA G.M. SOARES

2016-06-01

Full Text Available ABSTRACT This work evaluated the effects of ionizing radiation on the physico-chemical and sensory characteristics of the potato cultivar Ágata (Solanum tuberosum L., including budding and deterioration, with the end goal of increasing shelf life. For this, four groups of samples were harvested at the maturation stage. Three of them were separately exposed to a Co-60 source, receiving respective doses of 0.10, 0.15 and 2.00 kGy, while the non-irradiated group was kept as a control. All samples were stored for 35 days at 24 °C (± 2 and at 39% relative humidity. The following aspects were evaluated: budding, rot, loss of weight, texture, flesh color, moisture, external and internal appearance, aroma, soluble solids, titratable acidity, vitamin C, protein, starch and glucose. The results indicated that 0.15 kGy was the most effective dose to reduce sprouting and post-harvest losses, under the conditions studied.

MEDINA: MECCA Development in Accelerators – KPP Fortran to CUDA source-to-source Pre-processor

Directory of Open Access Journals (Sweden)

Michail Alvanos

2017-04-01

Full Text Available The global climate model ECHAM/MESSy Atmospheric Chemistry (EMAC is a modular global model that simulates climate change and air quality scenarios. The application includes different sub-models for the calculation of chemical species concentrations, their interaction with land and sea, and the human interaction. The paper presents a source-to-source parser that enables support for Graphics Processing Units (GPU by the Kinetic Pre-Processor (KPP general purpose open-source software tool. The requirements of the host system are also described. The source code of the source-to-source parser is available under the MIT License.

Photonic crystal light source

Science.gov (United States)

Fleming, James G [Albuquerque, NM; Lin, Shawn-Yu [Albuquerque, NM; Bur, James A [Corrales, NM

2004-07-27

A light source is provided by a photonic crystal having an enhanced photonic density-of-states over a band of frequencies and wherein at least one of the dielectric materials of the photonic crystal has a complex dielectric constant, thereby producing enhanced light emission at the band of frequencies when the photonic crystal is heated. The dielectric material can be a metal, such as tungsten. The spectral properties of the light source can be easily tuned by modification of the photonic crystal structure and materials. The photonic crystal light source can be heated electrically or other heating means. The light source can further include additional photonic crystals that exhibit enhanced light emission at a different band of frequencies to provide for color mixing. The photonic crystal light source may have applications in optical telecommunications, information displays, energy conversion, sensors, and other optical applications.

Land Streamer Surveying Using Multiple Sources

KAUST Repository

Mahmoud, Sherif

2014-12-11

Various examples are provided for land streamer seismic surveying using multiple sources. In one example, among others, a method includes disposing a land streamer in-line with first and second shot sources. The first shot source is at a first source location adjacent to a proximal end of the land streamer and the second shot source is at a second source location separated by a fixed length corresponding to a length of the land streamer. Shot gathers can be obtained when the shot sources are fired. In another example, a system includes a land streamer including a plurality of receivers, a first shot source located adjacent to the proximal end of the land streamer, and a second shot source located in-line with the land streamer and the first shot source. The second shot source is separated from the first shot source by a fixed overall length corresponding to the land streamer.

Leakage of caesium braquitherapy sources

International Nuclear Information System (INIS)

Lozada, J.A.

1998-01-01

In several Venezuelan public hospitals where cervix uteri tumours are treated by intracavitary radiotherapy, that use manual after loading Fletcher method, with Caesium 137 sources, the use of improper source holders, locally manufactured from pieces of drainage plastic tubing, which deteriorated and created a corrosive environment all around the sources, omission of manufacturer's recommendations regarding corrosion information, source storage, inspection and testing, violation of International Atomic Energy Agency Radiation Protection Procedures, and lack of proper regulatory control, resulted integrity damage to about sixty special form sources (ISO2919 C 63322), leakage of Cs-137 from a supposed insoluble refractory active content (caesium silicoaluminate), and contamination of applicators, floors and bedding. When the situation was detected by means removal contamination tests, after routine inspections, the sources were removed from the hospitals, decontaminated by means of immersion in 3% EDTA solution in ultrasonic bath, subjected to leaking assessment tests, and the ones that passed were placed in low cost stainless steel source holders, designed and built by the instituto Venezolano de Investigaciones Cientificas (IVIC) returned to the hospitals. The leaking sources were removed from use and considered radioactive waste. In order to avoid the occurrence of similar situations, all the importers of such sources are now required to send them to IVIC for testing and placement in proper source holders, before they are shipped to the hospitals. (author)

Economic explanations for concurrent sourcing

DEFF Research Database (Denmark)

Mols, Niels Peter

2010-01-01

Concurrent sourcing is a phenomenon where firms simultaneously make and buy the same good, i.e. they simultaneously use the governance modes of market and hierarchy. Though concurrent sourcing seems to be widespread, few studies of sourcing have focused on this phenomenon. This paper reviews...... different economic explanations for why firms use concurrent sourcing. The distinctive features of the explanations are compared, and it is discussed how they may serve as a springboard for research on concurrent sourcing. Managerial implications are also offered....

Plume rise from multiple sources

International Nuclear Information System (INIS)

Briggs, G.A.

1975-01-01

A simple enhancement factor for plume rise from multiple sources is proposed and tested against plume-rise observations. For bent-over buoyant plumes, this results in the recommendation that multiple-source rise be calculated as [(N + S)/(1 + S)]/sup 1/3/ times the single-source rise, Δh 1 , where N is the number of sources and S = 6 (total width of source configuration/N/sup 1/3/ Δh 1 )/sup 3/2/. For calm conditions a crude but simple method is suggested for predicting the height of plume merger and subsequent behavior which is based on the geometry and velocity variations of a single buoyant plume. Finally, it is suggested that large clusters of buoyant sources might occasionally give rise to concentrated vortices either within the source configuration or just downwind of it

Sources of pulsed radiation

International Nuclear Information System (INIS)

Sauer, M.C. Jr.

1981-01-01

Characteristics of various sources of pulsed radiation are examined from the viewpoint of their importance to the radiation chemist, and some examples of uses of such sources are mentioned. A summary is given of the application of methods of physical dosimetry to pulsed sources, and the calibration of convenient chemical dosimeters by physical dosimetry is outlined. 7 figures, 1 table

Degree of polarization and source counts of faint radio sources from Stacking Polarized intensity

International Nuclear Information System (INIS)

Stil, J. M.; George, S. J.; Keller, B. W.; Taylor, A. R.

2014-01-01

We present stacking polarized intensity as a means to study the polarization of sources that are too faint to be detected individually in surveys of polarized radio sources. Stacking offers not only high sensitivity to the median signal of a class of radio sources, but also avoids a detection threshold in polarized intensity, and therefore an arbitrary exclusion of sources with a low percentage of polarization. Correction for polarization bias is done through a Monte Carlo analysis and tested on a simulated survey. We show that the nonlinear relation between the real polarized signal and the detected signal requires knowledge of the shape of the distribution of fractional polarization, which we constrain using the ratio of the upper quartile to the lower quartile of the distribution of stacked polarized intensities. Stacking polarized intensity for NRAO VLA Sky Survey (NVSS) sources down to the detection limit in Stokes I, we find a gradual increase in median fractional polarization that is consistent with a trend that was noticed before for bright NVSS sources, but is much more gradual than found by previous deep surveys of radio polarization. Consequently, the polarized radio source counts derived from our stacking experiment predict fewer polarized radio sources for future surveys with the Square Kilometre Array and its pathfinders.

Calibrate the aerial surveying instrument by the limited surface source and the single point source that replace the unlimited surface source

CERN Document Server

Lu Cun Heng

1999-01-01

It is described that the calculating formula and surveying result is found on the basis of the stacking principle of gamma ray and the feature of hexagonal surface source when the limited surface source replaces the unlimited surface source to calibrate the aerial survey instrument on the ground, and that it is found in the light of the exchanged principle of the gamma ray when the single point source replaces the unlimited surface source to calibrate aerial surveying instrument in the air. Meanwhile through the theoretical analysis, the receiving rate of the crystal bottom and side surfaces is calculated when aerial surveying instrument receives gamma ray. The mathematical expression of the gamma ray decaying following height according to the Jinge function regularity is got. According to this regularity, the absorbing coefficient that air absorbs the gamma ray and the detective efficiency coefficient of the crystal is calculated based on the ground and air measuring value of the bottom surface receiving cou...

Pseudo-dynamic source modelling with 1-point and 2-point statistics of earthquake source parameters

KAUST Repository

Song, S. G.

2013-12-24

Ground motion prediction is an essential element in seismic hazard and risk analysis. Empirical ground motion prediction approaches have been widely used in the community, but efficient simulation-based ground motion prediction methods are needed to complement empirical approaches, especially in the regions with limited data constraints. Recently, dynamic rupture modelling has been successfully adopted in physics-based source and ground motion modelling, but it is still computationally demanding and many input parameters are not well constrained by observational data. Pseudo-dynamic source modelling keeps the form of kinematic modelling with its computational efficiency, but also tries to emulate the physics of source process. In this paper, we develop a statistical framework that governs the finite-fault rupture process with 1-point and 2-point statistics of source parameters in order to quantify the variability of finite source models for future scenario events. We test this method by extracting 1-point and 2-point statistics from dynamically derived source models and simulating a number of rupture scenarios, given target 1-point and 2-point statistics. We propose a new rupture model generator for stochastic source modelling with the covariance matrix constructed from target 2-point statistics, that is, auto- and cross-correlations. Our sensitivity analysis of near-source ground motions to 1-point and 2-point statistics of source parameters provides insights into relations between statistical rupture properties and ground motions. We observe that larger standard deviation and stronger correlation produce stronger peak ground motions in general. The proposed new source modelling approach will contribute to understanding the effect of earthquake source on near-source ground motion characteristics in a more quantitative and systematic way.

Editorial: Open Source in Government

Directory of Open Access Journals (Sweden)

Dru Lavigne

2009-04-01

Full Text Available Last summer, the Center for Strategic and International Studies published the sixth update to their Open Source Policy survey. The survey "tracks governmental policies on the use of open source software as reported in the press or other media." The report lists 275 open source policy initiatives. It also breaks down by country and by government level whether the policy on the use of open source is considered to be advisory, preferential, or mandatory. The editorial theme for the May issue of the OSBR is "open source in government" and we are pleased that the authors have drawn upon their experiences to provide insight into public policy regarding open source for many parts of the world.

Ion sources for electrostatic accelerators

International Nuclear Information System (INIS)

Hellborg, R.

1998-01-01

Maybe the most important part of an electrostatic accelerator system, and also often the most tricky part is the ion source. There has been a rapid growth in activity in ion-source research and development during the last two to three decades. Some of these developments have also been of benefit to electrostatic accelerator users. In this report some of the different types of ion sources used in electrostatic accelerators are described. The list is not complete but more an overview of some of the more commonly used sources. The description is divided into two groups; positive ion sources for single stage electrostatic accelerators and negative ion sources for two stages (i.e. tandem) accelerators

Radiation sources and technical services

International Nuclear Information System (INIS)

Stonek, K.; Satorie, Z.; Vyskocil, I.

1981-01-01

Work is briefly described of the department for sealed sources production of the Institute, including leak testing and surface contamination of sealed sources. The department also provides technical services including the inspections of sealed sources used in medicine and geology and repair of damaged sources. It carries out research of the mechanical and thermal strength of sealed sources and of the possibility of reprocessing used 226 Ra sources. The despatch department is responsible for supplying the entire country with home and imported radionuclides. The department of technical services is responsible for testing imported radionuclides, assembling materials testing, industrial and medical irradiation devices, and for the collection and storage of low-level wastes on a national scale. (M.D.)

DESIGN OF ALTERNATIVE ENERGY SOURCES

Directory of Open Access Journals (Sweden)

Popa Stefania

2013-11-01

Full Text Available By energy sources we understand technologies and materials used to obtain various forms of energy necessary for the development of society. These sources must be in adequate quantities and be conveniently exploited in terms of technical, economic and sustainable perspective. Alternative energy uses the inherent power of natural sources like wind, tides, the sun. Alternative energy is a term used for some energy sources and energy storage technologies. Generally it indicates energies that are nontraditional and have low impact to the environment. The alternative energy term is used in contrast with the term fossil fuel according to some sources, while other sources use it with the meaning of renewable energy purposes.

Categorization of radiation sources

International Nuclear Information System (INIS)

2000-12-01

The objective of this report is to develop a categorization scheme for radiation sources that could be relevant to decisions both in a retrospective application to bring sources under control and in a prospective sense to guide the application of the regulatory infrastructure. The Action Plan envisages that the preparation of guidance on national strategies and programmes for the detection and location of orphan sources and their subsequent management should commence after the categorization of sources has been carried out. In the prospective application of the system of notification, registration, and licensing, the categorization is relevant to prioritize a regulatory authority's resources and training activities; to guide the degree of detail necessary for a safety assessment; and to serve as a measure of the intensity of effort which a regulatory authority should apply to the safety and security of a particular type of source

Source SDK development essentials

CERN Document Server

Bernier, Brett

2014-01-01

The Source Authoring Tools are the pieces of software used to create custom content for games made with Valve's Source engine. Creating mods and maps for your games without any programming knowledge can be time consuming. These tools allow you to create your own maps and levels without the need for any coding knowledge. All the tools that you need to start creating your own levels are built-in and ready to go! This book will teach you how to use the Authoring Tools provided with Source games and will guide you in creating your first maps and mods (modifications) using Source. You will learn ho

Radiation Safety and Orphan Sources

International Nuclear Information System (INIS)

Janzekovic, H.; Krizman, M.

2006-01-01

The wide spread use of radioactive and particularly of nuclear materials which started in the last century very quickly also demonstrated negative sides. The external exposure and radiotoxicity of these materials could be easily used in a malevolent act. Due to the fact that these materials could not be detected without special equipment designed for that purpose, severe control over their use in all phases of a life cycle is required. An orphan source is a radioactive source which is not under regulatory control, either because it has never been under regulatory or because it has been abandoned, lost, misplaced, stolen or transferred without proper authorization. In the last ten years a few international conferences were dedicated to the improvement of the safety and security of radioactive sources. Three main tasks are focused, the maintenance of data bases related to events with orphan sources and the publications of such events, the preparation of recommendations and guidelines to national regulatory bodies in order to prevent and detect the events related to orphan sources as well as to develop the response strategies to radiological or nuclear emergency, appraisals of the national strategies of radioactive sources control. Concerning Slovenia, strengthening control over orphan sources in Slovenia started after the adoption of new legislation in 2002. It was carried out through several tasks with the aim to prevent orphan sources, as well as to identify the sources which could be potentially orphan sources. The comprehensive methodology was developed by the Slovenian nuclear safety administration (S.N.S.A.) based on international guidelines as well as on the study of national lesson learned cases. The methodology was developed and used in close cooperation with all parties involved, namely other regulatory authorities, police, customs, agency for radioactive waste management (A.R.A.O.), technical support organisations (T.S.O.), users of source, authorised

Radiation Safety and Orphan Sources

Energy Technology Data Exchange (ETDEWEB)

Janzekovic, H.; Krizman, M. [Slovenian Nuclear Safety Administration, Ljubljana (Slovenia)

2006-07-01

The wide spread use of radioactive and particularly of nuclear materials which started in the last century very quickly also demonstrated negative sides. The external exposure and radiotoxicity of these materials could be easily used in a malevolent act. Due to the fact that these materials could not be detected without special equipment designed for that purpose, severe control over their use in all phases of a life cycle is required. An orphan source is a radioactive source which is not under regulatory control, either because it has never been under regulatory or because it has been abandoned, lost, misplaced, stolen or transferred without proper authorization. In the last ten years a few international conferences were dedicated to the improvement of the safety and security of radioactive sources. Three main tasks are focused, the maintenance of data bases related to events with orphan sources and the publications of such events, the preparation of recommendations and guidelines to national regulatory bodies in order to prevent and detect the events related to orphan sources as well as to develop the response strategies to radiological or nuclear emergency, appraisals of the national strategies of radioactive sources control. Concerning Slovenia, strengthening control over orphan sources in Slovenia started after the adoption of new legislation in 2002. It was carried out through several tasks with the aim to prevent orphan sources, as well as to identify the sources which could be potentially orphan sources. The comprehensive methodology was developed by the Slovenian nuclear safety administration (S.N.S.A.) based on international guidelines as well as on the study of national lesson learned cases. The methodology was developed and used in close cooperation with all parties involved, namely other regulatory authorities, police, customs, agency for radioactive waste management (A.R.A.O.), technical support organisations (T.S.O.), users of source, authorised

Global inventory of NOx sources

International Nuclear Information System (INIS)

Delmas, R.; Serca, D.; Jambert, C.

1997-01-01

Nitrogen oxides are key compounds for the oxidation capacity of the troposphere. Their concentration depends on the proximity of sources because of their short atmospheric lifetime. An accurate knowledge of the distribution of their sources and sinks is therefore crucial. At the global scale, the dominant sources of nitrogen oxides - combustion of fossil fuel (about 50%) and biomass burning (about 20%) - are basically anthropogenic. Natural sources, including lightning and microbial activity in soils, represent therefore less than 30% of total emissions. Fertilizer use in agriculture constitutes an anthropogenic perturbation to the microbial source. The methods to estimate the magnitude and distribution of these dominant sources of nitrogen oxides are discussed. Some minor sources which may play a specific role in tropospheric chemistry such as NO x emission from aircraft in the upper troposphere or input from production in the stratosphere from N 2 O photodissociation are also considered

Radiation sources working group summary

International Nuclear Information System (INIS)

Fazio, M.V.

1998-01-01

The Radiation Sources Working Group addressed advanced concepts for the generation of RF energy to power advanced accelerators. The focus of the working group included advanced sources and technologies above 17 GHz. The topics discussed included RF sources above 17 GHz, pulse compression techniques to achieve extreme peak power levels, components technology, technology limitations and physical limits, and other advanced concepts. RF sources included gyroklystrons, magnicons, free-electron masers, two beam accelerators, and gyroharmonic and traveling wave devices. Technology components discussed included advanced cathodes and electron guns, high temperature superconductors for producing magnetic fields, RF breakdown physics and mitigation, and phenomena that impact source design such as fatigue in resonant structures due to RF heating. New approaches for RF source diagnostics located internal to the source were discussed for detecting plasma and beam phenomena existing in high energy density electrodynamic systems in order to help elucidate the reasons for performance limitations

Properties of neutron sources

International Nuclear Information System (INIS)

1987-03-01

The Conference presentations were divided into sessions devoted to the following topics: white neutron sources, primarily pulsed (6 papers); fast neutron fields (5 papers); Californium-252 prompt fission neutron spectra (14 papers); monoenergetic sources and filtered beams (11 papers); 14 MeV neutron sources (10 papers); selected special application (one paper); and a general interest session (4 papers). Individual abstracts were prepared separately for the papers

Investigation on Ion Source Parameters

CERN Document Server

M. Cheikh Mhamed, S. Essabaa, C. Lau

The EURISOL multi-mega-watt target station requires dedicated radioactive ion sources. Notably, they must be capable of operating under extremely hard radiations and with a larger fission target producing over 1014 fissions/s. The realisation of next-generation ion sources suitable for such operating conditions needs exhaustive studies and developments. In order to take up such a challenge, a review on radioactive ion sources was achieved and the investigation on ion source parameters was in particular focused on a plasma ion source through a R&D program.

Safe handling of radiation sources

International Nuclear Information System (INIS)

Abd Nasir Ibrahim; Azali Muhammad; Ab Razak Hamzah; Abd Aziz Mohamed; Mohammad Pauzi Ismail

2004-01-01

This chapter discussed the subjects related to the safe handling of radiation sources: type of radiation sources, method of use: transport within premises, transport outside premises; Disposal of Gamma Sources

Assessing Model Characterization of Single Source ...

Science.gov (United States)

Aircraft measurements made downwind from specific coal fired power plants during the 2013 Southeast Nexus field campaign provide a unique opportunity to evaluate single source photochemical model predictions of both O3 and secondary PM2.5 species. The model did well at predicting downwind plume placement. The model shows similar patterns of an increasing fraction of PM2.5 sulfate ion to the sum of SO2 and PM2.5 sulfate ion by distance from the source compared with ambient based estimates. The model was less consistent in capturing downwind ambient based trends in conversion of NOX to NOY from these sources. Source sensitivity approaches capture near-source O3 titration by fresh NO emissions, in particular subgrid plume treatment. However, capturing this near-source chemical feature did not translate into better downwind peak estimates of single source O3 impacts. The model estimated O3 production from these sources but often was lower than ambient based source production. The downwind transect ambient measurements, in particular secondary PM2.5 and O3, have some level of contribution from other sources which makes direct comparison with model source contribution challenging. Model source attribution results suggest contribution to secondary pollutants from multiple sources even where primary pollutants indicate the presence of a single source. The National Exposure Research Laboratory (NERL) Computational Exposure Division (CED) develops and evaluates data, deci

Recent negative ion source developments

International Nuclear Information System (INIS)

Alton, G.D.

1978-01-01

This report describes recent results obtained from studies associated with the development of negative ion sources which utilize sputtering in a diffuse cesium plasma as a means of ion beam generation. Data are presented which relate negative ion yield and important operational parameters such as cesium oven temperature and sputter probe voltage from each of the following sources: (1) A source based in principle according to the University of Aarhus design and (2) an axial geometry source. The important design aspects of the sources are given--along with a list of the negative ion intensities observed to date. Also a qualitative description and interpretation of the negative ion generation mechanism in sources which utilize sputtering in the presence of cesium is given

The status of DESY H- - sources

International Nuclear Information System (INIS)

Peters, J.

1996-01-01

Two different types of H - sources are operated at DESY, a magnetron source and an rf- driven volume source. H - sources for HERA have to run for long uninterrupted periods with a low duty factor and a high reliability. Several necessary improvements are under construction for our rf - driven volume source. The status of both our magnetron and our volume source will be discussed and the first LINAC III experiment with the rf-driven volume source will be presented. (author)

Separation of non-stationary multi-source sound field based on the interpolated time-domain equivalent source method

Science.gov (United States)

Bi, Chuan-Xing; Geng, Lin; Zhang, Xiao-Zheng

2016-05-01

In the sound field with multiple non-stationary sources, the measured pressure is the sum of the pressures generated by all sources, and thus cannot be used directly for studying the vibration and sound radiation characteristics of every source alone. This paper proposes a separation model based on the interpolated time-domain equivalent source method (ITDESM) to separate the pressure field belonging to every source from the non-stationary multi-source sound field. In the proposed method, ITDESM is first extended to establish the relationship between the mixed time-dependent pressure and all the equivalent sources distributed on every source with known location and geometry information, and all the equivalent source strengths at each time step are solved by an iterative solving process; then, the corresponding equivalent source strengths of one interested source are used to calculate the pressure field generated by that source alone. Numerical simulation of two baffled circular pistons demonstrates that the proposed method can be effective in separating the non-stationary pressure generated by every source alone in both time and space domains. An experiment with two speakers in a semi-anechoic chamber further evidences the effectiveness of the proposed method.

Compact radio sources

International Nuclear Information System (INIS)

Altschuler, D.R.

1975-01-01

Eighty-seven compact radio sources were monitored between 1971 and 1974 with the National Radio Astronomy Observatory interferometer. Both flux density and polarization were measured at intervals of about one month at wavelengths of 3.7 and 11.1 cms. Forty-four sources showed definite variability in their total and/or polarized flux density. The variations in polarization were of a shorter time scale than the corresponding flux density variations. Some of the qualitative features of an expanding source model were observed. The data suggest that some form of injection of relativistic electrons is taking place. The absence of significant depolarization in the variable sources indicates that only a small fraction of the mass of the radio outburst is in the form of non-relativistic plasma. Some of the objects observed belong to the BL-Lacertal class. It is shown that this class is very inhomogeneous in its radio properties. For the violently variable BL-Lacertal type objects the spectrum, flux variations and polarization data strongly suggest that these are very young objects

Open-source colorimeter.

Science.gov (United States)

Anzalone, Gerald C; Glover, Alexandra G; Pearce, Joshua M

2013-04-19

The high cost of what have historically been sophisticated research-related sensors and tools has limited their adoption to a relatively small group of well-funded researchers. This paper provides a methodology for applying an open-source approach to design and development of a colorimeter. A 3-D printable, open-source colorimeter utilizing only open-source hardware and software solutions and readily available discrete components is discussed and its performance compared to a commercial portable colorimeter. Performance is evaluated with commercial vials prepared for the closed reflux chemical oxygen demand (COD) method. This approach reduced the cost of reliable closed reflux COD by two orders of magnitude making it an economic alternative for the vast majority of potential users. The open-source colorimeter demonstrated good reproducibility and serves as a platform for further development and derivation of the design for other, similar purposes such as nephelometry. This approach promises unprecedented access to sophisticated instrumentation based on low-cost sensors by those most in need of it, under-developed and developing world laboratories.

Open-Source Colorimeter

Science.gov (United States)

Anzalone, Gerald C.; Glover, Alexandra G.; Pearce, Joshua M.

2013-01-01

The high cost of what have historically been sophisticated research-related sensors and tools has limited their adoption to a relatively small group of well-funded researchers. This paper provides a methodology for applying an open-source approach to design and development of a colorimeter. A 3-D printable, open-source colorimeter utilizing only open-source hardware and software solutions and readily available discrete components is discussed and its performance compared to a commercial portable colorimeter. Performance is evaluated with commercial vials prepared for the closed reflux chemical oxygen demand (COD) method. This approach reduced the cost of reliable closed reflux COD by two orders of magnitude making it an economic alternative for the vast majority of potential users. The open-source colorimeter demonstrated good reproducibility and serves as a platform for further development and derivation of the design for other, similar purposes such as nephelometry. This approach promises unprecedented access to sophisticated instrumentation based on low-cost sensors by those most in need of it, under-developed and developing world laboratories. PMID:23604032

Source and replica calculations

International Nuclear Information System (INIS)

Whalen, P.P.

1994-01-01

The starting point of the Hiroshima-Nagasaki Dose Reevaluation Program is the energy and directional distributions of the prompt neutron and gamma-ray radiation emitted from the exploding bombs. A brief introduction to the neutron source calculations is presented. The development of our current understanding of the source problem is outlined. It is recommended that adjoint calculations be used to modify source spectra to resolve the neutron discrepancy problem

sources

Directory of Open Access Journals (Sweden)

Shu-Yin Chiang

2002-01-01

Full Text Available In this paper, we study the simplified models of the ATM (Asynchronous Transfer Mode multiplexer network with Bernoulli random traffic sources. Based on the model, the performance measures are analyzed by the different output service schemes.

Some preliminary design considerations for the ANS [Advanced Neutron Source] reactor cold source

International Nuclear Information System (INIS)

Henderson, D.L.

1988-01-01

Two areas concerned with the design of the Advanced Neutron Source (ANS) cold source have been investigated by simple one-dimensional calculations. The gain factors computed for a possible liquid nitrogen-15 cold source moderator are considerably below those computed for the much colder liquid deuterium moderator, as is reasonable considering the difference in moderator temperature. Nevertheless, nitrogen-15 does represent a viable option should safety related issues prohibit the use of deuterium as a moderating material. The slab geometry calculations have indicated that reflection of neutrons may be the dominant moderating mechanism and should be a consideration in the design of the cold source. 9 refs., 2 figs

How Source Information Shapes Lay Interpretations of Science Conflicts: Interplay between Sourcing, Conflict Explanation, Source Evaluation, and Claim Evaluation

Science.gov (United States)

Thomm, Eva; Bromme, Rainer

2016-01-01

When laypeople read controversial scientific information in order to make a personally relevant decision, information on the source is a valuable resource with which to evaluate multiple, competing claims. Due to their bounded understanding, laypeople rely on the expertise of others and need to identify whether sources are credible. The present…

Determination of Key Risk Supervision Areas around River-Type Water Sources Affected by Multiple Risk Sources: A Case Study of Water Sources along the Yangtze’s Nanjing Section

Directory of Open Access Journals (Sweden)

Qi Zhou

2017-02-01

Full Text Available To provide a reference for risk management of water sources, this study screens the key risk supervision areas around river-type water sources (hereinafter referred to as the water sources threatened by multiple fixed risk sources (the risk sources, and establishes a comprehensive methodological system. Specifically, it comprises: (1 method of partitioning risk source concentrated sub-regions for screening water source perimeter key risk supervision areas; (2 approach of determining sub-regional risk indexes (SrRI, which characterizes the scale of sub-regional risks considering factors like risk distribution intensity within sub-regions, risk indexes of risk sources (RIRS, characterizing the risk scale of risk sources and the number of risk sources; and (3 method of calculating sub-region’s risk threats to the water sources (SrTWS which considers the positional relationship between water sources and sub-regions as well as SrRI, and the criteria for determining key supervision sub-regions. Favorable effects are achieved by applying this methodological system in determining water source perimeter sub-regions distributed along the Yangtze’s Nanjing section. Results revealed that for water sources, the key sub-regions needing supervision were SD16, SD06, SD21, SD26, SD15, SD03, SD02, SD32, SD10, SD11, SD14, SD05, SD27, etc., in the order of criticality. The sub-region with the greatest risk threats on the water sources was SD16, which was located in the middle reaches of Yangtze River. In general, sub-regions along the upper Yangtze reaches had greater threats to water sources than the lower reach sub-regions other than SD26 and SD21. Upstream water sources were less subject to the threats of sub-regions than the downstream sources other than NJ09B and NJ03.

Cobalt source calibration

International Nuclear Information System (INIS)

Rizvi, H.M.

1999-01-01

The data obtained from these tests determine the dose rate of the two cobalt sources in SRTC. Building 774-A houses one of these sources while the other resides in room C-067 of Building 773-A. The data from this experiment shows the following: (1) The dose rate of the No.2 cobalt source in Building 774-A measured 1.073 x 10 5 rad/h (June 17, 1999). The dose rate of the Shepherd Model 109 Gamma cobalt source in Building 773-A measured 9.27 x 10 5 rad/h (June 25, 1999). These rates come from placing the graduated cylinder containing the dosimeter solution in the center of the irradiation chamber. (2) Two calibration tests in the 774-A source placed the graduated cylinder with the dosimeter solution approximately 1.5 inches off center in the axial direction. This movement of the sample reduced the measured dose rate 0.92% from 1.083 x 10 5 rad/h to 1.073 x 10 5 rad/h. and (3) A similar test in the cobalt source in 773-A placed the graduated cylinder approximately 2.0 inches off center in the axial direction. This change in position reduced the measured dose rate by 10.34% from 1.036 x 10 6 to 9.27 x 10 5 . This testing used chemical dosimetry to measure the dose rate of a radioactive source. In this method, one determines the dose by the chemical change that takes place in the dosimeter. For this calibration experiment, the author used a Fricke (ferrous ammonium sulfate) dosimeter. This solution works well for dose rates to 10 7 rad/h. During irradiation of the Fricke dosimeter solution the Fe 2+ ions ionize to Fe 3+ . When this occurs, the solution acquires a slightly darker tint (not visible to the human eye). To determine the magnitude of the change in Fe ions, one places the solution in an UV-VIS Spectrophotometer. The UV-VIS Spectrophotometer measures the absorbency of the solution. Dividing the absorbency by the total time (in minutes) of exposure yields the dose rate

Categorization of radioactive sources. Revision of IAEA-TECDOC-1191, Categorization of radiation sources

International Nuclear Information System (INIS)

2003-07-01

Radioactive sources are used throughout the world for a wide variety of peaceful purposes in industry, medicine, agriculture, research and education; and they are also used in military applications. The International Basic Safety Standards provide an internationally harmonized basis for ensuring the safe and secure use of sources of ionizing radiation. Because of the wide variety of uses and activities of radiation sources, a categorization system is necessary so that the controls that are applied to the sources are commensurate with the radiological risks. In September 1998, following an assessment of the major findings of the first International Conference on the Safety of Radiation Sources and the Security of Radioactive Materials, held in Dijon, France, from 14 to 18 September 1998 (the Dijon Conference), the IAEA's General Conference (in resolution GC(42)/RES/12), inter alia, encouraged all governments 'to take steps to ensure the existence within their territories of effective national systems of control for ensuring the safety of radiation sources and the security of radioactive materials' and requested the Secretariat 'to prepare for the consideration of the Board of Governors a report on: (i) how national systems for ensuring the safety of radiation sources and the security of radioactive materials can be operated at a high level of effectiveness; and, (ii) whether international undertakings concerned with the effective operation of such systems and attracting broad adherence could be formulated'. In February 1999, the Secretariat submitted to the IAEA Board of Governors a report prepared in response to the request made of it by the General Conference. The Board took up the report at its March 1999 session and, inter alia, requested the Secretariat to prepare an action plan that took into account the conclusions and recommendations in the report, and the Board's discussion of the report. In August 1999, the Secretariat circulated a proposed Action Plan for

Natural sources of ionizing radiations

International Nuclear Information System (INIS)

Marej, A.N.

1984-01-01

Natural sources of ionizing radiations are described in detail. The sources are subdivided into sources of extraterrestrial origin (cosmic radiation) and sources of terrestrial origin. Data on the concentration of different nuclides in rocks, various soils, ground waters, atmospheric air, tissues of plants and animals, various food stuffs are presented. The content of natural radionuclides in environmental objects, related to human activities, is discussed

Power source system for nuclear fusion

International Nuclear Information System (INIS)

Nakagawa, Satoshi.

1975-01-01

Object: When using an external system power source and an exclusive power source in a power source circuit for supplying power to the coils of a nuclear fusion apparatus, to minimize the capacity of the exclusive power source and provide an economical power source circuit construction. Structure: In the initial stage of the power supply, rectifying means provided in individual blocks are connected in parallel on the AC side, and power is supplied to the coils of the nuclear fusion apparatus from an external system power source with the exclusive power source held in the disconnected state. Further, at an instant when the limit of permissible input is reached, the afore-mentioned parallel circuit consisting of rectifying means is disconnected, while at the same time the exclusive power source is connected to the input side of the rectifying means provided in a block corresponding to the exclusive power source side, thereby supplying power to the coils of the nuclear fusion apparatus from both the external system power source and exclusive power source. (Kamimura, M.)

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.

Magnesium-aerial primary current source

Directory of Open Access Journals (Sweden)

Barba I. N.

2007-12-01

Full Text Available Novel metal-air chemical power sources (CPS 3,0-ВМБ-7,5 have been developed. They have an unlimited shelf life and, even after decades of storage, give almost 100% of the designed capacity. These sources are water-activated. An aqueous salt solution is used as an electrolyte. Such sources are designed for single continuous or discontinuous discharge. The paper presents electrochemical reactions at the electrodes during CPS discharge. Comparison of electrical characteristics of the developed power source and various types of "dry cells" has shown that the developed sources have higher energy characteristics.

Rf power sources

International Nuclear Information System (INIS)

Allen, M.A.

1988-01-01

In this paper, the author reports on RF power sources for accelerator applications. The approach will be with particular customers in mind. These customers are high energy physicists who use accelerators as experimental tools in the study of the nucleus of the atom, and synchrotron light sources derived from electron or positron storage rings. The author pays close attention to electron- positron linear accelerators since the RF sources have always defined what is possible to achieve with these accelerators. Circular machines, cyclotrons, synchrotrons, etc. have usually not been limited by the RF power available and the machine builders have usually had their RF power source requirements met off the shelf. The main challenge for the RF scientist has been then in the areas of controls. An interesting example of this is in the Conceptual Design Report of the Superconducting Super Collider (SSC) where the RF system is described in six pages of text in a 700-page report. Also, the cost of that RF system is about one-third of a percent of the project's total cost. The RF system is well within the state of the art and no new power sources need to be developed. All the intellectual effort of the system designer would be devoted to the feedback systems necessary to stabilize beams during storage and acceleration, with the main engineering challenges (and costs) being in the superconducting magnet lattice

Pulsed spallation Neutron Sources

International Nuclear Information System (INIS)

Carpenter, J.M.

1994-01-01

This paper reviews the early history of pulsed spallation neutron source development at Argonne and provides an overview of existing sources world wide. A number of proposals for machines more powerful than currently exist are under development, which are briefly described. The author reviews the status of the Intense Pulsed Neutron Source, its instrumentation, and its user program, and provides a few examples of applications in fundamental condensed matter physics, materials science and technology

Source-circuit design overview

Science.gov (United States)

Ross, R. G., Jr.

1983-01-01

The source circuit is the fundamental electrical building block of a large central-station array; it consists of a series-parallel network of solar cells that develops full system voltage. The array field is generally made up of a large number of parallel source circuits. Source-circuit electrical configuration is driven by a number of design considerations, which must be considered simultaneously. Array fault tolerance and hot spot heating endurance are examined in detail.

Pulsed spallation neutron sources

International Nuclear Information System (INIS)

Carpenter, J.M.

1996-01-01

This paper reviews the early history of pulsed spallation neutron source development ar Argonne and provides an overview of existing sources world wide. A number of proposals for machines more powerful than currently exist are under development, which are briefly described. The author reviews the status of the Intense Pulsed Neutron Source, its instrumentation, and its user program, and provide a few examples of applications in fundamental condensed matter physics, materials science and technology

Improvements to the internal and external antenna H(-) ion sources at the Spallation Neutron Source.

Science.gov (United States)

Welton, R F; Dudnikov, V G; Han, B X; Murray, S N; Pennisi, T R; Pillar, C; Santana, M; Stockli, M P; Turvey, M W

2014-02-01

The Spallation Neutron Source (SNS), a large scale neutron production facility, routinely operates with 30-40 mA peak current in the linac. Recent measurements have shown that our RF-driven internal antenna, Cs-enhanced, multi-cusp ion sources injects ∼55 mA of H(-) beam current (∼1 ms, 60 Hz) at 65-kV into a Radio Frequency Quadrupole (RFQ) accelerator through a closely coupled electrostatic Low-Energy Beam Transport system. Over the last several years a decrease in RFQ transmission and issues with internal antennas has stimulated source development at the SNS both for the internal and external antenna ion sources. This report discusses progress in improving internal antenna reliability, H(-) yield improvements which resulted from modifications to the outlet aperture assembly (applicable to both internal and external antenna sources) and studies made of the long standing problem of beam persistence with the external antenna source. The current status of the external antenna ion source will also be presented.

75 FR 68296 - Standards of Performance for New Stationary Sources and Emission Guidelines for Existing Sources...

Science.gov (United States)

2010-11-05

... Standards of Performance for New Stationary Sources and Emission Guidelines for Existing Sources: Sewage... ``Standards of Performance for New Stationary Sources and Emission Guidelines for Existing Sources: Sewage... performance standards for new units and emission guidelines for existing units for specific categories of...

Energy sources

International Nuclear Information System (INIS)

Vajda, Gy.

1998-01-01

A comprehensive review is presented of the available sources of energy in the world is presented. About 80 percent of primary energy utilization is based on fossile fuels, and their dominant role is not expected to change in the foreseeable future. Data are given on petroleum, natural gas and coal based power production. The role and economic aspects of nuclear power are analyzed. A brief summary of renewable energy sources is presented. The future prospects of the world's energy resources are discussed, and the special position of Hungary regarding fossil, nuclear and renewable energy and the country's energy potential is evaluated. (R.P.)

Designing of RF ion source and the power sources system

International Nuclear Information System (INIS)

Rusdiyanto.

1978-01-01

An RF ion source prototype is being developed for the particle accelerator at the Gama Research Centre. Supply of the gas is fed into the plasma chamber by means of neadle valve system. Magnetic field strength of about 500 gauss is applied to the system to improve the ionization efficiency. Components and spare parts of the RF ion source are made based on locally available materials and are discussed in this report. (author)

Reducing the risk from radioactive sources

International Nuclear Information System (INIS)

MacKenzie, C.

2006-01-01

Each year the IAEA receives reports of serious injuries or deaths due to misuse or accidents involving sealed radioactive sources. Sealed radioactive sources are used widely in medicine, industry, and agriculture - by doctors to treat cancer, by radiographers to check welds in pipelines, or by specialists to irradiate food to prevent it from spoiling, for example. If these sources are lost or improperly discarded, a serious accident may result. In addition, the security of sealed sources has become a growing concern, particularly the potential that such a source could be used as a radioactive dispersal device or 'dirty bomb'. Preventing the loss or theft of sealed radioactive sources reduces both the risk of accidents and the risk that such sources could become an instrument of misuse. In most countries, radioactive materials and activities that produce radiation are regulated. Those working with sealed radioactive sources are required not just to have proper credentials, but also the needed training and support to deal with unexpected circumstances that may arise when a source is used. Despite these measures, accidents involving sealed sources continue to be reported to the IAEA. Among its many activities to improve the safety and security of sealed sources, the IAEA has been investigating the root causes of major accidents since the 1980s and publishing the findings so that others can learn from them. This information needs to be in the hands of those whose actions and decisions can reduce accidents by preventing a lost source from making it's way into scrap metal. The IAEA has also developed an international catalogue of sealed radioactive sources, and provides assistance to countries to safely contain sources no longer in use. To raise awareness, a Sealed Radioactive Sources Toolkit was issued that focuses on the long-term issues in safely and securely managing radioactive sealed sources. The target audiences are government agencies, radioactive sealed source

Granulocyte colony-stimulating factor decreases the Th1/Th2 ratio in peripheral blood mononuclear cells from patients with chronic immune thrombocytopenic purpura in vitro.

Science.gov (United States)

Ge, Fei; Zhang, Zhuo; Hou, Jinxiao; Cao, Fenglin; Zhang, Yingmei; Wang, Ping; Wei, Hong; Zhou, Jin

2016-12-01

Chronic immune thrombocytopenia purpura (ITP) is an autoimmune disease that exhibits an abnormally high Th1/Th2 ratio. Granulocyte colony-stimulating factor (G-CSF) has been shown to decrease the Th1/Th2 ratio in healthy donors. In this study, we investigated the effects of G-CSF treatment on the Th1/Th2 cells and the underlying mechanisms in patients with ITP in vitro. Peripheral blood mononuclear cells (PBMCs) isolated from patients with ITP and healthy controls were treated with G-CSF. Expression levels of interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-13 in supernatants were measured by enzyme-linked immunosorbent assays. The expression of IFN-γ, IL-4, and G-CSF receptor (G-CSFR) on Th1 and Th2 cells were examined by flow cytometry and confocal microscopy. The mRNA expression of IFN-γ, IL-2, IL-4, IL-13, and T-box expressed in T cells (T-bet) and GATA-binding protein 3 (GATA-3) in PBMCs was evaluated by reverse transcription polymerase chain reaction. The results showed that G-CSF could significantly reduce the Th1/Th2 ratio in PBMCs from patients with ITP in vitro. As the concentration of G-CSF increased, Th1/Th2 ([IFN-γ+IL-2]/[IL-4+IL-13]) cytokine ratios and T-bet/GATA-3 mRNA ratios decreased in a concentration-dependent manner. Th1 cells and Th2 cells both expressed G-CSFR. These results suggest that G-CSF could decrease the Th1/Th2 ratio in the context of ITP, and elucidate the direct and indirect immunomodulatory mechanisms underlying G-CSF functions in Th1/Th2 cells, thus supporting the therapeutic potential of G-CSF in the treatment of patients with ITP. Copyright © 2016 Elsevier Ltd. All rights reserved.

A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling.

Directory of Open Access Journals (Sweden)

Vijay Vedula

2017-10-01

Full Text Available Blood flow and mechanical forces in the ventricle are implicated in cardiac development and trabeculation. However, the mechanisms of mechanotransduction remain elusive. This is due in part to the challenges associated with accurately quantifying mechanical forces in the developing heart. We present a novel computational framework to simulate cardiac hemodynamics in developing zebrafish embryos by coupling 4-D light sheet imaging with a stabilized finite element flow solver, and extract time-dependent mechanical stimuli data. We employ deformable image registration methods to segment the motion of the ventricle from high resolution 4-D light sheet image data. This results in a robust and efficient workflow, as segmentation need only be performed at one cardiac phase, while wall position in the other cardiac phases is found by image registration. Ventricular hemodynamics are then quantified by numerically solving the Navier-Stokes equations in the moving wall domain with our validated flow solver. We demonstrate the applicability of the workflow in wild type zebrafish and three treated fish types that disrupt trabeculation: (a chemical treatment using AG1478, an ErbB2 signaling inhibitor that inhibits proliferation and differentiation of cardiac trabeculation; (b injection of gata1a morpholino oligomer (gata1aMO suppressing hematopoiesis and resulting in attenuated trabeculation; (c weak-atriumm58 mutant (wea with inhibited atrial contraction leading to a highly undeveloped ventricle and poor cardiac function. Our simulations reveal elevated wall shear stress (WSS in wild type and AG1478 compared to gata1aMO and wea. High oscillatory shear index (OSI in the grooves between trabeculae, compared to lower values on the ridges, in the wild type suggest oscillatory forces as a possible regulatory mechanism of cardiac trabeculation development. The framework has broad applicability for future cardiac developmental studies focused on quantitatively

Influence of Gestational Overfeeding on Cardiac Morphometry and Hypertrophic Protein Markers in Fetal Sheep

Science.gov (United States)

Fan, Xiujuan; Turdi, Subat; Ford, Stephen P.; Hua, Yinan; Nijland, Mark J.; Zhu, Meijun; Nathanielsz, Peter W.; Ren, Jun

2010-01-01

Intrauterine overnutrition is associated with development of cardiovascular disease in adulthood although the underlying mechanism has not been precisely elucidated. This study evaluated the effects of maternal overnutrition on fetal cardiac morphometry and hypertrophy-related mRNA/protein expression. Multiparous ewes were fed either 150% of NRC nutrient requirements (overfed group) or 100% of NRC requirements (control group) from 60 days before mating to day 75 (D75) of gestation, when ewes were euthanized. Cardiac morphometry, histology and expression of Akt, forkhead-3a (Foxo3a), glycogen synthase kinase-3β (GSK3β), mammalian target of rapamycin (mTOR), NFATc3 and GATA4, atrial natriuretic factor (ANF), calcineurin A and caspase-8 were examined. Crown rump length, left and right ventricular free wall weights and left ventricular wall thickness were increased in D75 overnourished fetuses. H&E staining revealed irregular myofiber orientation and increased interstitial space in heart tissues from overfed group. Masson’s trichrome staining displayed myofiber hypertrophy and fascicular disarray in heart tissues from overfed group. Overfeeding significantly enhanced Foxo3a phosphorylation in both ventricles while protein expression of Akt, Foxo3a, GSK3β and caspase-8 as well as phosphorylated Akt and GSK3β in either ventricle was unaffected. Overfeeding increased left ventricular mTOR, NFATc3 (both total and phosphorylated) and calcineurin A. GATA4, pGATA4 and ANF expression were unchanged in both ventricles. Collectively, our data suggested that overfeeding during early to mid gestation (D75) leads to morphometric changes without overt pathology which may be related to elevated expression of mTOR, NFATc3, calcineurin A and phosphorylation of Foxo3a, mTOR and NFATc3. PMID:20188535

Forward Programming of Cardiac Stem Cells by Homogeneous Transduction with MYOCD plus TBX5.

Directory of Open Access Journals (Sweden)

Elisa Belian

Full Text Available Adult cardiac stem cells (CSCs express many endogenous cardiogenic transcription factors including members of the Gata, Hand, Mef2, and T-box family. Unlike its DNA-binding targets, Myocardin (Myocd-a co-activator not only for serum response factor, but also for Gata4 and Tbx5-is not expressed in CSCs. We hypothesised that its absence was a limiting factor for reprogramming. Here, we sought to investigate the susceptibility of adult mouse Sca1+ side population CSCs to reprogramming by supplementing the triad of GATA4, MEF2C, and TBX5 (GMT, and more specifically by testing the effect of the missing co-activator, Myocd. Exogenous factors were expressed via doxycycline-inducible lentiviral vectors in various combinations. High throughput quantitative RT-PCR was used to test expression of 29 cardiac lineage markers two weeks post-induction. GMT induced more than half the analysed cardiac transcripts. However, no protein was detected for the induced sarcomeric genes Actc1, Myh6, and Myl2. Adding MYOCD to GMT affected only slightly the breadth and level of gene induction, but, importantly, triggered expression of all three proteins examined (α-cardiac actin, atrial natriuretic peptide, sarcomeric myosin heavy chains. MYOCD + TBX was the most effective pairwise combination in this system. In clonal derivatives homogenously expressing MYOCD + TBX at high levels, 93% of cardiac transcripts were up-regulated and all five proteins tested were visualized.(1 GMT induced cardiac genes in CSCs, but not cardiac proteins under the conditions used. (2 Complementing GMT with MYOCD induced cardiac protein expression, indicating a more complete cardiac differentiation program. (3 Homogeneous transduction with MYOCD + TBX5 facilitated the identification of differentiating cells and the validation of this combinatorial reprogramming strategy. Together, these results highlight the pivotal importance of MYOCD in driving CSCs toward a cardiac muscle fate.

Spallation Neutron Source (SNS)

Data.gov (United States)

Federal Laboratory Consortium — The SNS at Oak Ridge National Laboratory is a next-generation spallation neutron source for neutron scattering that is currently the most powerful neutron source in...

2011 NATA - Emissions Sources

Data.gov (United States)

U.S. Environmental Protection Agency — This dataset includes all emissions sources that were modeled in the 2011 National Air Toxics Assessment (NATA), inlcluding point, nonpoint, and mobile sources, and...

EV-GHG Mobile Source

Data.gov (United States)

U.S. Environmental Protection Agency — The EV-GHG Mobile Source Data asset contains measured mobile source GHG emissions summary compliance information on light-duty vehicles, by model, for certification...

Laser ion sources

Energy Technology Data Exchange (ETDEWEB)

Bykovskij, Yu

1979-02-01

The characteristics a laser source of multiply-ionized ions are described with regard to the interaction of laser radiation and matter, ion energy spectrum, angular ion distribution. The amount of multiple-ionization ions is evaluated. Out of laser source applications a laser injector of multiple-ionization ions and nuclei, laser mass spectrometry, laser X-ray microradiography, and a laser neutron generators are described.

Radioisotopic heat source

Science.gov (United States)

Jones, G.J.; Selle, J.E.; Teaney, P.E.

1975-09-30

Disclosed is a radioisotopic heat source and method for a long life electrical generator. The source includes plutonium dioxide shards and yttrium or hafnium in a container of tantalum-tungsten-hafnium alloy, all being in a nickel alloy outer container, and subjected to heat treatment of from about 1570$sup 0$F to about 1720$sup 0$F for about one h. (auth)

Offsite source recovery project - ten years of sealed source recovery and disposal

Energy Technology Data Exchange (ETDEWEB)

Whitworth, Julia Rose [Los Alamos National Laboratory; Pearson, Mike [Los Alamos National Laboratory; Witkowski, Ioana [Los Alamos National Laboratory; Wald - Hopkins, Mark [Los Alamos National Laboratory; Cuthbertson, A [NNSA

2010-01-01

The Global Threat Reduction Initiative's (GTRI) Offsite Source Recovery Project (OSRP) has been recovering excess and unwanted radioactive sealed sources for ten years. In January 2009, GTRI announced that the project had recovered 20,000 sealed radioactive sources (this number has since increased to more than 23,000). This project grew out of early efforts at Los Alamos National Laboratory (LANL) to recover and disposition excess Plutonium-239 (Pu-239) sealed sources that were distributed in the 1960s and 1970s under the Atoms for Peace Program. Decades later, these sources began to exceed their special form certifications or fall out of regular use. As OSRP has collected and stored sealed sources, initially using 'No Path Forward' waste exemptions for storage within the Department of Energy (DOE) complex, it has consistently worked to create disposal pathways for the material it has recovered. The project was initially restricted to recovering sealed sources that would meet the definition of Greater-than-Class-C (GTCC) low-level radioactive waste, assisting DOE in meeting its obligations under the Low-level Radioactive Waste Policy Act Amendments (PL 99-240) to provide disposal for this type of waste. After being transferred from DOE-Environmental Management (EM) to the U.S. National Nuclear Security Administration (NNSA) to be part of GTRI, OSRP's mission was expanded to include not only material that would be classified as GTCC when it became waste, but also any other materials that might constitute a 'national security consideration.' It was recognized at the time that the GTCC category was a waste designation having to do with environmental consequence, rather than the threat posed by deliberate or accidental misuse. The project faces barriers to recovery in many areas, but disposal continues to be one of the more difficult to overcome. This paper discusses OSRP's disposal efforts over its 10-year history. For sources

Performance evaluation of wideband bio-impedance spectroscopy using constant voltage source and constant current source

International Nuclear Information System (INIS)

Mohamadou, Youssoufa; Oh, Tong In; Wi, Hun; Sohal, Harsh; Farooq, Adnan; Woo, Eung Je; McEwan, Alistair Lee

2012-01-01

Current sources are widely used in bio-impedance spectroscopy (BIS) measurement systems to maximize current injection for increased signal to noise while keeping within medical safety specifications. High-performance current sources based on the Howland current pump with optimized impedance converters are able to minimize stray capacitance of the cables and setup. This approach is limited at high frequencies primarily due to the deteriorated output impedance of the constant current source when situated in a real measurement system. For this reason, voltage sources have been suggested, but they require a current sensing resistor, and the SNR reduces at low impedance loads due to the lower current required to maintain constant voltage. In this paper, we compare the performance of a current source-based BIS and a voltage source-based BIS, which use common components. The current source BIS is based on a Howland current pump and generalized impedance converters to maintain a high output impedance of more than 1 MΩ at 2 MHz. The voltage source BIS is based on voltage division between an internal current sensing resistor (R s ) and an external sample. To maintain high SNR, R s is varied so that the source voltage is divided more or less equally. In order to calibrate the systems, we measured the transfer function of the BIS systems with several known resistor and capacitor loads. From this we may estimate the resistance and capacitance of biological tissues using the least-squares method to minimize error between the measured transimpedance excluding the system transfer function and that from an impedance model. When tested on realistic loads including discrete resistors and capacitors, and saline and agar phantoms, the voltage source-based BIS system had a wider bandwidth of 10 Hz to 2.2 MHz with less than 1% deviation from the expected spectra compared to more than 10% with the current source. The voltage source also showed an SNR of at least 60 dB up to 2.2 MHz