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.

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

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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.

Science.gov (United States)

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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

OpenAIRE

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

IMPORTANCENitrogen source is

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

Directory of Open Access Journals (Sweden)

Sidnei Osmar Jadoski

2012-12-01

Full Text Available The cultivar Ágata is currently the most widely cultivated in areas of potato production in Brazil, however, are necessaries basic information about its characteristics, especially on the development of the canopy. The work was developed in experimental area of the Unit of Research in Potato Culture and Microclimate for Agriculture, in the department of Agronomy of the UniversidadeEstadual do Centro Oeste (Unicentro, in Guarapuava (PR. The aim was to evaluate the efficiency of the adjustment of different mathematic models to determine the leaf area of potato plants of the cultivar Ágata. The evaluations were performed considering the dimensions of a 100 seeds of several sizes which were randomly collected in the phase of maximum vegetative development of plants. The data obtained were submitted to analysis of regression, being tested six different mathematic models: linear, quadratic, cubic functions and the exponential models from growth, Gauss and Lorentz, using the length and the height of leaves as independent variable to the adjustment in function of the real leaf area measured in laboratory. The variable length and the product of length x width of the leaf were those who presented the best results of adjustments to the models tested. With more emphasis to the length, for which all the models testes present statistical significance. It was concluded that the leaf length is the most appropriated parameter to be used in evaluation of the leaf area of potato plants cultivar Ágata, being the exponential function of growth and Lorentz the less recommended since its lowest adjustment coefficient. A cultivar Ágata é atualmente a mais cultivada nas lavouras de produção de batata no Brasil, contudo, ainda são necessárias informações básicas sobre suas características, especialmente sobre o desenvolvimento do dossel vegetativo.O trabalho foi desenvolvido em área experimental da Unidade de Pesquisa em Bataticultura e Microclima para a

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.

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

OpenAIRE

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...

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

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.

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

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

Directory of Open Access Journals (Sweden)

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

Directory of Open Access Journals (Sweden)

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

Directory of Open Access Journals (Sweden)

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.

Research cooperation project in fiscal 2001. Research cooperation on putting into practical use of district complying type photovoltaic power generation system; 2001 nendo kenkyu kyoryoku jigyo. Chiiki tekigo gata taiyoko hatsuden system tou no jitsuyoka ni kansuru kenkyu kyoryoku

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-03-01

Research cooperation has been performed with an intention of establishing technologies to develop a design program for photovoltaic power generation systems suitable for the diverse natural and social conditions in China, the performance inspections and quality enhancement thereon. This paper summarizes the achievements in fiscal 2001. For installing the photovoltaic power generation system, procurement, transportation and installation were carried out in Gansu Province for a 8.4 kW integrated system and in Qinghai Province for 10 kW and 12 kW integrated systems. Visits were made to the sites to confirm the operating conditions, and maintenance and management conditions of the systems having been installed to date. With regard to performance evaluation devices of the cells and modules, some pieces of the equipment were repaired and re-adjusted, and training for using them was executed. Eight persons have visited Japan from China and participated in the training in Japan for utilization and operation of the photovoltaic power generation systems for the persons involved in the system operation. In addition, in order to determine the future information exchange directions, workshops were held with PV experts and manufacturers participating from Japan to exchange items of information. (NEDO)

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.

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

2011-01-01

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.

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 ...

Achievement report (2/2) on R and D in fiscal 1999 on environment adaptive next-generation supersonic propulsion system. R and D of environment adaptive next-generation supersonic propulsion engine; 1999 nendo seika hokokusho. Kankyo tekigo gata jisedai choonsoku suishin system no kenkyu kaihatsu - Kankyo tekigo gata jisedai choonsokuki you enjin kaihatsu (2/2)

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-12-01

With an objective to develop an environment adaptive next-generation supersonic propulsion system, research and development have been performed on noise reducing technologies, NOx exhaust reducing technologies, CO2 exhaust reducing technologies, and environment adaptive engine system technologies. This paper summarizes the achievements in fiscal 1999. In developing the CO2 exhaust reducing technologies, discussions were given on the following items as the researches on a technology to apply three-dimensional fiber-reinforced materials to large structures: application of metal-based composite materials (MMC) to the fan rotor; application of CMC, TiAl materials to turbine structural materials; TiAl shroud support, CMC shroud, high load turbine cascades supported by the composite materials, and application of the CMC, TiAl materials to the gas exhaust nozzle. In developing the environment adaptive engine system technologies, flows were established to judge the achievement of the project target of noise reduction, NOx exhaust reduction and CO2 exhaust suppression. Furthermore, in the demonstration and research of the engine integration, the setting was conducted on the engine test schedule, and so was the primary setting for criteria on parts to be assembled into the engine. (NEDO)

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

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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.

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.

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.

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.

Directory of Open Access Journals (Sweden)

Margarita Marroquin-Guzman

2015-04-01

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

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

Science.gov (United States)

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.

Science.gov (United States)

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

Surface modification of biocompatible materials. Seitai tekigo zairyo no hyomen kaishitsu

Energy Technology Data Exchange (ETDEWEB)

Tateishi, T [Mechanical Engineering Lab., Tsukuba, Ibaraki (Japan)

1993-07-05

The necessary conditions for biocompatible materials such as human bone, joints and teeth are mainly classified into biological condition and mechanical conditions. The former condition is consisted of chemical stability without causing poisoning or allergy, compatibility of good biological tissue, no carcinogenesis and not antigenicity, no decomposition and degradation inside human body, not causing adsorbate or precipitate. As for the latter, appropriate static strength, elastic modulus and hardness together with the characteristics like fatigue resistance, wear resistance and lubricating properties are given. As for other conditions for biomaterials, characteristics as a functional material, workability, adhesion and so forth are important. When surface nitrification of sintered Ti, forging Ti, sintered Ti-6Al-4V and forging Ti-6Al-4V is carried out, the solubility is decreased significantly by surface nitrification. The powder generated by the wear of nitriding Ti-6Al-4V with ultra high molecular weight polyethylene (UHMWPE) is less cell poisoning than the powder caused by the wear of the other alumina, stabilized zirconia, hydroxy apatite with UHMWPE. 16 refs., 2 figs., 1 tab.

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

Science.gov (United States)

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.

Directory of Open Access Journals (Sweden)

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

Directory of Open Access Journals (Sweden)

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.

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...

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

Directory of Open Access Journals (Sweden)

Rebecca A Helmer

Full Text Available HLTF/Hltf regulates transcription, remodels chromatin, and coordinates DNA damage repair. Hltf is expressed in mouse brain and heart during embryonic and postnatal development. Silencing Hltf is semilethal. Seventy-four percent of congenic C57BL/6J Hltf knockout mice died, 75% within 12-24 hours of birth. Previous studies in neonatal (6-8 hour postpartum brain revealed silencing Hltf disrupted cell cycle progression, and attenuated DNA damage repair. An RNA-Seq snapshot of neonatal heart transcriptome showed 1,536 of 20,000 total transcripts were altered (p < 0.05 - 10 up- and 1,526 downregulated. Pathway enrichment analysis with MetaCore™ showed Hltf's regulation of the G2/M transition (p=9.726E(-15 of the cell cycle in heart is nearly identical to its role in brain. In addition, Brca1 and 12 members of the Brca1 associated genome surveillance complex are also downregulated. Activation of caspase 3 coincides with transcriptional repression of Bcl-2. Hltf loss caused downregulation of Wt1/Gata4/Hif-1a signaling cascades as well as Myh7b/miR499 transcription. Hltf-specific binding to promoters and/or regulatory regions of these genes was authenticated by ChIP-PCR. Hif-1a targets for prolyl (P4ha1, P4ha2 and lysyl (Plod2 collagen hydroxylation, PPIase enzymes (Ppid, Ppif, Ppil3 for collagen trimerization, and lysyl oxidase (Loxl2 for collagen-elastin crosslinking were downregulated. However, transcription of genes for collagens, fibronectin, Mmps and their inhibitors (Timps was unaffected. The collective downregulation of genes whose protein products control collagen biogenesis caused disorganization of the interstitial and perivascular myocardial collagen fibrillar network as viewed with picrosirius red-staining, and authenticated with spectral imaging. Wavy collagen bundles in control hearts contrasted with collagen fibers that were thin, short and disorganized in Hltf null hearts. Collagen bundles in Hltf null hearts were tangled and

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.

Science.gov (United States)

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.

[The planned home care transfer by a local medical support hospital and the introduction to home intravenous hyper alimentation--the making of a home care patient's instruction plan document].

Science.gov (United States)

Shinobu, Akiko; Ohtsu, Yoko

2004-12-01

It is important to offer continuous medical service without interrupting everyone's various job functions at the Tama Numbu-Chiiki Hospitals in order to secure the quality and safety of home medical care to patients and their families. From 1998 up to the present, home intravenous hyper alimentation (home IVH) has been introduced by individually exchanging information that was based on items such as clinical case, doctor and caregiver in charge of the day, and introductory information. Five years have passed since we started an introduction of home IVH, and it appears that the medical cooperation of home IVH between the Minami-tama medical region and its neighboring area has been established. Then, we arranged an examination of the past 2 years based on the 57 patients who elected to choose home IVH instruction. Consequently, we created "home IVH introduction plan document" in standardizing a flow from home IVH introduction to post-hospital intervention. Since November of 2003, the plan document has been utilized and carried out to 5 patients by the end of February in 2004. This home IVH introduction plan document was able to clarify the role of medical person in connection with the patient. Therefore, we could not only share the information, but also could transfer medical care smoothly from the hospital to the patient's home.

Needs/seeds research committee of welfare apparatus; Fukushi kiki needs seeds tekigo chosa kenkyu

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

As to the development of welfare apparatus, a study was made on the present status of the periphery environment, problems, measures and policies. As subjects in production, the following were pointed out: small scale of the market, lots of brands/small quantity of production, various corporate sizes in the industry, no competition among countries, modular structuring, etc. As to the standardization, the necessity was asserted for the following: rationalization of production/consumption, security of product quality, provision of standards for accurate judgement of the purchase, simplification of inspection under the Pharmaceutical Law, benefit systems. In relation to evaluation/technical guidance, details of the evaluation, persons involved in the evaluation, and the evaluation form were arranged including not only the evaluation of individual tools, but grasp of the needs, selection of themes, and technical guidance under the development. The fundamental development of the welfare apparatus is being conducted in universities, national research institutes, etc., and necessities were pointed out for a study of trial use of the apparatus as a step next to the prototype making, and a system to support makers for the period from after the development up to the commercialization. 5 refs., 8 figs., 26 tabs.

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

Directory of Open Access Journals (Sweden)

Lucas Alécio Gomes

2013-05-01

Full Text Available Stroke is uncommon in animals compared with humans because of the lower incidence of atherosclerosis and primary hypertension. However with advanced imaging, vascular disease is being recognized with increasing frequency in veterinary medicine. Cerebrovascular disease can be subdivided into infarction and hemorrhage, although the two categories overlap in the case of hemorrhagic infarcts. The aim of thisarticle is to report the neurological manifestations associated with stroke (infarctions in at two-month old, domestic shorthair cat. Neurological evaluation revealed head tilt, tetraparesis, proprioceptive deficits in all four limbs, and decreased pupillary light reflex. Further, manifestations of neurological dysfunctions were acute and progressive. At the necropsy, grossly there were hemorrhage and necrosis at mid-brain and cerebellum. Histopathology confirmed liquefactive necrosis at the mid-brain and cerebellum. The neurological manifestations associated with the pathological findings are suggestive of an anoxic infarction probably due to vascular occlusion. Em animais é baixa a incidência de arterosclerose e hipertensão primária. Devido a tal característica, infarto cerebral é incomum nos mesmos. Entretanto, com o avanço das modalidades de imagem, doença vascular está sendo reconhecida com maio frequência na medicina veterinária. Doença cerebrovascular pode ser subdividida em infarto e hemorragia, embora as duas categorias se interponham no caso de infartos hemorrágicos. Assim sendo, o objetivo deste artigo é descrever as manifestações neurológicas associadas a acidente vascular (infartos em uma gata de dois meses de idade, sem raça definida e domiciliada. Na avaliação neurológica observou-se inclinação de cabeça, tetraparesia, déficits proprioceptivos nos quatro membros e diminuição do reflexo pupilar a luz. Além disso, os problemas neurológicos foram agudos e progressivos. Na necropsia macroscopicamente

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.

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.

Investigational research on welfare equipment needs/seeds adaptation; Fukushi kiki needs seeds tekigo chosa kenkyu

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-03-01

At the advent of the aging society, investigated are images of welfare equipment to be developed. In the range where the use of welfare equipment is to be studied, the following are included: self care, excretion, transfer, and support of work other than care, as assistance to daily life; exercise function, communication function, and environment arrangement, as assistance to social participation. Of the images of the welfare equipment classified by the overall evaluation, the following are cited as what supports daily life: a lift usable even in the existing houses, a bump remover by which bumps in the house are removed without making large repairs, a urine collector for females, a training device to prevent urinary incontinence, reduction in the bed-fast elderly, a device to prevent bedsore, a system for safely watching demented old people, a system in which clothes are automatically washed, dried, and hanged on a hanger, etc. What supports social participation are a system for sports experience by virtual reality, sound user interface, etc. For the aged to be healthy physically and mentally, it is essential to be taken good care of and create things to live for by participating the society. For this, it is necessary that the government establish the public policies and that a people be conscious of welfare. 9 figs., 33 tabs.

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

Directory of Open Access Journals (Sweden)

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.

A Study on consensus development through stake holder engagement for the use of nuclear energy in Japan

International Nuclear Information System (INIS)

Aoyama, Yoshiko; Sawada, Tetsuo; Fujii, Yasuhiko

2008-01-01

In order to alleviate the distrust surrounding the use of nuclear energy and operation of nuclear facilities, as well as to foster trust and find better ways to live in harmony with society, it is essential for the state and electric power utilities not to provide one-sided information, but to formulate adequate bilateral communication and dialogue with stake holders. In this study, we conducted a case study focused on four stake holder meetings with a view to ensuring safety in the use of nuclear energy and operation of nuclear facilities in Japan; the 'Community Meeting for Securing the Transparency of Kashiwazaki-Kariwa Nuclear Power Station (Chiiki-no-kai)'; the 'Monitoring and Evaluation Conference on Environmental Radiation', established by communities where nuclear facilities are installed; the 'Round-Table Conference on Nuclear Power Policy' and the 'Conference for Public Participation and Decision Making for Nuclear Energy Policy' organized by Japan Atomic Energy Commission. As a consequence, it has been observed that in each case varying opinions were summarized through stake holder meetings, but the fact that no system exists to reflect these opinions in design of the nuclear energy policy has emerged as a controversial point. This study suggests future efforts in regard to the requirements in Japan for stake holder meetings that are necessary for fostering trust and mutual understanding among stake holders including the state and local government, electric power utilities and local residents. (author)

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.

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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.

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

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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.

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

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

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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.

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.

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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

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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.

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 ...

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

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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.

Hiperplasia fibroepitelial mamária em felinos: cinco casos

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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.

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...

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.

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

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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.

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

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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.

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)

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

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

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

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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.

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

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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...

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

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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.

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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.

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

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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

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

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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...

Fiscal 1998 regional consortium R and D project (Regional consortium field). Report on R and D of production technology of hybrid-type biocompatible hard tissue replacing materials (1st fiscal year); 1998 nendo chiiki konsoshiamu kenkyu kaihatsu jigyo. Chiiki konsoshiamu bun'ya (hybrid gata seitai yugo kinosei kososhiki daitai sozai seizo gijutsu no kenkyu kaihatsu)

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

This project aims at development of high-strength high- biocompatible {beta}-type Ti alloy with lower modulli of elasticity composed of non-toxic elements, phosphate calcium ceramics for improving the biocompatibility and coating technology, and establishment of production technology of hybrid-type biocompatible hard tissue replacing materials. In fiscal 1998, the project promoted the following: Design of high-biocompatible {beta}-type Ti alloy materials, development of thermomechanical treatment for improving dynamic characteristics of such alloy, survey on practical melting and casting technologies and dental precision casting process, evaluation of the biocompatibility of the alloy by cytotoxicity, selection of tools for precision machining and surface finishing, control of contents, orientation and precipitation of biocompatible crystals such as {beta}- Ca(PO{sub 3}){sub 2} fibers for further improvement of the biocompatibility. This paper also outlines the survey results on the market needs, market size and market share for the feasibility of these materials. (NEDO)

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.

Granulocyte colony-stimulating factor decreases the Th1/Th2 ratio in peripheral blood mononuclear cells from patients with chronic immune thrombocytopenic purpura in vitro.

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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.

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.

A method to quantify mechanobiologic forces during zebrafish cardiac development using 4-D light sheet imaging and computational modeling.

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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

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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.

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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.

Characterization of the promoter of human CRTh2, a prostaglandin D{sub 2} receptor

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Quapp, Russell; Madsen, Norman [Department of Medicine, Division of Pulmonary Medicine, Pulmonary Research Group, 574B Heritage Medical Research Centre, University of Alberta, Edmonton, AB, T6G 2S2 (Canada); Cameron, Lisa [Department of Medicine, Division of Pulmonary Medicine, Pulmonary Research Group, 574B Heritage Medical Research Centre, University of Alberta, Edmonton, AB, T6G 2S2 (Canada)

2007-11-30

Chemoattractant-receptor homologous molecule expressed on Th2 cells (CRTh2) is a receptor for prostaglandin (PG)D{sub 2}, a lipid mediator involved in allergic inflammation. CRTh2 is expressed by Th2 cells, eosinophils and basophils and PDG{sub 2}-CRTh2 signaling induces calcium mobilization, cell migration and expression of the Th2 cytokines IL-4, IL-5, and IL-13. Despite the role of CRTh2 in allergic inflammation, transcriptional regulation of this gene has not been studied. Here, we demonstrated that a reporter construct of the CRTh2 promoter was induced following T cell stimulation. This activity could be further enhanced by over-expression of GATA-3, but not NFAT2 or STAT6. Electromobility shift assay demonstrated GATA-3 binding to a probe from the CRTh2 promoter. This study provides the first detailed analysis of transcriptional regulation of the human CRTh2 promoter. These findings may help identify strategies to attenuate expression of this gene and influence the maintenance and proliferation of Th2 cells in allergic inflammation.

Electrical conductivity of the nutrient solution and plant density in aeroponic production of seed potato under tropical conditions (winter/spring

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Alex Humberto Calori

Full Text Available ABSTRACT The recent introduction in Brazil of production of quality seed potatoes in hydroponic systems, such as aeroponics, demands studies on the nutritional and crop management. Thus, this study evaluated the influence of electrical conductivity of the nutrient solution and plant density on the seed potato minitubers production in aeroponics system. The Agata and Asterix cultivars were produced in a greenhouse under tropical conditions (winter/spring. The experimental design was a randomized block in a split-split plot design. The plot consisted of 4 electrical conductivities of the nutrient solution (1.0; 2.0; 3.0; and 4.0 dS∙m−1; the subplot, of 4 plant densities (25; 44; 66; and 100 plants∙m−2; and the subsubplot, of the 2 potato cultivars (Ágata and Asterix, totaling 4 blocks. The 2.2 and 2.1 dS∙m−1 electrical conductivities yielded the highest productivity of seed potato minitubers, for Ágata and Asterix cultivars, respectively, regardless of plant density. For both cultivars, the highest yield was observed for the 100 plants∙m−2 density.

Dietary Intervention with β-Lactoglobulin-Derived Peptides and a Specific Mixture of Fructo-Oligosaccharides and Bifidobacterium breve M-16V Facilitates the Prevention of Whey-Induced Allergy in Mice by Supporting a Tolerance-Prone Immune Environment

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Atanaska I. Kostadinova

2017-10-01

Full Text Available Cow’s milk allergy (CMA prevails in infants and brings increased risk of developing other allergic diseases. Oral administration of specific β-lactoglobulin (BLG-derived peptides (PepMix and a specific blend of short- and long-chain fructo-oligosaccharides and Bifidobacterium breve M-16V (FF/Bb was found to partially prevent CMA development in mice. In this study, we aimed to expand the knowledge on the preventive potential and the underlying mechanisms of this approach. Three-week-old female C3H/HeOuJ mice were orally exposed to PepMix±FF/Bb prior to a 5-week oral sensitization with whole whey and cholera toxin as an adjuvant. The acute allergic skin response was determined after an intradermal challenge with whole whey protein. Following an oral challenge with whey, regulatory T cells (Tregs in the small intestine lamina propria (SI-LP and mRNA expression of immune markers in the Peyer’s patches (PP were investigated. The early impact of PepMix and FF/Bb interventions on the immune system during the oral tolerance (OT induction phase was investigated after the last OT administration. Pre-exposing mice to PepMix+FF/Bb partially prevented the acute allergic skin response compared to PBS and increased Tregs and activated T cells in the SI-LP compared to sham-sensitized mice. It also increased the mRNA expression of Tbet over GATA3 in the PP of whey-sensitized mice. Directly upon the 6-day OT phase, FF/Bb intervention enhanced cecal content levels of propionic and butyric acid in PepMix-fed mice and the former was positively correlated with Foxp3+ cell numbers in the colon. In the PP of PepMix+FF/Bb-exposed mice, IL-22 mRNA expression increased and IL-10 followed the same tendency, while the Foxp3 expression was increased over GATA3 and RorγT. In the colon, the Tbet mRNA expression increased over GATA3, while IL-22 decreased. In addition, the Foxp3+/GATA3+ and regulatory/effector T cell ratios in the mesenteric lymph nodes and the CD11b

Peer Review

OpenAIRE

Rosdiana Natzir, Rosdiana Natzir

2017-01-01

Judul: Correlation Between GATA-3, Ki67 and p53 Expressions to Histopathology Grading of breast Caqncer in Makassar, Indonesia Jumlah Penulis: 9 Orang Status Penulis: Penulis Kedua Jurnal: Cancer Research Journal ISSN: 2330-8192 Vol. 4, No. 3, tahun 2016 Penerbit: Science Publishing Group DOI:10.11648/j.crj.20160403.11 Alamat Web: http ://www. sciencepublishinggroup .com/j/crj

Effect of Lactobacillus salivarius on Th1/Th2 cytokines and the number of spleen CD4⁺ CD25⁺ Foxp3⁺ Treg in asthma Balb/c mouse.

Science.gov (United States)

Yun, Xiang; Shang, Yunxiao; Li, Miao

2015-01-01

Bronchial asthma is a chronic airway inflammatory disease that involves T lymphocytes. In order to explore the effect of Lactobacillus salivarius on Th1/Th2 cytokines and the number of spleen CD4(+) CD25(+) Foxp3(+) Treg in asthma Balb/c mouse, we constructed acute asthma model with ovalbumin to observe the mouse behavior change in Balb/c mice. The expression of GATA-3 mRNA and T-bet mRNA was measured by real-time PCR. The proportion of CD4(+) CD25(+) Foxp3(+) Treg/CD4(+) was determined by flow cytometry. The results demonstrated that oral gavage with Lactobacillus salivarius before sensitization could alleviate the clinical symptoms, airway hyper-reactivity and airway inflammation in asthma mouse to some extent; Lactobacillus salivarius may improve the imbalance of Th1/Th2 in asthma mouse through increasing the expression of T-bet mRNA at the transcriptional level and inhibiting the expression of GATA-3 mRNA simultaneously. CD4(+) CD25(+) Foxp3(+) Treg cells may be involved in the pathogenesis of bronchial asthma, and may be the upstream regulatory mechanism of the improvement of Th1/Th2 imbalance by Lactobacillus salivarius.

Inhibitory function of NKT cells during early induction phase of nickel allergy.

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Okuno, Hironori; Satoh, Masashi; Takeuchi, Emiko; Eshima, Koji; Terashima, Masazumi; Komotori, Jun; Habu, Sonoko; Tamauchi, Hidekazu; Iwabuchi, Kazuya

2016-07-01

Until now, metal allergies have been regarded as a Th1-type immune response.　However, because the contribution of a Th2-type immune response has been suggested by clinical findings, we previously examined the Th2-type immune response during the development of metal allergies using a GATA-3 transgenic (GATA-3 Tg) mouse model. As a result, a Th2-type immunization reaction was suggested to be involved in the early phase of metal allergies. Recently, the involvement of NKT cells in metal allergies has been suggested. We examined this possibility using the activation of NKT cells and an NKT cell-deficient mouse model to determine the contribution of NKT cells to nickel allergy in the present study. In NKT cell-deficient mice, ear swelling was remarkably increased, compared with that in control mice. Also, in mice that had been treated with α-galactosylceramide (α-GalCer) to activate NKT cells, the ear swelling response was remarkably inhibited, compared with that in untreated mice. These facts show that NKT cells are involved in the inhibition of nickel allergy-induced ear swelling responses. Copyright © 2016 Elsevier GmbH. All rights reserved.

Still Heart Encodes a Structural HMT, SMYD1b, with Chaperone-Like Function during Fast Muscle Sarcomere Assembly.

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Kendal Prill

Full Text Available The vertebrate sarcomere is a complex and highly organized contractile structure whose assembly and function requires the coordination of hundreds of proteins. Proteins require proper folding and incorporation into the sarcomere by assembly factors, and they must also be maintained and replaced due to the constant physical stress of muscle contraction. Zebrafish mutants affecting muscle assembly and maintenance have proven to be an ideal tool for identification and analysis of factors necessary for these processes. The still heart mutant was identified due to motility defects and a nonfunctional heart. The cognate gene for the mutant was shown to be smyd1b and the still heart mutation results in an early nonsense codon. SMYD1 mutants show a lack of heart looping and chamber definition due to a lack of expression of heart morphogenesis factors gata4, gata5 and hand2. On a cellular level, fast muscle fibers in homozygous mutants do not form mature sarcomeres due to the lack of fast muscle myosin incorporation by SMYD1b when sarcomeres are first being assembled (19hpf, supporting SMYD1b as an assembly protein during sarcomere formation.

Systematic Analysis of Splice-Site-Creating Mutations in Cancer.

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Jayasinghe, Reyka G; Cao, Song; Gao, Qingsong; Wendl, Michael C; Vo, Nam Sy; Reynolds, Sheila M; Zhao, Yanyan; Climente-González, Héctor; Chai, Shengjie; Wang, Fang; Varghese, Rajees; Huang, Mo; Liang, Wen-Wei; Wyczalkowski, Matthew A; Sengupta, Sohini; Li, Zhi; Payne, Samuel H; Fenyö, David; Miner, Jeffrey H; Walter, Matthew J; Vincent, Benjamin; Eyras, Eduardo; Chen, Ken; Shmulevich, Ilya; Chen, Feng; Ding, Li

2018-04-03

For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

EZH2: a pivotal regulator in controlling cell differentiation.

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Chen, Ya-Huey; Hung, Mien-Chie; Li, Long-Yuan

2012-01-01

Epigenetic regulation plays an important role in stem cell self-renewal, maintenance and lineage differentiation. The epigenetic profiles of stem cells are related to their transcriptional signature. Enhancer of Zeste homlog 2 (EZH2), a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), has been shown to be a key regulator in controlling cellular differentiation. EZH2 is a histone methyltransferase that not only methylates histone H3 on Lys 27 (H3K27me3) but also interacts with and recruits DNA methyltransferases to methylate CpG at certain EZH2 target genes to establish firm repressive chromatin structures, contributing to tumor progression and the regulation of development and lineage commitment both in embryonic stem cells (ESCs) and adult stem cells. In addition to its well-recognized epigenetic gene silencing function, EZH2 also directly methylates nonhistone targets such as the cardiac transcription factor, GATA4, resulting in attenuated GATA4 transcriptional activity and gene repression. This review addresses recent progress toward the understanding of the biological functions and regulatory mechanisms of EZH2 and its targets as well as their roles in stem cell maintenance and cell differentiation.

Bentonite-like material sealing to high-level radioactive wastes storage

International Nuclear Information System (INIS)

Linares, J.; Linares Gonzalez, J.; Huertas Garcia, F.; Reyes Camacho.

1993-01-01

Among the most used materials for sealing of radioactive waste storage, bentonite shows a high number of advantages because of its plasticity, thermal and hydraulic conductivity, etc. The paper makes a review on different Spanish deposits of bentonite and their stability. Most of studies are focussed on the volcanic region at Cabo de Gata (Almeria). That area offers the most productive hydrothermal bentonite deposits in Spain

A Counterregulatory Mechanism Impacting Androgen Suppression Therapy

Science.gov (United States)

2016-08-01

Present position: Student, Hochschule Mannheim, Mannheim, Germany 2015 - 2015 Verena Martinez Rodriguez, B.Sc., Rotation Student Study area: Hedgehog ...and Childhood, 8th edition Philadelphia: Elsevier Mosby; 2014:1076-1102. 14. Bornstein SR, Wilson DB. Anatomy of the adrenal cortex. In: Martini L...supporting a patho- genic association between aberrant hedgehog signaling and the- comaefibroma development. Abundant expression of GATA4 and its cofactor

Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses.

Science.gov (United States)

De Grove, Katrien C; Provoost, Sharen; Hendriks, Rudi W; McKenzie, Andrew N J; Seys, Leen J M; Kumar, Smitha; Maes, Tania; Brusselle, Guy G; Joos, Guy F

2017-01-01

Although the prominent role of T H 2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can also contribute to orchestration of allergic responses. Several experimental and epidemiologic studies have provided evidence that allergen-induced airway responses can be further enhanced on exposure to environmental pollutants, such as diesel exhaust particles (DEPs). However, the components and pathways responsible remain incompletely known. We sought to investigate the relative contribution of ILC2 and adaptive T H 2 cell responses in a murine model of DEP-enhanced allergic airway inflammation. Wild-type, Gata-3 +/nlslacZ (Gata-3-haploinsufficient), RAR-related orphan receptor α (RORα) fl/fl IL7R Cre (ILC2-deficient), and recombination-activating gene (Rag) 2 -/- mice were challenged with saline, DEPs, or house dust mite (HDM) or DEP+HDM. Airway hyperresponsiveness, as well as inflammation, and intracellular cytokine expression in ILC2s and T H 2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed. Concomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and T H 2 cells, type 2 cytokine production, and airway hyperresponsiveness compared with sole DEPs or HDM. Reduced Gata-3 expression decreased the number of functional ILC2s and T H 2 cells in DEP+HDM-exposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. Interestingly, although the DEP-enhanced allergic inflammation was marginally reduced in ILC2-deficient mice that received combined DEP+HDM, it was abolished in DEP+HDM-exposed Rag2 -/- mice. These data indicate that dysregulation of ILC2s and T H 2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown on concomitant DEP+HDM exposure. Copyright © 2016 American

Evaluation value of intestinal flora detection for intestinal mucosal inflammation and immune response in patients with ulcerative colitis

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Yan Zou

2017-09-01

Full Text Available Objective: To study the evaluation value of intestinal flora detection for intestinal mucosal inflammatory response and immune response in patients with ulcerative colitis. Methods: The patients who were diagnosed with ulcerative colitis in Zigong Fifth People’s Hospital between March 2015 and February 2017 were selected as the UC group, and those who were diagnosed with colonic polyps were selected as the control group. Fresh excreta were collected to detect the number of intestinal flora, and the diseased intestinal mucosa tissue was collected to detect the expression of inflammatory response molecules and immune cell transcription factors. Results: enterococcus contents in intestinal tract and TLR4, NF-kB, TNF-α, HMGB-1, T-bet and RORC mRNA expression levels in intestinal mucosa of UC group were significantly higher than those of control group while bifidobacteria contents in intestinal tract and SOCS2, SOCS3, Foxp3 and GATA-3 mRNA expression levels were significantly lower than those of control group; TLR4, NF-kB, TNF-α, HMGB-1, T-bet and RORC mRNA expression levels in intestinal mucosa of UC patients with grade II and grade III flora disturbance were significantly higher than those of UC patients with normal flora and grade I flora disturbance while SOCS2, SOCS3, Foxp3 and GATA-3 mRNA expression levels were significantly lower than those of UC patients with normal flora and grade I flora disturbance; TLR4, NF-kB, TNF-α, HMGB-1, T-bet and RORC mRNA expression levels in intestinal mucosa of UC patients with grade III flora disturbance were significantly higher than those of UC patients with grade II flora disturbance while SOCS2, SOCS3, Foxp3 and GATA-3 mRNA expression levels were significantly lower than those of UC patients with grade II flora disturbance. Conclusion: The intestinal flora disturbance in patients with ulcerative colitis can result in inflammatory response activation and immune response disorder.

Identification of microRNAs regulating the developmental pathways of bone marrow derived mast cells.

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Yang Xiang

Full Text Available MicroRNAs (miRNAs play important roles in leukocyte differentiation, although those utilised for specific programs and key functions remain incompletely characterised. As a global approach to gain insights into the potential regulatory role of miRNA in mast cell differentiation we characterised expression in BM cultures from the initiation of differentiation. In cultures enriched in differentiating mast cells we characterised miRNA expression and identified miRNA targeting the mRNA of putative factors involved in differentiation pathways and cellular identity. Detailed pathway analysis identified a unique miRNA network that is intimately linked to the mast cell differentiation program.We identified 86 unique miRNAs with expression patterns that were up- or down- regulated at 5-fold or more during bone marrow derived mast cells (BMMC development. By employing TargetScan and MeSH databases, we identified 524 transcripts involved in 30 canonical pathways as potentially regulated by these specific 86 miRNAs. Furthermore, by applying miRanda and IPA analyses, we predict that 7 specific miRNAs of this group are directly associated with the expression of c-Kit and FcεRIα and likewise, that 18 miRNAs promote expression of Mitf, GATA1 and c/EBPα three core transcription factors that direct mast cell differentiation. Furthermore, we have identified 11 miRNAs that may regulate the expression of STATs-3, -5a/b, GATA2 and GATA3 during differentiation, along with 13 miRNAs that target transcripts encoding Ndst2, mMCP4 and mMCP6 and thus may regulate biosynthesis of mast cell secretory mediators.This investigation characterises changes in miRNA expression in whole BM cultures during the differentiation of mast cells and predicts functional links between miRNAs and their target mRNAs for the regulation of development. This information provides an important resource for further investigations of the contributions of miRNAs to mast cell differentiation and

Elevated Immune Gene Expression Is Associated with Poor Reproductive Success of Urban Blue Tits

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Pablo Capilla-Lasheras

2017-06-01

Full Text Available Urban and forest habitats differ in many aspects that can lead to modifications of the immune system of wild animals. Altered parasite communities, pollution, and artificial light at night in cities have been associated with exacerbated inflammatory responses, with possibly negative fitness consequences, but few data are available from free-living animals. Here, we investigate how urbanization affects major immune pathways and experimentally test potentially contributing factors in blue tits (Cyanistes caeruleus from an urban and forest site. We first compared breeding adults by quantifying the mRNA transcript levels of proteins associated with anti-bacterial, anti-malarial (TLR4, LY86 and anti-helminthic (Type 2 transcription factor GATA3 immune responses. Adult urban and forest blue tits differed in gene expression, with significantly increased TLR4 and GATA3, but not LY86, in the city. We then experimentally tested whether these differences were environmentally induced by cross-fostering eggs between the sites and measuring mRNA transcripts in nestlings. The populations differed in reduced reproductive success, with a lower fledging success and lower fledgling weight recorded at the urban site. This mirrors the findings of our twin study reporting that the urban site was severely resource limited when compared to the forest. Because of low urban survival, robust gene expression data were only obtained from nestlings reared in the forest. Transcript levels in these nestlings showed no (TLR4, LY86, or weak (GATA3, differences according to their origin from forest or city nests, suggesting little genetic or maternal contribution to nestling immune transcript levels. Lastly, to investigate differences in parasite pressure between urban and forest sites, we measured the prevalence of malaria in adult and nestling blood. Prevalence was invariably high across environments and not associated with the transcript levels of the studied immune genes. Our

Augmentation of the antibody response of Atlantic salmon by oral administration of alginate-encapsulated IPNV antigens.

Directory of Open Access Journals (Sweden)

Lihan Chen

Full Text Available The objective of the present study was to assess the effect of alginate-encapsulated infectious pancreatic necrosis virus antigens in inducing the immune response of Atlantic salmon as booster vaccines. One year after intraperitoneal injection with an oil-adjuvanted vaccine, post-smolts were orally boosted either by 1 alginate-encapsulated IPNV antigens (ENCAP; 2 soluble antigens (UNENCAP or 3 untreated feed (control. This was done twice, seven weeks apart. Sampling was done twice, firstly at 7 weeks post 1st oral boost and the 2nd, at 4 weeks after the 2nd oral boost. Samples included serum, head kidney, spleen and hindgut. Serum antibodies were analyzed by ELISA while tissues were used to assess the expression of IgM, IgT, CD4, GATA3, FOXP3, TGF-β and IL-10 genes by quantitative PCR. Compared to controls, fish fed with ENCAP had a significant increase (p<0.04 in serum antibodies following the 1st boost but not after the 2nd boost. This coincided with significant up-regulation of CD4 and GATA3 genes. In contrast, serum antibodies in the UNENCAP group decreased both after the 1st and 2nd oral boosts. This was associated with significant up-regulation of FOXP3, TGF-β and IL-10 genes. The expression of IgT was not induced in the hindgut after the 1st oral boost but was significantly up-regulated following the 2nd one. CD4 and GATA3 mRNA expressions exhibited a similar pattern to IgT in the hindgut. IgM mRNA expression on the other hand was not differentially regulated at any of the times examined. Our findings suggest that 1 Parenteral prime with oil-adjuvanted vaccines followed by oral boost with ENCAP results in augmentation of the systemic immune response; 2 Symmetrical prime and boost (mucosal with ENCAP results in augmentation of mucosal immune response and 3 Symmetrical priming and boosting (mucosal with soluble antigens results in the induction of systemic immune tolerance.

FOG-2 mediated recruitment of the NuRD complex regulates cardiomyocyte proliferation during heart development.

Science.gov (United States)

Garnatz, Audrey S; Gao, Zhiguang; Broman, Michael; Martens, Spencer; Earley, Judy U; Svensson, Eric C

2014-11-01

FOG-2 is a multi-zinc finger protein that binds the transcriptional activator GATA4 and modulates GATA4-mediated regulation of target genes during heart development. Our previous work has demonstrated that the Nucleosome Remodeling and Deacetylase (NuRD) complex physically interacts with FOG-2 and is necessary for FOG-2 mediated repression of GATA4 activity in vitro. However, the relevance of this interaction for FOG-2 function in vivo has remained unclear. In this report, we demonstrate the importance of FOG-2/NuRD interaction through the generation and characterization of mice homozygous for a mutation in FOG-2 that disrupts NuRD binding (FOG-2(R3K5A)). These mice exhibit a perinatal lethality and have multiple cardiac malformations, including ventricular and atrial septal defects and a thin ventricular myocardium. To investigate the etiology of the thin myocardium, we measured the rate of cardiomyocyte proliferation in wild-type and FOG-2(R3K5A) developing hearts. We found cardiomyocyte proliferation was reduced by 31±8% in FOG-2(R3K5A) mice. Gene expression analysis indicated that the cell cycle inhibitor Cdkn1a (p21(cip1)) is up-regulated 2.0±0.2-fold in FOG-2(R3K5A) hearts. In addition, we demonstrate that FOG-2 can directly repress the activity of the Cdkn1a gene promoter, suggesting a model by which FOG-2/NuRD promotes ventricular wall thickening by repression of this cell cycle inhibitor. Consistent with this notion, the genetic ablation of Cdkn1a in FOG-2(R3K5A) mice leads to an improvement in left ventricular function and a partial rescue of left ventricular wall thickness. Taken together, our results define a novel mechanism in which FOG-2/NuRD interaction is required for cardiomyocyte proliferation by directly down-regulating the cell cycle inhibitor Cdkn1a during heart development. Copyright © 2014 Elsevier Inc. All rights reserved.

Ginger Stimulates Hematopoiesis via Bmp Pathway in Zebrafish

Science.gov (United States)

Ferri-Lagneau, Karine F.; Moshal, Karni S.; Grimes, Matthew; Zahora, Braden; Lv, Lishuang; Sang, Shengmin; Leung, TinChung

2012-01-01

Background Anemia is a hematologic disorder with decreased number of erythrocytes. Erythropoiesis, the process by which red blood cells differentiate, are conserved in humans, mice and zebrafish. The only known agents available to treat pathological anemia are erythropoietin and its biologic derivatives. However, erythropoietin therapy elicits unwanted side-effects, high cost and intravenous or subcutaneous injection, warranting the development of a more cost effective and non-peptide alternative. Ginger (Zingiber officinale) has been widely used in traditional medicine; however, to date there is no scientific research documenting the potential of ginger to stimulate hematopoiesis. Methodology/Principal Findings Here, we utilized gata1:dsRed transgenic zebrafish embryos to investigate the effect of ginger extract on hematopoiesis in vivo and we identified its bioactive component, 10-gingerol. We confirmed that ginger and 10-gingerol promote the expression of gata1 in erythroid cells and increase the expression of hematopoietic progenitor markers cmyb and scl. We also demonstrated that ginger and 10-gingerol can promote the hematopoietic recovery from acute hemolytic anemia in zebrafish, by quantifying the number of circulating erythroid cells in the dorsal aorta using video microscopy. We found that ginger and 10-gingerol treatment during gastrulation results in an increase of bmp2b and bmp7a expression, and their downstream effectors, gata2 and eve1. At later stages ginger and 10-gingerol can induce bmp2b/7a, cmyb, scl and lmo2 expression in the caudal hematopoietic tissue area. We further confirmed that Bmp/Smad pathway mediates this hematopoiesis promoting effect of ginger by using the Bmp-activated Bmp type I receptor kinase inhibitors dorsomorphin, LND193189 and DMH1. Conclusions/Significance Our study provides a strong foundation to further evaluate the molecular mechanism of ginger and its bioactive components during hematopoiesis and to investigate their

The anti-allergic activity of Lactobacillus plantarum L67 and its application to yogurt.

Science.gov (United States)

Song, Sooyeon; Lee, Sei-Jung; Park, Dong-June; Oh, Sejong; Lim, Kye-Taek

2016-12-01

Recently, interest in the beneficial role of probiotics in the protection and management of allergic diseases caused by immune disorders has been increasing. This study investigated the inhibitory effect of Lactobacillus plantarum L67 on induced allergic inflammatory response in bisphenol A-treated rat basophilic leukemia 2H3 (RBL-2H3) cells and mouse splenocytes. We also evaluated the applicability of L. plantarum L67 as a yogurt starter culture. We measured the ability of Lactobacillus strains to induce the production of IL-12 and IFN- γ in cultured splenocytes by ELISA. Bisphenol A (50μM)-treated RBL-2H3 cells were cotreated with a glycoprotein (18kDa) isolated from L. plantarum L67 (5-100µg/mL) for 30min. We measured the expression of mitogen-activated protein kinase (ERK and p38), AP-1 (c-Fos and c-Jun), T-bet, and GATA-binding protein 3 (GATA-3) using Western blotting to examine the differentiation of T helper cells. Furthermore, we evaluated the gene expression of IL-1β, IL-6, and IL-10 using real-time quantitative PCR. Finally, we evaluated the applicability of L. plantarum L67 as a yogurt starter by measuring pH, enumeration of bacteria, and sensory scores. Our results showed that L67 protein inhibited the phosphorylation of ERK and p38 mitogen-activated protein kinase through the transcriptional activation of AP-1 in bisphenol A-treated RBL-2H3 cells. During differentiation of T helper cells, the expression of transcription factor GATA-3 was significantly suppressed by L67 protein (100µg/mL) treatment, whereas expression of transcription factor T-bet was increased. In addition, the L67 protein significantly attenuated the expression of T helper 2-linked cytokines IL-1β, IL-6, and IL-10. These results indicate that L. plantarum L67, made available as yogurt starters and dietary supplements, has the potential to prevent allergy-related immune disorders. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights

Regional new energy vision for Soryo Town, Hiroshima Prefecture; 2001 nendo Soryo cho chiiki shin energy vision. Chiiki shin energy vision sakutei tou jigyo

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-02-01

A regional new energy vision was formulated for the town for 'contributing to the solution of environmental problems' and 'contributing to the reenergization of the regional community through utilizing resources in the region.' The final energy consumption of the town is 103,315 times 10{sup 3} MJ, with the transportation sector accounting for a percentage higher than the nation-wide average. The town is characterized in that it has but a small number of manufacturers, offices, or stores. As for new energy, it was estimated that 9117 times 10{sup 3} MJ/year would be gained by methanol produced from cultured weed, 5696 times 10{sup 3} MJ/year by medium/small-scale hydropower generation, 5,233 times 10{sup 3} MJ/year by photovoltaic power generation, and so forth. New energy introduction projects were discussed, which included medium/small-scale hydropower generation at a counter dam; the introduction of photovoltaic power into principal public facilities, general households, and agricultural facilities; introduction of solar heat appliances into principal public facilities and general households; introduction of clean energy automobiles into the town office and general households; and the introduction of pellet-fired stoves into principal public facilities and general households. (NEDO)

Mild temperatures on bud breaking dormancy in peaches Temperaturas amenas na superação da dormência de pessegueiros

Directory of Open Access Journals (Sweden)

Geraldo Chavarria

2009-10-01

Full Text Available The search for low chill cultivars for peach production in areas with low chill accumulation (temperatures below 7.2°C has stimulated studies about the higher temperatures effects on low chill cultivars. The objective of this research was to evaluate the influence of mild temperatures on flowering and leafing of 'Turmalina' and 'Ágata' cultivars with low and medium low chilling requirements, respectively. Plants obtained by grafting flower twigs in the autumn, after the grafting, were submitted to chilling treatments (150, 250, 350, 500 and 672 hours at three temperature levels (5°C, 10°C and 15°C. After the end of the treatments, the plants had been taken to greenhouse (20°C±5°C and evaluated weekly. The results showed that satisfactory flower and leaf development occur even at temperatures as high as 15°C for a period of 150 hours, in 'Turmalina' peach. Temperatures of 10°C for a period equal or superior to 350 hours promote satisfactory leafing in 'Ágata' peach. Temperatures of 10°C and 15°C cause earlier development of flowers and leaves in both cultivars when compared to 5°C.A busca por cultivares pessegueiro com baixa necessidade em frio para regiões com pouco acúmulo de frio (temperaturas abaixo de 7,2°C tem estimulado estudos sobre o efeito de altas temperaturas sobre cultivares de baixa necessidade de frio. O objetivo desta pesquisa foi avaliar a influência de temperaturas amenas na floração e brotação da 'Turmalina' e 'Ágata', duas cultivares com baixa e média necessidade de frio, respectivamente. Plantas obtidas por enxertia no outono foram submetidas a tratamentos de frio (150, 250, 350, 500 e 672 horas em três níveis de temperatura (5°C, 10°C e 15°C. Após os tratamentos, estas plantas foram colocadas em casa de vegetação a temperatura de 20°C±5°C e avaliadas semanalmente. Conclui-se que temperatura de até 15°C por um período de 150 horas é capaz de resultar em floração e brotação satisfat

FY 2000 report on the results of the regional consortium R and D project - Regional consortium energy R and D. Third year report. R and D of a hybrid pulse plasma coating (HPPC) system; 2000 nendo chiiki consortium kenkyu kaihatsu jigyo - chiiki consortium energy kenkyu kaihatsu. Hybrid gata pulse plasma coating (HPPC) system no kenkyu kaihatsu (dai 3 nendo) seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

The development was proceeded with of the surface reforming technology system in which plasma CVD technology and PSII (plasma source ion implantation) technology are connected. HPPC forms DLC (diamond like carbon) layers excellent in adhesion and ceramic layers on the surface of work pieces such as complicatedly shaped dies and tools/sliding parts. Element technologies are the raw material gas pulse introducing technology for efficiently introducing raw materials into the reaction container in a state of gas, high density plasma formation technology and pulse plasma formation technology, minus pulse voltage application technology for vertically implanting various ions on the surface of complicatedly shaped work pieces, and advanced hybrid control technology enabling the control of ion species/implantation amount/layer formation speed. In FY 2000, using the prototype of the HPPC system, studies were made of the development of the DLC layer process and the low temperature DLC layer process, and development and commercialization of technology to improve throwing power, etc. (NEDO)

An RNAi-Enhanced Logic Circuit for Cancer Specific Detection and Destruction

Science.gov (United States)

2013-02-01

monomeric protein secreted by Corynebacterium diphtheriae, and pro-apoptotic members of Bcl-2 family: mBax (Mus musculus), hBax ( Homo sapiens ), and its...Gata3 mStaple. Intron- feature sequences – donor site, branch point, poly- pyrimidine tract, and acceptor site – were selected based on previously...sequences found in literature our intron features were chosen according SplicePort [4], an online analyzer that detects the likelihood of splicing to

Therapeutic effect of dioscin on collagen-induced arthritis through reduction of Th1/Th2.

Science.gov (United States)

Guo, Yachun; Xing, Enhong; Song, Hongru; Feng, Guiying; Liang, Xiujun; An, Gao; Zhao, Xiaofei; Wang, Mi

2016-10-01

The aim of this study was to detect the therapeutic effect of dioscin on collagen-induced arthritis (CIA). Mice model of CIA was induced by chicken collagen II and arthritis index was assessed. After suspension of dioscin (100mg/kg/d) or triptolide was intragastrically administered, the left paw swelling and body weight of each mouse were measured. Then tissue samples were assayed by histopathological analysis. The levels of Th1 and Th2 were detected by flow cytometry. The expression of p-STAT1, p-STAT4 and p-STAT6 was demonstrated by western blot analysis, and T-bet and GATA-3 expression was detected by RT-PCR. The paw swelling and arthritis index were decreased and body weight was increased in the high dose of dioscin group compared to the model group (PTh1/Th2 in the dioscin group (0.82±0.24) and triptolide group (0.99±0.44) was lower than that in the model group (1.84±0.70, PTh1/Th2 cells, which could reduce the expression of p-STAT4, increase the expression of p-STAT6 and GATA3 in the synovial tissue. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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.

Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Science.gov (United States)

2017-12-11

Acute Biphenotypic Leukemia; Acute Erythroid Leukemia in Remission; Acute Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2) or t(3;3) (q21.3;q26.2); GATA2, MECOM; Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2); GATA2, MECOM; Acute Myeloid Leukemia With Multilineage Dysplasia; Acute Myeloid Leukemia With t(6;9) (p23;q34.1); DEK-NUP214; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Complete Remission; B Acute Lymphoblastic Leukemia With t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1); B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Myelodysplastic Syndrome; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Acute Myeloid Leukemia; T Lymphoblastic Lymphoma

Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX.

Science.gov (United States)

Argentaro, Anthony; Yang, Ji-Chun; Chapman, Lynda; Kowalczyk, Monika S; Gibbons, Richard J; Higgs, Douglas R; Neuhaus, David; Rhodes, Daniela

2007-07-17

The chromatin-associated protein ATRX was originally identified because mutations in the ATRX gene cause a severe form of syndromal X-linked mental retardation associated with alpha-thalassemia. Half of all of the disease-associated missense mutations cluster in a cysteine-rich region in the N terminus of ATRX. This region was named the ATRX-DNMT3-DNMT3L (ADD) domain, based on sequence homology with a family of DNA methyltransferases. Here, we report the solution structure of the ADD domain of ATRX, which consists of an N-terminal GATA-like zinc finger, a plant homeodomain finger, and a long C-terminal alpha-helix that pack together to form a single globular domain. Interestingly, the alpha-helix of the GATA-like finger is exposed and highly basic, suggesting a DNA-binding function for ATRX. The disease-causing mutations fall into two groups: the majority affect buried residues and hence affect the structural integrity of the ADD domain; another group affects a cluster of surface residues, and these are likely to perturb a potential protein interaction site. The effects of individual point mutations on the folding state and stability of the ADD domain correlate well with the levels of mutant ATRX protein in patients, providing insights into the molecular pathophysiology of ATR-X syndrome.

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

Science.gov (United States)

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.

2018-03-22T21:54:14Z https://www.ajol.info/index.php/all/oai oai:ojs ...

African Journals Online (AJOL)

This study was carried out to investigate the genetic polymorphism of nine short tandem repeat (STR) loci including D2S1772, D6S1043, D7S3048, D8S1132, D11S2368, D12S391, D13S325, D18S1364 and D22GATA198B05 in Chinese Han population of Henan province and to assess its value in forensic science.

Analysis of genetic polymorphism of nine short tandem repeat loci in ...

African Journals Online (AJOL)

This study was carried out to investigate the genetic polymorphism of nine short tandem repeat (STR) loci including D2S1772, D6S1043, D7S3048, D8S1132, D11S2368, D12S391, D13S325, D18S1364 and D22GATA198B05 in Chinese Han population of Henan province and to assess its value in forensic science.

Breast Carcinoma With Unrecognized Neuroendocrine Differentiation Metastasizing to the Pancreas

DEFF Research Database (Denmark)

Christensen, Lene Svendstrup; Mortensen, Michael Bau; Detlefsen, Sönke

2016-01-01

, a second panel revealed positivity for estrogen receptors and GATA3. On review of the lumpectomy specimen, a significant neuroendocrine component was found, leading to the final diagnosis of breast carcinoma with neuroendocrine features metastasizing to the pancreas. Neuroendocrine markers...... are not routinely analyzed in breast tumors. Hence, metastases from breast carcinomas with unrecognized neuroendocrine features may lead to false diagnoses of primary neuroendocrine tumors at different metastatic sites, such as the pancreas....

Role of GATA Transcription Factors in the T Cell Lineage

NARCIS (Netherlands)

J.P. van Hamburg (Jan Piet)

2008-01-01

textabstractT lymphocytes play a central role in the mammalian immune response against potentially hazardous pathogens, such as parasites, bacteria, viruses and fungi. These cells have the remarkable capacity to specifically recognize foreign substances, termed antigens, to which they respond by

Bucket elevator type continuous unloader; Basket elevator gata renzokushiki anroda

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-04-20

This unloader was delivered to Wakayama branch of Sumikin Butsuryu in the site of Wakayama steel plant of Sumitomo Metal Industries Ltd. for landing sub-materials for ironworks. Main specifications: (1) Capacity: 400t/h for limestone, 280t/h for gypsum, (2) Kinds of ships: 5,000DWT maximum, (3) Boom swing radius: 20m. Features: (1) Simple light-weight unloader for not large ships for main materials but small coastal service ships which works with not swing motion but only traveling and normal-directional motion of the under structure of a bucket elevator unit, (2) Various useful functions such as ground conveyance, truck loading, back yard stacking and back yard shipment for handling of various sub-materials. (translated by NEDO)

Endoderm development in Caenorhabditis elegans: the synergistic action of ELT-2 and -7 mediates the specification→differentiation transition.

Science.gov (United States)

Sommermann, Erica M; Strohmaier, Keith R; Maduro, Morris F; Rothman, Joel H

2010-11-01

The transition from specification of cell identity to the differentiation of cells into an appropriate and enduring state is critical to the development of embryos. Transcriptional profiling in Caenorhabditis elegans has revealed a large number of genes that are expressed in the fully differentiated intestine; however, no regulatory factor has been found to be essential to initiate their expression once the endoderm has been specified. These gut-expressed genes possess a preponderance of GATA factor binding sites and one GATA factor, ELT-2, fulfills the expected characteristics of a key regulator of these genes based on its persistent expression exclusively in the developing and differentiated intestine and its ability to bind these regulatory sites. However, a striking characteristic of elt-2(0) knockout mutants is that while they die shortly after hatching owing to an obstructed gut passage, they nevertheless contain a gut that has undergone complete morphological differentiation. We have discovered a second gut-specific GATA factor, ELT-7, that profoundly synergizes with ELT-2 to create a transcriptional switch essential for gut cell differentiation. ELT-7 is first expressed in the early endoderm lineage and, when expressed ectopically, is sufficient to activate gut differentiation in nonendodermal progenitors. elt-7 is transcriptionally activated by the redundant endoderm-specifying factors END-1 and -3, and its product in turn activates both its own expression and that of elt-2, constituting an apparent positive feedback system. While elt-7 loss-of-function mutants lack a discernible phenotype, simultaneous loss of both elt-7 and elt-2 results in a striking all-or-none block to morphological differentiation of groups of gut cells with a region-specific bias, as well as reduced or abolished gut-specific expression of a number of terminal differentiation genes. ELT-2 and -7 synergize not only in activation of gene expression but also in repression of a gene that

Phenotype and Tissue Expression as a Function of Genetic Risk in Polycystic Ovary Syndrome.

Directory of Open Access Journals (Sweden)

Cindy T Pau

Full Text Available Genome-wide association studies and replication analyses have identified (n = 5 or replicated (n = 10 DNA variants associated with risk for polycystic ovary syndrome (PCOS in European women. However, the causal gene and underlying mechanism for PCOS risk at these loci have not been determined. We hypothesized that analysis of phenotype, gene expression and metformin response as a function of genotype would identify candidate genes and pathways that could provide insight into the underlying mechanism for risk at these loci. To test the hypothesis, subjects with PCOS (n = 427 diagnosed according to the NIH criteria (< 9 menses per year and clinical or biochemical hyperandrogenism and controls (n = 407 with extensive phenotyping were studied. A subset of subjects (n = 38 underwent a subcutaneous adipose tissue biopsy for RNA sequencing and were subsequently treated with metformin for 12 weeks with standardized outcomes measured. Data were analyzed according to genotype at PCOS risk loci and adjusted for the false discovery rate. A gene variant in the THADA locus was associated with response to metformin and metformin was a predicted upstream regulator at the same locus. Genotype at the FSHB locus was associated with LH levels. Genes near the PCOS risk loci demonstrated differences in expression as a function of genotype in adipose including BLK and NEIL2 (GATA4 locus, GLIPR1 and PHLDA1 (KRR1 locus. Based on the phenotypes, expression quantitative trait loci (eQTL, and upstream regulatory and pathway analyses we hypothesize that there are PCOS subtypes. FSHB, FHSR and LHR loci may influence PCOS risk based on their relationship to gonadotropin levels. The THADA, GATA4, ERBB4, SUMO1P1, KRR1 and RAB5B loci appear to confer risk through metabolic mechanisms. The IRF1, SUMO1P1 and KRR1 loci may confer PCOS risk in development. The TOX3 and GATA4 loci appear to be involved in inflammation and its consequences. The data suggest potential PCOS subtypes and

Profiles of mRNA expression of genes related to sex differentiation of the gonads in the chicken embryo.

Science.gov (United States)

Yamamoto, I; Tsukada, A; Saito, N; Shimada, K

2003-09-01

Sex is determined genetically in birds. The homogametic sex is male (ZZ), whereas the heterogametic sex is female (ZW). According to the genetic sex, gonads develop into testes or ovary. In this study, we performed experiments to reveal mRNA expression patterns in the gonad between d 5.5 and 8.5 of incubation and examined a possible role of Dss-Ahc critical region on the X chromosome 1 (Dax1), Steroidogenic factor 1 (Sf1), P450aromatase (P450arom), Estrogen receptor alpha (ER alpha), doublesex and mab3 related transcription factor 1 (Dmrt1), Sry-related HMG box gene 9 (Sox9), Gata binding protein 4 (Gata4), and anti-müllerian hormone (Amh) in sex differentiation in chicken embryonic gonads using RNase protection assay. In embryonic chicken gonads, Dax1 mRNA was expressed in both sexes but was higher in females than in males at d 6.5 and 7.5 of incubation. The Sf1 mRNA was expressed in both sexes, but it was expressed more in males at d 5.5 than in females but more in females than in males at d 7.5 and 8.5 of incubation. The P450arom mRNA was expressed only in female gonads from d 5.5 of incubation. The ER alpha mRNA was expressed in both sexes, but it did not show a sex difference. On the other hand, the Dmrt1 mRNA was expressed in both sexes, but it showed a male-specific expression pattern. The male-specific expression pattern was observed in Sox9 mRNA, but it was not expressed in female gonads. The Gata4 mRNA was expressed in both sexes, and sex differences were not revealed throughout the observational period. Amh mRNA was expressed in both sexes, but it had male-specific mRNA expression pattern at d 6.5 to 8.5 of incubation. These results indicate that Dax1, Sf1, and P450arom have possible roles in ovary formation, whereas Dmrt1, Sox9, and Amh are related to testis formation in differentiating chicken gonads at d 5.5 to 8.5 of incubation.

Šablonų naudojimas kuriant duomenų apdorojimo sistemas internete

OpenAIRE

Rutkauskaitė, Ramunė

2004-01-01

In this work object-oriented patterns were used for development of gata processing system on the Web. Nowadays a lot of systems are developing for they use in internet. In my final work these patterns were used: MVC, Page Controller, Front Controller, Intercepting Filter and others. Model-View-Controller pattern separates the modeling of domain, the presentation, and the actions based on user input into three separate classes: Model, View, Controller. This pattern is a fundamental design p...

An Alternative Transcript of the FOG-2 Gene Encodes a FOG-2 Isoform lacking the FOG Repression Motif

OpenAIRE

Dale, Rodney M.; Remo, Benjamin F.; Svensson, Eric C.

2007-01-01

The FOG family of transcriptional co-factors is composed of two members in mammals: FOG-1 and FOG-2. Both have been shown to bind to GATA factors and function as transcriptional co-repressors in specific cell and promoter contexts. We have previously defined a novel repression domain localized to the N-terminus of each FOG family member, the FOG Repression Motif, which is necessary for FOG-mediated transcriptional repression. In this report, we describe the identification and characterization...

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OpenAIRE

Islam, Andi Asadul

2016-01-01

- PEER REVIEW Correlation between GATA-3, Ki67 and Ki67 and p53 expressions to Histopathology grading of Breast Cancer bin Makassar, Indonesia. a. Nama Jurnal : Cancer Research Journal b. Nomor ISSN : P: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.sciencepublishinggroup.com/j/crj g. Terindeks di Scimagojr/ ...

Genomics studies on musical aptitude, music perception, and practice.

Science.gov (United States)

Järvelä, Irma

2018-03-23

When searching for genetic markers inherited together with musical aptitude, genes affecting inner ear development and brain function were identified. The alpha-synuclein gene (SNCA), located in the most significant linkage region of musical aptitude, was overexpressed when listening and performing music. The GATA-binding protein 2 gene (GATA2) was located in the best associated region of musical aptitude and regulates SNCA in dopaminergic neurons, thus linking DNA- and RNA-based studies of music-related traits together. In addition to SNCA, several other genes were linked to dopamine metabolism. Mutations in SNCA predispose to Lewy-body dementia and cause Parkinson disease in humans and affect song production in songbirds. Several other birdsong genes were found in transcriptome analysis, suggesting a common evolutionary background of sound perception and production in humans and songbirds. Regions of positive selection with musical aptitude contained genes affecting auditory perception, cognitive performance, memory, human language development, and song perception and production of songbirds. The data support the role of dopaminergic pathway and their link to the reward mechanism as a molecular determinant in positive selection of music. Integration of gene-level data from the literature across multiple species prioritized activity-dependent immediate early genes as candidate genes in musical aptitude and listening to and performing music. © 2018 New York Academy of Sciences.

Molecular Features and Methylation Status in Early Onset (≤40 Years Colorectal Cancer: A Population Based, Case-Control Study

Directory of Open Access Journals (Sweden)

Giulia Magnani

2015-01-01

Full Text Available Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%. KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02. Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.

Th9/IL-9 Profile in Human Echinococcosis: Their Involvement in Immune Response during Infection by Echinococcus granulosus

Directory of Open Access Journals (Sweden)

Nannan Pang

2014-01-01

Full Text Available Th9 cells have been reported to contribute to immune responses; however, the role of Th9 cells in Echinococcus granulosus infection is unknown. This study is to determine whether Th9 cells and IL-9 are involved in human Echinococcus granulosus infection. Compared with healthy controls (HC group, the mRNA levels of PU.1, IL-9, and GATA-3 were significantly increased in patients before therapy (CE group, as revealed by qRT-PCR. Flow cytometry analysis showed that the percentages of Th9 and Th2 cells in CE group were significantly higher. The levels of IL-9, IL-4, IL-10, and TGF-β in CE group were also significantly increased, as detected by CBA assay. The percentages of Th9 and Th2 cells in CE group were positively correlated. After treatments of surgery in combination with albendazole, the PU.1 and GATA-3 mRNA levels were significantly decreased in patients after therapy (PCE group compared with CE group. The numbers of Th9 and Th2 cells and levels of IL-9, IL-4, IL-10, and TGF-β were also significantly decreased in PCE group. In conclusion, the ratios of Th9 cells and IL-9 levels were significantly decreased after treatment, suggesting that Th9/IL-9 may be involved in immune response induced by Echinococcus granulosus infection.

Promoter motifs required for c-mpl gene expression induced by thrombopoietin in CMK cells.

Science.gov (United States)

Sunohara, Masataka; Sato, Iwao; Morikawa, Shigeru

2017-11-30

Thrombopoietin (TPO) and its receptor, c-Mpl, are the central regulators of megakaryocyte development and platelet production and are also crucial to regulate megakaryocytopoiesis. TPO remarkably elevated c-mpl promoter activity, while the protein kinase C (PKC) inhibitors, GF109203, H7 and Calphostin C, clearly reduced the steady level of its promoter activity.  In the present study, motifs crucial for c-mpl promoter activity induced by TPO treatment have been analyzed using a human megakaryoblastic cell line, CMK. Destruction of the -107Sp1 and the -57Sp1 sites in the c-mpl promoter enhancer region resulted in decrease of the promoter activity by 53.1% and 64.4%, respectively, and destruction of -69Ets and -28Ets elements dramatically decreased the promoter activity by 96.4% and 87.8%, respectively, while mutation of -77GATA moderately reduced the activity by 31.4%. The result was in agreement with our previous report that showed the crucial motifs in the c-mpl promoter for the promoter activity induced by PMA-treatment. This indicates that TPO-induced activation of the c-mpl promoter activity is fully modulated by transcription through a PKC-dependent pathway and the two Sp1 and two Ets motifs are crucial for the activation of the c-mpl promoter activity rather than a GATA motif in the c-mpl promoter of CMK cells.

Polarization of T Lymphocytes Is Regulated by Mesenchymal Stem Cells in NZBWF1 and BALB/c Mice

Directory of Open Access Journals (Sweden)

Yayi Hou

2007-05-01

Full Text Available Mesenchymal stem cells (MSCs have been shown to suppress proliferation andactivation of T lymphocytes in vivo and in vitro although the molecular mechanism of theimmunosuppressive effect is not completely understood. To investigate theimmunoregulatory effects of mice bone marrow mesenchymal stem cells on T lymphocyte,MSCs from NZBWF1 and BALB/c mice were isolated and expanded from bone marrow,and identified with cell morphology and the surface phenotypes. CD3+ T lymphocytesisolated by nylon wool columns were co-cultured with PMA with or without the two strainsof MSCs. Then T cell apoptosis and intercellular cytokines of T cell were assessed by flowcytometry. Quantification of transcription factors T-box (T-bet and GATA-binding protein3 (GATA-3 expressed in T cells was detected by RT-PCR and western blot. Our resultsshowed that there was a decrease of CD3+ T cell apoptosis when NW MSCs or Bc MSCswere added, and an increase of Th2 subset by NW MSCs and Th1 subset by Bc MSCs wereobserved by co-culturing MSCs with T lymphocytes. It is suggested that, by favoring Th1-cell development and inhibitory Th2-cell development, normal MSCs might interfere withthe SLE development, and that marrow-derived NW MSCs had defectiveimmunoregulatory function when compared with MSCs from healthy mouse strains.

Harmful algal blooms and climate change: Learning from the past and present to forecast the future

CSIR Research Space (South Africa)

Wells, ML

2015-11-01

Full Text Available Harmful algal blooms and climate change: Learning from the past and present to forecast the future Mark L. Wellsa,*, Vera L. Trainerb, Theodore J. Smaydac, Bengt S.O. Karlsond, Charles G. Tricke, Raphael M. Kudelaf, Akira Ishikawag, Stewart Bernardh... and Atmospheric Administration, 2725 Montlake Blvd. E., Seattle, WA 98112, USA c Graduate School of Oceanography, University of Rhode Island, Kingston, RI 02881, USA d SMHI Research & Development, Oceanography, Sven Ka¨llfelts gata 15, 426 71 Va¨stra Fro...

Twisted Gastrulation as a BMP Modulator during Mammary Gland Development and Tumorigenesis

Science.gov (United States)

2014-05-01

tissues ( Bonilla -Claudio et al., 2012). In WT TEBs (Fig. 8A–D) and mature ducts (Fig. 8I–L) almost all luminal cells expressed GATA-3. In contrast, Twsg1...PubMed: 12952901] Bonilla -Claudio M, Wang J, Bai Y, Klysik E, Selever J, Martin JF. Bmp signaling regulates a dosedependent transcriptional...deficient mice. Arch Oral Biol. 2006; 51:433–8. [PubMed: 16289463] Metallo CM, Ji L, de Pablo JJ, Palecek SP. Retinoic Acid and Bone Morphogenetic

2D resistivity survey in complex geological structure area. Application to the volcanic area; Fukuzatsuna chishitsu kozo chiiki ni okeru hiteiko nijigen tansa. Kazangan chiiki deno tekiorei

Energy Technology Data Exchange (ETDEWEB)

Asakawa, S; Ikuma, T; Tanifuji, R [DIA Consultants Co. Ltd., Tokyo (Japan)

1996-05-01

Introduced herein is an application of 2D resistivity survey to a volcanic rock area where the survey result is difficult to interpret because of its complex geological structure. In a dam site survey, main problems involve the permeability of water through faults and weathered, altered zones. At this site, a 2D resistivity survey was conducted, a 2D geological structure was deduced from the resistivity section, and the result was examined. It was found that resistivity distribution was closely related to hydrographic factors, but no obvious correlation was detected between rock classes and R, Q, and D. In conducting investigations into a section planned for a highway tunnel, it was learned that the problem was a volcanic ash layer to collapse instantly upon absorbing water, and the distribution of the ash layer, not to be disclosed by boring, was subjected to a 2D resistivity survey. The survey was conducted into the structure above where the tunnel would run, and further into the face, and studies were made about what layer was reflected by the resistivity distribution obtained by analysis. The result of the analysis agreed with the details of the layer that was disclosed afterward. 4 figs., 1 tab.

FY 2000 report on the results of the regional consortium R and D project - Regional consortium field. Third year report. R and D of the manufacturing technology of hybrid type biocompatible hard tissue substituting materials; 2000 nendo chiiki consortium kenkyu kaihatsu jigyo - chiiki consortium bun'ya. Hybrid gata seitai yugo kinosei kososhiki daitai sozai seizo gijutsu no kenkyu kaihatsu (dai 3 nendo) seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

As instrument materials substituting for hard tissue such as tooth root and artificial hip joint, the technology development is being proceeded with of the use of high-biocompatible {beta} Ti alloys coated by hydroxy apatite. Studies were made in the following 6 fields: 1) design of high-biocompatible {beta} Ti alloys, system control and dynamic evaluation; 2) development of high efficiency calcium phosphate ceramics (hydroxy apatite) and development of surface coating technology; 3) development of melting casting technology of high-biocompatible {beta} Ti alloys; 4) biological evaluation of biocompatibility of high-biocompatible {beta} Ti alloys and completion of dental precision casting technology; 5) basic research on affinity of low rigidity Ti alloys (trial manufacture); 6) development of technology of precision processing and precision finishing processing of alloys. In 5), in the test on affinity of the trial-manufactured alloys, stainless steel and existing Ti alloys, it was verified that the trial-manufactured alloys were excellent in affinity. (NEDO)

Generation of electrophysiologically functional cardiomyocytes from mouse induced pluripotent stem cells

Directory of Open Access Journals (Sweden)

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.

Intratumoral Th2 predisposition combines with an increased Th1 functional phenotype in clinical response to intravesical BCG in bladder cancer.

Science.gov (United States)

Pichler, Renate; Gruenbacher, Georg; Culig, Zoran; Brunner, Andrea; Fuchs, Dietmar; Fritz, Josef; Gander, Hubert; Rahm, Andrea; Thurnher, Martin

2017-04-01

Th1-type immunity is considered to be required for efficient response to BCG in bladder cancer, although Th2 predisposition of BCG responders has recently been reported. The aim was to evaluate the relationship of Th1 and Th2 components in 23 patients undergoing BCG treatment. Peripheral blood, serum and urine samples were prospectively collected at baseline, during and after BCG. Th1 (neopterin, tryptophan, kynurenine, kynurenine-to-tryptophan ratio (KTR), IL-12, IFN-γ, soluble TNF-R75 and IL-2Rα) and Th2 (IL-4, IL-10) biomarkers as well as CD4 expression in T helper (Th), effector and regulatory T cells were determined. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded cancer tissue by immunohistochemistry to examine expression of transcription factors that control Th1 (T-bet) and Th2-type (GATA3) immunity. We confirmed a Th2 predisposition with a mean GATA3/T-bet ratio of 5.51. BCG responders showed significantly higher levels of urinary (p = 0.003) and serum neopterin (p = 0.012), kynurenine (p = 0.015), KTR (p = 0.005), IFN-γ (p = 0.005) and IL-12 (p = 0.003) during therapy, whereas levels of IL-10 decreased significantly (p Th1-type immune responses and thus contribute to the BCG success.

The effect of histone deacetylase inhibitors on AHSP expression

Science.gov (United States)

Ziari, Katayoun; Ranjbaran, Reza; Nikouyan, Negin

2018-01-01

Alpha-hemoglobin stabilizing protein (AHSP) is a molecular chaperone that can reduce the damage caused by excess free α-globin to erythroid cells in patients with impaired β-globin chain synthesis. We assessed the effect of sodium phenylbutyrate and sodium valproate, two histone deacetylase inhibitors (HDIs) that are being studied for the treatment of hemoglobinopathies, on the expression of AHSP, BCL11A (all isoforms), γ-globin genes (HBG1/2), and some related transcription factors including GATA1, NFE2, EKLF, KLF4, and STAT3. For this purpose, the K562 cell line was cultured for 2, 4, and 6 days in the presence and absence of sodium phenylbutyrate and sodium valproate. Relative real-time qRT-PCR analysis of mRNA levels was performed to determine the effects of the two compounds on gene expression. Expression of all target mRNAs increased significantly (p sodium valproate had a more considerable effect than sodium phenylbutyrate (p sodium valproate after 6 days. Both compounds repressed the expression of BCL11A (-XL, -L, -S) and up-regulated GATA1, NFE2, EKLF, KLF4, STAT3, AHSP, and γ-globin genes expression. Moreover, sodium valproate showed a stronger effect on repressing BCL11A and escalating the expression of other target genes. The findings of this in vitro experiment could be considered in selecting drugs for clinical use in patients with β-hemoglobinopathies. PMID:29389946

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

Directory of Open Access Journals (Sweden)

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.

Systematic Analysis of Splice-Site-Creating Mutations in Cancer

Directory of Open Access Journals (Sweden)

Reyka G. Jayasinghe

2018-04-01

Full Text Available Summary: For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. : Jayasinghe et al. identify nearly 2,000 splice-site-creating mutations (SCMs from over 8,000 tumor samples across 33 cancer types. They provide a more accurate interpretation of previously mis-annotated mutations, highlighting the importance of integrating data types to understand the functional and the clinical implications of splicing mutations in human disease. Keywords: splicing, RNA, mutations of clinical relevance

Ovarian Brenner tumors and Walthard nests: a histologic and immunohistochemical study.

Science.gov (United States)

Roma, Andres A; Masand, Ramya P

2014-12-01

Brenner tumors are composed of urothelial/transitional-type epithelium and, hence, are morphologically similar to Walthard nests and tubal/mesothelial transitional metaplasia. In this study, we analyzed immunohistochemical markers on Brenner tumors to explore Müllerian as well as Wolffian and germ cell derivation. We also attempted to explore their possible association with tubal/paratubal Walthard nests/transitional metaplasia, using the same immunostains. Thirty-two consecutive cases of Brenner tumors were identified. Thirteen (43%) of the patients had Walthard nests in the tubal/periovarian soft tissue. All Brenner tumors were diffusely positive for GATA3 (strongly positive in 30/32 and weakly positive in the remaining 2) and negative for PAX8, PAX2, and SALL4. Similarly, all Walthard nests were positive for GATA3, whereas only 3 (23%) of 13 showed occasional PAX8 expression; all were negative for PAX2 and SALL4. In our study, more than 40% of Brenner tumors had associated Walthard nests. The similar morphology and immunoprofile of Brenner tumors and Walthard nests suggest a probable link between Brenner tumors and Walthard nests. Two additional cases presented highlight small transitional lesions involving the ovary: a possible precursor lesion or the initial steps of Brenner tumor formation. Brenner tumors and most Walthard nests lacked staining for Müllerian (PAX8 and PAX2) and germ cell tumor markers (SALL4). Copyright © 2014 Elsevier Inc. All rights reserved.

SATB1 packages densely-looped, transciptionally-active chromatinfor coordinated expression of cytokine genes

Energy Technology Data Exchange (ETDEWEB)

Cai, Shutao; Lee, Charles C.; Kohwi-Shigematsu, Terumi

2006-05-23

SATB1 is an important regulator of nuclear architecture that anchors specialized DNA sequences onto its cage-like network and recruits chromatin remodeling/modifying factors to control gene transcription. We studied the role of SATB1 in regulating the coordinated expression of Il5, Il4, and Il13 from the 200kb cytokine gene cluster region of mouse chromosome 11 during T-helper 2 (Th2)-cell activation. We show that upon cell activation, SATB1 is rapidly induced to form a unique transcriptionally-active chromatin structure that includes the cytokine gene region. Chromatin is folded into numerous small loops all anchored by SATB1, is histone H3 acetylated at lysine 9/14, and associated with Th2-specific factors, GATA3, STAT6, c-Maf, the chromatin-remodeling enzyme Brg-1, and RNA polymerase II across the 200kb region. Before activation, the chromatin displays some of these features, such as association with GATA3 and STAT6, but these were insufficient for cytokine gene expression. Using RNA interference (RNAi), we show that upon cell activation, SATB1 is not only required for chromatin folding into dense loops, but also for c-Maf induction and subsequently for Il4, Il5, and Il13 transcription. Our results show that SATB1 is an important determinant for chromatin architecture that constitutes a novel higher-order, transcriptionally-active chromatin structure upon Th2-cell activation.

KLRG1 impairs regulatory T-cell competitive fitness in the gut.

Science.gov (United States)

Meinicke, Holger; Bremser, Anna; Brack, Maria; Schrenk, Klaudia; Pircher, Hanspeter; Izcue, Ana

2017-09-01

Immune homeostasis requires the tight, tissue-specific control of the different CD4 + Foxp3 + regulatory T (Treg) cell populations. The cadherin-binding inhibitory receptor killer cell lectin-like receptor G1 (KLRG1) is expressed by a subpopulation of Treg cells with GATA3 + effector phenotype. Although such Treg cells are important for the immune balance, especially in the gut, the role of KLRG1 in Treg cells has not been assessed. Using KLRG1 knockout mice, we found that KLRG1 deficiency does not affect Treg cell frequencies in spleen, mesenteric lymph nodes or intestine, or frequencies of GATA3 + Treg cells in the gut. KLRG1-deficient Treg cells were also protective in a T-cell transfer model of colitis. Hence, KLRG1 is not essential for the development or activity of the general Treg cell population. We then checked the effects of KLRG1 on Treg cell activation. In line with KLRG1's reported inhibitory activity, in vitro KLRG1 cross-linking dampened the Treg cell T-cell receptor response. Consistently, lack of KLRG1 on Treg cells conferred on them a competitive advantage in the gut, but not in lymphoid organs. Hence, although absence of KLRG1 is not enough to increase intestinal Treg cells in KLRG1 knockout mice, KLRG1 ligation reduces T-cell receptor signals and the competitive fitness of individual Treg cells in the intestine. © 2017 John Wiley & Sons Ltd.

Toxicological effect of TiO2 nanoparticle-induced myocarditis in mice

Science.gov (United States)

Hong, Fashui; Wang, Ling; Yu, Xiaohong; Zhou, Yingjun; Hong, Jie; Sheng, Lei

2015-08-01

Currently, impacts of exposure to TiO2 nanoparticles (NPs) on the cardiovascular system are not well understood. The aim of this study was to investigate whether TiO2 NPs induce myocarditis and its underlying molecular mechanism in the cardiac inflammation in mice. Mice were exposed to TiO2 NPs for 6 months; biochemical parameters of serum and expression of Th1-related and Th2-related cytokines in the heart were investigated. The results showed that TiO2 NP exposure resulted in cardiac lesions coupling with pulmonary inflammation; increases of aspartate aminotransferase (AST), creatine kinase (CK), C-reaction protein (CRP), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) levels; and a reduction of nitric oxide (NOx) level in the serum. These were associated with increases of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, transforming growth factor-β (TGF-β), creatine kinase, CRP, adhesion molecule-1, and monocyte chemoattractant protein-1, interferon-γ (IFN-γ), signal transducers and activators of transcription (STAT)1, STAT3, or STAT6, GATA-binding domain-3, GATA-binding domain-4, endothelin-1 expression levels, and T-box expressed in T cells expression level that is the master regulator of pro-inflammatory cytokines and transcription factors in the heart. These findings imply that TiO2 NP exposure may increase the occurrence and development of cardiovascular diseases.

Data of 10 SSR markers for genomes of homo sapiens and monkeys.

Science.gov (United States)

Reddy, K K V V V S; Raju, S Viswanadha; Someswara Rao, Chinta

2017-06-01

In this data, we present 10 Simple Sequence Repeat(SSR) markers TAGA, TCAT, GAAT, AGAT, AGAA, GATA, TATC, CTTT, TCTG and TCTA which are extracted from the genomes of homo sapiens and monkeys using string matching mechanism [1]. All loci showed 4 Base Pair(bp) in allele size, indicating that there are some polymorphisms between individuals correlating to the number of SSR repeats that maybe useful for the detection of similarity among the genotypes. Collectively, these data show that the SSR extraction is a valuable method to illustrate genetic variation of genomes.

New energy vision in Kitakata City area; Kitakatashi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

A new energy vision was established in Kitakata City in Fukushima Prefecture. The population of Kitakata City in 2000 was 37,490, not having experienced extreme increase or decrease. Population employed in the tertiary industry occupies the largest ratio at 36.9%, followed by the secondary industry. The energy demand of the entire city is about 3300 trillion Joule, and carbon dioxide emitted therefrom is estimated about 77,000 t-C annually. Calculation of new energy amount in existence reveals about 4190 trillion Joule annually, which corresponds to about 1.3 times the energy demand quantity of the city. The new energy introducing project includes introduction of photovoltaic power generation into the public hall and schools, utilization of solar heat for greenhouses, introduction of solar heat and wind power hybrid power generation into the Green Tourism experiencing facilities, parks, street lights, and evacuation places, introduction of small to medium hydropower generation plants into Kitanogo, Kuranoyu and Happo-Ike, utilization of cold heat of snow, introduction of clean energy fueled automobiles into the public organizations, utilization of bio-mass energy, wastes burning power generation and heat utilization. (NEDO)

Regional new energy vision for Sakurae town; Sakuraecho chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

The town is situated in a mountainous region typical of the Iwami district, Shimane Prefecture, rich in natural energy resources with as many as four hydroelectric power stations in service. Such local features were taken into account fully when a regional new energy vision was formulated for showing the town the course to follow for promoting the introduction of new energy which is environmentally friendly. The results of related efforts are described in eight chapters, which are (1) the outline of the vision, (2) survey of the trend of new energy, (3) description of Sakurae town, (4) townspeople's awareness of energy matters, (5) rate of energy consumption, (6) available amount of new energy, (7) basic policy for introducing new energy, and (8) projects for introducing new energy. Part (8) covers a photovoltaic project, wind power project, ligneous biomass energy introduction project, and the introduction of clean energy vehicles. Under the ligneous biomass energy introduction project, business profitability is discussed of a scrap wood fueled power plant. (NEDO)

New energy vision in Daito Town area; Daitocho chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

A new energy vision was established in the Daito Township area in Iwate Prefecture. The energy consumed by Daito town as a whole in fiscal 1998 is about 213,685 two-hundred-kL drums, accounted for by the consumer department at 35.7%, the transportation department at 33.3%, and the industrial department at 31.0%. Carbon dioxide emission amount is estimated to be 109,647 t-CO2. General households in the town consume fossil fuel largely for room heating, whose energy conservation or substitution by new energies is important. The utilizable quantity of new energies in the town include solar energy, forest bio-mass, agricultural resource bio-mass, livestock excreta bio-mass, and refuses, whose total quantity is estimated to be 23,161 drums. The new energy utilization project includes enlightenment activities by introducing a photovoltaic power generator and a small wind power generator into Daito Middle School and the Murone Plateau Natural Energy Park, introduction of solar heat generated hot water supply devices for public facilities and town-operated houses, a discussion on a pellet production line in the wood processing industrial complex, and introduction of pellet boilers into public facilities. (NEDO)

Regional new energy vision for Fukuoka city; Fukuokashi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

A regional new energy vision has been formulated for Fukuoka city, Fukuoka Prefecture, which will serve as a basic guide to the promotion of new energy introduction which is one of the measures for coping with environmental problems. The vision is described in five chapters of (1) the local characteristics of Fukuoka city, (2) energy situation in Fukuoka city, (3) basic program, (4) high priority plans, and (5) efforts to enhance the vision toward realization. Discussed as high priority plans are the introduction of new energy into public buildings above all others, high efficiency utilization of refuse-derived energy, utilization of new energy at water supply and drainage facilities, utilization of water temperature difference energy, introduction of clean energy vehicles, promotion of a new energy industry, and the extension of assistance for encouraging citizens and industrialists to adopt new energy. In extending assistance for encouraging the introduction of new energy, studies are made about measures for introducing new energy into individual residences and about a citizenry-involving new energy adopting industry (offering a site to the power generation industry) under the basal conditions that information be supplied sufficiently and that the citizenry and administration cooperate with each other in driving forward the vision. (NEDO)

Magnetic structure of Akita-Yakeyama volcano; Akita Yakeyama chiiki no jikiteki kozo

Energy Technology Data Exchange (ETDEWEB)

Okuma, S [Geological Survey of Japan, Tsukuba (Japan)

1996-10-01

Akita-Yakeyama is a Quaternary volcano located in the north-western part of the Sengan geothermal area. Geothermal resource surveys have been performed from the middle of the 1970s in the Sengan geothermal area, and the Sumikawa geothermal power plant started its operation in 1995. By the analysis, the magnetic basement depth became lower in the north of Yakeyama body. However, the distribution including low magnetic anomaly in the south of Yakeyama body could not be explained only by a simple magnetic structure model. In this study, the magnetic anomaly in this area was analyzed in detail, and a construction of the magnetic structure model was intended by taking borehole data into account. The low magnetic intensity zone with low amplitude agreed well with the geothermal alteration zone. The high magnetic intensity zone and the low magnetic intensity zone corresponded with the distributions of volcanic rocks magnetized normally and reversely, respectively. Kakkonda and Matsukawa geothermal power plants were located in the distinct low magnetic intensity zones. There was a low magnetic intensity zone with long wave length over the whole Sengan geothermal area. A high magnetic intensity zone was observed in the northern foot of this area. From the magnetic measurements of borehole sample rocks, this was found to correspond with the newly formed granite body. 9 refs., 4 figs.

New energy vision in Tochigi Prefectural area; Tochigiken chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

With an objective to structure a circulation type society that imposes less load on the environment, a new energy vision was established in the Tochigi Prefectural area. This plan is an overall plan to promote introduction of new energies, and at the same time serves as a guideline when prefectural residents, business entities and the administration attempt to introduce new energies. The plan was prepared upon viewing the year 2010. The new energy introduction quantity in 2010 was estimated to be 470,000 kL as converted into crude oil (4.7% of the consumption in fiscal 1997). The plan document covers the following five fields: 1) the basic conception of the vision establishment, 2) the current status and problems surrounding the energies, 3) the basic directionality in introducing new energies, 4) policy systems and role sharing toward introducing new energies, and 5) case studies and case presentation. Item 4 is composed of policy systems for new energy introduction, projects to be implemented with emphasis, roles of working organizations, and institutions for promotion. The projects to be executed with emphasis consist of five items including initiative introduction into facilities utilized by the prefectural residents. (NEDO)

Regional new energy vision for Yakumo village; Yakumomura chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

A regional new energy vision has been formulated for Yakumo village, Shimane Prefecture, which abides with the village doctrines of introducing new energy for quality life and building a community advanced in terms of environmental protection. Yakumo village, which has a population of approximately 6,800 engaged mainly in agriculture or forestry, consumed 5 times 10{sup 5} GJ in energy in fiscal 1998. The results of activities conducted in this connection are summarized in nine chapters which are (1) the trends of affairs surrounding new energy, (2) Yakumo village's local characteristics as seen from the new energy viewpoint, (3) collection of information on new energy measures taken by local governments, (4) estimation of demand for energy in Yakumo village, (5) estimation of the existing amount and available amount of new energy in Yakumo village, (6) study of the basic concept and basic policy of the vision, (7) study of new energy introduction, (8) approach to the issue by thinking, and (9) reference materials. In concrete terms, discussion is held about introduction into public facilities of photovoltaic power generation and water heaters, wind power generation, cogeneration, and waste heat utilization. For the sake of gardening at public facilities, for instance, the introduction of photovoltaic power generation is taken up. (NEDO)

Regional new energy vision for Aogaki town; Aogakicho chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

A regional new energy vision has been formulated as part of Phase 4 of the Town Development Program of Aogaki town, Hyogo Prefecture, calling for 'building a town, comfortable to live in and full of hope, by utilizing rich natural environments.' The results of activities conducted in this connection are summarized in five chapters, which are (1) the description of the new energy vision, (2) Aogaki-town's energy characteristics, (3) basic plan, (4) driving forward of prioritized plans, and (5) toward the driving forward of the new energy vision. Chapter (4) comprises the goal of the formulation of the prioritized plans, the definition of the prioritized plans, and the establishment of individual projects. Established as the individual projects are the introduction of new energy linked to the inhibition of carbon dioxide gas emissions, use of wind energy for multiple purposes, public facilities preceding others in the introduction of new energy, building of environmentally symbiotic residences utilizing new energy, utilization of new energy at recreation facilities, and the popularization of and enlightening about new energy and its introduction through the participation of the local population. (NEDO)

Energy saving type area hot water supply system using heat of hot waste water from the sludge center as hot source for hot water; New energy rokko airando CITY. Surajjisenta karano onhaisuinetsu wo kyuyuyo netsugen ni riyosuru sho energy gata chiiki onsui kyokyu system

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-01-01

Heat source of area hot water supply system in Rokko island City (man-made island) is heat of combustion at the sludge center (sludge incineration plant) in this island. Dehydrated sludge cakes (230ton/day) brought from seven sewage disposal plants in Kobe City is combusted (850degC) in the fluid bed hearth. Combustion gas washed in the scrubber, hot waste water after the washing give heat into heat transfer water in the first heat exchanger. Temperature being 64degC in summer and about 50degC in winter, this heat transfer water is sent into the second heat exchanger at every condominium building throughout the pipe line system circulating in the area. At each home, gas heater and hot water supply devices fitted, additional combustion is not necessary in summer but is used according to demand in other seasons. This hot water supply service has been carried out since 1988 and at present has been used by 3600 homes. Amount of supplying hot water being about 3000cu.m/day, saving is calculated roughly as 60% of gas for hot water supply. Fee for this system is 1500/yen/month uniformly for each home. 14 figs.

Association of CD30 transcripts with Th1 responses and proinflammatory cytokines in patients with end-stage renal disease.

Science.gov (United States)

Velásquez, Sonia Y; Opelz, Gerhard; Rojas, Mauricio; Süsal, Caner; Alvarez, Cristiam M

2016-05-01

High serum sCD30 levels are associated with inflammatory disorders and poor outcome in renal transplantation. The contribution to these phenomena of transcripts and proteins related to CD30-activation and -cleavage is unknown. We assessed in peripheral blood of end-stage renal disease patients (ESRDP) transcripts of CD30-activation proteins CD30 and CD30L, CD30-cleavage proteins ADAM10 and ADAM17, and Th1- and Th2-type immunity-related factors t-bet and GATA3. Additionally, we evaluated the same transcripts and release of sCD30 and 32 cytokines after allogeneic and polyclonal T-cell activation. In peripheral blood, ESRDP showed increased levels of t-bet and GATA3 transcripts compared to healthy controls (HC) (both PCD30, CD30L, ADAM10 and ADAM17 transcripts were similar. Polyclonal and allogeneic stimulation induced higher levels of CD30 transcripts in ESRDP than in HC (both PsCD30, the Th-1 cytokine IFN-γ, MIP-1α, RANTES, sIL-2Rα, MIP-1β, TNF-β, MDC, GM-CSF and IL-5, and another one consisting of CD30 and t-bet transcripts, IL-13 and proinflammatory proteins IP-10, IL-8, IL-1Rα and MCP-1. Reflecting an activated immune state, ESRDP exhibited after allostimulation upregulation of CD30 transcripts in T cells, which was associated with Th1 and proinflammatory responses. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance.

Science.gov (United States)

Zhang, Chengliang; Gui, Ling; Xu, Yanjiao; Wu, Tao; Liu, Dong

2013-08-01

Andrographolide, an active component in traditional anti-diabetic herbal plants, is a diterpenoid lactone isolated from Andrographis paniculata because of its potent anti-inflammatory and hypoglycemic effects. However, the effect of andrographolide on the development of diabetes in autoimmune non-obese diabetic (NOD) mice remains unknown. This study aimed to investigate the protective effects of andrographolide on the development of autoimmune diabetes and clarify the underlying mechanism. NOD mice were randomly divided into four groups and administered with water and andrographolide at 50, 100, and 150mg/kg body weight for four weeks. ICR mice were also selected as the control group. Oral glucose tolerance and histopathological insulitis were examined. Th1/Th2/Th17 cytokine secretion was determined by ELISA. The transcriptional profiles of T-bet, GATA3, and RORγt in the pancreatic lymphatic node samples derived from the NOD mice were detected by RT-PCR. After four weeks of oral supplementation, andrographolide significantly inhibited insulitis, delayed the onset, and suppressed the development of diabetes in 30-week-old NOD mice in a dose dependent manner. This protective status was correlated with a substantially decreased production of interferon (IFN)-γ and interleukin (IL)-2, increased IL-10 and transforming growth factor (TGF)-β, and a reduced IL-17. Andrographolide also increased GATA3 mRNA expression but decreased T-bet and RORγt mRNA expressions. Our results suggested that andrographolide prevented type 1 diabetes by maintaining Th1/Th2/Th17 homeostasis. Copyright © 2013 Elsevier B.V. All rights reserved.

The role of tumor suppressor p15Ink4b in the regulation of hematopoietic progenitor cell fate

International Nuclear Information System (INIS)

Humeniuk, R; Rosu-Myles, M; Fares, J; Koller, R; Bies, J; Wolff, L

2013-01-01

Epigenetic silencing of the tumor suppressor gene p15Ink4b (CDKN2B) is a frequent event in blood disorders like acute myeloid leukemia and myelodysplastic syndromes. The molecular function of p15Ink4b in hematopoietic differentiation still remains to be elucidated. Our previous study demonstrated that loss of p15Ink4b in mice results in skewing of the differentiation pattern of the common myeloid progenitor towards the myeloid lineage. Here, we investigated a function of p15Ink4b tumor suppressor gene in driving erythroid lineage commitment in hematopoietic progenitors. It was found that p15Ink4b is expressed more highly in committed megakaryocyte–erythroid progenitors than granulocyte–macrophage progenitors. More importantly, mice lacking p15Ink4b have lower numbers of primitive red cell progenitors and a severely impaired response to 5-fluorouracil- and phenylhydrazine-induced hematopoietic stress. Introduction of p15Ink4b into multipotential progenitors produced changes at the molecular level, including activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling, increase GATA-1, erythropoietin receptor (EpoR) and decrease Pu1, GATA-2 expression. These changes rendered cells more permissive to erythroid commitment and less permissive to myeloid commitment, as demonstrated by an increase in early burst-forming unit-erythroid formation with concomitant decrease in myeloid colonies. Our results indicate that p15Ink4b functions in hematopoiesis, by maintaining proper lineage commitment of progenitors and assisting in rapid red blood cells replenishment following stress

Identification of the MUC2 Promoter as a Strong Promoter for Intestinal Gene Expression through Generation of Transgenic Quail Expressing GFP in Gut Epithelial Cells

Directory of Open Access Journals (Sweden)

Rachel M. Woodfint

2017-01-01

Full Text Available Identification of tissue- and stage-specific gene promoters is valuable for delineating the functional roles of specific genes in genetically engineered animals. Here, through the comparison of gene expression in different tissues by analysis of a microarray database, the intestinal specificity of mucin 2 (MUC2 expression was identified in mice and humans, and further confirmed in chickens by RT-PCR (reverse transcription-PCR analysis. An analysis of cis-acting elements in avian MUC2 gene promoters revealed conservation of binding sites, within a 2.9 kb proximal promoter region, for transcription factors such as caudal type homeobox 2 (CDX2, GATA binding protein 4 (GATA4, hepatocyte nuclear factor 4 α (HNF4A, and transcription factor 4 (TCF4 that are important for maintaining intestinal homeostasis and functional integrity. By generating transgenic quail, we demonstrated that the 2.9 kb chicken MUC2 promoter could drive green fluorescent protein (GFP reporter expression exclusively in the small intestine, large intestine, and ceca. Fluorescence image analysis further revealed GFP expression in intestine epithelial cells. The GFP expression was barely detectable in the embryonic intestine, but increased during post-hatch development. The spatiotemporal expression pattern of the reporter gene confirmed that the 2.9 kb MUC2 promoter could retain the regulatory element to drive expression of target genes in intestinal tissues after hatching. This new transgene expression system, using the MUC2 promoter, will provide a new method of overexpressing target genes to study gene function in the avian intestine.

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

Science.gov (United States)

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

MNS16A tandem repeat minisatellite of human telomerase gene: functional studies in colorectal, lung and prostate cancer.

Science.gov (United States)

Hofer, Philipp; Zöchmeister, Cornelia; Behm, Christian; Brezina, Stefanie; Baierl, Andreas; Doriguzzi, Angelina; Vanas, Vanita; Holzmann, Klaus; Sutterlüty-Fall, Hedwig; Gsur, Andrea

2017-04-25

MNS16A, a functional polymorphic tandem repeat minisatellite, is located in the promoter region of an antisense transcript of the human telomerase reverse transcriptase gene. MNS16A promoter activity depends on the variable number of tandem repeats (VNTR) presenting varying numbers of transcription factor binding sites for GATA binding protein 1. Although MNS16A has been investigated in multiple cancer epidemiology studies with incongruent findings, functional data of only two VNTRs (VNTR-243 and VNTR-302) were available thus far, linking the shorter VNTR to higher promoter activity.For the first time, we investigated promoter activity of all six VNTRs of MNS16A in cell lines of colorectal, lung and prostate cancer using Luciferase reporter assay. In all investigated cell lines shorter VNTRs showed higher promoter activity. While this anticipated indirect linear relationship was affirmed for colorectal cancer SW480 (P = 0.006), a piecewise linear regression model provided significantly better model fit in lung cancer A-427 (P = 6.9 × 10-9) and prostate cancer LNCaP (P = 0.039). In silico search for transcription factor binding sites in MNS16A core repeat element suggested a higher degree of complexity involving X-box binding protein 1, general transcription factor II-I, and glucocorticoid receptor alpha in addition to GATA binding protein 1.Further functional studies in additional cancers are requested to extend our knowledge of MNS16A functionality uncovering potential cancer type-specific differences. Risk alleles may vary in different malignancies and their determination in vitro could be relevant for interpretation of genotype data.

Investigating β-adrenergic-induced cardiac hypertrophy through computational approach: classical and non-classical pathways.

Science.gov (United States)

Khalilimeybodi, Ali; Daneshmehr, Alireza; Sharif-Kashani, Babak

2018-07-01

The chronic stimulation of β-adrenergic receptors plays a crucial role in cardiac hypertrophy and its progression to heart failure. In β-adrenergic signaling, in addition to the well-established classical pathway, Gs/AC/cAMP/PKA, activation of non-classical pathways such as Gi/PI3K/Akt/GSK3β and Gi/Ras/Raf/MEK/ERK contribute in cardiac hypertrophy. The signaling network of β-adrenergic-induced hypertrophy is very complex and not fully understood. So, we use a computational approach to investigate the dynamic response and contribution of β-adrenergic mediators in cardiac hypertrophy. The proposed computational model provides insights into the effects of β-adrenergic classical and non-classical pathways on the activity of hypertrophic transcription factors CREB and GATA4. The results illustrate that the model captures the dynamics of the main signaling mediators and reproduces the experimental observations well. The results also show that despite the low portion of β2 receptors out of total cardiac β-adrenergic receptors, their contribution in the activation of hypertrophic mediators and regulation of β-adrenergic-induced hypertrophy is noticeable and variations in β1/β2 receptors ratio greatly affect the ISO-induced hypertrophic response. The model results illustrate that GSK3β deactivation after β-adrenergic receptor stimulation has a major influence on CREB and GATA4 activation and consequent cardiac hypertrophy. Also, it is found through sensitivity analysis that PKB (Akt) activation has both pro-hypertrophic and anti-hypertrophic effects in β-adrenergic signaling.

LDB1-mediated enhancer looping can be established independent of mediator and cohesin.

Science.gov (United States)

Krivega, Ivan; Dean, Ann

2017-08-21

Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected. Additional deletion of the promoter GATA1 site eliminated LDB1 complex and mediator occupancy and resulted in loss of LCR/β-globin proximity. To separate the roles of LDB1 and mediator in LCR looping, we expressed a looping-competent but transcription-activation deficient form of LDB1 in LDB1 knock down cells: LCR/β-globin proximity was restored without mediator core occupancy. Further, Cas9-directed tethering of mutant LDB1 to the β-globin promoter forced LCR loop formation in the absence of mediator or cohesin occupancy. Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs. Thus, lineage specific factors largely mediate enhancer-promoter looping in erythroid cells independent of mediator and cohesin. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

Direct targets of pSTAT5 signalling in erythropoiesis.

Directory of Open Access Journals (Sweden)

Kevin R Gillinder

Full Text Available Erythropoietin (EPO acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS. The majority of pSTAT5 peaks contain a central palindromic GAS element, TTCYXRGAA. There was significant enrichment for GATA motifs and CACCC-box motifs within the neighbourhood of pSTAT5-bound peaks, and GATA1 and/or KLF1 co-occupancy at many sites. Using 4sU-RNA-seq we determined the EPO-induced transcriptome and validated differentially expressed genes using dynamic CAGE data and qRT-PCR. We identified known direct pSTAT5 target genes such as Bcl2l1, Pim1 and Cish, and many new targets likely to be involved in driving erythroid cell differentiation including those involved in mRNA splicing (Rbm25, epigenetic regulation (Suv420h2, and EpoR turnover (Clint1/EpsinR. Some of these new EpoR-JAK2-pSTAT5 target genes could be used as biomarkers for monitoring disease activity in polycythaemia vera, and for monitoring responses to JAK inhibitors.

Expression and clinical significance of NF-毷B, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy

Directory of Open Access Journals (Sweden)

Cheng-Luo Hao

2016-06-01

Full Text Available Objective: To study the expression and clinical significance of NF-kB, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy. Methods: A total of 25 nephropathy patients diagnosed with IgA nephropathy and 25 patients receiving nephrectomy due to trauma or tumor in our hospital were studied. Peripheral blood and kidney tissues were collected to test NF-kB, CTGF, OPN, T-bet, GATA-3, RORγT and Foxp3 expressions. Results: CTGF and OPN percentages in peripheral blood mononuclear cells and kidney tissues of nephropathy patients were higher than those of the control group. NF-kB, CTGF and OPN expressions were significantly higher in M1, E1, S1 group patients’ peripheral blood mononuclear cells and renal tissues than those in M0, E1 and S1 group. T-bet, GATA-3 and RORγT expressions in nephropathy patients’ peripheral blood were significantly higher than those in the control group, and were positively correlated with NF-kB, CTGF and OPN expressions. The expression of Foxp3 was significantly lower than that of control group, and was negatively correlated with NF-kB, CTGF and OPN expressions. Conclusions: The expression of NF-kB, CTGF and OPN in peripheral blood mononuclear cells and renal tissue in patients with IgA nephropathy is abnormally high and can evaluate the prognosis of the disease and the differentiation of CD4+T cells.

Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin β gene promoter

Energy Technology Data Exchange (ETDEWEB)

Matsui, Keiji; Oda, Kasumi; Mizuta, Shumpei; Ishino, Ruri; Urahama, Norinaga; Hasegawa, Natsumi [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Roeder, Robert G. [Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Ito, Mitsuhiro, E-mail: itomi@med.kobe-u.ac.jp [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Department of Family and Community Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 654-0142 (Japan); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan)

2013-10-11

Highlights: •MED1 is a bona fide T3-dependent coactivator on TSHB promoter. •Mice with LxxLL-mutant MED1 have attenuated TSHβ mRNA and thyroid hormone levels. •MED1 activates TSHB promoter T3-dependently in cultured cells. •T3-dependent MED1 action is enhanced when SRC1/SRC2 or HDAC2 is downregulated. •MED1 is also a T3-independent GATA2/Pit1 coactivator on TSHB promoter. -- Abstract: The MED1 subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor β (TRβ) on the TSHβ gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MED1 is a ligand-dependent positive cofactor on this promoter. TSHβ gene transcription was attenuated in MED1 mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSHβ gene promoter activity in a ligand-independent manner in cultured cells. MED1 also stimulated transcription from the TSHβ gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSHβ gene promoter.

Genome-wide transcriptome analysis of gametophyte development in Physcomitrella patens

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Xiao Lihong

2011-12-01

Full Text Available Abstract Background Regulation of gene expression plays a pivotal role in controlling the development of multicellular plants. To explore the molecular mechanism of plant developmental-stage transition and cell-fate determination, a genome-wide analysis was undertaken of sequential developmental time-points and individual tissue types in the model moss Physcomitrella patens because of the short life cycle and relative structural simplicity of this plant. Results Gene expression was analyzed by digital gene expression tag profiling of samples taken from P. patens protonema at 3, 14 and 24 days, and from leafy shoot tissues at 30 days, after protoplast isolation, and from 14-day-old caulonemal and chloronemal tissues. In total, 4333 genes were identified as differentially displayed. Among these genes, 4129 were developmental-stage specific and 423 were preferentially expressed in either chloronemal or caulonemal tissues. Most of the differentially displayed genes were assigned to functions in organic substance and energy metabolism or macromolecule biosynthetic and catabolic processes based on gene ontology descriptions. In addition, some regulatory genes identified as candidates might be involved in controlling the developmental-stage transition and cell differentiation, namely MYB-like, HB-8, AL3, zinc finger family proteins, bHLH superfamily, GATA superfamily, GATA and bZIP transcription factors, protein kinases, genes related to protein/amino acid methylation, and auxin, ethylene, and cytokinin signaling pathways. Conclusions These genes that show highly dynamic changes in expression during development in P. patens are potential targets for further functional characterization and evolutionary developmental biology studies.

Karyotypic variation of Glanidium ribeiroi Haseman, 1911 (Siluriformes, Auchenipteridae along the Iguazu river basin

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R. L. Lui

Full Text Available Abstract The Iguazu river is a tributary of the left margin of the Paraná river, isolated from this basin about 22 million years ago with the appearance of the Iguazu Falls. The Iguazu river is characterized by high endemism due to two factors: its rugged topography and the old isolation caused by formation of the Iguazu Falls. This study analyzed cytogenetically a population of Glanidium ribeiroi collected in a region at the final stretch of this basin, by Giemsa staining, C-banding, impregnation by silver nitrate, and FISH with probes of 5S rDNA, 18S rDNA, telomeric sequence [TTAGGG]n, and [GATA]n repeats. The diploid number was equal to 58 chromosomes. The heterochromatin was present in the terminal region of almost all chromosomes. The Ag-NORs were simple and presented interstitially on the short arm of the submetacentric pair 14, which was confirmed by FISH with 18S rDNA probe. The 5S rDNA-FISH marked only the submetacentric pair 16 on the long arm in interstitial position. The FISH with [TTAGGG]n probe presented all telomeres labeled as expected, with an absence of Interstitial Telomeric Sequence (ITS. The repetitive [GATA]n sequence was dispersed throughout the genome, with preferential location in the terminal region of all chromosomes. The data obtained are discussed herein with other species of Auchenipteridae, and other previously analyzed populations of G. ribeiroi from the Iguazu river, verifying differences among these populations, which should be mainly related to the rugged topography of this basin.

Differential transcriptional regulation of banana sucrose phosphate synthase gene in response to ethylene, auxin, wounding, low temperature and different photoperiods during fruit ripening and functional analysis of banana SPS gene promoter.

Science.gov (United States)

Roy Choudhury, Swarup; Roy, Sujit; Das, Ranjan; Sengupta, Dibyendu N

2008-12-01

Sucrose phosphate synthase (SPS) (EC 2.3.1.14) is the key regulatory component in sucrose formation in banana (Musa acuminata subgroup Cavendish, cv Giant governor) fruit during ripening. This report illustrates differential transcriptional responses of banana SPS gene following ethylene, auxin, wounding, low temperature and different photoperiods during ripening in banana fruit. Whereas ethylene strongly stimulated SPS transcript accumulation, auxin and cold treatment only marginally increased the abundance of SPS mRNA level, while wounding negatively regulated SPS gene expression. Conversely, SPS transcript level was distinctly increased by constant exposure to white light. Protein level, enzymatic activity of SPS and sucrose synthesis were substantially increased by ethylene and increased exposure to white light conditions as compared to other treatments. To further study the transcriptional regulation of SPS in banana fruit, the promoter region of SPS gene was cloned and some cis-acting regulatory elements such as a reverse GCC-box ERE, two ARE motifs (TGTCTC), one LTRE (CCGAA), a GAGA-box (GAGA...) and a GATA-box LRE (GATAAG) were identified along with the TATA and CAAT-box. DNA-protein interaction studies using these cis-elements indicated a highly specific cis-trans interaction in the banana nuclear extract. Furthermore, we specifically studied the light responsive characteristics of GATA-box containing synthetic as well as native banana SPS promoter. Transient expression assays using banana SPS promoter have also indicated the functional importance of the SPS promoter in regulating gene expression. Together, these results provide insights into the transcriptional regulation of banana SPS gene in response to phytohormones and other environmental factors during fruit ripening.

Estudo retrospectivo de 207 casos de tumores mamários em gatas

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Monique Togni

2013-03-01

Full Text Available Este estudo teve como objetivos determinar os tumores mais prevalentes em gatos e relacionar os tumores mamários a alguns de seus fatores prognósticos. Os arquivos do Laboratório de Patologia Veterinária (LPV da Universidade Federal de Santa Maria (UFSM foram revisados e um total de 1.427 protocolos de biopsias e necropsias de felinos, entre 2000 e 2011, foi encontrado. Com base nas informações dos arquivos, foi estabelecida a relação entre os tumores e alguns fatores como sexo, idade, raça, estado reprodutivo, uso de contraceptivos, número e localização das glândulas afetadas, ulcerações, tamanho do neoplasma, metástases distantes e para os linfonodos. Assim, observou-se que os tumores de mama foram o segundo diagnóstico mais prevalente, após os tumores de pele. Todos os gatos com tumores mamários eram fêmeas, sendo os sem raça definida e os idosos os mais afetados. Os neoplasmas malignos foram diagnosticados com maior frequência, seguidos pelos tumores não neoplásicos e pelos neoplasmas benignos. Os tumores menores eram, na sua maioria, carcinomas. Ulcerações estavam presentes não só em neoplasmas malignos, mas também em alterações não neoplásicas. Metástases distantes foram encontradas principalmente nos pulmões e na pele.

Mutational Analysis of GATA4 and NKX2.5 Genes in Dilated ...

African Journals Online (AJOL)

All rights reserved. Available ... Results: Evaluation of the age and sex of the patients indicated that DCM was more prevalent among ... NKX 2.5 are essential for cardiac development, and .... severe left ventricular dysfunction and a lower.

Identification of functionally related genes using data mining and data integration: a breast cancer case study

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Zucchi Ileana

2009-10-01

. Two genes among the predicted putative partners of TBX3 (GLI3 and GATA3 were confirmed by in vivo binding assays (crosslinking immunoprecipitation, X-ChIP in which the putative DNA enhancer sequence sites of GATA3 and GLI3 were found to be bound by the Tbx3 protein. Conclusion The presented strategy is demonstrated to be an effective approach to identify genes that establish functional relationships. The methodology identifies and characterises genes with a similar expression profile, through data mining and integrating data from publicly available resources, to contribute to a better understanding of gene regulation and cell function. The prediction of the TBX3 target genes GLI3 and GATA3 was experimentally confirmed.

New energy introduction guidebook for Chugoku area; Shin energy donyu guidebook. Chugoku chiiki

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-05

A guidebook was edited for the purpose of assisting introduction of new energies. Sections consist of Section 1, new energies available in the Chugoku area; Section 2, procedure for new energy introduction; Section 3, assistance institutions by energy; and Section 4, the status of new energy introduction in the Chugoku area, the future introduction targets, and referential materials. Section 1, upon defining the new energies, summarized features of photovoltaic power generation, solar heat utilization, wind power generation, wastes power generation, cogeneration, fuel cells, clean energy fueled automobiles, and introduction records up to the year 2000. Section 2 summarizes the general roles of local governments in the introduction, processing procedures for individual programs, related regulations, and summary of the assistance institutions. Section 3 puts into order the assistance institutions by energy. Section 4 summarizes precautions, targets and records in introduction by each new energy. The referential materials include a list of the Japanese assistance institutions, and subsidy institutions related to new energies for local governments in the Chugoku area. (NEDO)

FLT3 mutations in early T-cell precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors.

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Martin Neumann

Full Text Available Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68 in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%. Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-, a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3 and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements. The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%. To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup.

Haplotype diversity of 17 Y-chromosomal STRs in three native Sarawak populations (Iban, Bidayuh and Melanau) in East Malaysia.

Science.gov (United States)

Chang, Yuet Meng; Swaran, Yuvaneswari; Phoon, Yoong Keat; Sothirasan, Kavin; Sim, Hang Thiew; Lim, Kong Boon; Kuehn, Daniel

2009-06-01

17 Y-STRs (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635 or Y-GATA C4, DYS392, Y-GATA H4, DYS437, DYS438 and DYS448) have been analyzed in 320 male individuals from Sarawak, an eastern state of Malaysia on the Borneo island using the AmpFlSTR Y-filer (Applied Biosystems, Foster City, CA). These individuals were from three indigenous ethnic groups in Sarawak comprising of 103 Ibans, 113 Bidayuhs and 104 Melanaus. 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 groups. Analysis of molecular variance (AMOVA) indicated that 87.6% of the haplotypic variation was found within population and 12.4% between populations (fixation index F(ST)=0.124, p=0.000). This study has revealed that the indigenous populations in Sarawak are distinctly different to each other, and to the three major ethnic groups in Malaysia (Malays, Chinese and Indians), with the Melanaus having a strikingly high degree of shared haplotypes within. There are rare unusual variants and microvariants that were not present in Malaysian Malay, Chinese or Indian groups. In addition, occurrences of DYS385 duplications which were only noticeably present in Chinese group previously was also observed in the Iban group whilst null alleles were detected at several Y-loci (namely DYS19, DYS392, DYS389II and DYS448) in the Iban and Melanau groups.

Transcriptional activation of prostate specific homeobox gene NKX3-1 in subsets of T-cell lymphoblastic leukemia (T-ALL.

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Stefan Nagel

Full Text Available Homeobox genes encode transcription factors impacting key developmental processes including embryogenesis, organogenesis, and cell differentiation. Reflecting their tight transcriptional control, homeobox genes are often embedded in large non-coding, cis-regulatory regions, containing tissue specific elements. In T-cell acute lymphoblastic leukemia (T-ALL homeobox genes are frequently deregulated by chromosomal aberrations, notably translocations adding T-cell specific activatory elements. NKX3-1 is a prostate specific homeobox gene activated in T-ALL patients expressing oncogenic TAL1 or displaying immature T-cell characteristics. After investigating regulation of NKX3-1 in primary cells and cell lines, we report its ectopic expression in T-ALL cells independent of chromosomal rearrangements. Using siRNAs and expression profiling, we exploited NKX3-1 positive T-ALL cell lines as tools to investigate aberrant activatory mechanisms. Our data confirmed NKX3-1 activation by TAL1/GATA3/LMO and identified LYL1 as an alternative activator in immature T-ALL cells devoid of GATA3. Moreover, we showed that NKX3-1 is directly activated by early T-cell homeodomain factor MSX2. These activators were regulated by MLL and/or by IL7-, BMP4- and IGF2-signalling. Finally, we demonstrated homeobox gene SIX6 as a direct leukemic target of NKX3-1 in T-ALL. In conclusion, we identified three major mechanisms of NKX3-1 regulation in T-ALL cell lines which are represented by activators TAL1, LYL1 and MSX2, corresponding to particular T-ALL subtypes described in patients. These results may contribute to the understanding of leukemic transcriptional networks underlying disturbed T-cell differentiation in T-ALL.

Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2.

Science.gov (United States)

Jin, Li; Lin, Ming Quan; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Sun, Simei; Kee, Hae Jin; Jeong, Myung Ho

2017-07-01

Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism. Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting. Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis. These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.

Characterization of TRPS1 and ERAS as oncogenes implicated in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Lopez Gonzalez, L.

2015-07-01

New high throughput technologies have made possible to identify putative oncogenes in breast cancer. In this project we aim to relate and characterise two novel putative oncogenes, ERAS and TRPS1, in their role in human breast cancer. TRPS1, an atypical GATA factor, modulates cell proliferation and controls cell cycle progression through repression of GATA-regulated genes, therefore acting as a tumour suppressor gene. Conversely, TRPS1 expression has been shown to be significantly elevated in luminal and in a lesser extent in basal breast cancer cells, presenting roles both as an oncogene and as a tumour suppressor gene in breast cancer development. The aim of this project is therefore to determine the characteristics of TRPS1 either as a putative novel human oncogene or as a tumour suppressor gene in breast cancer cells. To this aim, we have cloned a novel isoform of TRPS1 and introduced it into several breast cancer cell lines. Our results show that overexpression of this isoform of TRPS1 results in variations in motility in non-carcinogenic cell lines, as well as in a series of EMT-like changes such as the down-regulation of the EMT marker E-cadherin, both of which can be associated to an increase in malignancy, suggesting an oncogenic behaviour for TRPS1. Furthermore, our results suggest that constitutively active members of the RAS protein family induce the expression of TRPS1, establishing a relationship between both genes. We can conclude that the effects of TRPS1 overexpression are moderate, inducing some changes but not fully transforming the cells. Therefore we cannot confirm that TRPS1 is a putative oncogene in breast cancer. (Author)

Na-smectite s in the Cala de Tomate bentonite deposit (Spain): a natural analogue of the salinity effect on the bentonite barrier of a rad waste disposal

Energy Technology Data Exchange (ETDEWEB)

Perez del Villar, L.; Pelayo, M.; Fernandez, A.M.; Cozar, J.S. [CIEMAT - Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT/DIRE/CEAGP), Madrid (Spain); Delgado, A.; Reyes, E. [Ciencias de la Tierra y Quimica Ambiental Estacion Experimental del Zaidin Dpt., Granada (Spain); Fernandez-Soler, J.M. [Granada Univ., Dpt. de Mineralogia y Petrologia (Spain); Tsige, M. [Facultad de Ciencias Geologicas, Dpt. de Geodinamica, Madrid (Spain)

2005-07-01

Within the framework of the ENRESA programme for the assessment of the long-term behaviour of the bentonite-engineered barrier for a deep radwaste geological repository, analogue studies on several bentonite deposits are conducted at CIEMAT. Among these analogue studies, the thermal effect induced by volcanic intrusions on bentonite deposits is highlighted. In the Cabo de Gata volcanic region, there are several analogue scenarios where these studies have been performed, such as the Cala de Tomate bentonite deposit that was intruded by a pyroxene andesite volcanic dome. However, geological, mineralogical, physicochemical, geochemical and stable isotopic data obtained from the smectites do not allow to establish any analogy with the thermal effect expected on the bentonite-engineered barrier of a deep geological repository after burial. Thus, the bentonitisation processes took place after the intrusion of the dome, as a result of meteoric diagenesis intensively developed on faulting zone affecting the parent pyroclastic acid tuffs. This faulting process occurred after the dome intrusion. However, the physicochemical characteristics of these smectites, specially the exchangeable cations, allow to consider this bentonite deposit as a natural analogue of the saline effect on the clayey barrier. This analogy has been established because Na-smectites are present in this deposit and, up to our present knowledge, it is the first time that these smectites occur naturally in the Cabo de Gata-La Serrata de Nijar volcanic region. As a consequence, the main objectives of this work are: i) to characterise these smectites; ii) to establish their genesis and processes affecting them after their formation and iii) to identify the effects on the bentonite-engineered barrier should it were affected by a Na-rich saline waterfront. (authors)

FY 2000 report on the survey of extraction of areas promising in strategic geothermal development. Kurikoma peripheral region; 2000 nendo senryakuteki chinetsu kaihatsu yubo chiiki chushutsu chosa hokokusho. Kurikoma shuhen chiiki

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

An investigational study was conducted for the Kurikoma peripheral region with the aim of contributing to the selection of important areas for survey, plans to be worked out for introduction of medium-term/long-term and effective geothermal development promotion survey, estimation of the developmental resource amount in the areas, etc. In the study, based on the geological survey, geochemical survey, physical survey and well survey which were conducted directly for the Kurikoma peripheral region, the data needed to elucidate geothermal structure elements were extracted and re-analyzed to make geothermal models. Based on the geothermal system conceptual model made, the data on the areas already developed, etc. were arranged to make criteria for extraction of promising areas. By the criteria, the following three areas were selected, and geothermal structure models were made for the areas: promising area 1 in geothermal development (Sanzugawa-Oyu spa, 66km{sup 2}), promising area 2 (Wasabizawa-Akinomiya area, 37km{sup 2}), promising area 3 (Onikobe-Kamitaki spa, 21km{sup 2}). These promising areas were evaluated by the resource amount density, data likelihood, regulation by the natural park law, etc. Important areas for survey were selected and the resource amount was calculated. (NEDO)

FY 2000 report on the survey for extraction of areas promising in strategic exploration geothermal development. Kirishima region; 2000 nendo senryakuteki chosa chinetsu kaihatsu yubo chiiki chushutsu chosa hokokusho. Kirishima chiiki

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

An investigational study was conducted for the Kirishima region with the aim of contributing to working out future medium- and long-term plans of geothermal development promotion survey, estimation of the developmental resource amount, extraction of technology development subjects effectively connecting to the increase in kW, etc. In the study, literature is collected such as reports of the surveys already made in the Kirishima region and the periphery, the data were re-analyzed and divided into geological structure elements and geological structure elements, and a conceptual model of the geothermal system in the whole Kirishima region was made. As a result, two areas were extracted for which the existence of high temperature geothermal reservoirs is expected. The total resource amount was estimated at 2,785MWe at promising area 1 and at 3,237MWe at promising area 2. With the resource amount density, data likelihood and distribution status of national/quasi-national parks as extraction criteria, 6 out of these promising areas were focused on important areas for survey. Geothermal structure models were made for each of the 6 areas, and the evaluation of the resource amount using evaluation assist tools was carried out. (NEDO)

FY 2000 report on the survey of extraction of areas promising in strategic geothermal development. Hachimantai south region; 2000 nendo senryakuteki chinetsu kaihatsu yubo chiiki chushutsu chosa hokokusho. Hachimantai nanbu chiiki

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

An investigational study was conducted for the Hachimantai south region with the aim of contributing to plans to be worked out for introduction of medium-term/long-term and important geothermal development promotion surveys, estimation of the developmental resource amount, etc. In the survey, the data were widely collected/arranged on the geothermal development surveys so far made in the Hachimantai south region, and wide-area geothermal system conceptual models in this region were constructed. Based on the wide-area geothermal system conceptual models and the manual for strategic survey, the following were extracted as areas for which the existence of geothermal reservoir structures is expected: Toshichi spa and the southeast area, Kakkonda-Matsukawa-Iwateyama area, Nyuto spa and the southwest area. Further, from the criteria for extraction such as the resource amount density, the natural park law and data likelihood, extracted were the Moroedake area (9km{sup 2}), Matsukawa east area (10km{sup 2}), Omatsukurayama south area (9km{sup 2}) and Kakkonda east area (14km{sup 2}). In the Monte Carlo analysis by the stored heat method, the resource amount was estimated as 5MWe, 14MWe, 4MWe and 48MWe, respectively. (NEDO)

Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1

DEFF Research Database (Denmark)

Glubb, Dylan M; Maranian, Mel J; Michailidou, Kyriaki

2015-01-01

evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent......CHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3...

Atividade respiratória e aspectos microbiológicos de cultivares de batatas minimamente processadas e armazenadas em diferentes temperaturas Respiratory activity and microbiological aspects of minimally processed potatoes cultivars stored at different temperatures

Directory of Open Access Journals (Sweden)

Maria Carolina Dario Vitti

2010-02-01

Full Text Available O presente trabalho teve como objetivo avaliar aspectos fisiológicos e microbiológicos de diferentes cultivares de batatas minimamente processadas. Batatas das cultivares 'Ágata', 'Asterix' e 'Monalisa' foram selecionadas, classificadas, lavadas e descascadas por abrasão, sendo em seguida cortadas em cubos, sanitizadas e centrifugadas. Depois foram colocadas em frascos herméticos e armazenadas a 5, 15 e 25°C. Foram determinadas a atividade respiratória e a produção de etileno logo após o processamento e durante 10 horas. As análises microbiológicas foram realizadas no dia do processamento e após nove, cinco e um dia de conservação, a 5, 15 e 25°C, respectivamente. Observou-se que as batatas 'Asterix' apresentaram maiores taxas respiratórias em relação às cultivares 'Ágata' e 'Monalisa', independentemente da temperatura de armazenamento. Nas temperaturas de 15 e 25oC, as batatas 'Ágata' e 'Monalisa' apresentaram comportamentos semelhantes entre si. As contagens de bactérias psicrotróficas e coliformes totais, para todas as cultivares armazenadas 5oC, mantiveram-se dentro dos limites aceitáveis durante nove dias de armazenamento. Não foram detectados coliformes a 45°C e Salmonella. Ficou evidenciada a eficiência do armazenamento a 5°C no controle da atividade metabólica e na segurança microbiológica de batatas minimamente processadas.The purpose of the present research was to evaluate physiological and microbiological aspects of different minimally processed potatoes cultivars. Potatoes cultivar 'Agata', 'Asterix' and 'Monalisa' were selected, classified, washed and abrasion peeled before being diced, sanitized and centrifuged. They were then placed in hermetically closed flasks and stored at 5, 15 and 25°C. The respiratory activity and ethylene production were determined immediately after the processing and during 10 hours. Microbiological analyses were carried out on the processing day and after one, five and

Rho-associated kinase inhibitors promote the cardiac differentiation of embryonic and induced pluripotent stem cells.

Science.gov (United States)

Cheng, Ya-Ting; Yeih, Dong-Feng; Liang, Shu-Man; Chien, Chia-Ying; Yu, Yen-Ling; Ko, Bor-Sheng; Jan, Yee-Jee; Kuo, Cheng-Chin; Sung, Li-Ying; Shyue, Song-Kun; Chen, Ming-Fong; Yet, Shaw-Fang; Wu, Kenneth K; Liou, Jun-Yang

2015-12-15

Rho-associated kinase (ROCK) plays an important role in maintaining embryonic stem (ES) cell pluripotency. To determine whether ROCK is involved in ES cell differentiation into cardiac and hematopoietic lineages, we evaluated the effect of ROCK inhibitors, Y-27632 and fasudil on murine ES and induced pluripotent stem (iPS) cell differentiation. Gene expression levels were determined by real-time PCR, Western blot analysis and immunofluorescent confocal microscopy. Cell transplantation of induced differentiated cells were assessed in vivo in a mouse model (three groups, n=8/group) of acute myocardial infarction (MI). The cell engraftment was examined by immunohistochemical staining and the outcome was analyzed by echocardiography. Cells were cultured in hematopoietic differentiation medium in the presence or absence of ROCK inhibitor and colony formation as well as markers of ES, hematopoietic stem cells (HSC) and cells of cardiac lineages were analyzed. ROCK inhibition resulted in a drastic change in colony morphology accompanied by loss of hematopoietic markers (GATA-1, CD41 and β-Major) and expressed markers of cardiac lineages (GATA-4, Isl-1, Tbx-5, Tbx-20, MLC-2a, MLC-2v, α-MHC, cTnI and cTnT) in murine ES and iPS cells. Fasudil-induced cardiac progenitor (Mesp-1 expressing) cells were infused into a murine MI model. They engrafted into the peri-infarct and infarct regions and preserved left ventricular function. These findings provide new insights into the signaling required for ES cell differentiation into hematopoietic as well as cardiac lineages and suggest that ROCK inhibitors are useful in directing iPS cell differentiation into cardiac progenitor cells for cell therapy of cardiovascular diseases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Increased levels of NOTCH1, NF-kappaB, and other interconnected transcription factors characterize primitive sets of hematopoietic stem cells.

Science.gov (United States)

Panepucci, Rodrigo Alexandre; Oliveira, Lucila Habib B; Zanette, Dalila Luciola; Viu Carrara, Rita de Cassia; Araujo, Amélia Goes; Orellana, Maristela Delgado; Bonini de Palma, Patrícia Vianna; Menezes, Camila C B O; Covas, Dimas Tadeu; Zago, Marco Antonio

2010-03-01

As previously shown, higher levels of NOTCH1 and increased NF-kappaB signaling is a distinctive feature of the more primitive umbilical cord blood (UCB) CD34+ hematopoietic stem cells (HSCs), as compared to bone marrow (BM). Differences between BM and UCB cell composition also account for this finding. The CD133 marker defines a more primitive cell subset among CD34+ HSC with a proposed hemangioblast potential. To further evaluate the molecular basis related to the more primitive characteristics of UCB and CD133+ HSC, immunomagnetically purified human CD34+ and CD133+ cells from BM and UCB were used on gene expression microarrays studies. UCB CD34+ cells contained a significantly higher proportion of CD133+ cells than BM (70% and 40%, respectively). Cluster analysis showed that BM CD133+ cells grouped with the UCB cells (CD133+ and CD34+) rather than to BM CD34+ cells. Compared with CD34+ cells, CD133+ had a higher expression of many transcription factors (TFs). Promoter analysis on all these TF genes revealed a significantly higher frequency (than expected by chance) of NF-kappaB-binding sites (BS), including potentially novel NF-kappaB targets such as RUNX1, GATA3, and USF1. Selected transcripts of TF related to primitive hematopoiesis and self-renewal, such as RUNX1, GATA3, USF1, TAL1, HOXA9, HOXB4, NOTCH1, RELB, and NFKB2 were evaluated by real-time PCR and were all significantly positively correlated. Taken together, our data indicate the existence of an interconnected transcriptional network characterized by higher levels of NOTCH1, NF-kappaB, and other important TFs on more primitive HSC sets.

Long-term outcome for Down syndrome patients with hematopoietic disorders.

Science.gov (United States)

Li, Meng-Ju; Lee, Ni-Chung; Yang, Yung-Li; Yen, Hsiu-Ju; Chang, Hsiu-Hao; Chien, Yin-Hsiu; Lu, Meng-Yao; Jou, Shiann-Tarng; Lin, Kai-Hsin; Hwu, Wuh-Liang; Lin, Dong-Tsamn

2016-02-01

Although Down syndrome (DS) patients have a higher risk of developing transient myeloproliferative disorder (TMD) and acute leukemia, very little data is available on long-term outcome in Taiwanese patients. The current study was designed to determine the clinical characteristics and treatment outcome of DS patients with TMD or acute leukemia (AL). In 25 consecutive DS patients with TMD or AL enrolled from 1990 to 2012, clinical manifestations and treatment protocols were investigated and GATA1 (GATA binding protein 1) mutations were identified. Among 16 DS-acute myeloid leukemia (DS-AML) patients, clinical outcomes were compared between survivors and nonsurvivors. Most of our DS patients had TMD (32%), acute megakaryoblastic leukemia (24%), or acute erythromegakaryoblastic leukemia (16%). The median follow-up time was 22.5 months (1-230 months). The age was younger and the hemoglobin (Hb) level and platelet count were higher in TMD patients than in leukemia patients. Among DS-AML patients, the Hb level was higher in survivors than nonsurvivors (8.8 ± 2.7 g/dL vs. 5.8 ± 2.4 g/dL; p = 0.044) and the age was older in relapsed patients than in nonrelapsed patients (43.8 ± 18 months old vs. 21.6 ± 8.6 months old; p = 0.025). The 3-year overall survival (OS) rate was 44%, higher in patients receiving appropriate chemotherapy than in those receiving inadequate treatment (63.6% vs. 0%, p = 0.001), and higher in those diagnosed with TMD or AL after 2008 than before 2008 (33.3% vs. 75%; p = 0.119). Outcome in DS-AML patients is optimal if appropriate treatment is provided. With modification of the treatment strategy in 2008, OS increased in Taiwan. Copyright © 2015. Published by Elsevier B.V.

Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct.

Science.gov (United States)

Yu, Ming-Jiun; Miller, R Lance; Uawithya, Panapat; Rinschen, Markus M; Khositseth, Sookkasem; Braucht, Drew W W; Chou, Chung-Lin; Pisitkun, Trairak; Nelson, Raoul D; Knepper, Mark A

2009-02-17

We used a systems biology-based approach to investigate the basis of cell-specific expression of the water channel aquaporin-2 (AQP2) in the renal collecting duct. Computational analysis of the 5'-flanking region of the AQP2 gene (Genomatix) revealed 2 conserved clusters of putative transcriptional regulator (TR) binding elements (BEs) centered at -513 bp (corresponding to the SF1, NFAT, and FKHD TR families) and -224 bp (corresponding to the AP2, SRF, CREB, GATA, and HOX TR families). Three other conserved motifs corresponded to the ETS, EBOX, and RXR TR families. To identify TRs that potentially bind to these BEs, we carried out mRNA profiling (Affymetrix) in mouse mpkCCDc14 collecting duct cells, revealing expression of 25 TRs that are also expressed in native inner medullary collecting duct. One showed a significant positive correlation with AQP2 mRNA abundance among mpkCCD subclones (Ets1), and 2 showed a significant negative correlation (Elf1 and an orphan nuclear receptor Nr1h2). Transcriptomic profiling in native proximal tubules (PT), medullary thick ascending limbs (MTAL), and IMCDs from kidney identified 14 TRs (including Ets1 and HoxD3) expressed in the IMCD but not PT or MTAL (candidate AQP2 enhancer roles), and 5 TRs (including HoxA5, HoxA9 and HoxA10) expressed in PT and MTAL but not in IMCD (candidate AQP2 repressor roles). In luciferase reporter assays, overexpression of 3 ETS family TRs transactivated the mouse proximal AQP2 promoter. The results implicate ETS family TRs in cell-specific expression of AQP2 and point to HOX, RXR, CREB and GATA family TRs as playing likely additional roles.

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.

Multilayered epithelium in a rat model and human Barrett's esophagus: Similar expression patterns of transcription factors and differentiation markers

Directory of Open Access Journals (Sweden)

Yang Chung S

2008-01-01

Full Text Available Abstract Background In rats, esophagogastroduodenal anastomosis (EGDA without concomitant chemical carcinogen treatment leads to gastroesophageal reflux disease, multilayered epithelium (MLE, a presumed precursor in intestinal metaplasia, columnar-lined esophagus, dysplasia, and esophageal adenocarcinoma. Previously we have shown that columnar-lined esophagus in EGDA rats resembled human Barrett's esophagus (BE in its morphology, mucin features and expression of differentiation markers (Lab. Invest. 2004;84:753–765. The purpose of this study was to compare the phenotype of rat MLE with human MLE, in order to gain insight into the nature of MLE and its potential role in the development of BE. Methods Serial sectioning was performed on tissue samples from 32 EGDA rats and 13 patients with established BE. Tissue sections were immunohistochemically stained for a variety of transcription factors and differentiation markers of esophageal squamous epithelium and intestinal columnar epithelium. Results We detected MLE in 56.3% (18/32 of EGDA rats, and in all human samples. As expected, both rat and human squamous epithelium, but not intestinal metaplasia, expressed squamous transcription factors and differentiation markers (p63, Sox2, CK14 and CK4 in all cases. Both rat and human intestinal metaplasia, but not squamous epithelium, expressed intestinal transcription factors and differentiation markers (Cdx2, GATA4, HNF1α, villin and Muc2 in all cases. Rat MLE shared expression patterns of Sox2, CK4, Cdx2, GATA4, villin and Muc2 with human MLE. However, p63 and CK14 were expressed in a higher proportion of rat MLE compared to humans. Conclusion These data indicate that rat MLE shares similar properties to human MLE in its expression pattern of these markers, not withstanding small differences, and support the concept that MLE may be a transitional stage in the metaplastic conversion of squamous to columnar epithelium in BE.

Molecular dissection of prethymic progenitor entry into the T lymphocyte developmental pathway

Energy Technology Data Exchange (ETDEWEB)

Fung, Elizabeth-sharon [Los Alamos National Laboratory

2008-01-01

Notch signaling activates T lineage differentiation from hemopoietic progenitors, but relatively few regulators that initiate this program have been identified, e.g., GATA3 and T cell factor-I (TCF-1) (gene name Tcli). To identify additional regulators of T cell specification, a cDNA libnlrY from mouse Pro-T cells was screened for genes that are specifically up-regulated in intrathymic T cell precursors as compared with myeloid progenitors. Over 90 genes of interest were identified, and 35 of 44 tested were confirmed to be more highly expressed in T lineage precursors relative to precursors of B and/or myeloid lineage. To a remarkable extent, however, expression of these T lineage-enriched genes, including zinc finger transcription factor, helicase, and signaling adaptor genes, was also shared by stem cells (Lin{sup -}Sca-1{sup +}Kit{sup +}CD27{sup -}) and multipotent progenitors (Lin{sup -}Sca-l{sup +}Kit{sup +}CD27{sup +}), although down-regulated in other lineages. Thus, a major fraction of these early T lineage genes are a regulatory legacy from stem cells. The few genes sharply up-regulated between multipotent progenitors and Pro-T cell stages included those encoding transcription factors Bclllb, TCF-I (Tcli), and HEBalt, Notch target Deltexl, Deltex3L, Fkbp5, Eval, and Tmem13l. Like GATA3 and Deltexl, Bclllb, Fkbp5, and Eval were dependent on Notch/Delta signaling for induction in fetal liver precursors, but only BcIlI band HEBalt were up-regulated between the first two stages of intrathymic T cell development (double negative I and double negative 2) corresponding to T lineage specification. Bclllb was uniquely T lineage restricted and induced by NotchlDelta signaling specifically upon entry into the T lineage differentiation pathway.

Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen.

Directory of Open Access Journals (Sweden)

William P Lafuse

Full Text Available Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (α-globin, β-globin, ALAS2 were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR and transcription factors (GATA1, GATA2, FOG1 were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL, was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by

Elastin receptor (S-gal) occupancy by elastin peptides modulates T-cell response during murine emphysema.

Science.gov (United States)

Meghraoui-Kheddar, Aïda; Pierre, Alexandre; Sellami, Mehdi; Audonnet, Sandra; Lemaire, Flora; Le Naour, Richard

2017-09-01

Chronic obstructive pulmonary disease and emphysema are associated with increased elastin peptides (EP) production because of excessive breakdown of lung connective tissue. We recently reported that exposure of mice to EP elicited hallmark features of emphysema. EP effects are largely mediated through a receptor complex that includes the elastin-binding protein spliced-galactosidase (S-gal). In previous studies, we established a correlation between cytokine production and S-gal protein expression in EP-treated immune cells. In this study, we investigated the S-gal-dependent EP effects on T-helper (Th) and T-cytotoxic (Tc) responses during murine EP-triggered pulmonary inflammation. C57BL/6J mice were endotracheally instilled with the valine-glycine-valine-alanine-proline-glycine (VGVAPG) elastin peptide, and, 21 days after treatment, local and systemic T-lymphocyte phenotypes were analyzed at cytokine and transcription factor expression levels by multicolor flow cytometry. Exposure of mice to the VGVAPG peptide resulted in a significant increase in the proportion of the CD4 + and CD8 + T cells expressing the cytokines IFN-γ or IL-17a and the transcription factors T-box expressed in T cells or retinoic acid-related orphan receptor-γt (RORγt) without effects on IL-4 and Gata-binding protein 3 to DNA sequence [A/T]GATA[A/G] expression. These effects were maximized when each T-cell subpopulation was challenged ex vivo with EP, and they were inhibited in vivo when an analogous peptide antagonizing the EP/S-gal interactions was instilled together with the VGVAPG peptide. This study demonstrates that, during murine emphysema, EP-S-gal interactions contribute to a Th-1 and Th-17 proinflammatory T-cell response combined with a Tc-1 response. Our study also highlights the S-gal receptor as a putative pharmacological target to modulate such an immune response. Copyright © 2017 the American Physiological Society.

Nkx2.5 enhances the efficacy of mesenchymal stem cells transplantation in treatment heart failure in rats.

Science.gov (United States)

Deng, Bo; Wang, Jin Xin; Hu, Xing Xing; Duan, Peng; Wang, Lin; Li, Yang; Zhu, Qing Lei

2017-08-01

The aim of this study is to determine whether Nkx2.5 transfection of transplanted bone marrow mesenchymal stem cells (MSCs) improves the efficacy of treatment of adriamycin-induced heart failure in a rat model. Nkx2.5 was transfected in MSCs by lentiviral vector transduction. The expressions of Nkx2.5 and cardiac specific genes in MSCs and Nkx2.5 transfected mesenchymal stem cells (MSCs-Nkx2.5) were analyzed with quantitative real-time PCR and Western blot in vitro. Heart failure models of rats were induced by adriamycin and were then randomly divided into 3 groups: injected saline, MSCs or MSCs-Nkx2.5 via the femoral vein respectively. Four weeks after injection, the cardiac function, expressions of cardiac specific gene, fibrosis formation and collagen volume fraction in the myocardium as well as the expressions of GATA4 and MEF2 in rats were analyzed with echocardiography, immunohistochemistry, Masson staining, quantitative real-time PCR and Western blot, respectively. Nkx2.5 enhanced cardiac specific gene expressions including α-MHC, TNI, CKMB, connexin-43 in MSCs-Nkx2.5 in vitro. Both MSCs and MSCs-Nkx2.5 improved cardiac function, promoted the differentiation of transplanted MSCs into cardiomyocyte-like cells, decreased fibrosis formation and collagen volume fraction in the myocardium, as well as increased the expressions of GATA4 and MEF2 in adriamycin-induced rat heart failure models. Moreover, the effect was much more remarkable in MSCs-Nkx2.5 than in MSCs group. This study has found that Nkx2.5 enhances the efficacy of MSCs transplantation in treatment adriamycin-induced heart failure in rats. Nkx2.5 transfected to transplanted MSCs provides a potential effective approach to heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

ETS-4 is a transcriptional regulator of life span in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Bargavi Thyagarajan

2010-09-01

Full Text Available Aging is a complex phenotype responsive to a plethora of environmental inputs; yet only a limited number of transcriptional regulators are known to influence life span. How the downstream expression programs mediated by these factors (or others are coordinated into common or distinct set of aging effectors is an addressable question in model organisms, such as C. elegans. Here, we establish the transcription factor ETS-4, an ortholog of vertebrate SPDEF, as a longevity determinant. Adult worms with ets-4 mutations had a significant extension of mean life span. Restoring ETS-4 activity in the intestine, but not neurons, of ets-4 mutant worms rescued life span to wild-type levels. Using RNAi, we demonstrated that ets-4 is required post-developmentally to regulate adult life span; thus uncoupling the role of ETS-4 in aging from potential functions in worm intestinal development. Seventy ETS-4-regulated genes, identified by gene expression profiling of two distinct ets-4 alleles and analyzed by bioinformatics, were enriched for known longevity effectors that function in lipid transport, lipid metabolism, and innate immunity. Putative target genes were enriched for ones that change expression during normal aging, the majority of which are controlled by the GATA factors. Also, some ETS-4-regulated genes function downstream of the FOXO factor, DAF-16 and the insulin/IGF-1 signaling pathway. However, epistasis and phenotypic analyses indicate that ets-4 functioned in parallel to the insulin/IGF-1 receptor, daf-2 and akt-1/2 kinases. Furthermore, ets-4 required daf-16 to modulate aging, suggesting overlap in function at the level of common targets that affect life span. In conclusion, ETS-4 is a new transcriptional regulator of aging, which shares transcriptional targets with GATA and FOXO factors, suggesting that overlapping pathways direct common sets of lifespan-related genes.

District energy-saving visions for Town of Towa; Towa machi chiiki sho energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

The energy-saving visions are drawn for Town of Towa, Iwate Pref., to promote energy saving and abatement of gas emissions which cause global warming. The priority projects in the energy-saving visions include introduction of energy-saving type vehicles, houses/buildings, illuminators; introduction of solar energy utilization systems and alternative energy (e.g., wood, wastes from domestic animals and microhydroelectric power generation); and monitoring/observation of energy consumption situations and energy-saving education. The energy-saving target is set at 3,120kL as crude oil. The energy-saving activities studied for the administrative and public sectors include introduction of energy-saving type vehicles and buildings; introduction of solar energy utilization systems (for roads and public facilities when they are replaced) and microhydroelectric power generation; and monitoring/observation of energy consumption situations and energy-saving education. The energy-saving target is set at 80kL as crude oil. (NEDO)

New energy vision in Iwaizumi Township area; 2000 nendo Iwaizumicho chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

A new energy vision was established in the Iwaizumi Township area in Iwate Prefecture. The heat energy consumed by each household in Iwaizumi Town is 20.5 two-hundred-liter drums, while transportation (railways, buses, trucks and private cars) consumes 12.2 drums annually, and the electric energy field 4.7 drums annually. As the town as a whole, the ratio of utilization as heat energy is relatively high. Therefore, new energy introduction should be focused importantly on use of solar heat hot water supply device and high-level utilization of forestry fuels. The new energy introduction project includes introduction of bio-mass energy to produce heat energy and electric power using livestock excreta, cut woods, thinned woods, and kitchen refuses as the resources, structuring a new energy model for the 'Communication Land Iwaizumi', activation of the central urban area by introducing micro hydropower generation, assistance to proliferation of new energies to town-operated houses, households, and business entities, introduction of new energies into the disaster prevention center, schools, and insurance, medical and welfare facilities, introduction of clean energy automobiles, and uplift of consciousness of town people. (NEDO)

New energy visions for the Town of Ichinohe district; Ichinohecho chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

The new energy visions are drawn for Town of Ichinohe, Iwate Pref. The town's population has been generally decreasing since 1975, from 21,433 to 17,906 in 1995. The town consumed energy totaling 288,691Gcal in 1998, of which the transportation sector accounts for 55%, followed by the domestic, commercial and industrial sectors, in this order, the industrial sector accounting for only 7%. The estimated new energy sources available to the town are wind power, power generated by temperature difference at rivers or using snow, solar energy, biomass energy and energy from wastes, in the order of quantity, totaling 137GWh/y as electrical power and 45.6Tcal/y as heat. The priority projects include making Ichinohe Primary School an eco-school, construction of a biomass demonstration plant in the Okunakayama district, introduction of a boiler firing wood chips at Okunakayama Heights, construction of a wind power mill at Takamori Heights, and introduction of new energies by the citizens. (NEDO)

New energy vision of Oshimizu Town; 2001 nendo Oshimizu machi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-02-01

For the purpose of promoting the introduction of new energy and enhancing the awareness of it in Oshimizu Town, Ishikawa Prefecture, an investigational study was conducted of the energy consumption amount of the city, existence amount of new energy and project for new energy introduction, and a vision was worked out. The energy consumption amount of the city was 3.02 x 10{sup 11} kcal, out of which electric power was 1.53 x 10{sup 11} kcal, petroleum 1.33 x 10{sup 11} kcal, and LPG 1.59 x 10{sup 10} kcal. As the project for new energy introduction, the following were studied: introduction of photovoltaic power generation to the general center/Oshimizu Junior High School/general household; solar energy utilization for the general center/general household; introduction of wind power generation to the Azuma Line of forest road; biomass power generation project using cattle feces/hog feces; RDF project for waste from Oshimizu Town; introduction of clean energy vehicle (hybrid car/electric car). The amount of new energy introduction from these was estimated at 1,716kL in crude oil conversion, which is equal to 5.3% of the energy demand amount. (NEDO)

New energy vision in Gamagori City area (Aichi Prefecture); Gamagorishi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

With an objective of early realization of a district society harmonized with the natural environment, a vision was established as a guideline to achieve systematic and effective introduction of new energies, with cooperation from citizens, business entities, and the administration. The activity achievements were put into order by the following six items: 1) movements in introducing new energy systems, 2) identification of the characteristics of the district and major relevant measures, 3) identification of the current status and characteristics of the energy demand structure in the district, 4) estimation of existence and utilizable quantity of new energies, 5) needs of introduction of new energies in the area, and 6) introduction possibilities, realization measures, and proliferation acceleration measures. Item 6 is composed of considerations given from the result of the initial stage investigation, basic ideas, targets of the introduction, introduction policies, and promotion of energy countermeasures. Plans were made on a solar heat hot water supply system, a photovoltaic power generation system, a wind power generation system, and introduction of clean energy fueled automobiles. Annual supply of 221,790 GJ was estimated. The major components are the automobiles, solar heat hot water system, and power generation systems. (NEDO)

Seismic microzonation on peak ground acceleration for Sapporo area; Sapporo chiiki no seismic microzonation

Energy Technology Data Exchange (ETDEWEB)

Hattori, S [Muroran Institute of Technology, Hokkaido (Japan); Vuetibau, L

1997-10-22

With an objective for use as fundamental information and data for measures to prevent disasters from regional earthquakes, microzonation was carried out on the Sapporo area. The present study has conducted comparisons and discussions on frequency distributions of maximum surface acceleration in the Sapporo area and the previously analyzed Muroran, Tomakomai and Obihiro areas. In the Muroran area, the frequency is distributed widely from 50 to 220 gal, while it is distributed narrowly from 110 to 170 gal in the Tomakomai area, and 90 to 160 gal in the Obihiro area. Such distributions have been formed possibly because the Muroran area has different kinds of grounds exist with hills and lowlands tangled, while the Tomakomai and Obihiro areas have nearly the same ground conditions with the topography being flat and the areas being located in an alluvial plain with soft Quaternary bed having been grown to a great thickness. The Sapporo area showed distribution close to that in the Muroran area. The maximum surface acceleration may vary even in the same mesh. This indicates that more detailed seismic microzonation is necessary to establish more effective means to prevent disasters from earthquakes. 10 refs., 4 figs., 1 tab.

New energy vision in Mobara City area (Chiba Prefecture); Mobarashi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

With the saying {sup M}obara, you find good when you live in it' as the target, the 'new energy vision for Mobara City area' was established. The vision is intended to utilize natural gas existing around the city, and utilize energy saving and new energy technologies. Specifically, the vision was established by a discussion committee composed of people of experience and academic standing, related business entities, and organizations, who took into consideration the natural environment, status of energy existence, and economic activities. The activity achievements were put into order by the following seven items: 1) the situation surrounding new energies, 2) district characteristics and viewpoints of introducing new energies, 3) energy demand, 4) existence quantity of new energies, 5) actual status of new energy introduction, and result of hearing investigations, 6) directionality and conception of introducing new energies, and 7) specific project objectives related to new energy introduction. Five projects were set up, including introduction of natural gas fueled automobiles, natural gas utilizing cogeneration and fuel cells, and effective utilization of wastes and bio-mass. (NEDO)

New energy visions for the Town of Ichinohe district; Ichinohecho chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

The new energy visions are drawn for Town of Ichinohe, Iwate Pref. The town's population has been generally decreasing since 1975, from 21,433 to 17,906 in 1995. The town consumed energy totaling 288,691Gcal in 1998, of which the transportation sector accounts for 55%, followed by the domestic, commercial and industrial sectors, in this order, the industrial sector accounting for only 7%. The estimated new energy sources available to the town are wind power, power generated by temperature difference at rivers or using snow, solar energy, biomass energy and energy from wastes, in the order of quantity, totaling 137GWh/y as electrical power and 45.6Tcal/y as heat. The priority projects include making Ichinohe Primary School an eco-school, construction of a biomass demonstration plant in the Okunakayama district, introduction of a boiler firing wood chips at Okunakayama Heights, construction of a wind power mill at Takamori Heights, and introduction of new energies by the citizens. (NEDO)

New energy vision in Murone Village area; 2000 nendo Muronemura chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

A new energy vision was established in the Murone Village area in Iwate Prefecture. The population of the village as of 1995 was 6,552 persons, which has continued with slow decrease in the last decade, revealing remarkable departure from agriculture. Energy consumption in this village per person is 11.5 two-hundred-liter drums, and carbon dioxide discharge per person is 5.6t-CO2. This is about 60% of the national average, because of no existence of thermal power plants and factories. The existing quantity of new energies is occupied by bio-mass as the largest because more than 70% of the village area is forest, followed by solar beam and heat. However, in the case of forest, since the energy is actually utilized only from the felled woods, the utilizable quantity is considerably small, whereas the availability of solar beam and heat is higher. With regard to introduction of new energies, the efforts of the introduction thereof are directed to introduction into primary schools, the village office, the special nursing home for elderly people, and the meal providing center for middle schools, in addition to proliferation and enlightenment of household solar systems, and photovoltaic power generation systems. Furthermore, discussions were given on introduction of a pellet burning power plant utilizing waste woods. (NEDO)

New energy vision in Shioya Town area (Tochigi Prefecture); Shioyacho chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

A new energy vision in Shioya Town area was established with objectives to make clear what is to be tackled by the administration and the residents in their respective standings, and elevate their consciousness to the environmental preservation and consciousness regarding the energy problems. The target for new energy introduction quantity in fiscal 2010 was set as CO2 emission quantity reduction to about 3,900 t-c/year, a reduction of 5% of the quantity in fiscal 1999. The activity achievements were put into order by the following seven items: 1) summary of implementing investigations, 2) basic district characteristics, 3) the current status and estimation of energy consumption, 4) estimated calculation on possibility of new energy utilization, 5) discussions and problems on possibilities of the introduction as seen from the district characteristics, 6) the new energy vision, and 7) the future assignments. Item 6 is composed of the introduction target, measures for introduction to achieve the target in fiscal 2010, and development of the leading projects. The projects include small to middle size hydropower generation, photovoltaic and wind power hybrid type power generation, and introduction of clean energy fueled automobiles. (NEDO)

Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1

DEFF Research Database (Denmark)

Robert-Moreno, Àlex; Robert-Moreno, Àlex; Guiu, Jordi

2008-01-01

Specific deletion of Notch1 and RBPjκ in the mouse results in abrogation of definitive haematopoiesis concomitant with the loss of arterial identity at embryonic stage. As prior arterial determination is likely to be required for the generation of embryonic haematopoiesis, it is difficult...... to establish the specific haematopoietic role of Notch in these mutants. By analysing different Notch-ligand-null embryos, we now show that Jagged1 is not required for the establishment of the arterial fate but it is required for the correct execution of the definitive haematopoietic programme, including...... activation of Notch1 is responsible for regulating GATA2 expression in the AGM, which in turn is essential for definitive haematopoiesis in the mouse....

Experience of pain in a patient with BRONJ

Directory of Open Access Journals (Sweden)

Bakal O

2015-07-01

Full Text Available Ömer Bakal, Ali Alper Tirnava, Huseyin SenDepartment of Anesthesiology and Reanimation, GATA Haydarpasa Training Hospital, Istanbul, TurkeyWe read with great interest the case report concerning a patient with bisphosphonate-related osteonecrosis of the jaw (BRONJ reported by Manzon et al.1 In this report, they describe BRONJ complicated by a temporal abscess in an elderly woman with rheumatoid arthritis. We congratulate Manzon et al on their successful treatment of this patient. They briefly discussed the evidence for the relationship between bisphosphonate therapy and BRONJ, and the effects of co-occurring factors, such as rheumatoid arthritis, dental surgery, and concomitant corticosteroid therapy.Read the original article

AcEST: DK954588 [AcEST

Lifescience Database Archive (English)

Full Text Available ults ■■ - Swiss-Prot (release 56.9) Link to BlastX Result : Swiss-Prot sp_hit_id Q94FY7 Definition sp|Q94FY7|TOCC_ARATH Toco...ts) Value sp|Q94FY7|TOCC_ARATH Tocopherol cyclase, chloroplastic OS=Arabid... 174... 4e-43 sp|Q94FY8|TOCC_MAIZE Probable tocopherol cyclase, chloroplastic ... 173 7e-43 sp|Q12VH1|GATA_METBU Gl...utamyl-tRNA(Gln) amidotransferase subunit... 33 1.2 >sp|Q94FY7|TOCC_ARATH Tocopherol cyclase, chloroplastic ... 625 RV +G+Q TP WHQG Sbjct: 193 RRVSEGFQATPFWHQG 208 >sp|Q94FY8|TOCC_MAIZE Probable tocopherol cyclase, chlo

Macular edema in siliconized eyes

Directory of Open Access Journals (Sweden)

Kaya A

2016-05-01

Full Text Available Abdullah Kaya,1 Yakup Aksoy,2 Yıldıray Yildirim,3 Murat Sonmez3 1Department of Ophthalmology, Anittepe Military Dispensary, Ankara, Turkey; 2Department of Ophthalmology, Girne Military Hospital, Girne, Cyprus; 3Department of Ophthalmology, GATA Haydarpasa Training Hospital, Istanbul, TurkeyWe read with great interest the article titled “Value of optical coherence tomography in the detection of macular pathology before the removal of silicone oil” by Rashad et al.1 The authors have evaluated the optical coherence tomography (OCT findings before the removal of silicone oil (SiO. We congratulate the authors for this well-organized study and would like to contribute to their findings.View original paper by Rashad and colleagues.

The effect of centaurein on interferon-γ expression and Listeria infection in mice

International Nuclear Information System (INIS)

Chang, S.-L.; Yeh, H.-H.; Lin, Y.-S.; Chiang, Y.-M.; Wu, T.-K.; Yang, W.-C.

2007-01-01

We previously found that centaurein enhanced IFN-γ transcription in T cells. Here, we demonstrate that centaurein increased the IFN-γ expression in T and NK cells and the serum IFN-γ level in mice. Centaurein elevated the transcription of T-bet but not GATA-3, which is consistent with its effect on that of IFN-γ but not IL-4. Additionally, centaurein effectively protected mice against Listeria infection. Moreover, centaurein per se or in combination with antibiotics could treat Listeria infection. Our mechanistic studies suggest that centaurein augments IFN-γ expression via a transcriptional up-regulation of T-bet and that centaurein protects against or treats Listeria infection via a modulation of IFN-γ expression

Report on strategic survey on promising areas for geothermal development in fiscal 1999. Hohi Area (second report); 1999 nendo chinetsu kaihatsu yubo chiiki wo taisho to shita senryakuteki chosa hokokusho. 2. Hohi chiiki

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-03-01

This paper describes a strategic consideration on promising areas for geothermal development in fiscal 1999. Areas of importance to be given surveys corresponding to the geothermal development promotion survey range C were extracted from the promising areas extracted in the previous year, based on further objective analysis and evaluation criteria. Geothermal structure models were prepared on each promising area from geological and geothermal structural elements according to the standard method for the geothermal structure model structuring technology. Amount of geothermal resources in the promising areas was evaluated by using the evaluation supporting tools. In order to extract the areas of importance to be given the surveys, the extraction criteria were discussed based on the resource density, the Natural Park Law, and the data accuracy. Furthermore, comprehensive evaluation was given on geothermal structure properties, location and environmental conditions based on the geothermal structure models. Areas expected of effective achievements in the development promotion survey were selected, and a reservoir conception model was prepared. Assuming the single flash power generation, the resource amount was evaluated by using the Monte Carlo analysis of the Stored Heat Law. Social and environmental issues were also considered. A draft of the optimum survey program corresponding to each survey stage was prepared, with the areas of importance to be given the survey as the object. (NEDO)

Manufacturing process of rewritable CD and DVD; Kakikae gata CD, DVD no seizo process

Energy Technology Data Exchange (ETDEWEB)

Horie, M. [Mitsubishi Chemical Corp., Tokyo (Japan)

1998-11-05

Development of rewritable DVD is desired which has feedback compatibility with the existing players and ROM drives. The DVD is formed on a substrate with a thickness of 0.6 mm (dummy plate), and is composed of the multilayer film, i.e., protective coating made of UV hardening resin, reflective layer, dielectric protective layer, phase change type recording layer, and polycarbonate layer from the lower in order. A pair of dummy plates are pasted to enhance the mechanical strength, which has the same thickness of 1.2 mm as CD. Since the grooves and prepits are very fine, injection molding is more difficult compared with CD. Since a great stress change occurs during the formation and initialization processes of multilayer of phase change recording medium layer which is particular to DVD manufacturing process, control of warping is significant. Control of warping of the substrate is also significant, which affects the pasting and the whole process. The recording layer, dielectric protective layer and reflective layer are formed by the discharge spattering. The initialization is a particular process to the phase change medium. Complete non-recording state can be obtained by crystallizing the amorphous recording layer after the film formation. 3 figs.

Static characteristics of a pilot relief valve; Baransupisuton gata ririfu ben no sei tokusei

Energy Technology Data Exchange (ETDEWEB)

Washio, S.; Yonguang YU; Nakamura, Y. [Okayama Univ. (Japan). School of Engineering

1997-09-25

Among a lot of hydraulic valves, relief valve is the most fundamental and important valve which takes change of pressure control. It is essential to know the working characteristics accurately, in order to predict the performance of . system. So far, the numerical simulation of relief valve has been tried and the mathematical models of individual component characteristics based on the knowledge of hydraulics are proposed. In this report, it was revealed that the static relation among the pressure drop, flow rate and opening area for a constriction can be represented, not by the traditional hydraulic orifice equation which has always been used for the purpose but by a new one including an additional pressure loss proportional to the flow rate and the fluid viscosity and inversely proportional to the square of the opening area. The new characteristic equation has proved to consistently forecast the experimental findings in which the rise in oil temperature results in an increase in the piston displacement, but causes little changes as regards regulated pressure. It has also turned out that contrary to conventional preconception, the fluid force exerted on a poppet is negligible. 6 refs., 14 figs., 1 tab.

Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch

NARCIS (Netherlands)

Amsen, Derk; Antov, Andrey; Jankovic, Dragana; Sher, Alan; Radtke, Freddy; Souabni, Abdallah; Busslinger, Meinrad; McCright, Brent; Gridley, Thomas; Flavell, Richard A.

2007-01-01

CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using

Expresión de citoquinas de la respuesta Th2 en mucosa intestinal de crías de alpaca

OpenAIRE

Burga Cisterna, Cesar Abel

2016-01-01

Evalúa la expresión génica de las citoquinas IL-4, IL-5, IL-6, IL-10, TGF- y el factor transcripcional GATA3 en la mucosa intestinal de crías de alpacas clínicamente sanas de 2 a 47 días de edad. Para lo cual se formaron grupos etarios conformados por alpacas de 2 a 8 días (grupo 1), 10 a 21 días (grupo 2) y 26 a 47 días de edad (grupo 3) sin importar sexo, raza y desprovistos de signos clínicos de enfermedad. Se tomó la porción media del yeyuno de cada animal de las cuales se extrajeron el ...

Report on new energy vision in Koushida Town area; Koushidacho chiiki shin energy vision hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

A new energy vision was established in the Koushida Town area in Miyagi Prefecture. The population of Koushida Town has leveled off in recent years at 20,245 persons in fiscal 2000. However, number of people working outside the town is increasing, and the ratio of the daytime population is decreasing slowly. Agriculture in this town depends mainly on production rice of such brands as 'Hitomebore' and 'Sasanishiki', wherein the agricultural production amount is 3 billion 260 million yen in fiscal 1998. Commercial activities are decreasing its power with the annual retail sales amount of 17 billion 800 million yen, while the product shipping amount from the attracted factories is on the increasing trend, at 25 billion 700 million yen in 1998. The energy consumption is 526 times 10{sup 9} kcal in total, accounted for by the business department at 42.0%, the transportation department at 32.3%, and the consumer department at 25.7%. The annual utilizable quantity of new energies amounts to 28,816 times 10{sup 6} kcal, made available from solar power, wind power, bio-mass, and refuses, which is about 5.5% of the final energy consumption of the town. The new energy introducing project includes introduction of photovoltaic power generation into the town office building, facilities for interchange of citizens and schools, conversion of the automobiles used in the official organizations into clean energy fueled automobiles, the Eco-town Plan for the east side of Koushida Station, and the project of utilizing bio-mass supplied from the livestock market. (NEDO)

Report on new energy vision in Koushida Town area; Koushidacho chiiki shin energy vision hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

A new energy vision was established in the Koushida Town area in Miyagi Prefecture. The population of Koushida Town has leveled off in recent years at 20,245 persons in fiscal 2000. However, number of people working outside the town is increasing, and the ratio of the daytime population is decreasing slowly. Agriculture in this town depends mainly on production rice of such brands as 'Hitomebore' and 'Sasanishiki', wherein the agricultural production amount is 3 billion 260 million yen in fiscal 1998. Commercial activities are decreasing its power with the annual retail sales amount of 17 billion 800 million yen, while the product shipping amount from the attracted factories is on the increasing trend, at 25 billion 700 million yen in 1998. The energy consumption is 526 times 10{sup 9} kcal in total, accounted for by the business department at 42.0%, the transportation department at 32.3%, and the consumer department at 25.7%. The annual utilizable quantity of new energies amounts to 28,816 times 10{sup 6} kcal, made available from solar power, wind power, bio-mass, and refuses, which is about 5.5% of the final energy consumption of the town. The new energy introducing project includes introduction of photovoltaic power generation into the town office building, facilities for interchange of citizens and schools, conversion of the automobiles used in the official organizations into clean energy fueled automobiles, the Eco-town Plan for the east side of Koushida Station, and the project of utilizing bio-mass supplied from the livestock market. (NEDO)

Regional new energy vision for Hita City; 2001 nendo Hita shi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-02-01

For promoting the introduction of new energy and for elevating people's consciousness of such in Hita City, Oita Prefecture, surveys and studies were conducted concerning the energy supply/demand trend in the city, the amount of new energy resources in existence, and new energy introduction plans, and a vision was formulated. The city's energy consumption is estimated at 16,216,376 GJ, with the industrial sector responsible for 78.23%, the transportation sector for 11.35%, and the residential and commercial sector for 9.73%. It is in the public sector, general households, forestry, and hog raising that new energy will be utilized. Key projects for new energy introduction were discussed, which covered a residence incorporating a combination of new energies such as solar heat for water heating and photovoltaic power; lumber drying facilities utilizing forestry generated biomass; cogeneration fueled by methane gas from livestock excrements and garbage; photovoltaic power for schools, the city office, etc.; use of photovoltaic power, temperature difference energy, and methane gas at purification centers, etc.; use of clean energy vehicles for official use; etc. (NEDO)

Report on regional new energy vision for Kahoku town; Kahokucho chiiki shin energy vision hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

A regional new energy vision has been formulated for Kahoku town, Kochi Prefecture, which features the introduction of recoverable energy harmonious with nature and friendly to human life and environments. The results of activities conducted in this connection are compiled into nine chapters, which cover (1) Kahoku-town's local characteristics relative to new energy, (2) survey of townspeople's awareness of new energy, (3) amounts of new energy in existence, (4) basic policy toward introduction, (5) study of concrete measures for promoting introduction, (6) study of prioritized projects, (7) establishment of target amounts for introduction, (8) coordination with energy conservation measures, and (9) a system for thrusting forward the regional new energy vision toward embodiment. Chapter (7) comprises the way of setting target values for introduction; study of the target values to be achieved by the industry, administration, and citizenry, respectively; and a conclusion on the target values. Studies are conducted in the chapter about the introduction of solar energy, wind power generation, small scale hydroelectric power generation, cogeneration, clean energy vehicles, and the like. It is predicted that 960 kl/year will be introduced in fiscal 2010 in terms of oil, which accounts for 12% of energy consumption. (NEDO)

Characteristics of microtremors in Hanshin area; Hanshin chiiki ni okeru bido no kihon tokusei nitsuite

Energy Technology Data Exchange (ETDEWEB)

Suzuki, H; Suzuki, K; Yamanaka, H; Seo, K [Tokyo Institute of Technology, Tokyo (Japan)

1996-10-01

To increase general understandings of fundamental characteristics of microtremors in Hanshin area, microtremors have been observed at Sumiyoshi River-side, Rokko Island, and Nishinomiya. Relations were discussed among the stability of predominant period, successive fluctuation and meteorological conditions. For the analysis, cosine-type taper was conducted before and after 10% of the observed records, and Fourier spectrum was calculated by smoothing using Parzen window with a band width 0.3 Hz. Geometrical mean of two components was used as a horizontal component. At the observation points except Sumiyoshi River-side, predominance in the short period side was not distinct, and was not stable due to the successive fluctuation of predominant period. However, there was less successive fluctuation of spectrum ratio between different two points in the band with period more than 1 sec. Since there was a close correlation between the successive fluctuation in this band and the wind velocity or air pressure, the microtremors in this band was affected by a single vibration source. Ground characteristics could be illustrated by the averages of ratio against base points of moving observation. 14 refs.

Report on new energy vision in Fudai Village area; Fudaimura chiiki shin energy vision hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

A new energy vision was established in the Fudai Village area in Iwate Prefecture. The population of Fudai Village is decreasing from the peak of 4,103 persons in 1985. Its basic industry is fishery and agricultural industries, with the fish and marine product raising industry particularly active. The energy consumption in Fudai Village is, in the decreasing order, the transportation field (48.5%), the social and household field (26.5%), social industry, and manufacturing industry. Homes consume room heating energy at a greater extent. Energies are supplied by fuel oil at 53,554 Gcal (79.3%) and electric power at 11,551 Gcal (17.1%). The new energy introducing project has discussed introduction of cogeneration into the Kurosaki House, introduction of photovoltaic power generation and solar heat utilization systems, and introduction wind power generation as a tourism symbol. Discussions were also given on conversion of the automobiles used in the official organizations into clean energy automobiles. Further discussions were given on introduction of small new energy facilities, such as hybrid illumination, small wind power generation, and photovoltaic power generation, into the village office, the station square, the fish market, facilities in the fishing port, the children's hall, and the Road Station. (NEDO)

Report on energy saving vision in Santo-cho region; Santocho chiiki sho energy vision hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

An energy-saving vision was decided on in Santo-cho region in Hyogo Prefecture, with its outline reported. This town is such that about 80% of the region is mountains, forests and wilderness and that aging is advancing at the rate above that of Hyogo Prefecture or the national average. Nearly entire energy of the town is dependent on the supply from outside. The energy consumption is somewhat increasing as a whole, with that of the people's livelihood/domestic sector and of transportation sector are rising. In the classification of fuels, electricity is growing in consumption. As an energy-saving vision, it aimed principally at personal surroundings in which every one got into the habit of saving energy continuously without being forced. The basic plan for the energy conservation drive consisted of inducement to an energy-saving life style, energy conservation to be spread by the next generation children, continuation of energy saving activity rooted in the region, and promotion of energy conservation as a basis for introducing new energy. The diffusion and enlightenment for children destined to lead the next generation were defined as a particularly important assignment, as was the promotion of energy conservation and environmental education. (NEDO)

Regional new energy vision for Joetsu City; 2001 nendo Joetsu shi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-02-01

For promoting the introduction of new energy and for enhancing people's consciousness of such at Joetsu City, Niigata Prefecture, surveys and studies were conducted involving energy consumption of the city, the amount of new energy resources in existence, and new energy introduction projects, and a vision was formulated. The city consumes 3,593 times 10{sup 9} kcal in energy, with the industrial sector responsible for 47.5%, the transportation sector 28.1%, and the residential/commercial sector 24.3%. As for the energy type, oil based fuel accounts for 58.3%, electric power 26.8%, and town gas 8.6%. The amount of carbon dioxide emissions due to energy consumption is estimated at 1,160 kt-CO2. Studies conducted for new energy introduction covered the supply of photovoltaic power to a project on municipal housing construction and a project on promoting the buildup of environment preservation facilities; the installation of a photovoltaic power generation system for a Citizens' Forest buildup project; the installation of a wind power generation system at the Minowadai Square of Recreation and Relaxation for the citizens; the installation of eco-stations to deal with gasoline, propane gas, and natural gas; the extension of financial support for the purchase of low-pollution vehicles; and so forth. (NEDO)

Regional new energy vision for Tadami Town; 2001 nendo Tadami machi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-02-01

For promoting the introduction of new energy and for enhancing people's consciousness of such at Tadami Town, Fukushima Prefecture, surveys and studies were conducted involving the energy demand characteristics of the town, the amount of new energy resources in existence, and new energy introduction projects, and a vision was formulated. Though there is not a great change through the year in town's demand for power, more power is necessary in winter for heating and lighting. As for demand for gas and oil, demand for heating oil reaches its peak in winter. New energy introduction projects were discussed, which would utilize snow for the dynamization of industries, and studies were conducted about the selection of items to be stored in snow rooms, selection of proper cold heat utilization systems, care to be taken in the designing of facilities, installation of snow rooms, development of specialty goods proper to the town, and so forth. Eco-school development was also studied as an environmental education project harmonizing with the local circumstances. Discussed for the fostering of welfare were an energy business for a Welfare House, snow handling measures linked to new energy utilization systems, and the like. (NEDO)

FY 2000 report on the results of the regional consortium R and D project - Regional consortium energy field. Second year report. Development of the energy saving manufacturing process of smart materials having electromagnetic wave absorbing function using the microwave-hydrothermal method; 2000 nendo chiiki consortium kenkyu kaihatsu jigyo - chiiki contortium energy bun'ya. Micro ha - suinetsuho wo riyoshita denjiha kyushu kino wo yusuru smart zairyo no sho energy gata seizo process no kaihatsu (dai 2 nendo) seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

The development was proceeded with of electromagnetic wave absorbing materials (board) which dispersed carbon fiber as conducting material and ferrite as magnetic material to matrices such as resin and cement. With the multi-layer structure as a basis, the material has wave absorbing ability in the area of 300MHz-60GHz band. The material is presumed to be applied to wall construction use materials and bodies of electronic equipment since it prevents the radio wave reflection caused by structures such as bridges. Ferrite was synthesized by microwave-hydrothermal method (500kPa, 2.54GHz). Further, carbon fiber was covered with ferrite for improvement of absorption characteristics. Studies were made in the following 5 fields: 1) design of smart materials and development of hybrid process technology; 2) study on the evaluation of wave absorbing function; 3) R and D of the manufacturing process of smart forming materials; 4) development of the fiber surface processing process using ocean resource; 5) comprehensive investigational study. In 1), study was conducted on relations among electromagnetic shielding characteristics of the ferrite-covering carbon fiber, fiber length and fiber content. (NEDO)

Upregulation of Tim-3 on CD4(+) T cells is associated with Th1/Th2 imbalance in patients with allergic asthma.

Science.gov (United States)

Tang, Fei; Wang, Fukun; An, Liyun; Wang, Xianling

2015-01-01

T cell Ig and mucin domain-containing molecule-3 (Tim-3) is a negative regulator preferentially expressed on Th1 cells. Allergic asthma is a clinical syndrome well characterized by Th1/Th2 imbalance. To investigate the role of Tim-3 in the pathogenesis of asthma and its relationship with Th1/Th2 imbalance, a total of 40 patients with allergic asthma and 40 healthy controls were enrolled. Expression of Tim-3 and Th1/Th2 imbalance as well as the relationship between them was analyzed by flow cytometry and real-time PCR. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro and anti-Tim-3 was used to block Tim-3 signaling; Th1/Th2 cytokines in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). CD4(+) T cells and B cells were sorted and co-cultured in vitro, and anti-Tim-3 was used to block Tim-3 signaling; Total IgG/IgE in the culture supernatant was detected by ELISA. The mRNA level of T-bet and IFN-γ were significantly decreased in allergic asthma patients, while GATA-3 and IL-4 were significantly increased. Expression of Tim-3 on CD4(+) T cells was much higher in allergic asthma patients and it was negatively correlated with T-bet/GATA-3 ratio or IFN-γ/IL-4 ratio. Blocking of Tim-3 significantly increased Th1 cytokines (TNF-α and IFN-γ) and decreased Th2 cytokines (IL-4, IL-5, IL-13) in the culture supernatant of PBMCs. Blocking of Tim-3 dramatically reduced the production of IgG and IgE in the co-culture supernatant of CD4(+) T cells and B cells. In conclusion, Tim-3 was up-regulated in allergic asthma patients and related with the Th1/Th2 imbalance. Blocking of Tim-3 may be of therapeutic benefit by enhancing the Th1 cytokines response, down-regulating the Th2 cytokines response, and reducing IgG/IgE production.

CD4+ T helper cells and regulatory T cells in active lupus nephritis: an imbalance towards a predominant Th1 response?

Science.gov (United States)

Mesquita, D; Kirsztajn, G Mastroianni; Franco, M F; Reis, L A; Perazzio, S F; Mesquita, F V; Ferreira, V da Silva; Andrade, L E Coelho; de Souza, A W Silva

2018-01-01

The objective of this study was to evaluate the frequency of CD4 + T cell subsets in peripheral blood mononuclear cells (PBMC), urine and renal tissue from patients with lupus nephritis (LN). PBMC and urinary cells were collected from 17 patients with active LN, 20 disease controls (DC) with primary glomerulonephritis and 10 healthy controls (HC) and were analysed by flow cytometry with markers for T helper type 1 (Th1), Th2, Th17 and regulatory T cells (T reg ) cells. T cell subsets were assessed by immunohistochemistry from LN biopsy specimens from 12 LN patients. T cell subtypes in PBMC were re-evaluated at 6 months of therapy. CD4 + T cells were decreased in PBMC in LN compared with DC and HC (P = 0·0001). No differences were observed in urinary CD4 + T cell subsets between LN and DC. The frequency of urinary Th17 cells was higher in patients with non-proliferative than in proliferative LN (P = 0·041). CD3 + and T-box 21 ( Tbet+) cells were found in glomeruli and interstitium of LN patients, while forkhead box protein 3 (FoxP3), retinoid-related orphan receptor gamma (ROR-γ) and GATA binding protein 3 (GATA-3) were present only in glomeruli. Th1 cells in PBMC were correlated negatively with urinary Th1 cells (Rho = -0·531; P = 0·028) and with T bet in renal interstitium (Rho = -0·782; P = 0·004). At 6 months, LN patients showed an increase in Th17 cells in PBMC. In conclusion, the inverse association between Th1 cells from PBMC and urinary/renal tissue indicate a role for Th1 in LN pathophysiology. Urinary Th17 cells were associated with less severe LN, and Th17 increased in PBMC during therapy. Urinary CD4 + T cells were not different between LN and DC. © 2017 British Society for Immunology.

spv locus aggravates Salmonella infection of zebrafish adult by inducing Th1/Th2 shift to Th2 polarization.

Science.gov (United States)

Wu, Shu-Yan; Wang, Li-Dan; Xu, Guang-Mei; Yang, Si-di; Deng, Qi-Feng; Li, Yuan-Yuan; Huang, Rui

2017-08-01

Salmonella enterica serovar typhimurium (S. typhimurium) are facultative intracellular enteric pathogens causing disease with a broad range of hosts. It was known that Th1-type cytokines such as IFN-γ, IL-12, and TNF-α etc. could induce protective immunity against intracellular pathogens, while Th2-type cytokines such as IL-4, IL-10, and IL-13 etc. are proved to help pathogens survive inside hosts and cause severe infection. One of the critical virulence factor attributes to the pathogenesis of S. typhimurium is Salmonella plasmid virulence genes (spv). Until now, the interaction between spv locus and the predictable generation of Th1 or Th2 immune responses to Salmonella has not been identified. In this study, zebrafish adults were employed to explore the effect of spv locus on Salmonella pathogenesis as well as host adaptive immune responses especially shift of Th1/Th2 balance. The pathological changes of intestines and livers in zebrafish were observed by hematoxylin-eosin (HE) staining and electron microscopy. Levels of the transcription factors of Th1 (Tbx21) and Th2 (GATA3) were measured by real-time quantitative PCR (RT-qPCR). Expression of cytokines were determined by using RT-qPCR and ELISA, respectively. Results showed that spv operon aggravates damage of zebrafish. Furthermore, it demonstrated that spv locus could inhibit the transcription of tbx21 gene and suppress the expression of cytokines IFN-γ, IL-12 and TNF-α. On the contrary, the transcription of gata3 gene could be promoted and the expression of cytokines IL-4, IL-10 and IL-13 were enhanced by spv locus. Taken together, our data revealed that spv locus could aggravate Salmonella infection of zebrafish adult by inducing an imbalance of Th1/Th2 immune response and resulting in a detrimental Th2 bias of host. Copyright © 2017. Published by Elsevier Ltd.

Derp1-modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis.

Science.gov (United States)

Yu, Shaoqing; Han, Bing; Liu, Shuangxi; Wang, Hong; Zhuang, Wenjie; Huang, Yu; Zhang, Ruxin

2017-10-01

The CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR). The frequency of sneezing and scratching, eosinophil cell count, and Th1/Th2 ratio in the spleen were measured for all groups. The percentage of CD4 + CD25 + Foxp3 + Tregs in peripheral blood mononuclear cells was measured using flow cytometry; serum IgE, IgG1, and histamine were measured using enzyme-linked immunosorbent assay; expression levels of transcription factors T-bet, GATA3, Foxp3+ and IL-10 were analyzed using reverse transcription-polymerase chain reaction, and Western blot used in analyzed expression of Foxp3+ and IL-10 in nasal mucosa. Treatment with Derp1-modified DCs ameliorated the allergic response. The Derp1DC-AR group had significantly lower eosinophil cell count and the IgE, IgG1, and histamine levels than the AR and DC-AR groups, and higher mRNA levels of Th1 transcription factors T-bet, IL-10 and Foxp3 in nasal mucosa than DC-AR mice, but Th2 transcription factors GATA3 mRNA expression level has the opposite results. Furthermore, the Th1/Th2 ratio and percentage of CD4 + CD25 + Foxp3 + Tregs was significantly lower in the AR group (pTh1/Th2, showing an immunotherapeutic effect against AR. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of histone deacetylase inhibitors on AHSP expression.

Directory of Open Access Journals (Sweden)

Mohammad Ali Okhovat

Full Text Available Alpha-hemoglobin stabilizing protein (AHSP is a molecular chaperone that can reduce the damage caused by excess free α-globin to erythroid cells in patients with impaired β-globin chain synthesis. We assessed the effect of sodium phenylbutyrate and sodium valproate, two histone deacetylase inhibitors (HDIs that are being studied for the treatment of hemoglobinopathies, on the expression of AHSP, BCL11A (all isoforms, γ-globin genes (HBG1/2, and some related transcription factors including GATA1, NFE2, EKLF, KLF4, and STAT3. For this purpose, the K562 cell line was cultured for 2, 4, and 6 days in the presence and absence of sodium phenylbutyrate and sodium valproate. Relative real-time qRT-PCR analysis of mRNA levels was performed to determine the effects of the two compounds on gene expression. Expression of all target mRNAs increased significantly (p < 0.05, except for the expression of BCL11A, which was down-regulated (p < 0.05 in the cells treated with both compounds relative to the levels measured for untreated cells. The findings indicated that sodium valproate had a more considerable effect than sodium phenylbutyrate (p < 0.0005 on BCL11A repression and the up-regulation of other studied genes. γ-Globin and AHSP gene expression continuously increased during the culture period in the treated cells, with the highest gene expression observed for 1 mM sodium valproate after 6 days. Both compounds repressed the expression of BCL11A (-XL, -L, -S and up-regulated GATA1, NFE2, EKLF, KLF4, STAT3, AHSP, and γ-globin genes expression. Moreover, sodium valproate showed a stronger effect on repressing BCL11A and escalating the expression of other target genes. The findings of this in vitro experiment could be considered in selecting drugs for clinical use in patients with β-hemoglobinopathies.

Effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy

Institute of Scientific and Technical Information of China (English)

Yi-Qun He; Fa-Qun He; Shao-Long Wang

2017-01-01

Objective:To study the effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy.Methods:Patients with advanced cervical cancer who received chemotherapy in the First Affiliated Hospital of Chengdu Medical College between May 2014 and June 2016 were selected, HAMA scores and HAMD scores were used to assess anxiety and depression and divide the patients into control group, depression group, anxiety group and depression + anxiety group. The contents of monoamine neurotransmitters and immune cytokines in serum as well as the expression of immune transcription factors in peripheral blood mononuclear cells were detected.Results:Serum NE, E, 5-HT, 5-HIAA and DOPAC contents of depression group and depression + anxiety group were significantly lower than those of control group, and serum NE, E, 5-HT, 5-HIAA and DOPAC contents of anxiety group were significantly higher than those of control group; peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression group, anxiety group and depression + anxiety group were significantly lower than those of control group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of control group; peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression + anxiety group were significantly lower than those of depression group and anxiety group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of depression group and anxiety group. Conclusion: Anxiety and depression in patients with cervical cancer chemotherapy can affect the secretion of monoamine neurotransmitters, the differentiation of CD4+T cell subsets and the antitumor immune response mediated by them.

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

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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.

Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses.

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Jumpei Ito

2017-07-01

Full Text Available Human endogenous retroviruses (HERVs and other long terminal repeat (LTR-type retrotransposons (HERV/LTRs have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs. Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified "HERV/LTR-shared regulatory element (HSRE," defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG, embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2, hematopoietic TFs (e.g., SPI1 (PU1, GATA1/2, and TAL1, and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/. This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into

House dust mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes.

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Pevec, Branko; Radulovic Pevec, Mira; Stipic Markovic, Asja; Batista, Irena; Rijavec, Matija; Silar, Mira; Kosnik, Mitja; Korosec, Peter

2012-01-01

Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG(4), nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Decreased wheal sizes and VAS scores, negative challenges and increased sIgG(4) levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal

Identification of differentially expressed placental transcripts during multiple gestations in the Eurasian beaver (Castor fiber L.).

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Lipka, A; Paukszto, L; Majewska, M; Jastrzebski, J P; Myszczynski, K; Panasiewicz, G; Szafranska, B

2017-09-01

The Eurasian beaver is one of the largest rodents that, despite its high impact on the environment, is a non-model species that lacks a reference genome. Characterising genes critical for pregnancy outcome can serve as a basis for identifying mechanisms underlying effective reproduction, which is required for the success of endangered species conservation programs. In the present study, high-throughput RNA sequencing (RNA-seq) was used to analyse global changes in the Castor fiber subplacenta transcriptome during multiple pregnancy. De novo reconstruction of the C. fiber subplacenta transcriptome was used to identify genes that were differentially expressed in placentas (n=5) from two females (in advanced twin and triple pregnancy). Analyses of the expression values revealed 124 contigs with significantly different expression; of these, 55 genes were identified using MegaBLAST. Within this group of differentially expressed genes (DEGs), 18 were upregulated and 37 were downregulated in twins. Most DEGs were associated with the following gene ontology terms: cellular process, single organism process, response to stimulus, metabolic process and biological regulation. Some genes were also assigned to the developmental process, the reproductive process or reproduction. Among this group, four genes (namely keratin 19 (Krt19) and wingless-type MMTV integration site family - member 2 (Wnt2), which were downregulated in twins, and Nik-related kinase (Nrk) and gap junction protein β2 (Gjb2), which were upregulated in twins) were assigned to placental development and nine (Krt19, Wnt2 and integrin α 7 (Itga7), downregulated in twins, and Nrk, gap junction protein β6 (Gjb6), GATA binding protein 6 (Gata6), apolipoprotein A-I (ApoA1), apolipoprotein B (ApoB) and haemoglobin subunit α 1 (HbA1), upregulated in twins) were assigned to embryo development. The results of the present study indicate that the number of fetuses affects the expression profile in the C. fiber

Midbrain and forebrain patterning delivers immunocytochemically and functionally similar populations of neuropeptide Y containing GABAergic neurons.

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Khaira, S K; Nefzger, C M; Beh, S J; Pouton, C W; Haynes, J M

2011-09-01

Neurons differentiated in vitro from embryonic stem cells (ESCs) have the potential to serve both as models of disease states and in drug discovery programs. In this study, we use sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF-8) to enrich for forebrain and midbrain phenotypes from mouse ESCs. We then investigate, using Ca(2+) imaging and [(3)H]-GABA release studies, whether the GABAergic neurons produced exhibit distinct functional phenotypes. At day 24 of differentiation, reverse transcriptase-PCR showed the presence of both forebrain (Bf-1, Hesx1, Pgc-1α, Six3) and midbrain (GATA2, GATA3) selective mRNA markers in developing forebrain-enriched cultures. All markers were present in midbrain cultures except for Bf-1 and Pgc-1α. Irrespective of culture conditions all GABA immunoreactive neurons were also immunoreactive to neuropeptide Y (NPY) antibodies. Forebrain and midbrain GABAergic neurons responded to ATP (1 mM), L-glutamate (30 μM), noradrenaline (30 μM), acetylcholine (30 μM) and dopamine (30 μM), with similar elevations of intracellular Ca(2+)([Ca(2+)](i)). The presence of GABA(A) and GABA(B) antagonists, bicuculline (30 μM) and CGP55845 (1 μM), increased the elevation of [Ca(2+)](i) in response to dopamine (30 μM) in midbrain, but not forebrain GABAergic neurons. All agonists, except dopamine, elicited similar [(3)H]-GABA release from forebrain and midbrain cultures. Dopamine (30 μM) did not stimulate significant [(3)H]-GABA release in midbrain cultures, although it was effective in forebrain cultures. This study shows that differentiating neurons toward a midbrain fate restricts the expression of forebrain markers. Forebrain differentiation results in the expression of forebrain and midbrain markers. All GABA(+) neurons contain NPY, and show similar agonist-induced elevations of [Ca(2+)](i) and [(3)H]-GABA release. This study indicates that the pharmacological phenotype of these particular neurons may be independent of the addition of

Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease.

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Mattoo, Hamid; Mahajan, Vinay S; Maehara, Takashi; Deshpande, Vikram; Della-Torre, Emanuel; Wallace, Zachary S; Kulikova, Maria; Drijvers, Jefte M; Daccache, Joe; Carruthers, Mollie N; Castelino, Flavia V; Stone, James R; Stone, John H; Pillai, Shiv

2016-09-01

IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4(+) T cells constitute the major inflammatory cell population in IgG4-RD lesions. We used an unbiased approach to characterize CD4(+) T-cell subsets in patients with IgG4-RD based on their clonal expansion and ability to infiltrate affected tissue sites. We used flow cytometry to identify CD4(+) effector/memory T cells in a cohort of 101 patients with IgG4-RD. These expanded cells were characterized by means of gene expression analysis and flow cytometry. Next-generation sequencing of the T-cell receptor β chain gene was performed on CD4(+)SLAMF7(+) cytotoxic T lymphocytes (CTLs) and CD4(+)GATA3(+) TH2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined by using quantitative multicolor imaging. CD4(+) effector/memory T cells with a cytolytic phenotype were expanded in patients with IgG4-RD. Next-generation sequencing revealed prominent clonal expansions of these CD4(+) CTLs but not CD4(+)GATA3(+) memory TH2 cells in patients with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-RD tissue sites were clonally expanded CD4(+) CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B-cell depletion was associated with a reduction in numbers of disease-associated CD4(+) CTLs. IgG4-RD is prominently linked to clonally expanded IL-1β- and TGF-β1-secreting CD4(+) CTLs in both peripheral blood and inflammatory tissue lesions. These active, terminally differentiated, cytokine-secreting effector CD4(+) T cells are now linked to a human disease characterized by chronic inflammation and fibrosis. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Clonal expansion of CD4+ Cytotoxic T Lymphocytes in IgG4-related disease

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Mattoo, Hamid; Mahajan, Vinay S.; Maehara, Takashi; Deshpande, Vikram; Della-Torre, Emanuel; Wallace, Zachary S.; Kulikova, Maria; Drijvers, Jefte M.; Daccache, Joe; Carruthers, Mollie N.; Castellino, Flavia; Stone, James R.; Stone, John H.; Pillai, Shiv

2016-01-01

Background IgG4-related disease (IgG4-RD) is a systemic condition of unknown etiology, characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4+ T cells constitute the major inflammatory cell population in IgG4-RD lesions. Objective We used an unbiased approach to characterize CD4+ T cell subsets in IgG4-RD subjects based on their clonal expansion and their ability to infiltrate affected tissue sites. Methods We used flow cytometry to identify CD4+ effector/memory T cells (TEM) in a cohort of 101 IgG4-related disease (IgG4-RD) patients. These expanded cells were characterized by gene expression analysis and flow cytometry. Next-generation sequencing of the T cell receptor β chain gene was performed on CD4+SLAMF7+ CTLs and CD4+GATA3+ TH2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined using quantitative multi-color imaging. Results CD4+ effector/memory T cells with a cytolytic phenotype were expanded in IgG4-RD patients. Next-generation sequencing revealed prominent clonal expansions of these CD4+CTLs but not CD4+GATA3+ memory TH2 cells in subjects with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-RD tissue sites were clonally-expanded CD4+CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B cell depletion was associated with a reduction in disease-associated CD4+ CTLs Conclusions IgG4-RD is prominently linked to clonally-expanded, IL-1β, and TGF- β1 secreting, CD4+ CTLs in peripheral blood as well as in inflammatory tissue lesions. These active, terminally-differentiated, cytokine-secreting effector CD4+ T cells are now linked to a human disease characterized by chronic inflammation and fibrosis. PMID:26971690

Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

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Biaoru Li

Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan.

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Bansal, Ankita; Kwon, Eun-Soo; Conte, Darryl; Liu, Haibo; Gilchrist, Michael J; MacNeil, Lesley T; Tissenbaum, Heidi A

2014-01-01

Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is the primary target of insulin/IGF-1 signaling, and multiple isoforms of DAF-16 (a, b, and d/f) modulate lifespan, metabolism, dauer formation, and stress resistance. Thus far, across phylogeny modulation of mammalian FOXOs and DAF-16 have focused on post-translational regulation with little focus on transcriptional regulation. In C. elegans, we have previously shown that DAF-16d/f cooperates with DAF-16a to promote longevity. In this study, we generated transgenic strains expressing near-endogenous levels of either daf-16a or daf-16d/f, and examined temporal expression of the isoforms to further define how these isoforms contribute to lifespan regulation. Here, we show that DAF-16a is sensitive both to changes in gene dosage and to alterations in the level of insulin/IGF-1 signaling. Interestingly, we find that as worms age, the intestinal expression of daf-16d/f but not daf-16a is dramatically upregulated at the level of transcription. Preventing this transcriptional upregulation shortens lifespan, indicating that transcriptional regulation of daf-16d/f promotes longevity. In an RNAi screen of transcriptional regulators, we identify elt-2 (GATA transcription factor) and swsn-1 (core subunit of SWI/SNF complex) as key modulators of daf-16d/f gene expression. ELT-2 and another GATA factor, ELT-4, promote longevity via both DAF-16a and DAF-16d/f while the components of SWI/SNF complex promote longevity specifically via DAF-16d/f. Our findings indicate that transcriptional control of C. elegans FOXO/daf-16 is an essential regulatory event. Considering the conservation of FOXO across species, our findings identify a new layer of FOXO regulation as a potential determinant of mammalian longevity and age-related diseases such as cancer and diabetes.

In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors.

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Matteo Vecellio

Full Text Available Adult human cardiac mesenchymal-like stromal cells (CStC represent a relatively accessible cell type useful for therapy. In this light, their conversion into cardiovascular precursors represents a potential successful strategy for cardiac repair. The aim of the present work was to reprogram CStC into functionally competent cardiovascular precursors using epigenetically active small molecules. CStC were exposed to low serum (5% FBS in the presence of 5 µM all-trans Retinoic Acid (ATRA, 5 µM Phenyl Butyrate (PB, and 200 µM diethylenetriamine/nitric oxide (DETA/NO, to create a novel epigenetically active cocktail (EpiC. Upon treatment the expression of markers typical of cardiac resident stem cells such as c-Kit and MDR-1 were up-regulated, together with the expression of a number of cardiovascular-associated genes including KDR, GATA6, Nkx2.5, GATA4, HCN4, NaV1.5, and α-MHC. In addition, profiling analysis revealed that a significant number of microRNA involved in cardiomyocyte biology and cell differentiation/proliferation, including miR 133a, 210 and 34a, were up-regulated. Remarkably, almost 45% of EpiC-treated cells exhibited a TTX-sensitive sodium current and, to a lower extent in a few cells, also the pacemaker I(f current. Mechanistically, the exposure to EpiC treatment introduced global histone modifications, characterized by increased levels of H3K4Me3 and H4K16Ac, as well as reduced H4K20Me3 and H3s10P, a pattern compatible with reduced proliferation and chromatin relaxation. Consistently, ChIP experiments performed with H3K4me3 or H3s10P histone modifications revealed the presence of a specific EpiC-dependent pattern in c-Kit, MDR-1, and Nkx2.5 promoter regions, possibly contributing to their modified expression. Taken together, these data indicate that CStC may be epigenetically reprogrammed to acquire molecular and biological properties associated with competent cardiovascular precursors.

HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans.

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Won Hee Jung

2010-11-01

Full Text Available The fungal pathogen Cryptococcus neoformans is a major cause of illness in immunocompromised individuals such as AIDS patients. The ability of the fungus to acquire nutrients during proliferation in host tissue and the ability to elaborate a polysaccharide capsule are critical determinants of disease outcome. We previously showed that the GATA factor, Cir1, is a major regulator both of the iron uptake functions needed for growth in host tissue and the key virulence factors such as capsule, melanin and growth at 37°C. We are interested in further defining the mechanisms of iron acquisition from inorganic and host-derived iron sources with the goal of understanding the nutritional adaptation of C. neoformans to the host environment. In this study, we investigated the roles of the HAP3 and HAPX genes in iron utilization and virulence. As in other fungi, the C. neoformans Hap proteins negatively influence the expression of genes encoding respiratory and TCA cycle functions under low-iron conditions. However, we also found that HapX plays both positive and negative roles in the regulation of gene expression, including a positive regulatory role in siderophore transporter expression. In addition, HapX also positively regulated the expression of the CIR1 transcript. This situation is in contrast to the negative regulation by HapX of genes encoding GATA iron regulatory factors in Aspergillus nidulans and Schizosaccharomyces pombe. Although both hapX and hap3 mutants were defective in heme utilization in culture, only HapX made a contribution to virulence, and loss of HapX in a strain lacking the high-affinity iron uptake system did not cause further attenuation of disease. Therefore, HapX appears to have a minimal role during infection of mammalian hosts and instead may be an important regulator of environmental iron uptake functions. Overall, these results indicated that C. neoformans employs multiple strategies for iron acquisition during infection.

Report of the results of the fiscal 1997 regional consortium R and D project. Regional consortium energy field / research and development of a reverse engineering system for local industrial articles (first fiscal year); 1997 nendo chiiki consortium kenkyu kaihatsu jigyo. Chiiki consortium bun`ya / chiiki kogeihin muke reverse engineering system no kenkyu kaihatsu (daiichi nendo) seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-03-01

The paper described the fiscal 1997 result of the research on the application of local industrial article use reverse engineering (RE, it had been regarded as imitation and reproduction technology, but has recently been as a part of the production information integration). With the actual local industrial article as standard, which has features in design and was added with local traditionality, such as glass having 3D free-form surface, 3D shape information modeling technology RE is developed, and a system for direct automatic metal mold processing is established, aiming at shortening of delivery date, cost reduction and higher grade. The target of the research is Okinawa prefecture. In fiscal 1997, study was made of the speeding-up of the non-contact 3D shape information inputting (multi-point simultaneous inputting by CCD of the laser reflected light of the actual model) and the data storage technology. Cast iron was selected as molding materials, judging from reactivity/machinability with heat resistant glass. Also studied was the blend of glass materials suitable for press forming. Further, studies were proceeded with of development of intellectual cutting tools into which sensor function is integrated and of virtual reality for facilitating/accelerating the design up to metal mold manufacturing. 39 refs., 88 figs., 21 tabs.

Transmural dispersion of repolarization and atrial electromechanical coupling: complementary indices for quantifying cardiac electrical heterogeneity in patients with conversion disorder

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Tokatli A

2015-07-01

Full Text Available Alptug Tokatli,1 Omer Yiginer,2 Gokhan Degirmencioglu,2 Fethi Kilicaslan,3 Mehmet Uzun2 1Department of Cardiology, Golcuk Military Hospital, Kocaeli, 2Department of Cardiology, GATA Haydarpasa Hospital, 3Department of Cardiology, Medipol University, Istanbul, TurkeyWe read with great interest the article entitled “P-wave and QT dispersion in patients with conversion disorder” by Izci et al1 in Therapeutics and Clinical Risk Management. In this well designed research, Izci et al studied QT dispersion (QTd and P-wave dispersion (Pd in patients with conversion disorder (CD. In conclusion, they reported that corrected QT (QTc and QTd values were significantly altered in patients with CD when compared to healthy controls, but that there was no significant difference in terms of Pd.Read the original article

Functional Variants at the 11q13 Risk Locus for Breast Cancer Regulate Cyclin D1 Expression through Long-Range Enhancers

Science.gov (United States)

French, Juliet D.; Ghoussaini, Maya; Edwards, Stacey L.; Meyer, Kerstin B.; Michailidou, Kyriaki; Ahmed, Shahana; Khan, Sofia; Maranian, Mel J.; O’Reilly, Martin; Hillman, Kristine M.; Betts, Joshua A.; Carroll, Thomas; Bailey, Peter J.; Dicks, Ed; Beesley, Jonathan; Tyrer, Jonathan; Maia, Ana-Teresa; Beck, Andrew; Knoblauch, Nicholas W.; Chen, Constance; Kraft, Peter; Barnes, Daniel; González-Neira, Anna; Alonso, M. Rosario; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Conroy, Don; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Loehberg, Christian R.; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Aitken, Zoe; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Benitez, Javier; Anton-Culver, Hoda; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Engel, Christoph; Brauch, Hiltrud; Hamann, Ute; Justenhoven, Christina; Aaltonen, Kirsimari; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Peeters, Stephanie; Smeets, Ann; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Sardella, Domenico; Couch, Fergus J.; Wang, Xianshu; Pankratz, Vernon S.; Lee, Adam; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Ng, Char-Hong; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Schoof, Nils; Hooning, Maartje J.; Martens, John W.M.; Collée, J. Margriet; Tilanus-Linthorst, Madeleine; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Balasubramanian, Sabapathy P.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D.P.; Healey, Catherine S.; Shah, Mitul; Pooley, Karen A.; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Sng, Jen-Hwei; Sim, Xueling; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; McKay, James; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Godwin, Andrew K.; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Chen, Shou-Tung; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Ponder, Bruce A.J.; Nevanlinna, Heli; Brown, Melissa A.; Chenevix-Trench, Georgia; Easton, Douglas F.; Dunning, Alison M.

2013-01-01

Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1. PMID:23540573

Immunophenotyping of circulating T cells in a mucosal leishmaniasis patient coinfected with HIV

Directory of Open Access Journals (Sweden)

Lúcio Roberto Castellano

2011-08-01

Full Text Available HIV coinfection modifies the clinical course of leishmaniasis by promoting a Th2 pattern of cytokine production. However, little information is available regarding the lymphocytic response in untreated coinfected patients. This work presents the immunophenotyping of Leishmania-stimulated T cells from a treatment-naÏve HIV+ patient with ML. Leishmania braziliensis antigens induced CD69 expression on CD3+CD4+ and CD3+CD8+ cells. It also increased IL-4 intracellular staining on CD3+CD4+GATA3- population and decreased the percentage of CD3+CD4+IL-17+ cells. This suggests that modulations in the IL-4R/STAT6 pathway and the Th17 population may serve as parasitic evasion mechanisms in HIV/ML. Further studies are required to confirm these results.

A 3.0-kb deletion including an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene in an individual with the Bm phenotype.

Science.gov (United States)

Sano, R; Kuboya, E; Nakajima, T; Takahashi, Y; Takahashi, K; Kubo, R; Kominato, Y; Takeshita, H; Yamao, H; Kishida, T; Isa, K; Ogasawara, K; Uchikawa, M

2015-04-01

We developed a sequence-specific primer PCR (SSP-PCR) for detection of a 5.8-kb deletion (B(m) 5.8) involving an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene. Using this SSP-PCR, we performed genetic analysis of 382 individuals with Bm or ABm. The 5.8-kb deletion was found in 380 individuals, and disruption of the GATA motif in the regulatory element was found in one individual. Furthermore, a novel 3.0-kb deletion involving the element (B(m) 3.0) was demonstrated in the remaining individual. Comparisons of single-nucleotide polymorphisms and microsatellites in intron 1 between B(m) 5.8 and B(m) 3.0 suggested that these deletions occurred independently. © 2014 International Society of Blood Transfusion.

A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia

NARCIS (Netherlands)

Gröschel, Stefan; Sanders, Mathijs A; Hoogenboezem, Remco; de Wit, Elzo; Bouwman, Britta A M; Erpelinck, Claudia; van der Velden, Vincent H J; Havermans, Marije; Avellino, Roberto; van Lom, Kirsten; Rombouts, Elwin J; van Duin, Mark; Döhner, Konstanze; Beverloo, H Berna; Bradner, James E; Döhner, Hartmut; Löwenberg, Bob; Valk, Peter J M; Bindels, Eric M J; de Laat, Wouter; Delwel, Ruud

2014-01-01

Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional

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.

New energy vision of the Ehime prefecture area; 2001 nendo Ehime ken chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-03-01

For the contribution to environmental preservation and stable supply of energy, 'a new energy vision of the Ehime prefecture area' was worked out which is to be a guide for new energy introduction using photovoltaic power, wind power, etc. In the Uma area, the following were proposed: introduction of waste energy cogeneration to the paper manufacturing industry; study of introduction of small wind turbine to household and business establishment. In the Niihama/Saijo area, introduction of cogeneration to business establishment; creation of the processing/assembly industry for materials/parts of equipment of photovoltaic power generation/wind power generation. In the Imabari area, introduction of natural gas cogeneration to business establishment, creation of the industry for equipment/parts of photovoltaic power generation. In the Matsuyama area, introduction of cogeneration to business establishment; utilization of biomass energy; creation of the industry of production/processing of resin for solar module use. In the Yawatahama/Oozu area, utilization of wind energy for agriculture/forestry, fisheries and tourism fields; study of introduction of biomass energy. In the Uwajima area, utilization of wind power energy for agriculture/fisheries, fisheries and tourism fields; introduction of biomass energy. (NEDO)

New energy vision of the Kosaka town area; 2001 nendo Kosaka machi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-03-01

For the purpose of promoting the introduction of new energy and enhancing the awareness of it in Kosaka Town, Akita Prefecture, an investigational study was conducted of the energy demand of the town, existence amount of new energy, project on new energy introduction, etc., and a new energy vision was worked out. The amount of energy demand of the town was 2,442,464 GJ/y. The energy demand consists of C heavy oil (about 1/3) and electric power (about 1/3) in the industrial sector, which are outstanding, and others including kerosene (about 12%) in the commercial/residential sector and light oil (about 10%) and gasoline (about 7%) in the transportation sector. The CO2 emissions from these are 60,000 t-C/y. As the project on the new energy introduction, study was made on the introduction of solar energy/snow cold energy space cooling to the insurance welfare center/interchange center, introduction of the photovoltaic power generation to the Korakukan area/elementary school/junior high school, introduction of the snow melting system using soil heat to town street/sidewalk, use of clean energy vehicle to public vehicle, use of ligneous biomass energy, etc. (NEDO)

New energy vision of the Noogata city area; 2001 nendo Noogata shi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-02-01

For the purpose of promoting the introduction of new energy and enhancing the awareness of it in Noogata City, Fukuoka Prefecture, an investigational study was conducted of the energy demand amount of the city, existence amount of new energy, project for new energy introduction, etc., and a vision was worked out. The energy consumption amount of the city was estimated at 4,825.4 x 10{sup 6} MJ/y. It consisted of 47.1% in the industrial sector, 26.1% in the commercial/residential sector and 24.9% in the transportation sector. The rate of energy source was 65.7% of petroleum-base energy and 25.1% of electric power. As the project for new energy introduction, the following were studied: introduction of wind power generation/photovoltaic power generation to the flower park at the foot of Mt. Fukuchi and Nakanoshima park on the sandbank of the Onga river; introduction of photovoltaic power generation to library. Moreover, as future models of the introduction, the potential study was made on the following: installation of the stockbreeding waste biogas plant at the compost center; installation of fuel cell system using digestion gas from night soil treatment facilities; installation of the natural gas cogeneration system in the project on redevelopment of the urban area, etc. (NEDO)

Feasibility study of Copahue geothermal development project, Argentina; Aruzenchin kyowakoku Copahue chiiki no chinetsu kaihatsu chosa

Energy Technology Data Exchange (ETDEWEB)

Abe, M.; Yamada, M.; Nakanishi, S.; Todaka, N. [Electric Power Development Co. Ltd., Tokyo (Japan); Fujita, T.

1996-03-15

Geothermal resources have been evaluated in the Copahue district. For this survey administrated by JICA, drilling of a deep test well with a small bore (COP-3) and blowout tests were conducted. This district is located at the east side of the Andes elongated in the N-S direction. Volcanoes with similar active periods and active states are distributed in the N-S direction, which forms a divide with the Pacific Ocean side. The Copahue-Caviahue composite volcano in the surveyed area is located nearly in the central part of the volcanic zone, which forms a special ring topography. Geology of the Copahue district consists of volcanic effusive rocks during the Tertiary and Quaternary periods. There are five prospecting fields with geothermal indications in the surveyed area. From the survey, an area of about 13 km{sup 2} was evaluated as a geothermal resource field. Especially, in the area of about 4 km{sup 2} including COP-1, 2 and 3 wells, the steam predominant type reservoirs were found out. As a result of estimation of the geothermal resource potential by the volumetric method, a highly prospective power generation potential of 30 MW was evaluated in the field where the steam predominant type reservoirs were confirmed by the boring wells. 7 refs., 13 figs., 1 tab.

New energy vision of the Gotsu city area; 2001 nendo Gotsu shi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-02-01

For the purpose of promoting the introduction of new energy and enhancing the awareness of it in Gotsu City, Shimane Prefecture, an investigational study was conducted of the energy consumption amount of the city, existence amount of new energy, project for new energy introduction, etc., and a new energy vision was worked out. The energy consumption amount of the city was estimated at 1,558,022 Gcal. By sector, the energy consumption amount consisted of 80.0% in the industrial sector, 11.2% of in the transportation sector, 5.8% in the residential sector and 3.0% in the business sector. In the industrial sector, the main energy consumption industries were the paper manufacturing industry and tile industry. As the project for new energy introduction, the following were studied: project for the wind farm where a lot of wind power generators are installed; park as a symbol having 1 or 2 wind power generators; introduction of solar energy use water warmer/photovoltaic power generation to public facilities; system for promotion of the introduction of solar energy use water warmer/photovoltaic power generation to households; project on CO2 reduction by installation of LNG station; refuse/waste power generation project; project on utilization of the waste heat from tile makers. (NEDO)

Performance analysis in Japanese field test program; Field test data kara no chiiki hatsuden kaiseki hoho

Energy Technology Data Exchange (ETDEWEB)

Sugiyama, H.; Kurokawa, K.; Uchida, D. [Tokyo University of Agriculture and Technology, Tokyo (Japan); Otani, K.; Sakuta, K.; Tsuda, I. [Electrotechnical Laboratory, Tsukuba (Japan); Oshiro, T.; Sakamoto, K. [Japan Quality Assurance Organization, Tokyo (Japan)

1997-11-25

Power generation characteristics are investigated using data collected in photovoltaic power generation field tests being undertaken by NEDO (New Energy and Industrial Technology Development Organization). The photovoltaic power generation system performance is evaluated by examining loss factors leading to degradation in system performance, with weather conditions such as variation in insolation and air temperature, inverter performance, and shadows cast by surrounding buildings taken into consideration. As the result, it is found that the important loss factors are degradation in module performance due to elevated temperature, drift in the maximum output control, degraded inverter performance due to input power variation, effect of shadows, etc. It is learned that system is greatly affected by degradation in module performance due to increased temperature in summer and by shadows in winter, the two being responsible for the output coefficient dropping to approximately 75% throughout the year. The output coefficient frequency distribution charts for the 75 test sites confirm that the rate is as low as 70-80% at many sites. As for the system operating time, it tends to be longer in West Japan where the annual insolation rate is higher. 3 refs., 10 figs.

New energy vision of the Akita city area; 2001 nendo Akita shi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-03-01

For the purpose of promoting the introduction of new energy and enhancing the awareness of it in Akita City, an investigational study was conducted of the energy demand of the town, existence amount of new energy, project on new energy introduction, etc., and a new energy vision was worked out. The population of Akita City was 317,868 as of December 31, 2000, which is continuously on the increase. The amount of energy demand of the whole city was 990,000 kL/y. The energy demand consists of fossil fuels such as petroleum, coal and propane gas (77.7%) and electric power (22.3%). The CO2 emissions from these are 2,908,000 t-CO2. As the project on the new energy introduction, study was made on the installation of the photovoltaic power system and wind power system at base centers and introduction of the waste power system at the Goshono Works. As the model project, study was made on the introduction of the photovoltaic power generation and wind power generation to street light and public facilities, road snow melting/space heating and cooling using soil heat, introduction of clean energy vehicles, BDF introduction using waste cooking oil and rate blossoms, etc. (NEDO)

New energy vision of the Yokohama town area; 2001 nendo Yokohama machi chiiki shin energy vision

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-02-01

For the purpose of promoting the introduction of new energy and enhancing the awareness of it in Yokohama Town, Aomori Prefecture, an investigational study was conducted of the structure of energy demand of the town, existence amount of new energy, introduction of new energy, etc., and a new energy vision was worked out. The population of Yokohama Town was 5,508 as of October 2000, which is slightly decreasing. The number of household was unchanged, though. The amount of energy demand was estimated at 21,368 kL/y in crude oil conversion. The energy demand consisted of petroleum-base energy such as kerosene, light oil, heavy oil and gasoline (about 70%), electric power (20%) and LPG (10%). In the action plan for new energy introduction, the following were studied: wind power generation of which the plan has already been worked on by a private company (15 x 1,750kW class generator), introduction of the photovoltaic power generation to Yokohama Junior High School, hothouse vegetable cultivation using exhaust heat from hot spring, and 'Yokohama Rape Blossoms Eco Project' that mainly includes the agricultural land protection/oil squeezing from rapeseed/recycle of waste cooking oil as fuel, for which rape blossoms as one of the most important resources in Yokohama Town are used. (NEDO)

Magnetotelluric (MT) surveying in the Kakkonda geothermal area; Kakkonda chinetsu chiiki deno MT ho tansa jikken

Energy Technology Data Exchange (ETDEWEB)

Ogawa, Y; Takakura, S [Geological Survey of Japan, Tsukuba (Japan); Uchida, T [New Energy and Industrial Technology Development Organization, Tokyo, (Japan)

1997-05-27

This paper describes the MT surveying conducted at the vicinity of a deep well (WD-1) in the Kakkonda geothermal area. For the MT surveying, the interval between measuring points was 300 m. Electric field dipole with a length of 300 m was given in the direction of traverse line, and that with a length of 50 m was given in the direction perpendicular to the line. Three components of magnetic field were measured using induction coil. Frequency band of the data was between 0.0005 Hz and 300 Hz. Characteristics of specific resistance model obtained from the MT surveying were illustrated. Low specific resistance zone less than 30 ohm-m was observed in the shallow zone below the altitude 0 m. This zone was comparable to the distribution of montmorillonite. High specific resistance anomaly was analyzed at the western half of the traverse line in the altitude between 0 m and -2000 m, which corresponded to the collective part of focuses. The bottom surface of the anomaly agreed well with the upper surface of neo-granite, i.e., the lower limits of earthquakes. Low specific resistance was observed in the altitude below -2000 m. 17 refs., 5 figs.

Energy saving vision in Miyazu City region (FY2000); Miyazushi chiiki sho energy vision (2000 nendo)

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

An energy-saving vision was decided on in Miyazu City, Kyoto Prefecture, with its outline reported. The city promulgated the 'Miyazu City plan for the prevention of global warming' earlier this year, aiming at reduction in carbon dioxide exhaust by 25% in ten years ending 2010, and accordingly, also formulated the energy-saving vision on the basis of the plan. The measures with the citizens' life in mind were, for example, encouragement to participate in energy-saving monitor activity, publication of data of survey result, implementation of 'Miyazu eco-life school', support for citizens' voluntary action, utilization of public information/home pages, renewal of equipment and facilities, and preparation of performance/price data for new housing construction and so on. In addition, survey on actual condition, examination for improvements, etc., were among the measures intended for such sectors as hotels/inns, public transportation, manufacturing, and construction, and for the City administration itself. Furthermore, as measures to collaborate with energy suppliers, building an information exchange system is under consideration. (NEDO)

Fiscal 2000 achievement report on the venture business assisting type regional consortium - Minor business creation base type. Development of 1-chip multifunctional motion sensor and its application to intelligent module; 2000 nendo chiiki consortium kenkyu kaihatsu jigyo seika hokokusho. 1 chip gata takino undo sensor no kaihatsu to intelligent module eno tekiyo

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

The aim is to embody an intelligent micromodule for sensing bodily motions. For this purpose, technologies were established for high accuracy/high aspect ratio etching of crystals and for detecting angular velocity and acceleration, and a 1-chip multifunctional motion sensor was developed. The results of the efforts are briefly described below. A 1-chip multifunctional motion sensor (device size: 16 times 6 times 0.3mm) was developed, capable of simultaneously detecting uniaxial acceleration and uniaxial angular velocity, and an operating circuit was established for the detection. Using the 1-chip multifunctional motion sensor, a wrist watch type intelligent module was developed, capable of discriminating between various patterns of human behavior (walking, jogging, desk work, etc.). An intelligent module and the host computer were connected by wire or radio enabling the real-time observation of a patient's kinetic behavior, and this helped develop an application program allowing the quantification of the rate of recovery of patients undergoing rehabilitation. Using an intelligent module, an application program was developed enabling a laryngeal patient to establish communication by a physical action in case of emergency. (NEDO)

Bioinformatics Interpretation of Exome Sequencing: Blood Cancer

Directory of Open Access Journals (Sweden)

Jiwoong Kim

2013-03-01

Full Text Available We had analyzed 10 exome sequencing data and single nucleotide polymorphism chips for blood cancer provided by the PGM21 (The National Project for Personalized Genomic Medicine Award program. We had removed sample G06 because the pair is not correct and G10 because of possible contamination. In-house software somatic copy-number and heterozygosity alteration estimation (SCHALE was used to detect one loss of heterozygosity region in G05. We had discovered 27 functionally important mutations. Network and pathway analyses gave us clues that NPM1, GATA2, and CEBPA were major driver genes. By comparing with previous somatic mutation profiles, we had concluded that the provided data originated from acute myeloid leukemia. Protein structure modeling showed that somatic mutations in IDH2, RASGEF1B, and MSH4 can affect protein structures.

Molecular characterization of apocrine carcinoma of the breast: validation of an apocrine protein signature in a well-defined cohort

DEFF Research Database (Denmark)

Celis, J.E.; Cabezon, T.; Moreira, José

2009-01-01

Invasive apocrine carcinomas (IACs), as defined by morphological features, correspond to 0.3-4% of all invasive ductal carcinomas (IDC), and despite the fact that they are histologically distinct from other breast lesions there are currently no standard molecular criteria available...... characterize these lesions as well as to dissect some of the steps in the processes underlying breast apocrine metaplasia and development of precancerous apocrine lesions. Establishing these apocrine-specific markers as best practice for the routine pathology evaluation of breast cancer, however, will require......1), in addition to a set of categorizing markers that are consistently expressed (AR, CD24) or not expressed (ERalpha, PgR, Bcl-2, and GATA-3) by apocrine metaplasia in benign breast lesions and apocrine sweat glands. This panel was used to analyze a well-defined cohort consisting of 14 apocrine...

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

OpenAIRE

Giuliano Queiroz Mostachio; Wilter Ricardo Russiano Vicente; Diogo José Cardilli; Tathiana Ferguson Motheo; Gilson Hélio Toniollo

2008-01-01

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 sho...

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.

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

DEFF Research Database (Denmark)

Seidelin, Jakob Benedict; Coskun, Mehmet; Kvist, Peter Helding

2015-01-01

of the immune response in experimental colitis (piroxicam-accelerated colitis (PAC) in IL-10 -/- mice, dextran sodium sulfate (DSS) model) and UC.METHODS: Colonic IL-33 expression was determined in UC (8 active UC, 8 quiescent UC, and 7 controls) and experimental colitis. Mesenteric lymph node (MesLN) T cells...

FY 2000 report on the results of the regional consortium R and D project - Regional new technology creation R and D. First year report. R and D of medicine toxicity assessment use hepatocyte chip; 2000 nendo chiiki consortium kenkyu kaihatsu jigyo. Chiiki consortium kenkyu kaihatsu / chiiki shingijutsu soshutsu kenkyu kaihatsu. Dokubutsu dokusei hyokayo kansaibo chip no kenkyu kaihatsu (dai 1 nendo) seika hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

Judging that in the beginning of the toxicity test, the necessary information/knowledge are acquired not by using animal itself but only by using liver system (hepatocyte), the development was proceeded with of the hepatocyte chip substituting for the animal experiment. Studies were made in the following five fields: 1) design of functional matrices; 2) development of the pharmacological assessment technology; 3) development of cell sensing technology/biosensor fabrication; 4) study of a possibility and the limit of cell patterning technology; 5) survey of the market scale. In 1), studies were made of the establishment of the 3D culture method for hepatocyte and the construction of hepatocyte models for medicine assessment using pieces of liver. In the latter, by including capsule using the sugar introduced with galactose residue which is special sugar of hepatocyte to alginic acid and chitosan which are natural polymer and also hepatocyte isolated into sponge, aggregate was formed, and its use as a medicine assessment use liver model was tried to be made. (NEDO)

Krüppel-like factor 2 is required for normal mouse cardiac development.

Directory of Open Access Journals (Sweden)

Aditi R Chiplunkar

Full Text Available Krüppel-like factor 2 (KLF2 is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5 in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2-/- embryos die earlier, by E11.5. E9.5 FVB/N KLF2-/- hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By E10.5, traditional and endothelial-specific FVB/N KLF2-/- AV cushions are hypocellular, suggesting that the cells accumulating at the AV canal have a defect in endothelial to mesenchymal transformation (EMT. E10.5 FVB/N KLF2-/- hearts have reduced glycosaminoglycans in the cardiac jelly, correlating with the reduced EMT. However, the number of mesenchymal cells migrating from FVB/N KLF2-/- AV explants into a collagen matrix is reduced considerably compared to wild-type, suggesting that the EMT defect is not due solely to abnormal cardiac jelly. Echocardiography of E10.5 FVB/N KLF2-/- embryos indicates that they have abnormal heart function compared to wild-type. E10.5 C57BL/6 KLF2-/- hearts have largely normal AV cushions. However, E10.5 FVB/N and C57BL/6 KLF2-/- embryos have a delay in the formation of the atrial septum that is not observed in a defined mixed background. KLF2 ablation results in reduced Sox9, UDP-glucose dehydrogenase (Ugdh, Gata4 and Tbx5 mRNA in FVB/N AV canals. KLF2 binds to the Gata4, Tbx5 and Ugdh promoters in chromatin immunoprecipitation assays, indicating that KLF2 could directly regulate these genes. In conclusion, KLF2-/- heart phenotypes are genetic background-dependent. KLF2 plays a role in EMT through its regulation of important cardiovascular genes.

Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6.

Science.gov (United States)

Liu, Wan-Ju; Reece-Hoyes, John S; Walhout, Albertha J M; Eisenmann, David M

2014-05-13

Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39 expression in the embryo, and hint at a

Inhibitor of DNA binding 1 (Id1) induces differentiation and proliferation of mouse embryonic carcinoma P19CL6 cells

International Nuclear Information System (INIS)

Meng, Qingzhen; Jia, Zhuqing; Wang, Weiping; Li, Binhong; Ma, Kangtao; Zhou, Chunyan

2011-01-01

Highlights: → Id1 was upregulated during the cardiac differentiation process of P19CL6 cells. → Id1 upregulated expression of cardiac specific genes Gata4, α-MHC and ISL1. → Id1 promoted proliferation of P19CL6 cells. → Overexpression of Id1 increased activity of TOP flash. → Wnt3a or LiCl treatment promoted Id1 expression in P19CL6 cells. -- Abstract: The inhibitor of DNA binding (Id) family of genes encodes negative regulators of basic helix-loop-helix transcription factors and has been implicated in such diverse cellular processes as differentiation, proliferation, apoptosis and migration. Id knockout mouse embryos display multiple cardiac defects but the specific role of Id1 in cardiac differentiation is unclear. In the present study, we investigated the function of Id1 in DMSO-induced P19CL6 cells, a widely-accepted cell model of cardiac differentiation. We found that Id1 was upregulated during the cardiac differentiation of P19CL6 cells. The expression of cardiac specific marker genes, Gata4, α-MHC and ISL1, was upregulated in P19CL6 cells stably transfected with Id1 (P19CL6-Id1) during cardiac differentiation. The overexpression of Id1 reduced the number of cells in G1 phase and increased the cell population in G2, M and S phases, while knockdown of Id1 increased the number of cells in G1 phase from 48.6 ± 2.51% to 62.2 ± 1.52% at day 0 of cardiac induction, and from 52.5 ± 3.41% to 63.7 ± 1.02% at day 3 after cardiac induction, indicating that Id1 promoted proliferation of P19CL6 cells. Luciferase assays showed that the activity of TOP flash was higher in P19CL6-Id1 cells than wildtype P19CL6 cells, while Id1 expression was also upregulated in P19CL6 cells treated with Wnt3a or LiCl. This indicates that there may be positive feedback between Id1 and Wnt signaling which plays an important role in cardiac differentiation.

Occupational exposure to 50 Hz magnetic fields does not alter responses of inflammatory genes and activation of splenic lymphocytes in mice

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Xue Luo

2016-04-01

Full Text Available Objectives: The objective of the present study was to observe the effects of 50 Hz magnetic fields (MFs on the immune function of splenic lymphocytes in mice. Material and Methods: Twenty male Kunming mice (6 weeks old, weighing 18– 25 g, were randomly divided into sham exposure (N = 10 and 500 μT MFs (N = 10 groups. The mice in the MFs group were exposed to 500 μT MFs for 8 h daily (5 days/week for up to 60 days. In vitro study was carried out to examine the effects of 50 Hz MFs on the expression of inflammatory factor genes and a cluster of differentiation 69 (CD69 in mouse prime splenic lymphocytes activated by para-Methoxyamphetamine (PMA and ionomycin. In the in vitro experiments, lymphocytes were isolated from the spleen of 10 healthy Kunming mice, the cells were cultured in the Roswell Park Memorial Institute 1640 medium (RPMI-1640 and exposed to 0 μT, 250 μT, 500 μT, or 1 mT MFs in an incubator under 5% carbon dioxide (CO2 at 37°C for 6 h. The levels of interleukin-2 (IL-2, IL-4, interferon-gamma (IFN-γ, GATA binding protein 3 (GATA-3 and T cell-specific T-box transcription factor (T-bet were assessed by the real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR, respectively. The expression of CD69 was checked using the flow cytometry. Results: Under our experimental conditions, body weight of the mice exposed to occupational, extremely low frequency- electromagnetic fields (ELF-EMFs significantly decreased on day 20 and day 30. There were no significant changes observed in vivo in spleen weight, splenic coefficient, splenic histology profile and cytokine production in spleen tissues. Our in vitro experiments showed that 50 Hz MFs had no effect on the expression of these genes and CD69 to primary splenic cells. Conclusions: In conclusion, under the applied experimental conditions, occupational exposure to 50 Hz magnetic field did not alter responses of inflammatory genes and activation of splenic

Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy.

Science.gov (United States)

Gueguen, Claire; Bouley, Julien; Moussu, Hélène; Luce, Sonia; Duchateau, Magalie; Chamot-Rooke, Julia; Pallardy, Marc; Lombardi, Vincent; Nony, Emmanuel; Baron-Bodo, Véronique; Mascarell, Laurent; Moingeon, Philippe

2016-02-01

Regulatory dendritic cell (DC) markers, such as C1Q, are upregulated in PBMCs of patients with grass pollen allergy exhibiting clinical benefit during allergen immunotherapy (AIT). We sought to define markers differentially expressed in human monocyte-derived DCs differentiated toward a proallergic (DCs driving the differentiation of TH2 cells [DC2s]) phenotype and investigate whether changes in such markers in the blood correlate with AIT efficacy. Transcriptomes and proteomes of monocyte-derived DCs polarized toward DCs driving the differentiation of TH1 cells (DC1s), DC2s, or DCs driving the differentiation of regulatory T cells (DCreg cells) profiles were compared by using genome-wide cDNA microarrays and label-free quantitative proteomics, respectively. Markers differentially regulated in DC2s and DCreg cells were assessed by means of quantitative PCR in PBMCs from 80 patients with grass pollen allergy before and after 2 or 4 months of sublingual AIT in parallel with rhinoconjunctivitis symptom scores. We identified 20 and 26 new genes/proteins overexpressed in DC2s and DCreg cells, respectively. At an individual patient level, DC2-associated markers, such as CD141, GATA3, OX40 ligand, and receptor-interacting serine/threonine-protein kinase 4 (RIPK4), were downregulated after a 4-month sublingual AIT course concomitantly with an upregulation of DCreg cell-associated markers, including complement C1q subcomponent subunit A (C1QA), FcγRIIIA, ferritin light chain (FTL), and solute carrier organic anion transporter family member 2B1 (SLCO2B1), in the blood of clinical responders as opposed to nonresponders. Changes in such markers were better correlated with clinical benefit than alterations of allergen-specific CD4(+) T-cell or IgG responses. A combination of 5 markers predominantly expressed by blood DCs (ie, C1Q and CD141) or shared with lymphoid cells (ie, FcγRIIIA, GATA3, and RIPK4) reflecting changes in the balance of regulatory/proallergic responses

Report on new energy vision establishment in Oga City area; Ogashi chiiki shin energy vision sakutei hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

A new energy vision was established in Oga City in Akita Prefecture. The population of the city is continuing the decreasing trend since 1955 to 30,462 persons as of 2000. The number of employed people by industry is in the trend of decreasing in the primary industry, leveling off in the second industry, and increasing in the tertiary industry. The annual energy demand in this city is 838,000 MWh in electric power and 302 times 10{sup 13} J, accounted for by the consumer department at about 44.4%, the transportation department at about 28.3% and the industrial department at 27.3%. The carbon dioxide emission amount therefrom is estimated 68,100 t-C. The expected usable quantity of new energies in the city would be available in solar heat as the largest source, followed by solar beam and wind power, whose amount is estimated 136.41 times 10{sup 13}J annually in total. The new energy introducing project includes introduction of wind power generation into Namahage Line and its vicinity and the Ikari area, manufacture of fuel from refuses, introduction of clean energy fueled automobiles into the cars used by the city office, introduction of photovoltaic into the general gymnasium and primary and middle schools, and solar heat utilization at the general gymnasium. (NEDO)

Plan to promote new energy introduction in Niigata Prefecture area; Niigataken chiiki shin energy donyu suishin keikaku

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

The 'Plan to promote new energy introduction in Niigata Prefecture area' was established to leave the conditions that everybody can live with affluence and comfort in the next generation. The plan lasts for ten years until 2010. Upon identifying the district characteristics of Niigata Prefecture, and based on the results of investigations on new energy existence quantity, utilization possibility thereof, and consciousness of residents of the prefecture, considerations were given that the plan shows the basic policy to promote proliferation of the new energies, and serves as the guideline for practical implementation. The plan document is composed of the following four items: 1) the foreword, 2) the current status of energies, 3) new energies expected of introduction, and 4) basic measures. The energy consumption was estimated to increase to 1.345 times that of fiscal 1990 in the year 2010, the increase being mainly in consumer and household use. The targeted quantity for new energy introduction was set to 90,000 kl annually as converted to petroleum. Expected new energy applications would include photovoltaic power generation, snow energy and solar heat utilization, and cogeneration utilizing natural gas. (NEDO)

[Function and modulation of type Ⅱ innate lymphoid cells and their role in chronic upper airway inflammatory diseases].

Science.gov (United States)

Liu, Y; Liu, Z

2017-02-07

Type Ⅱ innate lymphoid cells (ILC2) is a family of innate immune lymphocytes, which provide effective immune responses to cytokines. ILC2 are regulated by the nuclear transcription factor ROR alpha and GATA3, secreting cytokines IL-5 and IL-13, etc. Animal models have shown that ILC2 are involved in allergic diseases, such as asthma and atopic dermatitis, and also play a very important role in the metabolic balance. In addition, recent reports suggest that ILC2 not only play a role in the initial stages of the disease, but also can lead to chronic pathological changes in the disease, such as fibrosis, and may have an effect on acquired immunity. This paper mainly focus in the role and regulation of ILC2 cells, and review the research status of ILC2 in the field of chronic upper airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.

Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion

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Sandra Capellera-Garcia

2016-06-01

Full Text Available Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs. We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.

Comparative study of hematopoietic stem and progenitor cells between sexes in mice under physiological conditions along time.

Science.gov (United States)

Gasco, Samanta; Rando, Amaya; Zaragoza, Pilar; García-Redondo, Alberto; Calvo, Ana Cristina; Osta, Rosario

2017-12-01

Hematopoietic stem and progenitor cells (HSPCs) are attractive targets in regenerative medicine, although the differences in their homeostatic maintenance between sexes along time are still under debate. We accurately monitored hematopoietic stem cells (HSCs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs) frequencies by flow cytometry, by performing serial peripheral blood extractions from male and female B6SJL wild-type mice and found no significant differences. Only modest differences were found in the gene expression profile of Slamf1 and Gata2. Our findings suggest that both sexes could be used indistinctly to perform descriptive studies in the murine hematopoietic system, especially for flow cytometry studies in peripheral blood. This would allow diminishing the number of animals needed for the experimental procedures. In addition, the use of serial extractions in the same animals drastically decreases the number of animals needed. © 2017 International Federation for Cell Biology.

Temporal distribution of Pu and Am in the Marine Environment of Southern Coast of Spain

Energy Technology Data Exchange (ETDEWEB)

Iranzo, E.; Gasco, C.; Romero, L.; Martinez, A.; Mingarro, E.; Rivas, P.

1989-07-01

The distribution of transuranides and 137Cs in selected sediment cores from southern Spanish coast has been studied. The area is of special interest as an accidental release of transuranides (four nuclear bombs fallen down) occurred near the seaside in 1966 (Palomares). The possible transference to the coast by the river (contaminated by one bomb, surface contamination: 12-120 {alpha} Bq/m2) or by aerosol produced in the explosion had never been studied. Several sediments cores between Cape of Palos and Cape of Gata and surface sediments were raised. The profiles of transuranides distribution were determined and were dated in order to determine the year of the contributions. An enhanced concentration of transuranides has been observed at southern area of Palomares coast, the causes of this fenomena have been analyzed in this paper. The accuracy of radiochemical analysis was checked by analyzing standard material and duplicated samples. (Author)

Temporal distribution of Pu and Am in the Marine Environment of Southern Coast of Spain

International Nuclear Information System (INIS)

Iranzo, E.; Gasco, C.; Romero, L.; Martinez, A.; Mingarro, E.; Rivas, P.

1989-01-01

The distribution of transuranides and 137Cs in selected sediment cores from southern Spanish coast has been studied. The area is of special interest as an accidental release of transuranides (four nuclear bombs fallen down) occurred near the seaside in 1966 (Palomares). The possible transference to the coast by the river (contaminated by one bomb, surface contamination: 12-120 α Bq/m2) or by aerosol produced in the explosion had never been studied. Several sediments cores between Cape of Palos and Cape of Gata and surface sediments were raised. The profiles of transuranides distribution were determined and were dated in order to determine the year of the contributions. An enhanced concentration of transuranides has been observed at southern area of Palomares coast, the causes of this fenomena have been analyzed in this paper. The accuracy of radiochemical analysis was checked by analyzing standard material and duplicated samples. (Author)

Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

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Koen M.A. Dreijerink

2017-03-01

Full Text Available While the multiple endocrine neoplasia type 1 (MEN1 gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER+ cells. In primary mammary cells, MEN1 exerts an anti-proliferative function by regulating a distinct expression signature. Our findings clarify the cell-type-specific functions of MEN1 and inform the development of menin-directed treatments for breast cancer.

Mutations in the VEGFR3 signaling pathway explain 36% of familial lymphedema

DEFF Research Database (Denmark)

Mendola, A; Schlögel, M J; Ghalamkarpour, A

2013-01-01

Lymphedema is caused by dysfunction of lymphatic vessels, leading to disabling swelling that occurs mostly on the extremities. Lymphedema can be either primary (congenital) or secondary (acquired). Familial primary lymphedema commonly segregates in an autosomal dominant or recessive manner. It can...... of these putative genes. We screened 78 index patients from families with inherited lymphedema for mutations in FLT4, GJC2, FOXC2, SOX18, GATA2, CCBE1, and PTPN14. Altogether, we discovered 28 mutations explaining 36% of the cases. Additionally, 149 patients with sporadic primary lymphedema were screened for FLT4......, FOXC2, SOX18, CCBE1, and PTPN14. Twelve mutations were found that explain 8% of the cases. Still unidentified is the genetic cause of primary lymphedema in 64% of patients with a family history and 92% of sporadic cases. Identification of those genes is important for understanding of etiopathogenesis...

LIF supports primitive endoderm expansion during pre-implantation development

DEFF Research Database (Denmark)

Morgani, Sophie M; Brickman, Joshua M

2015-01-01

Embryonic stem cells (ESCs) are pluripotent cell lines that can be maintained indefinitely in an early developmental state. ESC culture conditions almost always require the cytokine LIF to maintain self-renewal. As ESCs are not homogeneous but contain multiple populations reminiscent...... of the blastocyst, identifying the target cells of LIF is necessary to understand the propagation of pluripotency. We recently found that LIF acts under self-renewing conditions to stimulate the fraction of ESCs that express extraembryonic markers, but has little impact on pluripotent gene expression. Here, we...... derivatives, whereas the increase in PrE is mediated both by an increase in proliferation and inhibition of PrE apoptosis that is normally triggered in embryos with an excess of GATA6(+) cells. Thus, it appears that the relative size of the PrE is determined by the number of LIF-producing cells in the embryo...

Solar cell array for driving MOS type FET gate. MOS gata EFT gate kudoyo taiyo denchi array

Energy Technology Data Exchange (ETDEWEB)

Murakami, S; Yoshida, K; Yoshiki, T; Yamaguchi, Y; Nakayama, T; Owada, Y

1990-03-12

There has been a semiconductor relay utilizing MOS type FET (field effect transistor). Concerning the solar cells used for a semiconductor relay, it is required to separate the cells by forming insulating oxide films first and to form semiconductor layers by using many mask patterns, since a crystal semiconductor is used. Thereby its manufacturing process becomes complicated and laminification as well as thin film formation are difficult, In view of the above, this invention proposes a solar cell array for driving a MOS type FET gate consisting of amorphous silicon semiconductor cells, which are used for a semiconductor relay with solar cells generating electromotive power by the light of a light emitting diode and a MOS type FET that the power output of the above solar cells is supplied to its gate, and which are connected in series with many steps. 9 figs.

Condrossarcoma mesenquimal extraesquelético em um gato: relato de caso

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T.N. Guim

2014-04-01

Full Text Available Condrossarcoma mesenquimal extraesquelético (CME é um neoplasma maligno e raro em animais domésticos. Descreve-se um caso de CME em uma gata que apresentava uma massa firme, branco-amarelada, medindo 18cm de diâmetro, aderida à musculatura do membro pélvico esquerdo. O exame citológico revelou presença de células fusiformes individualizadas pleomórficas e agregados de pequenas células ovais, sem bordas definidas em meio à matriz intercelular amorfa. Devido à impossibilidade de tratamento e ao prognóstico desfavorável, foi realizada eutanásia. Microscopicamente foram observadas células fusiformes indiferenciadas e agregados de células condroides pleomórficas. O diagnóstico de CME foi confirmado pelas técnicas de azul alciano, tricrômico de Masson e pela prova imunoistoquímica, utilizando-se anticorpos antivimentina.

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

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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.

Embryonic stem-like cells derived from in vitro produced bovine blastocysts

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Erika Regina Leal de Freitas

2011-06-01

Full Text Available The aim of this work was to study the derivation of bovine embryonic stem-like (ES-like cells from the inner cell mass (ICM of in vitro produced blastocysts. The ICMs were mechanically isolated and six out of seventeen (35% ICMs could attach to a monolayer of murine embryonic fibroblasts (MEF. Ten days after, primary outgrowths were mechanically dissected into several small clumps and transferred to a new MEF layer. Cells were further propagated and passaged by physical dissociation over a 60 days period. The pluripotency of the bovine ES-like cells was confirmed by RT-PCR of Oct-4 and STAT-3 gene markers. The colonies were weakly stained for alkaline phosphatase and the mesoderm and endoderm differentiation gene markers such as GATA-4 and Flk-1, respectively, were not expressed. Embryoid bodies were spontaneously formed at the seventh passage. Results showed that bovine ES-like cells could be obtained and passaged by mechanical procedures from the fresh in vitro produced blastocysts.

Random small interfering RNA library screen identifies siRNAs that induce human erythroleukemia cell differentiation.

Science.gov (United States)

Fan, Cuiqing; Xiong, Yuan; Zhu, Ning; Lu, Yabin; Zhang, Jiewen; Wang, Song; Liang, Zicai; Shen, Yan; Chen, Meihong

2011-03-01

Cancers are characterized by poor differentiation. Differentiation therapy is a strategy to alleviate malignant phenotypes by inducing cancer cell differentiation. Here we carried out a combinatorial high-throughput screen with a random siRNA library on human erythroleukemia K-562 cell differentiation. Two siRNAs screened from the library were validated to be able to induce erythroid differentiation to varying degrees, determined by CD235 and globin up-regulation, GATA-2 down-regulation, and cell growth inhibition. The screen we performed here is the first trial of screening cancer differentiation-inducing agents from a random siRNA library, demonstrating that a random siRNA library can be considered as a new resource in efforts to seek new therapeutic agents for cancers. As a random siRNA library has a broad coverage for the entire genome, including known/unknown genes and protein coding/non-coding sequences, screening using a random siRNA library can be expected to greatly augment the repertoire of therapeutic siRNAs for cancers.

Management of guttate psoriasis in patients with associated streptococcal infection

Directory of Open Access Journals (Sweden)

Karabudak Abuaf O

2012-11-01

Full Text Available Özlem Karabudak Abuaf, Bilal DoganDepartment of Dermatology, GATA Haydarpasa Teaching Hospital, Istanbul, TurkeyAbstract: Psoriasis is a T cell-mediated inflammatory skin disease. It can be provoked or exacerbated by environmental factors, particularly medications and infections. Guttate psoriasis is a distinctive acute form of psoriasis that generally occurs in children and young adults. The association between guttate psoriasis and Streptococcus pyogenes is well established in medical literature; however, the exact mechanism can only be theorized. Treatment guidelines are not established, and it is unclear how necessary antibiotics are for acute state guttate psoriasis. Many dermatologists have recommended using antibiotic therapy or tonsillectomy, especially for patients with recurrent streptococcal infections. This paper briefly summarizes the possible mechanisms of pathogenesis and the recent research results on this topic and examines under what conditions a curative treatment of streptococcal infection by tonsillectomy or antibiotic treatment may benefit psoriasis patients.Keywords: guttate, psoriasis, treatment, Streptococcus pyogenes

Temporal distribution of Pu and Am in the marine environment of southern coast of Spain

International Nuclear Information System (INIS)

Iranzo, E.; Gascon, C.; Romero, L.; Martinez, M.; Mingarro, E.; Rivas, P.

1989-01-01

The distribution of trasuranides and Cs-137 in selected sediment cores from southern Spanish coast has been studied. The area is of special interest as an accidental release of transuranides (four nuclear bombs fallen down) occured near the seasidse in 1966 (Palomare-s). The possible transference to the coast by the river (contaminated by one bomb, surface contamination: 12-120 alpha Bq/m2) or by aerosol produced in the explosion had never been estudied. Several sediments cores between Cape of Palos ands Cape of Gata and surface sediments were raised. The profiles of transuranides distribution were determined and were dated in order to determine the year of the contributions. An enhaced concentration of transuranides has been observed at southern area of Palomares coast, the causes of this fenomena have been analyzed in this paper. The accuracy of radiochemical analysis was checked by analyzing standard material and duplicated samples. (Author). 15 figs.; 27 refs

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

Science.gov (United States)

Ciriello, Giovanni; Gatza, Michael L; Beck, Andrew H; Wilkerson, Matthew D; Rhie, Suhn K; Pastore, Alessandro; Zhang, Hailei; McLellan, Michael; Yau, Christina; Kandoth, Cyriac; Bowlby, Reanne; Shen, Hui; Hayat, Sikander; Fieldhouse, Robert; Lester, Susan C; Tse, Gary M K; Factor, Rachel E; Collins, Laura C; Allison, Kimberly H; Chen, Yunn-Yi; Jensen, Kristin; Johnson, Nicole B; Oesterreich, Steffi; Mills, Gordon B; Cherniack, Andrew D; Robertson, Gordon; Benz, Christopher; Sander, Chris; Laird, Peter W; Hoadley, Katherine A; King, Tari A; Perou, Charles M

2015-10-08

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options. Copyright © 2015 Elsevier Inc. All rights reserved.

Breast cancer metastasizing to the stomach mimicking primary gastric cancer: A case report.

Science.gov (United States)

Yim, Kwangil; Ro, Sang Mi; Lee, Jieun

2017-03-28

Breast cancer with stomach metastasis rare with an incidence of 1% or less among metastatic breast cancer patients. We experienced a case of breast cancer metastasizing to the stomach in 65-year-old female patient. She experienced dyspepsia and poor oral intake before visiting the clinic. Diffuse infiltration with nodular mucosal thickening of the stomach wall was observed, suggesting advanced gastric cancer based on gross endoscopic finding. Spread of poorly cohesive tumor cells in the gastric mucosa observed upon hematoxylin and eosin stain resembled signet ring cell carcinoma, but diffuse positive staining for GATA3 in immunohistochemical stain allowed for a conclusive diagnosis of breast cancer metastasizing to the stomach. Based on the final diagnosis, systemic chemotherapy was administered instead of primary surgical resection. After 2 cycles of docetaxel administration, she showed a partial response based on abdominal computed tomography scan. This case is an unusual presentation of breast cancer metastasizing to the gastrointestinal tract.

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

Science.gov (United States)

Moreau, Thomas; Evans, Amanda L; Vasquez, Louella; Tijssen, Marloes R; Yan, Ying; Trotter, Matthew W; Howard, Daniel; Colzani, Maria; Arumugam, Meera; Wu, Wing Han; Dalby, Amanda; Lampela, Riina; Bouet, Guenaelle; Hobbs, Catherine M; Pask, Dean C; Payne, Holly; Ponomaryov, Tatyana; Brill, Alexander; Soranzo, Nicole; Ouwehand, Willem H; Pedersen, Roger A; Ghevaert, Cedric

2016-04-07

The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.

In vitro Th1 and Th2 cell polarization is severely influenced by the initial ratio of naïve and memory CD4+ T cells

DEFF Research Database (Denmark)

Blom, Lars; Poulsen, Lars K.

2013-01-01

by even small percentages (99% naïve CD4+ T cells resulted in better Th1 and Th2 polarization with significant reduced fractions of IL-4+ and IFN-γ+ CD4+ T cells, respectively. Moreover, the Th2 primed >99% naïve CD4+ T cells showed significantly higher ratio of IL-4+:IFN-γ+ (>4 fold) and GATA-3:+T......-bet+ (>3 fold) CD4+ T cells when compared with the standard purified >90-95% naïve CD4+ T cells primed under the same culture conditions. This suggests immunomagnetic bead separation, a low cost and easy available technique, with few modifications to the manufacturer's protocol as an attractive alternative...... for laboratories not having a cell sorter. Taken together, we report that it is essential to use rigorously purified (>99%) naïve CD4+ T cells for optimal initial in vitro Th1 and Th2 priming....

E-LEARNING CHANGE MANAGEMENT: Challenges and opportunities

Directory of Open Access Journals (Sweden)

Alaattin PARLAKKILIC

2013-10-01

Full Text Available The role of e-learning technologies entirely depends on the acceptance and execution of required-change in the thinking and behaviour of the users of institutions. The research are constantly reporting that many e-learning projects are falling short of their objectives due to many reasons but on the top is the user resistance to change according to the digital requirements of new era. It is argued that the suitable way for change management in e-learning environment is the training and persuading of users with a view to enhance their digital literacy and thus gradually changing the users’ attitude in positive direction. This paper discusses change management in transition to e-learning system considering pedagogical, cost and technical implications. It also discusses challenges and opportunities for integrating these technologies in higher learning institutions with examples from Turkey GATA (Gülhane Askeri Tıp Akademisi-Gülhane Military Medical Academy.

An Expandable, Inducible Hemangioblast State Regulated by Fibroblast Growth Factor

Directory of Open Access Journals (Sweden)

David T. Vereide

2014-12-01

Full Text Available During development, the hematopoietic and vascular lineages are thought to descend from common mesodermal progenitors called hemangioblasts. Here we identify six transcription factors, Gata2, Lmo2, Mycn, Pitx2, Sox17, and Tal1, that “trap” murine cells in a proliferative state and endow them with a hemangioblast potential. These “expandable” hemangioblasts (eHBs are capable, once released from the control of the ectopic factors, to give rise to functional endothelial cells, multilineage hematopoietic cells, and smooth muscle cells. The eHBs can be derived from embryonic stem cells, from fetal liver cells, or poorly from fibroblasts. The eHBs reveal a central role for fibroblast growth factor, which not only promotes their expansion, but also facilitates their ability to give rise to endothelial cells and leukocytes, but not erythrocytes. This study serves as a demonstration that ephemeral progenitor states can be harnessed in vitro, enabling the creation of tractable progenitor cell lines.

Common marmoset embryonic stem cell can differentiate into cardiomyocytes

International Nuclear Information System (INIS)

Chen Hao; Hattori, Fumiyuki; Murata, Mitsushige; Li Weizhen; Yuasa, Shinsuke; Onizuka, Takeshi; Shimoji, Kenichiro; Ohno, Yohei; Sasaki, Erika; Kimura, Kensuke; Hakuno, Daihiko

2008-01-01

Common marmoset monkeys have recently attracted much attention as a primate research model, and are preferred to rhesus and cynomolgus monkeys due to their small bodies, easy handling and efficient breeding. We recently reported the establishment of common marmoset embryonic stem cell (CMESC) lines that could differentiate into three germ layers. Here, we report that our CMESC can also differentiate into cardiomyocytes and investigated their characteristics. After induction, FOG-2 was expressed, followed by GATA4 and Tbx20, then Nkx2.5 and Tbx5. Spontaneous beating could be detected at days 12-15. Immunofluorescent staining and ultrastructural analyses revealed that they possessed characteristics typical of functional cardiomyocytes. They showed sinus node-like action potentials, and the beating rate was augmented by isoproterenol stimulation. The BrdU incorporation assay revealed that CMESC-derived cardiomyocytes retained a high proliferative potential for up to 24 weeks. We believe that CMESC-derived cardiomyocytes will advance preclinical studies in cardiovascular regenerative medicine

Genetic analysis of eight population groups living in Taiwan using a 13 X-chromosomal STR loci multiplex system.

Science.gov (United States)

Hwa, Hsiao-Lin; Lee, James Chun-I; Chang, Yih-Yuan; Yin, Hsiang-Yi; Chen, Ya-Hui; Tseng, Li-Hui; Su, Yi-Ning; Ko, Tsang-Ming

2011-01-01

A 13 X-chromosomal short tandem repeat (STR) multiplex system (DXS6807, DXS8378, DSX9902, DXS7132, DXS9898, DXS6809, DXS6789, DXS7424, DXS101, GATA172D05, HPRTB, DXS8377, and DXS7423) was tested on 1,037 DNA samples from eight population groups currently living in Taiwan. Different distributions of the allelic frequencies in different populations were presented. DXS8377 and DXS101 were the two most polymorphic loci in these eight populations, whereas DXS7423 was the least informative marker in most of the populations studied. The genetic distances between the populations and the constructed phylogenetic tree revealed a long genetic distance between Asian and Caucasian populations as well as isolation of the Tao population. The phylogenetic tree grouped populations into clusters compatible with their ethnogeographic relationships. This 13 X-chromosomal short tandem repeat multiplex system offers a considerable number of polymorphic patterns in different populations. This system can be useful in forensic identification casework and ethnogeographic research.

Innate lymphoid cells are pivotal actors in allergic, inflammatory and autoimmune diseases.

Science.gov (United States)

Sanati, Golshid; Aryan, Zahra; Barbadi, Mehri; Rezaei, Nima

2015-01-01

Innate lymphoid cells (ILCs) are lymphoid cells that do not express V(D)J-rearranged receptors and play a role in the innate immune system. ILCs are categorized into three groups with respect to their function in the immune system. ILC1 induces production of IFN-γ via T-box expressed on T cells, ILC2 promotes production of type 2 cytokines via GATA-binding protein-3 and ILC3 promotes IL-17 and IL-22 production via retinoic acid receptor-related orphan receptor-γt. ILCs can maintain homeostasis in epithelial surfaces by responding to locally produced cytokines or direct recognition of danger patterns. Altered epithelial barrier function seems to be a key point in inappropriate activation of ILCs to promote inflammatory and allergic responses. ILCs play an essential role in initiation and maintenance of defense against infections as well as immune-mediated diseases. In this paper, we discuss the role of ILCs in inflammatory, allergic and autoimmune diseases.

Rural Destination Development Based on Olive Oil Tourism: The Impact of Residents’ Community Attachment and Quality of Life on Their Support for Tourism Development

Directory of Open Access Journals (Sweden)

Ana María Campón-Cerro

2017-09-01

Full Text Available Residents are an essential part of tourism destinations, which makes gaining a deeper understanding of residents’ attitudes towards tourism development necessary because their favourable attitudes can contribute to destinations’ success. This study sought to understand to what extent rural residents’ perceptions of tourism development in their region affect their intention to support further tourism development. The present research also focused on the influence of the variables of community attachment and perceived quality of life on the relationship between residents’ perceptions of and intentions to support this development. This study concentrated on the case of olive oil tourism development in the Sierra de Gata and Las Hurdes districts in Spain. To test the proposed model, the data were collected from a sample of 245 residents in this region. Partial least squares was used to assess the model’s accuracy. The results highlight the importance of residents’ perceptions and their community attachment and perceived quality of life to destination managers who plan and develop tourism projects.

Genetic predisposition syndromes: when should they be considered in the work-up of MDS?

Science.gov (United States)

Babushok, Daria V; Bessler, Monica

2015-03-01

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes. Here, we will discuss the importance of recognizing an underlying genetic predisposition syndrome a patient with MDS, will review clinical scenarios when genetic predisposition should be considered, and will provide a practical overview of the common BMFS and familial MDS/AML syndromes which may be encountered in adult patients with MDS. Copyright © 2014 Elsevier Ltd. All rights reserved.

Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

Science.gov (United States)

Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

2017-09-01

Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

Expression analysis for inverted effects of serotonin transporter inactivation

International Nuclear Information System (INIS)

Ichikawa, Manabu; Okamura-Oho, Yuko; Shimokawa, Kazuro; Kondo, Shinji; Nakamura, Sakiko; Yokota, Hideo; Himeno, Ryutaro; Lesch, Klaus-Peter; Hayashizaki, Yoshihide

2008-01-01

Inactivation of serotonin transporter (HTT) by pharmacologically in the neonate or genetically increases risk for depression in adulthood, whereas pharmacological inhibition of HTT ameliorates symptoms in depressed patients. The differing role of HTT function during early development and in adult brain plasticity in causing or reversing depression remains an unexplained paradox. To address this we profiled the gene expression of adult Htt knockout (Htt KO) mice and HTT inhibitor-treated mice. Inverted profile changes between the two experimental conditions were seen in 30 genes. Consistent results of the upstream regulatory element search and the co-localization search of these genes indicated that the regulation may be executed by Pax5, Pax7 and Gata3, known to be involved in the survival, proliferation, and migration of serotonergic neurons in the developing brain, and these factors are supposed to keep functioning to regulate downstream genes related to serotonin system in the adult brain

Fiscal 1999 edition. Guidebook for introducing new energies in Kinki District; Kinki chiiki shin energy donyu guide book

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-09-01

The captioned guidebook is composed of the following subjects: (1) the current status and problems of new energies (the energy status and the current status of new energies in Japan, and approaches to new energies in Japan); (2) the status of introduction and works in Kinki District (the outline of introduction and works in Kinki District on photovoltaic electric power generation, solar heat utilization, wind power generation, wastes power generation, clean energy fueled automobiles, cogeneration, fuel cells, unused energies, and other reproducible energies); (3) NEDO related supportive institutions (new energy introduction promotion projects by NEDO, and the outline of different supportive institutions); (4) new energy introduction flow (total flow leading to the introduction, and introduction flow by new energies); (5) the grand new energy prize in Kinki District (what is the grand new energy prize? and cases of prizes awarded in Kinki District); (6) new energy related supportive institutions (a list of the related institutions, and the outline of different supportive institutions); and (7) new energy consultation windows and contacts (consultation windows and contacts for general new energy aspects and the government related supportive institutions, and consultation windows by new energies). The grand new energy prize is awarded by New Energy Foundation as the 'institution for public recognition of new energy devices of the 21st century type'. (NEDO)

Report on new energy vision at Hinase Town area; 2001 nendo Hinase cho chiiki shin energy vision hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-03-01

With an objective of accelerating introduction of and uplifting consciousness on new energies at Hinase Town in Hyogo Prefecture, investigations and discussions were given on the energy demand, quantity of new energies available, and the new energy introduction projects for the town, thus a new energy vision was established. The estimated amount of energy consumption in Hinase Town is 242,814,320,000 kcal in fiscal 2000. The amount of carbon dioxide discharge associated therewith is 76.57 t-CO2/year. Regarding the energy consumption by departments, the industrial department consumes the most, followed by the transportation department, civil household department, and civil business department. The new energy introduction projects have discussed servicing of the bio-gas plant utilizing organic wastes and cogeneration, the new energy introduction projects for the Natural Energy Island at Kakui Island and the ocean ranch consisted of the use of solar heat water warmer, solar cell powered street lights, photovoltaic power generation, and electric cars for sightseeing visitors, the Eco-school promotion project for primary schools, introduction of energy saving devices into the town office, and the new energy proliferation and enlightenment project. (NEDO)

Report of regional new energy vision for Kannami Town; 2001 nendo Kannami cho chiiki shin energy vision hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-03-01

For promoting the introduction of new energy and for enhancing people's consciousness of such at Kannami Town, Shizuoka Prefecture, surveys and studies were conducted involving the energy consumption structure of the town, the amount of new energy resources in existence, and new energy introduction projects, and a vision was formulated. The town consumes approximately 5-million GJ/year, with the industrial sector consuming 47%, the transportation sector 29%, and the residential and commercial sector 26%. When a comparison is made, the percentages of the residential/commercial and transportation sectors are relatively higher than the national average. Projects for new energy introduction were studied, which involved photovoltaic power generation for the town office, community hall, primary and junior high schools, nursery schools, and general residences; solar heat utilization for public facilities, greenhouses, and general residences; wind power generation for sightseeing facilities, public gardens, and emergency evaluation areas; utilization of sewage waste heat for the sewage purification center; utilization of hot spa waste heat in the urban area; a biomass-fueled power plant; medium- and mini-scale hydroelectric power generation for the drinking water treatment plant; refuse-fueled power generation at refuse incineration facilities; use of clean-energy automobiles; natural gas-fueled cogeneration for public organizations; and so forth. (NEDO)

Fiscal 1999 edition. Guidebook for introducing new energies in Kinki District; Kinki chiiki shin energy donyu guide book

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-09-01

The captioned guidebook is composed of the following subjects: (1) the current status and problems of new energies (the energy status and the current status of new energies in Japan, and approaches to new energies in Japan); (2) the status of introduction and works in Kinki District (the outline of introduction and works in Kinki District on photovoltaic electric power generation, solar heat utilization, wind power generation, wastes power generation, clean energy fueled automobiles, cogeneration, fuel cells, unused energies, and other reproducible energies); (3) NEDO related supportive institutions (new energy introduction promotion projects by NEDO, and the outline of different supportive institutions); (4) new energy introduction flow (total flow leading to the introduction, and introduction flow by new energies); (5) the grand new energy prize in Kinki District (what is the grand new energy prize? and cases of prizes awarded in Kinki District); (6) new energy related supportive institutions (a list of the related institutions, and the outline of different supportive institutions); and (7) new energy consultation windows and contacts (consultation windows and contacts for general new energy aspects and the government related supportive institutions, and consultation windows by new energies). The grand new energy prize is awarded by New Energy Foundation as the 'institution for public recognition of new energy devices of the 21st century type'. (NEDO)

MT2-D inversion analysis in Kakkonda geothermal field; Kakkonda chinetsu chiiki ni okeru MT ho nijigen kaiseki

Energy Technology Data Exchange (ETDEWEB)

Yamane, K; Takasugi, S [Geothermal Energy Research and Development Co. Ltd., Tokyo (Japan); Miyazaki, S [Japan Metals and Chemicals Co. Ltd., Tokyo (Japan); Uchida, T [New Energy and Industrial Technology Development Organization, Tokyo, (Japan)

1996-05-01

Data, collected from an MT method-assisted survey conducted in the Kakkonda geothermal region in 1987, was re-examined, and a new structure was found. The review was carried out by use of a 2D analysis in the TM mode. According to the 1D analysis of 1987 and the geological data gathered then, it is estimated that the resistivity structure of this region runs in the northwest-southeast direction. A northeast-southwest traverse line was set for this analysis, orthogonal to the strike, and the impedance at each observation spot was caused to rotate to this direction across the whole range of frequency. Furthermore, in 1994-95, surveys were conducted using arrayed CSMT/MT methods. All these sum up to indicate that a high-resistivity region extends northwest in the southwestern part of the Kakkonda river but that there exists a low-resistivity region of several 10 Ohm m centering about the B traverse line. The high-resistivity region deep in the ground being the target of excavation in the Kakkonda region, to collect knowledge about this high-resistivity is important, and here the effectiveness of the 2d analysis has been verified. 5 refs., 11 figs.

Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice.

Science.gov (United States)

Feng, Yu; Tian, Jijing; Xie, Heidi Qunhui; She, Jianwen; Xu, Sherry Li; Xu, Tuan; Tian, Wenjing; Fu, Hualing; Li, Shuaizhang; Tao, Wuqun; Wang, Lingyun; Chen, Yangsheng; Zhang, Songyan; Zhang, Wanglong; Guo, Tai L; Zhao, Bin

2016-09-01

Although the chlorinated flame retardant Dechlorane (Dec) 602 has been detected in food, human blood, and breast milk, there is limited information on potential health effects, including possible immunotoxicity. We determined the immunotoxic potential of Dec 602 in mice by examining the expression of phenotypic markers on thymocyte and splenic lymphocyte subsets, Th1/Th2 transcription factors, and the production of cytokines and antibodies. Adult male C57BL/6 mice were orally exposed to environmentally relevant doses of Dec 602 (1 and 10 μg/kg body weight per day) for 7 consecutive days. Thymocyte and splenic CD4 and CD8 subsets and splenocyte apoptosis were examined by flow cytometric analysis. Cytokine expression was measured at both the mRNA and the protein levels. Levels of the transcription factors Th1 (T-bet and STAT1) and Th2 (GATA3) were determined using quantitative real-time polymerase chain reaction (qPCR). Serum levels of immunoglobulins IgG1, IgG2a, IgG2b and IgE were measured by enzyme-linked immunosorbent assay (ELISA). Splenic CD4+ and CD8+ T cell subsets were decreased compared with vehicle controls, and apoptosis was significantly increased in splenic CD4+ T cells. Expression (mRNA and protein) of Th2 cytokines [interleukin (IL)-4, IL-10, and IL-13] increased, and that of Th1 cytokines [IL-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] decreased. The Th2 transcriptional factor GATA3 increased, whereas the Th1 transcriptional factors T-bet and STAT1 decreased. As additional indicators of the Th2-Th1 imbalance, production of IgG1 was significantly increased, whereas IgG2a was reduced. To our knowledge, we are the first to report evidence of the effects of Dec 602 on immune function in mice, with findings indicating that Dec 602 exposure favored Th2 responses and reduced Th1 function. Feng Y, Tian J, Xie HQ, She J, Xu SL, Xu T, Tian W, Fu H, Li S, Tao W, Wang L, Chen Y, Zhang S, Zhang W, Guo TL, Zhao B. 2016. Effects of acute low

Integrated expression profiling and ChIP-seq analyses of the growth inhibition response program of the androgen receptor.

Directory of Open Access Journals (Sweden)

Biaoyang Lin

2009-08-01

, GATA (GATA transcription factors, OCT (octamer transcription factors and PU1 (PU.1 transcription factor.Our data provide a valuable data set in understanding the molecular basis for growth inhibition response program of the AR in prostate cancer cells, which can be exploited for developing novel prostate cancer therapeutic strategies.

Promoting effect of small molecules in cardiomyogenic and neurogenic differentiation of rat bone marrow-derived mesenchymal stem cells

Directory of Open Access Journals (Sweden)

Khanabdali R

2015-12-01

Full Text Available Ramin Khanabdali,1 Anbarieh Saadat,1 Maizatul Fazilah,1 Khairul Fidaa’ Khairul Bazli,1 Rida-e-Maria Qazi,2 Ramla Sana Khalid,2 Durriyyah Sharifah Hasan Adli,1 Soheil Zorofchian Moghadamtousi,1 Nadia Naeem,2 Irfan Khan,2 Asmat Salim,2 ShamsulAzlin Ahmad Shamsuddin,1 Gokula Mohan1 1Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 2Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan Abstract: Small molecules, growth factors, and cytokines have been used to induce differentiation of stem cells into different lineages. Similarly, demethylating agents can trigger differentiation in adult stem cells. Here, we investigated the in vitro differentiation of rat bone marrow mesenchymal stem cells (MSCs into cardiomyocytes by a demethylating agent, zebularine, as well as neuronal-like cells by β-mercaptoethanol in a growth factor or cytokines-free media. Isolated bone marrow-derived MSCs cultured in Dulbecco’s Modified Eagle’s Medium exhibited a fibroblast-like morphology. These cells expressed positive markers for CD29, CD44, and CD117 and were negative for CD34 and CD45. After treatment with 1 µM zebularine for 24 hours, the MSCs formed myotube-like structures after 10 days in culture. Expression of cardiac-specific genes showed that treated MSCs expressed significantly higher levels of cardiac troponin-T, Nkx2.5, and GATA-4 compared with untreated cells. Immunocytochemical analysis showed that differentiated cells also expressed cardiac proteins, GATA-4, Nkx 2.5, and cardiac troponin-T. For neuronal differentiation, MSCs were treated with 1 and 10 mM β-mercaptoethanol overnight for 3 hours in complete and serum-free Dulbecco’s Modified Eagle’s Medium, respectively. Following overnight treatment, neuron-like cells with axonal and dendritic-like projections originating from the

Aberrant gene promoter methylation associated with sporadic multiple colorectal cancer.

Directory of Open Access Journals (Sweden)

Victoria Gonzalo

Full Text Available BACKGROUND: Colorectal cancer (CRC multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. METHODOLOGY/PRINCIPAL FINDINGS: We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2, RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008 and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047 as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006. Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17, SFRP1 (r = 0.83, 0.06, HPP1 (r = 0.64, p = 0.17, 3OST2 (r = 0.83, p = 0.06 and GATA4 (r = 0.6, p = 0.24. Methylation in normal appearing colorectal mucosa from patients with multiple and solitary CRC showed no relevant

New energy vision of Rokunohe Town. Maple green plan (Town creation using the riches of Nature and industries of the area); 2001 nendo Rokunohe machi chiiki shin energy vision. Meipuru Green keikaku - Yutaka na shizen to chiiki no sangyo wo ikashita machidukuri

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-02-01

For the purpose of promoting the introduction of new energy and enhancing the awareness of it in Rokunohe Town, Aomori Prefecture, an investigational study was conducted of the state of energy supply/demand, existence amount of new energy, introduction of new energy, etc., and a vision was worked out. The population of Rokunohe Town was 10,481 according to the results of the national census taken in 2000, which is slightly decreasing. The energy consumption amount of the town is 16,063.6t in oil conversion, and the consumption depends on fossil fuels such as electric power, gasoline, light oil, heavy oil and LPG gas. For the action plan for introduction of new energy, the following were cited: field study of the photovoltaic power generation, preparation of the shopping street/school street which are safe and unfrozen (snow melting of sidewalk), potential study of the agricultural development of snow/ice energy, use of the agricultural waste such as animal feces and waste vegetable (study of introduction of small-scale bio-system), promotion of recycle of cooking oil (study of the use of clean energy vehicles for official vehicles and use of diesel substituting fuel), study of use of energy crops for the idle field, various education projects, etc. (NEDO)

Studies on energy system for an energy-saving society; Sho energy gata shakai ni okeru energy system kento

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

The system to which new energy technology and energy saving technology were introduced was constructed for case studies of urban areas including core cities and the peripheral areas, and the quantitative analysis was conducted on environmental effects, etc. In the energy supply system model, the following element technologies were all considered: cogeneration system, sewage water heat, river water heat, the photovoltaic power generation, energy storage/heat storage/cold heat storage, adsorption type refrigerator, etc. Also considered were power interchange between clusters, system power buying/power selling, heat interchange or no heat interchange, etc. As a result, it was found that when constructing the energy system which synthetically takes into account thermoelectric ratios, rates of simultaneous loads, ratios of daytime/nighttime in the energy supply and demand in the urban area, the energy saving effect multiplicatively increases, and the energy system using cogeneration and unused energy such as refuse and sewage in the urban area and river water brings an energy saving effect of 32% especially in the concentrated cluster. 83 figs., 45 tabs.

Experimental study on power augmentation of Savonius rotor; Savonius gata fusha no shutsuryoku zokyo ni kansuru jikkenteki kenkyu

Energy Technology Data Exchange (ETDEWEB)

Sato, S; Kikuchi, K; Ushiyama, I [Ashikaga Institute of Technology, Tochigi (Japan)

1997-11-25

Wind power now being used is mostly for power generation, and the power generating rotor is represented by the horizontal propeller type. The vertical type, such as Savonius rotor which uses drag force, may be used for special purposes. The Savonius rotor has been used for water pumping-up and ventilation for its characteristics of low rotational speed and high torque. The authors have proposed, based on the data collected by operating a wind mill of 10W, a method for reducing resistance by deflecting wind flowing onto the return bucket to augment drag force, in an attempt to make the system more functional. The Savonius rotor is equipped with a semi-cylindrical cover, and guide and side plates, to follow their effects. It is found that these plates work to augment power without needing expansion of sweeping area. 4 refs., 12 figs.

Preliminary study of airborne electromagnetic survey using grounded source; Chihyo source gata kuchu denji tansa no kisoteki kenkyu

Energy Technology Data Exchange (ETDEWEB)

Mogi, T [Kyushu University, Fukuoka (Japan). Faculty of Engineering; Shimoizumi, M [Kitakyushu Polytechnic College, Kitakyushu (Japan); Kusunoki, K [Central Research Institute of Electric Power Industry, Tokyo (Japan); Morikawa, T [Dowa Engineering Co. Ltd., Okayama (Japan); Jomori, N [Chiba Electronics Research Institute, Chiba (Japan)

1996-05-01

For the development of an airborne electromagnetic prospecting method capable of deeper exploration, a basic study was made about a system wherein a transmitter (source) is positioned on the ground and the receiving is done in the sky. Even in case of this airborne electromagnetic method, the TDEM method is supposedly advantageous over others as in case of groundborne exploration. In the study, the transient response of an airborne vertical magnetic field to a horizontal layered structure was calculated. The current source was 2000m long with a capacity of 30A. The one-layer structure was a 10 Ohm m semi-infinite ground, and the two-layer structure had a 100 Ohm m structure just under the one-layer structure. The result of the calculation suggests that, in the absence of a layer of extremely low resistivity, observation of an approximately 1 second long transient response aboard a helicopter flying at approximately 50km/h will enable an approximately 1000m deep exploration. Problems to affect airborne observation, such as swinging, natural magnetic field fluctuation, and artificially produced noises were investigated by use of a magnetometer suspended from a helicopter in flight. 2 refs., 6 figs.

Drilling series. 4. ; Planning geothermal drilling (rotary type). Kussaku series. 4. ; Chinetsusei no kussaku keikaku (shutoshite rotary gata)

Energy Technology Data Exchange (ETDEWEB)

Ito, T. (S.K. Engineering Co. Ltd., Tokyo (Japan))

1994-01-31

The present report explained how to plan the drilling of geothermal well, and select the easing, drilling mud water and drilling rig in order to obtain the steam and hot water. The geothermal wells can be generally classified into exploration wells, production wells and reduction wells. The exploration well is a well to survey the underground strata, geological structure, and existence of steam and hot water, while the production well is a well to produce the steam and hot water. The reduction well is a well to condense the hot water produced by the production well and steam having passed through the power-generating turbine, and return them as condensate underground. The geothermal well is characterized by its high temperature, mud leakage, corrosive matter and scale, all of which make its drilling difficult and its management troublesome for the production and reduction. To plan the drilling, the order of processing are distinct conditioning of drilling differently by type of well, collection of geological survey data, programing for the casing and selection of drilling rig. The present report also gave the stress to affect the casing and standard of steel pipes to be used for the casing. 3 figs., 4 tabs.

Quantitative controls on location and architecture of carbonate depositional sequences: upper miocene, cabo de gata region, se Spain

Science.gov (United States)

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

1998-01-01

Sequence stratigraphy, pinning-point relative sea-level curves, and magnetostratigraphy provide the quantitative data necessary to understand how rates of sea-level change and different substrate paleoslopes are dominant controls on accumulation rate, carbonate depositional sequence location, and internal architecture. Five third-order (1-10 my) and fourth-order (0.1-1.0 my) upper Miocene carbonate depositional sequences (DS1A, DS1B, DS2, DS3, TCC) formed with superimposed higher-frequency sea-level cycles in an archipelago setting in SE Spain. Overall, our study indicates when areas of high substrate slope (> 15??) are in shallow water, independent of climate, the location and internal architecture of carbonate deposits are not directly linked to sea-level position but, instead, are controlled by location of gently sloping substrates and processes of bypass. In contrast, if carbonate sediments are generated where substrates of low slope ( 15.6 cm/ky to ??? 2 cm/ky and overall relative sea level rose at rates of 17-21.4 cm/ky. Higher frequency sea-level rates were about 111 to more than 260 cm/ky, producing onlapping, fining- (deepening-) upward cycles. Decreasing accumulation rates resulted from decreasing surface area for shallow-water sediment production, drowning of shallow-water substrates, and complex sediment dispersal related to the archipelago setting. Typical systems tract and parasequence development should not be expected in "bypass ramp" settings; facies of onlapping strata do not track base level and are likely to be significantly different compared to onlapping strata associated with coastal onlap. Basal and upper DS2 reef megabreccias (indicating the transition from cool to warmer climatic conditions) were eroded from steep upslope positions and redeposited downslope onto areas of gentle substrate during rapid sea-level falls (> 22.7 cm/ky) of short duration. Such rapid sea-level falls and presence of steep slopes are not conducive to formation of forced regressive systems tracts composed of downstepping reef clinoforms. The DS3 reefal platform formed where shallow water coincided with gently sloping substrates created by earlier deposition. Slow progradation (0.39-1.45 km/my) is best explained by the lack of an extensive bank top, progressively falling sea level, and low productivity resulting from siliciclastic debris and excess nutrients shed from nearby volcanic islands. Although DS3 strata were deposited during a third-order relative sea-level cycle, a typical transgresse??e systems tract is not recognizable, indicating that the initial relative rise in sea level was too rapid (??? 19 cm/ky). Downstepping reefs, forming a forced regressive systems tract, were deposited during the relative sea-level fall at the end of DS3, indicating that relatively slow rates of fall (10 cm/ky or less) over favorable paleoslope conditions are conducive to generation of forced regressive systems tracts consisting of downstepping reef clinoforms. The TCC sequence consists of four shallow -water sedimentary cycles that were deposited during a 400 ky to 100 ky time span. Such shallow-water cycles, typical of many platforms, form only where shallow water intersects gently sloping substrates. The relative thicknesses of cycles (< 2 m to 15 m thick), magnitudes of relative sea-level fluctuations associated with each cycle (25-30 m), high rates of relative sea-level fluctuations (minimum of 25-120 cm/ky), and the widespread distribution of similar TCC cycles in the Mediterranean and elsewhere are supportive of a glacio-eustati

Basic survey report on regional new energy vision for Ehime Prefecture; Ehimeken chiiki shin energy vision kiso chosa hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-03-01

A new energy vision has been formulated to establish guidelines for popularizing and utilizing new energy which generates but a small amount of environmental impact. The results of surveys conducted in this connection are described in five chapters, which cover (1) the trend of new energy, (2) current situation of new energy in Ehime Prefecture, (3) calculation of the existing amount and available amount of new energy, (4) calculation of the introducible amount of new energy, and (5) the basic policy toward the introduction of new energy. Part (4) covers solar energy, wind energy, waste-derived energy, temperature difference energy, minor scale hydroelectric power generation, biomass energy, and like others. It states that a total of 540,000 kl/year will be available in terms of oil, equivalent to approximately 6% of Ehime Prefecture's 1997 energy consumption, and that it is expected that in fiscal 2010 photovoltaic/passive solar energy utilization, cogeneration, and wind power will yield 152,000, 314,000, and 27,000 kl/year respectively. (NEDO)

Report on a regional new energy vision establishment in Yatsuka Township; Yatsukamachi chiiki shin energy vision sakutei jigyo hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

Surveys and discussions were given on establishing a new energy vision in Yatsuka Township in Shimane Prefecture. For the survey on available amount of natural energies (sunlight and wind), all-weather insolation required for solar energy power generation was analyzed by using the NEDO information, and wind was analyzed based on observations at Matsue Meteorological Observatory, Sakai-minato Observatory, and Nakaura Water Gate. In discussing the system, power generation amount in the Matsue area was estimated for the case when solar cells of single crystal silicon plus amorphous hybrid type HIP-H48B1 are used. For wind power generation, power generation amount was calculated from observation values derived at the Nakaura water gate when wind mills with diameters from 2 to 10 m are used. Furthermore, calculations were performed on power amount generated uniformly by using a hybrid system using solar energy power generation and wind power generation. As a result of the discussions, a plan was established to introduce the new energies by means of a solar and wind energy hybrid power generation system to the greenhouse 'Green Stellar' symbolizing the Japan's largest peony production, being capable of year-round peony cultivation. The system is planned to be introduced to the town office building and other public organizations sequentially according to annual programs. (NEDO)

Plans for promoting district energy-saving visions for City of Wakkanai; Wakkanai-shi chiiki sho energy vision suishin keikakusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-02-01

The district energy-saving visions and promotion plans therefor are drawn for City of Wakkanai, to promote energy saving and abatement of gas emissions which cause global warming. The conception of the energy-saving introduction project includes introduction of co-generation systems in the facilities of pivotal functions in the city center, and energy-saving systems in a municipal heated pool and public hot spring facilities. The facilities of pivotal functions in the city, e.g., the municipal office buildings, municipal hospital and all-around culture center of the city are supplied with heat in a centralized manner from the energy center, and the energy-saving effect is expected when co-generation systems are introduced in the energy center. The study results indicate that introduction of the co-generation systems in the energy center has a potential energy-saving effect of 2,400Gcal/y. The energy-saving effects are also analyzed for each of the municipal office buildings, municipal hospital, all-around culture center, municipal heated pool and public hot spring facilities, including those potentially realized by improving illumination and air supply/discharge facilities. (NEDO)