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Academic literature on the topic 'GATA-1'

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Published: 4 June 2021
Last updated: 1 February 2022

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Journal articles on the topic "GATA-1"

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Sartori, Daniel J., Christopher J. Wilbur, Simon Y. Long, Matthew M. Rankin, Changhong Li, Jonathan P. Bradfield, Hakon Hakonarson, Struan F. A. Grant, William T. Pu, and Jake A. Kushner. "GATA Factors Promote ER Integrity and β-Cell Survival and Contribute to Type 1 Diabetes Risk." Molecular Endocrinology 28, no. 1 (January 1, 2014): 28–39. http://dx.doi.org/10.1210/me.2013-1265.

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Abstract Pancreatic β-cell survival remains poorly understood despite decades of research. GATA transcription factors broadly regulate embryogenesis and influence survival of several cell types, but their role in adult β-cells remains undefined. To investigate the role of GATA factors in adult β-cells, we derived β-cell-inducible Gata4- and Gata6-knockout mice, along with whole-body inducible Gata4 knockouts. β-Cell Gata4 deletion modestly increased the proportion of dying β-cells in situ with ultrastructural abnormalities suggesting endoplasmic reticulum (ER) stress. Notably, glucose homeostasis was not grossly altered in Gata4- and Gata6-knockout mice, suggesting that GATA factors do not have essential roles in β-cells. Several ER stress signals were up-regulated in Gata4 and Gata6 knockouts, most notably CHOP, a known regulator of ER stress-induced apoptosis. However, ER stress signals were not elevated to levels observed after acute thapsigargin administration, suggesting that GATA deficiency only caused mild ER stress. Simultaneous deletion of Gata4 and CHOP partially restored β-cell survival. In contrast, whole-body inducible Gata4 knockouts displayed no evidence of ER stress in other GATA4-enriched tissues, such as heart. Indeed, distinct GATA transcriptional targets were differentially expressed in islets compared with heart. Such β-cell-specific findings prompted study of a large meta-analysis dataset to investigate single nucleotide polymorphisms harbored within the human GATA4 locus, revealing several variants significantly associated with type 1 diabetes mellitus. We conclude that GATA factors have important but nonessential roles to promote ER integrity and β-cell survival in a tissue-specific manner and that GATA factors likely contribute to type 1 diabetes mellitus pathogenesis.
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Crispino, John D., and Marshall S. Horwitz. "GATA factor mutations in hematologic disease." Blood 129, no. 15 (April 13, 2017): 2103–10. http://dx.doi.org/10.1182/blood-2016-09-687889.

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Abstract GATA family proteins play essential roles in development of many cell types, including hematopoietic, cardiac, and endodermal lineages. The first three factors, GATAs 1, 2, and 3, are essential for normal hematopoiesis, and their mutations are responsible for a variety of blood disorders. Acquired and inherited GATA1 mutations contribute to Diamond-Blackfan anemia, acute megakaryoblastic leukemia, transient myeloproliferative disorder, and a group of related congenital dyserythropoietic anemias with thrombocytopenia. Conversely, germ line mutations in GATA2 are associated with GATA2 deficiency syndrome, whereas acquired mutations are seen in myelodysplastic syndrome, acute myeloid leukemia, and in blast crisis transformation of chronic myeloid leukemia. The fact that mutations in these genes are commonly seen in blood disorders underscores their critical roles and highlights the need to develop targeted therapies for transcription factors. This review focuses on hematopoietic disorders that are associated with mutations in two prominent GATA family members, GATA1 and GATA2.
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Capo-chichi, Callinice D., Jennifer L. Smedberg, Malgorzata Rula, Emmanuelle Nicolas, Anthony T. Yeung, Richard F. Adamo, Andrey Frolov, Andrew K. Godwin, and Xiang-Xi Xu. "Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells." Stem Cells International 2010 (2010): 1–15. http://dx.doi.org/10.4061/2010/602068.

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Background. Mouse embryonic stem (ES) cells can be differentiated in vitro by aggregation and/or retinoic acid (RA) treatment. The principal differentiation lineage in vitro is extraembryonic primitive endoderm. Dab2, Laminin, GATA4, GATA5, and GATA6 are expressed in embryonic primitive endoderm and play critical roles in its lineage commitment.Results. We found that in the absence of GATA4 or GATA5, RA-induced primitive endoderm differentiation of ES cells was reduced. GATA4 (−/−) ES cells express higher level of GATA5, GATA6, and hepatocyte nuclear factor 4 alpha marker of visceral endoderm lineage. GATA5 (−/−) ES cells express higher level of alpha fetoprotein marker of early liver development. GATA6 (−/−) ES cells express higher level of GATA5 as well as mesoderm and cardiomyocyte markers which are collagen III alpha-1 and tropomyosin1 alpha. Thus, deletion of GATA6 precluded endoderm differentiation but promoted mesoderm lineages.Conclusions. GATA4, GATA5, and GATA6 each convey a unique gene expression pattern and influences ES cell differentiation. We showed that ES cells can be directed to avoid differentiating into primitive endoderm and to adopt unique lineages in vitro by modulating GATA factors. The finding offers a potential approach to produce desirable cell types from ES cells, useful for regenerative cell therapy.
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Dore, Louis C., Timothy M. Chlon, Zan Huang, and John Crispino. "Identification of a GATA Switch In Megakaryocytic Development." Blood 116, no. 21 (November 19, 2010): 2605. http://dx.doi.org/10.1182/blood.v116.21.2605.2605.

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Abstract Abstract 2605 GATA family transcription factors play critical roles in various mammalian developmental processes, including hematopoiesis. In particular, GATA-1 expression is necessary for proper terminal differentiation of mast cells, red blood cells, eosinophils, and megakaryocytes. GATA-2 is required for proliferation and survival of hematopoietic stem and progenitor cells, and is also expressed in erythroid precursors, mast cells, and early megakaryocytes. In developing erythrocytes, GATA-2 and GATA-1 are responsible for temporal control of a multi-factor transcriptional regulatory network that involves (a) GATA-2 positively regulating its own gene transcription, (b) GATA-2 positively regulating the expression of the Gata1 gene, (c) GATA-1 positively regulating its own gene transcription, and (d) GATA-1 negatively regulating Gata2 gene transcription. During this sequence of events, a “GATA switch” occurs, wherein GATA-1 replaces GATA-2 at canonical GATA binding sites within the regulatory regions of the Gata2 and Gata1 genes, as well as at many other genomic loci that encode genes responsible for proliferation or differentiation of erythroid progenitors. Similarly, in early megakaryocytic progenitors, GATA-2 promotes proliferation and suppresses expression of alternative-lineage genes; subsequent activation of GATA-1 precipitates terminal differentiation with concomitant downregulation of proliferative genes and activation of megakaryocyte-specific genes. The presence or role of a GATA switch in megakaryocytes has not yet been formally investigated. To address the role of the GATA switch in megakaryocytic differentiation, we performed massively parallel sequencing of chromatin immunoprecipitation (ChIP-Seq) material for GATA-2 and GATA-1 before or after GATA-1 restoration in the GATA1-null megakaryocytic progenitor cell line, G1ME. We obtained 22 million unique GATA-2 tags and 10 million unique GATA-1 tags and identified 14985 and 5102 high-confidence GATA-2 and GATA-1 binding sites, respectively. Additionally, we used 13 million tags from ChIP for H3K4me3 to identify 24909 genomic sites enriched for the presence of trimethylated lysine-4 on histone H3. Trimethylated H3K4 marks nearly half of all GATA-1 bound sites and one-third of GATA-2 bound sites. Over 40% of the sites bound by GATA-1 in differentiating G1ME cells were also bound by GATA-2 in proliferating G1ME cells, indicating that a GATA switch does indeed occur during megakaryocyte development. Coordinated analyses of these occupancy data with previously published gene expression datasets show that the lists of bound genes are significantly enriched for differentially expressed genes and the data depict a generally antagonistic relationship between GATA-2 and GATA-1. Interestingly, we find that even among genes that don't contain GATA switch sites, greater than 40% of those bound by GATA-1 were also occupied by GATA-2 at distinct sites. To further characterize the occupied loci, we surveyed the genomic regions bound by GATA-1 and GATA-2 to detect motifs enriched in the sequences surrounding the peak calls. As expected, we found that over 80% contained the canonical WGATAR binding motif. In contrast to reports of motifs enriched in GATA-1 ChIP studies in erythroid cells, we failed to observe significant enrichment of LRF binding motifs. Rather, the GATA-1 and GATA-2 bound regions in megakaryocytes are strongly enriched for motifs that match the binding sites for Ets family transcription factors. Finally, we have found that these genomic regions are indeed occupied by one or more Ets factors in proliferating G1ME cells. Together, these data establish the presence of a GATA switch in megakaryocyte development and provide novel insights into coordinated gene regulation by GATA factors and the differences between the closely related erythroid and megakaryocyte lineages. Disclosures: No relevant conflicts of interest to declare.
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Grass, Jeffrey A., Huie Jing, Shin-Il Kim, Melissa L. Martowicz, Saumen Pal, Gerd A. Blobel, and Emery H. Bresnick. "Distinct Functions of Dispersed GATA Factor Complexes at an Endogenous Gene Locus." Molecular and Cellular Biology 26, no. 19 (October 1, 2006): 7056–67. http://dx.doi.org/10.1128/mcb.01033-06.

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ABSTRACT The reciprocal expression of GATA-1 and GATA-2 during hematopoiesis is an important determinant of red blood cell development. Whereas Gata2 is preferentially transcribed early in hematopoiesis, elevated GATA-1 levels result in GATA-1 occupancy at sites upstream of the Gata2 locus and transcriptional repression. GATA-2 occupies these sites in the transcriptionally active locus, suggesting that a “GATA switch” abrogates GATA-2-mediated positive autoregulation. Chromatin immunoprecipitation (ChIP) coupled with genomic microarray analysis and quantitative ChIP analysis with GATA-1-null cells expressing an estrogen receptor ligand binding domain fusion to GATA-1 revealed additional GATA switches 77 kb upstream of Gata2 and within intron 4 at +9.5 kb. Despite indistinguishable GATA-1 occupancy at −77 kb and +9.5 kb versus other GATA switch sites, GATA-1 functioned uniquely at the different regions. GATA-1 induced histone deacetylation at and near Gata2 but not at the −77 kb region. The −77 kb region, which was DNase I hypersensitive in both active and inactive states, conferred equivalent enhancer activities in GATA-1- and GATA-2-expressing cells. By contrast, the +9.5 kb region exhibited considerably stronger enhancer activity in GATA-2- than in GATA-1-expressing cells, and other GATA switch sites were active only in GATA-1- or GATA-2-expressing cells. Chromosome conformation capture analysis demonstrated higher-order interactions between the −77 kb region and Gata2 in the active and repressed states. These results indicate that dispersed GATA factor complexes function via long-range chromatin interactions and qualitatively distinct activities to regulate Gata2 transcription.
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Bouchard, Marie France, Hiroaki Taniguchi, and Robert S. Viger. "Protein Kinase A-Dependent Synergism between GATA Factors and the Nuclear Receptor, Liver Receptor Homolog-1, Regulates Human Aromatase (CYP19) PII Promoter Activity in Breast Cancer Cells." Endocrinology 146, no. 11 (November 1, 2005): 4905–16. http://dx.doi.org/10.1210/en.2005-0187.

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Cancers, including that of the breast, are the result of multiple contributing factors including aberrant gene expression. Indeed, the CYP19 gene encoding P450 aromatase, the key enzyme for estrogen biosynthesis, is up-regulated in breast tumors predominantly via the cAMP-responsive gonad-type PII promoter, ultimately leading to increased intratumoral estrogen production and tumor growth. Thus, identifying the molecular factors involved in aromatase PII promoter regulation is essential for our understanding and treatment of the disease. Because we have previously shown activity of the murine aromatase PII promoter to be markedly up-regulated by GATA factors with respect to the gonads, we hypothesized that GATA factors are also key determinants of human PII promoter-driven aromatase transcription in breast tumors. We now show that GATA3 and GATA4 are indeed expressed in several breast cancer cells lines. Consistent with the cAMP dependence of the PII promoter, activation elicited by GATA3 or GATA4 alone and the striking synergism between GATA3 or GATA4 and the nuclear receptor liver receptor homolog (LRH)-1 was intimately linked to forskolin treatment or overexpression of protein kinase A (PKA) catalytic subunit. PKA-mediated phosphorylation increases the interaction between GATA3 and LRH-1 and the requirement for PKA in aromatase PII promoter stimulation involves at least three specific amino acid residues: GATA3 Ser308, GATA4 Ser261, and LRH-1 Ser469. Finally, we show that the human LRH-1 promoter is itself a target for GATA factors. Thus, taken together, our results suggest that GATA factors likely contribute to aberrant aromatase expression in breast tumors through two distinct, yet complementary mechanisms.
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Doré, Louis C., Timothy M. Chlon, Christopher D. Brown, Kevin P. White, and John D. Crispino. "Chromatin occupancy analysis reveals genome-wide GATA factor switching during hematopoiesis." Blood 119, no. 16 (April 19, 2012): 3724–33. http://dx.doi.org/10.1182/blood-2011-09-380634.

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Abstract There are many examples of transcription factor families whose members control gene expression profiles of diverse cell types. However, the mechanism by which closely related factors occupy distinct regulatory elements and impart lineage specificity is largely undefined. Here we demonstrate on a genome wide scale that the hematopoietic GATA factors GATA-1 and GATA-2 bind overlapping sets of genes, often at distinct sites, as a means to differentially regulate target gene expression and to regulate the balance between proliferation and differentiation. We also reveal that the GATA switch, which entails a chromatin occupancy exchange between GATA2 and GATA1 in the course of differentiation, operates on more than one-third of GATA1 bound genes. The switch is equally likely to lead to transcriptional activation or repression; and in general, GATA1 and GATA2 act oppositely on switch target genes. In addition, we show that genomic regions co-occupied by GATA2 and the ETS factor ETS1 are strongly enriched for regions marked by H3K4me3 and occupied by Pol II. Finally, by comparing GATA1 occupancy in erythroid cells and megakaryocytes, we find that the presence of ETS factor motifs is a major discriminator of megakaryocyte versus red cell specification.
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Muntean, Andrew G., and John D. Crispino. "Differential requirements for the activation domain and FOG-interaction surface of GATA-1 in megakaryocyte gene expression and development." Blood 106, no. 4 (August 15, 2005): 1223–31. http://dx.doi.org/10.1182/blood-2005-02-0551.

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Abstract GATA1 is mutated in patients with 2 different disorders. First, individuals with a GATA1 mutation that blocks the interaction between GATA-1 and its cofactor Friend of GATA-1 (FOG-1) suffer from dyserythropoietic anemia and thrombocytopenia. Second, children with Down syndrome who develop acute megakaryoblastic leukemia harbor mutations in GATA1 that lead to the exclusive expression of a shorter isoform named GATA-1s. To determine the effect of these patient-specific mutations on GATA-1 function, we first compared the gene expression profile between wild-type and GATA-1–deficient megakaryocytes. Next, we introduced either GATA-1s or a FOG-binding mutant (V205G) into GATA-1–deficient megakaryocytes and assessed the effect on differentiation and gene expression. Whereas GATA-1–deficient megakaryocytes failed to undergo terminal differentiation and proliferated excessively in vitro, GATA-1s–expressing cells displayed proplatelet formation and other features of terminal maturation, but continued to proliferate aberrantly. In contrast, megakaryocytes that expressed V205G GATA-1 exhibited reduced proliferation, but failed to undergo maturation. Examination of the expression of megakaryocyte-specific genes in the various rescued cells correlated with the observed phenotypic differences. These studies show that GATA-1 is required for both normal regulation of proliferation and terminal maturation of megakaryocytes, and further, that these functions can be uncoupled by mutations in GATA1.
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Onodera, Koichi, Tohru Fujiwara, Yasushi Onishi, Ari Itoh-Nakadai, Yoko Okitsu, Noriko Fukuhara, Kenichi Ishizawa, Ritsuko Shimizu, Masayuki Yamamoto, and Hideo Harigae. "GATA-2 Regulates Dendritic Cell Differentiation." Blood 126, no. 23 (December 3, 2015): 2382. http://dx.doi.org/10.1182/blood.v126.23.2382.2382.

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Abstract (Background) Dendritic cells (DCs) are critical regulators of the immune response, but their differentiation mechanism remains unclear. Heterozygous germline GATA-2 mutations in humans cause MonoMAC syndrome, characterized by monocytopenia and predisposition to myelodysplasia/acute myeloid leukemia. In this syndrome, DC count decreases profoundly, with an increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. In the present study, we analyzed the role of GATA-2 in DC differentiation and the underlying molecular mechanisms. (Method) Gata2 haploinsufficient mice (Gata2+/−: Tsai et al. Nature 1994) and tamoxifen-inducible Gata2-knockout mice (Gata2flox/flox/ER-Cre: Charles et al. Molecular Endocrinology 2006) were used. To generate conditional Gata2 knockouts in vivo, Gata2flox/flox/ER-Cre mice were intraperitoneally injected with 1-μg tamoxifen on days 1-3 and 8-10 and evaluated on days 20-22. Isolation of splenic DCs and bone marrow (BM) precursors, including LSK (Lin- Sca1+ Kit+ cell), CMP (common myeloid-restricted progenitor), GMP (granulocyte-macrophage progenitor), CLP (common lymphoid-restricted progenitor), and CDP (common dendritic cell precursor), were separated with both MACS (Miltenyi Biotech) and BD FACSAria II (BD Biosciences). For the in vitro analysis of Gata2-knockout, BM cells were cultured with CD45.1+ BM feeder cells from SJL mice (The Jackson Laboratory) with FLT3L (200 ng/mL) and 4-hydroxytamoxifen (Sigma). For transcription profiling, SurePrint G3 mouse GE microarray (Agilent) was used, and the data was subsequently analyzed with ImmGen database (http://www.immgen.org). Promoter assay was conducted with Dual Luciferase Reporter Assay system (Promega). Quantitative chromatin immunoprecipitation (ChIP) analysis was performed using CMP fraction and erythroid-myeloid-lymphoid (EML) hematopoietic precursor cell line (ATCC) with antibodies to GATA-2 (sc-9008, Santa Cruz Biotechnology). (Results) Quantitative RT-PCR analysis showed abundant Gata2 expression in LSK and CMP fractions, with detectable expression in GMP, CLP, and CDP fractions and in vitro differentiated DCs. Although the DC count did not change in Gata2 haploinsufficient mice, it significantly and profoundly decreased in Gata2 conditional knockout mice. To examine the role of GATA-2 during DC differentiation, we knocked out Gata2 during in vitro DC differentiation, starting from LSK, CMP, GMP, CLP, and CDP fractions obtained from Gata2flox/flox/ER-Cre mice. Gata2 knockout significantly decreased CD11c+ DC counts from LSK, CMP, and CDP fractions, while those from CLP and GMP were unaffected, implying the importance of GATA-2 during DC differentiation in the pathway from LSK to CDP via CMP, not via CLP nor GMP. To elucidate the underlying molecular mechanisms, we performed expression profiling with control and Gata2 -knockout DC progenitors from CMP of Gata2flox/flox/ER-Cre mice. Gata2 knockout caused >5-fold upregulation and downregulation of 67 and 63 genes, respectively. Although genes critical for the DC differentiation, e.g., Spi1, Ikzf1, and Gfi1, were not detected among the GATA-2-regulated gene ensemble, we found significant enrichment of myeloid-related and T lymphocyte-related genes among the downregulated and upregulated gene ensembles, respectively. We focused on Gata3 upregulation (7.33-fold) as a potential key mechanism contributing to Gata2 knockout-related impaired DC differentiation. Quantitative ChIP analysis with both CMP fraction and EML cell line demonstrated obvious GATA-2 chromatin occupancy at the consensus GATA-binding motif within Gata3+190 kb, which was conserved with human. Furthermore, addition of Gata3 +190 kb region to the Gata3 promoter (~0.5 kb) significantly decreased luciferase activity, which was significantly recovered by the deletion of GATA sequence within Gata3 +190 kb, in EML cells. (Conclusion) GATA-2 seems to play an important role for cell fate specification toward myeloid versus T lymphocytes, and thus contributing to the DC differentiation. Our data offer a better understanding of the pathophysiology of MonoMAC syndrome. Disclosures Fujiwara: Chugai Pharmaceuticals. Co., Ltd.: Research Funding. Fukuhara:Gilead Sciences: Research Funding. Ishizawa:GSK: Research Funding; Takeda: Research Funding; Celgin: Speakers Bureau; Kyowa Kirin: Research Funding; Celgin: Research Funding; Janssen: Research Funding; Takeda: Speakers Bureau; Kyowa Kirin: Speakers Bureau; Pfizer: Speakers Bureau.
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Hosoya-Ohmura, Sakie, Naomi Mochizuki, Mikiko Suzuki, Osamu Ohneda, Kinuko Ohneda, and Masayuki Yamamoto. "GATA-4 Incompletely Substitutes for GATA-1 in Promoting Both Primitive and Definitive Erythropoiesis in Vivo." Journal of Biological Chemistry 281, no. 43 (August 30, 2006): 32820–30. http://dx.doi.org/10.1074/jbc.m605735200.

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Vertebrate GATA transcription factors have been classified into two subgroups; GATA-1, GATA-2, and GATA-3 are expressed in hematopoietic cells, whereas GATA-4, GATA-5, and GATA-6 are expressed in mesoendoderm-derived tissues. We previously discovered that expression of GATA-2 or GATA-3 under the transcriptional control for the Gata1 gene eliminates lethal anemia in Gata1 germ line mutant mice (Gata1.05/Y). Here, we show that the GATA-4 expression by the same regulatory cassette prolongs the life span of Gata1.05/Y embryos from embryonic day 12.5 to 15.5 but fails to abrogate its embryonic lethality. Gata1.05/Y mice bearing the GATA-4 transgene showed impaired maturation of both primitive and definitive erythroid cells and defective erythroid cell expansion in fetal liver. Moreover, the incidence of apoptosis was observed prominently in primitive erythroid cells. In contrast, a GATA-4-GATA-1 chimeric protein prepared by linking the N-terminal region of GATA-4 to the C-terminal region of GATA-1 significantly promoted the differentiation and survival of primitive erythroid cells, although this protein is still insufficient for rescuing Gata1.05/Y embryos from lethal anemia. These data thus show a functional incompatibility between hematopoietic and endodermal GATA factors in vivo and provide evidence indicating specific roles of the C-terminal region of GATA-1 in primitive erythropoiesis.
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Dissertations / Theses on the topic "GATA-1"

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Whyatt, David John. "Erythroid development and GATA-1." Thesis, Open University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239713.

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Halsey, Christina. "The role of GATA-1 isoforms in haematopoiesis." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/870/.

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GATA-1 is a key haematopoietic transcription factor which plays a pivotal role in differentiation of the erythroid, megakaryocytic, eosinophilic, mast cell and dendritic cell lineages. Since its initial cloning and characterisation in 1989 a huge amount of information has been gathered on the molecular mechanisms of action of GATA-1. This knowledge has helped understanding of the processes by which cells enact differentiation programmes and suppress alternative lineage choices. GATA-1 produces at least two protein isoforms – the well characterised GATA-1 full-length (GATA-1FL) isoform and a truncated isoform – GATA-1 short (GATA-1s). GATA-1FL comprises two conserved Zinc fingers (which interact with DNA and essential co-factors), a C-terminal tail (of mostly unknown function) and an N-terminal domain (thought to confer activation properties to the molecule, but which may also be involved in transcriptional repression). GATA-1s lacks the N-terminal domain but is otherwise identical. The biological role of GATA-1s is unknown and this isoform received scant attention until the discovery that GATA-1FL mutations were linked to a rare, but highly informative, acute megakaryoblastic leukaemia seen in children with Down syndrome (constitutional trisomy 21). This discovery was particularly interesting, not only because the association between trisomy 21 and the X-linked GATA-1 mutation was extremely tight (being seen in 100% of the cases examined), but also because the GATA-1FL mutations were not randomly located, but rather clustered within the N-terminus, allowing unhindered production of the GATA-1s isoform. This finding led to interest in the pathological and physiological role of GATA-1s in haematopoiesis. Some insight has been gained into the pathological role of GATA-1s by creation of a GATA-1s knock-in transgenic mouse and by experiments looking at the ability of GATA-1s to rescue GATA-1 deficient embryonic stem (ES) cell lines. GATA-1s produces hyper-proliferation of fetal liver meg-erythroid progenitors but allows at least partial differentiation of these cells. However, a number of key questions remain. In particular what is the physiological role of GATA-1s and the reason for the tight association between trisomy 21 and GATA-1s mutations? Given this background, this thesis describes experiments designed to address the physiological role of GATA-1s, to establish whether additional GATA-1 isoforms exist, and to investigate the association between GATA-1 isoform expression and trisomy 21. Firstly a comprehensive expression analysis was performed in murine and human primary tissues and cell lines. This aimed to identify whether GATA-1s had a unique expression profile, either in particular lineages, or at distinct stages of haematological ontogeny. Reverse-transcriptase polymerase chain reaction (RT-PCR) and western blot analyses showed that the expression patterns of GATA-1s and GATA-1FL were virtually identical, with the possible exception of one human primary monocytic cell preparation which appeared to preferentially express GATA-1s. Before proceeding to further analysis of GATA-1s a search was made for additional GATA-1 isoforms using in silico analysis, RT-PCR and western blotting. This led to identification of a clone carrying a GATA-1 mutation involving the C-terminal tail, derived from a patient with chronic myeloid leukaemia. An analysis of the properties of this clone was performed, confirming its altered C-terminus and demonstrating that this conferred increased transactivation properties on the molecule as measured by luciferase assays. This observation suggests that the C-terminal tail may be an important, and previously under-recognised, functional region of the GATA-1 molecule. The discovery of this potentially hyper-functioning GATA-1 mutation led to investigation of whether GATA-1 mutations could be a widespread phenomenon in CML. However, GATA-1 mutational analysis in 21 patient samples from CML blast crisis did not reveal any additional coding mutations. To address the physiological role of GATA-1s, attempts were made to perform gene targeting in murine embryonic stem cells to produce isoform specific knock-out cells i.e. ES cells engineered so that they exclusively express the GATA-1FL isoform (a GATA-1s knock-out) or the GATA-1s isoform (a GATA-1FL knockout). These cells could then be used in in vitro haematopoietic differentiation assays and for transcriptional profiling. In this way it was hoped to establish whether GATA-1s fulfilled any unique roles in primitive or definitive haematopoiesis that could not be compensated for by the presence of the GATA-1FL isoform. Unfortunately, despite evidence of apparently successful targeting from PCR screening of ES cell clones, it was impossible to confirm the existence of endogenously targeted alleles on Southern blotting. Following exhaustive attempts at screening further clones and subclones (more than 1000 clones in total), this approach was abandoned in favour of transgenic expression of GATA-1 isoforms in cell lines. Transgenic expression studies in murine ES cells showed that whilst GATA-1FL expression led to an expansion in numbers and maturity of erythroid and non-erythroid haematopoietic colonies in vitro, GATA-1s was incapable of supporting colony formation in this assay. Studies then moved on to human cell lines. Two cell lines were identified, both capable of in vitro haematopoietic differentiation into megakaryocytic and erythroid cells, but one carrying trisomy 21 (Meg-01) and the other disomic for chromosome 21 (K562). GATA-1FL expression in these cells generally drove differentiation along the megakaryocytic or erythroid lineage as measured by DNA ploidy analysis, haemoglobinisation, upregulation of erythroid or megakaryocytic gene expression (by quantitative PCR) and suppression of alternative lineage genes (PU.1 and Ikaros) and genes associated with progenitor proliferation (cyclin D2 and c-myb). GATA-1s, in contrast, produced less evidence of differentiation with lower DNA ploidy, less up-regulation of erythroid genes and failure to repress other lineage and haematopoietic progenitor associated genes. Examination of the link with trisomy 21 confirmed that that the chromosome 21 candidate gene Erg3 was upregulated in trisomic cells and that expression of GATA-1s appeared to confer a selective advantage in the presence of trisomy 21. However, no clear mechanistic reasons for the selective advantage could be identified. Overall, these studies show widespread GATA-1s expression in haematopoietic cells, confirm the association with inadequate repression of genes associated with primitive progenitors, and suggest that the C-terminal tail of GATA-1 may be an important functional part of the molecule. Finally, these observations have generated a number of testable hypotheses which could form the basis for future work.
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Eisbacher, Michael School of Medical Science UNSW. "The regulation of megakaryocyte-specific genes by Fli-1 and GATA-1." Awarded by:University of New South Wales. School of Medical Science, 2003. http://handle.unsw.edu.au/1959.4/19171.

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The successive activation of tissue-specific genes during cellular differentiation is orchestrated by the formation of transcriptional complexes consisting of cellspecific and ubiquitous transcription factors. Understanding the molecular events associated with normal megakaryocyte (Mk) differentiation is an issue of central importance to haematology. The aims of this study were therefore to: (i) define the transcription factors responsible for regulating the expression of Mkspecific genes such as Glycoprotein IX, (ii) identify the protein partners of such important Mk-regulatory transcription factors and (iii) examine the mechanisms utilised by these factors to regulate gene expression. First, the regulatory elements in the GPIX promoter required for basal and inducible expression were examined in megakaryoblastic Dami cells stimulated to undergo differentiation. The resulting data suggested that an Ets site in the GPIX promoter binding the Ets-family member Fli-1 was crucial in regulating both constitutive and inducible GPIX expression. Second, a two-hybrid screen of a K-562 cDNA library was used to identify transcription factors that interacted with Fli-1 and were potential regulators of Mk development. Results of this screen identified a novel protein-protein interaction with GATA-1, a previously well-characterised zinc finger transcription factor also implicated in erythroid and Mk development. Mapping of the domains required for the interaction show that the zinc fingers of GATA-1 interact with the Ets domain of Fli-1. The biological significance of the Fli-1/GATA-1 interaction was demonstrated in transient transfection assays, which resulted in synergistic activation of Mkspecific promoters. Analysis of Fli-1 and GATA-1 expression in a series of erythroleukaemic and megakaryoblastic cell lines demonstrated that the Fli- 1/GATA-1 combination correlates with a Mk-phenotype. Moreover, expression of Fli-1 in K-562 cells (a line rich in GATA-1 but normally lacking Fli-1) induces endogenous GPIX expression. Quantitative mobility shift assays reveal that Fli- 1 and GATA-1 exhibit cooperative DNA-binding in which the binding of GATA-1 to DNA is increased approximately 26 fold in the presence of Fli-1. This data provides a mechanism for the observed transcriptional synergy. In conclusion, this work suggests that Fli-1 and GATA-1 work together through protein-protein interaction and cooperative DNA-binding to activate the expression of genes associated with the terminal differentiation of Mks.
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4

Lefevre, Carine. "Mécanismes de régulation de la balance prolifération/différenciation érythroïde par les facteurs de transcription GATA-1, FOG-1, E2F et la voie de signalisation Akt." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T010/document.

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Avec plus de 100 milliards de globules rouges produits chaque jour, le lignage érythroïde présente la plus grande capacité de production cellulaire chez le mammifère adulte. Cette production requiert une balance fine entre la prolifération cellulaire, régulée principalement par la voie de signalisation érythropoïétine (Epo)/PI3K/Akt, et la différenciation érythroïde induite par le couple de facteurs de transcription GATA-1/FOG-1. Des interconnexions entre ces deux grands systèmes ont été décrites dans le laboratoire : 1) le facteur de transcription GATA-1 est phosphorylé par Akt en réponse à l’Epo et cette phosphorylation semble avoir un rôle dans la différenciation érythroïde ; 2) GATA-1 est capable d’interagir avec la protéine du rétinoblastome pRb, impliquée dans la régulation du cycle cellulaire, et le complexe formé est nécessaire à l’érythropoïèse terminale.L'objectif de ma thèse était d’étudier les mécanismes moléculaires impliqués dans la balance prolifération/différenciation cellulaire au cours de l’érythropoïèse, et en particulier de déterminer le rôle moléculaire et physiologique de la phosphorylation de GATA-1 par Akt en réponse à l’Epo. Nos travaux ont montré que cette phosphorylation est une des clefs de la dynamique de l’érythropoïèse. Dans sa forme non phosphorylée, GATA-1 ralentit le cycle cellulaire via le complexe GATA-1/pRb/E2F. Cette étape préliminaire est nécessaire à la mise en place de la différenciation érythroïde terminale. La phosphorylation de GATA-1 induit d’une part la dissociation de GATA-1/pRb/E2F favorisant l’expansion cellulaire, et d’autre part la formation du complexe GATA-1/FOG-1 nécessaire à l’activation des gènes érythroïdes. Ce modèle apporte une explication moléculaire au blocage de la différenciation érythroïde terminale induite par le mutant GATA-1V205G qui n’interagit pas avec FOG-1. Ainsi, la phosphorylation constitutive de GATA-1V205G et l’augmentation de la quantité relative de FOG-1 permettent de restaurer la différenciation érythroïde induite par ce mutant in vitro. Enfin, l’étude d’un modèle murin exprimant une protéine GATA-1 non phosphorylable par Akt montre l’apparition d’une anémie létale lorsque la voie IGF-1 est inhibée. Cela démontre l’importance de la dynamique moléculaire induite par la phosphorylation de GATA-1, et met en évidence le rôle majeur de l’IGF-1 dans l’érythropoïèse in vivo.En conclusion, nous proposons un nouveau modèle moléculaire de la régulation de la balance prolifération/différenciation érythroïde dans lequel la phosphorylation de GATA-1 par Akt coordonne la distribution de GATA-1 dans deux complexes protéiques fonctionnels différents : GATA-1/pRb/E2F versus GATA-1/FOG-1. Nous mettons également en évidence l’IGF-1 comme acteur central de la compensation mise en place in vivo pour pallier à l’absence de phosphorylation de GATA-1
With more than 100 billion red blood cells generated every day, the erythroid lineage has the largest output of cell production in adult mammals. This production requires a tight balance between cell proliferation, mainly controlled by erythropoietin (Epo)/PI3K/Akt signaling pathway, and erythroid differentiation induced by GATA-1 and FOG-1 transcription factors. Various links between these two processes have been previously demonstrated in the laboratory: 1) Epo-activated Akt directly phosphorylates GATA-1 transcription factors, and this phosphorylation seems to be involved in erythroid differentiation; 2) GATA-1 binds to the cell cycle regulator retinoblastoma protein (pRb), and the resulting complex is essential for terminal erythropoiesis.We investigated the molecular mechanisms involved in the cell proliferation/differentiation balance during terminal erythropoiesis; in particular, we studied the molecular and physiological role of Epo-induced GATA-1 phosphorylation. Our findings suggest that this phosphorylation is one of the key processes in erythropoiesis dynamics. In its unphosphorylated form, GATA-1 can break cell cycle progression via GATA-1/pRb/E2F complex. This preliminary step is necessary for terminal erythroid differentiation. GATA-1 phosphorylation promotes GATA-1/pRb/E2F dissociation, allowing cell cycle progression, and GATA-1/FOG-1 binding, necessary to activate erythroid genes. Our model provides a molecular explanation for the arrest of terminal erythroid differentiation observed in the non-FOG-1-binding mutant GATA-1V205G. We show that the constitutive phosphorylation of GATA-1V205G and the increase of FOG-1 protein amount rescue erythroid differentiation in vitro. Finally, knock-in expression of unphosphorylatable GATA-1 in mice leads to lethal anemia when the IGF-1 signaling pathway is inhibited. This shows the importance of the molecular dynamics of GATA-1 phosphorylation, and highlights the major role of IGF-1 in erythropoiesis, in vivo.In conclusion, we propose a new molecular model for the control of the balance between proliferation and erythroid differentiation. GATA-1 phosphorylation by Akt coordinates the involvement of GATA-1 in two different functional protein complexes: GATA-1/pRb/E2F and GATA-1/FOG-1. We also highlight the major role of IGF-1 in compensating for the lack of GATA-1 phosphorylation in vivo
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5

Itagaki, Tetsurō. "Interlayer organic modification of 1:1 type clay mineral kaolinite = 1:1-gata nendo kōbutsu kaorinaito no sōkan yūki shūshoku /." Electronic version of text Electronic version of summary Electronic version of examination, 2003. http://www.wul.waseda.ac.jp/gakui/honbun/3450/.

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6

Penglong, Tipparat. "Molecular Basis of Erythroid Cell Proliferation and Differentiation." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T022.

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Pour assurer la production de milliards de globules rouges, l’érythropoièse doit parfaitement contrôler les processus de prolifération et de différenciation. Ces deux processus sont régulés par l’expression de gènes spécifiques dépendant d’une coordination entre l’activité des facteurs de transcription (FT) et les fonctions épigénétiques portées par exemple par les protéines à bromodomaine. Cette étude se concentre sur les conséquences de l’association ou la dissociation du FT clef de l’érythropoièse GATA-1 avec les FT déterminant pour le cycle cellulaire, pRb et E2F. Dans la première partie de ma thèse, j’ai participé à l’étude du rôle de l’association/dissociation de GATA-1 et FOG-2 avec pRb/E2F dans le contrôle la balance prolifération/différenciation cellulaire. Nos résultats montrent que les souris exprimant une mutation de GATA-1 sur la sérine 310 (GATA-1S310A), qui a la capacité accrue à séquestrer E2F-2, présentent une anémie létale lorsqu’un mécanisme de compensation de production de E2F-2 induit par l’IGF-1 est inhibé. Puis, nous avons trouvé que les propriétés décrites pour GATA-1 sont partagées par le FT FOG-2 et montré que l’abrogation de sa fixation avec pRb induit une perturbation de l’adiposité dans des souris FOG-2pRb-. Dans la deuxième partie, l’expression de c-Myc étant régulé différentiellement par GATA-1 et E2F, j’ai testé si la drogue « JQ1 », premier inhibiteur épigenétique chimique de l’expression de c-Myc, pouvait contrôler l’érythropoièse. Pour cela, j’ai utilisé la ligné érythroleucémique UT7 qui prolifère sans se différencier en présence d’érythropoiétine (stade proérythroblaste). Les résultats montrent que le traitement par JQ1 bloque la prolifération des cellules UT7 et permet de réinitier le programme de différentiation érythroide terminale. J’ai alors recherché les mécanismes moléculaires impliqués dans cette régulation et trouvé que l’inhibition transcriptionnelle de c-Myc par JQ1 est associée à l’inhibition de l’activité transcriptionnelle de STAT5 sans modification de son état de phosphorylation. Enfin, j’ai montré que JQ1 pouvait avoir une activité comparable à celle du TGF-b mais sans implication les voies Smad. Des études in vivo montre que JQ1 augmente la viabilité cellulaire et accélère la maturation des cellules érythroides à la fois chez les souris sauvages et thalassémiques. Cette différence d’action de JQ1 sur l’érythropoièse normale et pathologique implique des modifications épigénétiques différentielles entre ces deux types cellulaires et sont à la base de nouvelles stratégies du traitement du cancer. Le rôle clef de la régulation de l’association/dissociation de GATA-1 ou FOG-2 avec pRb/E2F dans l’érythropoièse et l’adipogénèse, nous a conduit, dans une troisième partie, à déterminer in vivo, les conséquences physiologiques de la séquestration de E2F par pRb. Pour cela nous avons crée une souris transgénique exprimant de façon conditionnelle un peptide contenant la partie N terminale de GATA-1 qui se fixe à pRb (GATA-1Nter). In vitro, ce peptide séquestre E2F dans le complexe GATA-1Nter/pRb et inhibe la prolifération cellulaire de façon irréversible. In vivo, aucune souris transgéniques exprimant le peptide GATA-1Nter n’a pu être sélectionnée et une mortalité au stade embryonnaire est observée. Une expression induite de ce peptide au stade adulte ne produit que des souris chimériques avec une fréquence de recombinaison du transgène GATA-1Nter importante. L’établissement de lignées stables de souris exprimant le peptide GATA-1Nter permettra de déterminer les conséquences physiologiques de la séquestration de E2F dans le complexe GATA-1Nter/pRb
To ensure the generation of billions of erythrocytes daily, erythropoiesis must be well controlled by proliferation and differentiation processes. These two processes are regulated by expressions of specific genes, coordinated by transcription factors (TFs) and epigenetic factors, such as bromodomain proteins. This study focused on the effects of the binding and dissociation of a key erythroid TF, GATA-1, to the crucial cell cycle TFs, pRb and E2F. In the first part of this thesis, the role of GATA-1 and FOG-2 binding to pRb/E2F in a control balances between cell proliferation and differentiation was studied. Mice bearing a GATA-1 mutation (GATA-1S310A) displayed higher levels of E2F2 sequestration and suffered from fatal anemia when the compensatory pathway of E2F2 production via IGF-1 signaling was also inhibited. The properties described for GATA-1 were found to be common to FOG-2, and the abolition of FOG-2 binding to pRb led to obesity resistance in FOG-2pRb- mice. In the second part of this work, as c-Myc is regulated by GATA-1 and E2F, the first chemical epigenetic inhibitor repressing c-Myc expression to be described, JQ1, was investigated to see if it could control erythropoiesis. The UT7 erythroleukemia cell line, which proliferates without differentiating was used. This cell line stops differentiation at the proerythroblast stage, in response to erythropoietin. JQ1 treatment inhibited UT7 proliferation and restored terminal erythroid differentiation. The molecular mechanism underlying this regulation by JQ1 was shown that the inhibition of c-Myc expression was associated with the inhibition of STAT5 transcription, with no change in the phosphorylation of this protein. It was found that JQ1 had a putative TGF--like activity, which did not involve the Smad pathway. It was shown in the ex vivo studies that JQ1 increased the viability of erythroid cells and accelerated the maturation of these cells in both WT and thalassemic mice. The observed differences between leukemic and normal erythropoiesis involved differential epigenetic modifications that could be at the basis of new strategies regarding cancer treatment.The key role of the association of GATA-1 or FOG-2 had with pRb/E2F, and the dissociation of these factors, in erythropoiesis and adipogenesis, respectively, led us to investigate, in vivo, the physiological consequences of E2F sequestration by pRb. As a result, transgenic mice displaying conditional expression of a peptide containing the N-terminal part of GATA-1 that binds to pRb (GATA-1Nter) were developed. In vitro, this peptide traps E2F in a GATA-1Nter/pRb complex, resulting in the irreversible inhibition of cell proliferation. The yield of transgenic mice expressing the GATA-1Nter peptide in vivo was unsuccessful, as this expression lead to lethality at the embryonic stage. Using an alternative approach, based on the inducible expression of the peptide in adults, chimeric mice with a high frequency of recombination of the GATA-1Nter transgene were obtained for this study. The establishment of a stable mouse line expressing the GATA-1Nter peptide should make it possible to determine the pathophysiological consequences of E2F sequestration in the GATA-1Nter/pRb complex
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Rio, Sarah. "Etude des métabolismes du fer et de l’hème au cours de l’érythropoïèse normale et pathologique (anémie de Blackfan-Diamond)." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB055/document.

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L’anémie de Blackfan-Diamond (ABD) est une maladie hématologique rare qui touche 4 à 7 individus/ million de naissances. Cette maladie se manifeste par une érythroblastopénie congénitale sévère (≤ 5% de précurseurs érythroïdes dans la moelle osseuse). L’anémie est arégénérative et souvent macrocytaire et associée à des malformations osseuses dans 40% des cas. 70% des patients sont porteurs d’une mutation hétérozygote pour un gène de protéine ribosomique impliquée dans la traduction cellulaire. Les gènes les plus fréquemment mutés sont les gènes RPS19 (25%), RPL11 (5%) et RPL5 (7%). La maladie est hétérogène et évolutive. Les liens entre la traduction cellulaire et l’érythropoïèse ne sont pas bien élucidés. Les objectifs de cette thèse ont été d’étudier les métabolismes de l’hème et du fer ainsi que l’expression des globines dans des cellules de patients atteints d'ABD et dans un modèle shARN ciblant l'expression de ces trois gènes afin de comprendre les causes du tropisme érythroïde de la maladie. Ce travail de recherche a permis de mettre en évidence un défaut majeur de synthèse des globines ayant pour conséquence une augmentation de la quantité d’hème libre et une production de formes réactives de l'oxygène toxiques dans les cellules des patients qui pourraient expliquer en partie l’apoptose cellulaire et le déficit de globules rouges. Alors que le métabolisme du fer ne semblait pas altéré dans l'ABD, l’étude de l’expression de différentes protéines importantes pour l’érythropoïèse au cours de la différenciation érythroïde in vitro dans des conditions contrôles et chez des patients a permis de confirmer et de caractériser le retard de différenciation cellulaire en cas de mutation des gènes RPL5 et RPL11. Ce travail montre que le retard de différenciation et le défaut d'hémoglobinisation mis en évidence s'expliquent par un déficit du facteur de transcription GATA-1 qui est primordial au cours de l'érythropoïèse. Ce déficit de GATA-1 dans des cellules déficitaires en RPL11 est dû à une dégradation de sa protéine chaperonne HSP70. La restauration de HSP70, permet d'augmenter l'expression de GATA-1 et d'améliorer la différenciation érythroïde et l'hémoglobinisation cellulaire pour le gène RPL11. Ces résultats permettent de mieux comprendre le tropisme érythroïde de l'ABD et de proposer HSP70 comme une cible thérapeutique prometteuse dans son traitement
Diamond-Blackfan anemia (DBA) is a rare hematologic disease that affects 4 to 7 individuals / million births. This disease is characterized by a severe congenital erythroblastopenia (less than 5% erythroid precursors in the bone marrow). Anemia is agerenative, often macrocytic and associated with bone malformations in 40% of cases. 70% of patients carry a heterozygous mutation for a ribosomal protein gene involved in cell translation. The most frequently mutated genes are RPS19 (25%), RPL11 (5%) and RPL5 (7%) genes. The disease is heterogeneous and can evolve. The link between cell translation and erythropoiesis is not well understood. The objectives of this thesis were to study haem and iron metabolisms as well as the expression of globins in DBA patients cells and CD34+ cells transduced with shRNA targeting the expression of these three genes in order to understand the causes of the erythroid tropism of the disease. This research has highlighted a major defect of globin synthesis resulting in an increase in the amount of free heme and a production of toxic ROS in patients' cells that could explain in part cell apoptosis and red blood cell deficiency. While iron metabolism did not appear to be altered in DBA, the study of the expression of various important proteins for erythropoiesis in normal CD34+ or DBA cells during erythroid differentiation in vitro confirmed a strong cell differentiation delay for RPL5 and RPL11 mutations. This work shows that the delay of differentiation and the lack of hemoglobinization can be explained by a deficiency of the transcription factor GATA-1, which is essential during erythropoiesis. This deficiency of GATA-1 in shRPL11 cells is due to a degradation of its chaperone protein HSP70. The restoration of HSP70 increases the expression of GATA-1 and improves erythroid differentiation and cellular hemoglobinization for the shRPL11 condition. These results provide a better understanding of the erythroid tropism of ABD and suggest a role for HSP70 as a promising therapeutic target in its treatment
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Arlet, Jean-Benoît. "Rôle de la chaperonne HSP 70 dans l'éythropoïèse inefficace des béta-thalassémies majeures." Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-01059816.

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L'érythropoïèse inefficace joue un rôle central dans la physiopathologie de l'anémie des β-TM. Ses caractéristiques sont triple: accélération de la différenciation érythroïde, arrêt de maturation au stade d'érythroblaste polychromatophile et mort par apoptose à ce stade de différenciation. Les mécanismes précis de cette apoptose et de l'arrêt de la maturation n'ont pas encore été élucidés. Il a été montré, au cours de l'érythropoïèse physiologique, que la protéine chaperonne Hsp70, en se localisant dans le noyau des érythroblastes en cours de différenciation, protège GATA-1 (facteur de transcription érythroïde majeur) de sa destruction par la caspase-3. Cette enzyme clé de l'apoptose est en effet activée physiologiquement au cours de la différenciation érythroïde et peut cliver GATA-1. Notre travail se base sur l'hypothèse suivante : Hsp70 pourrait, au cours de l'érythropoïèse des β-TM, être séquestrée dans le cytoplasme des érythroblastes matures (stade d'une intense hémoglobinisation) afin d'exercer son rôle de chaperonne des chaînes d'-globine libres. Cela aurait comme conséquence néfaste l'absence de localisation nucléaire d'Hsp70 et, en conséquence, la destruction de GATA-1 à l'origine de l'arrêt de maturation et de la mort cellulaire. Nous avons montré dans ce travail qu'Hsp70 était localisée principalement dans le cytoplasme des érythroblastes matures dans la moelle de patients β-TM, avec un défaut d'expression nucléaire. Par ailleurs, GATA-1 n'est plus exprimé dans ces cellules. Nous avons confirmé ces résultats dans un système de culture cellulaire érythroïde humaine en milieu liquide reproduisant les étapes de la différenciation érythroïde terminale. Une intéraction physique directe entre Hsp70 et l'-globine a été identifiée par techniques de microscopie confocale, d'immunoprécipitation et de double hybride. Enfin, la transduction dans les érythroblastes de β-TM d'un mutant d'Hsp70-S400A, principalement nucléaire, ou d'un mutant de GATA-1 non clivable par la caspase-3 corrige l'érythropoïèse inefficace.Une modélisation mathématique du complexe Hsp70/-globine nous a permis de préciser les domaines impliqués dans l'intéraction, ce qui ouvre la voie à une possibilité de criblage de petites molécules permettant la rupture de ce complexe afin de ramener Hsp70 dans le noyau avec un espoir thérapeutique pour améliorer l'érythropoïèse inefficace des β-TM.
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Sharma, Sribava. "Deletion of ΔdblGata Motif Leads to Increased Predisposition and Severity of IgE-mediated Food-induced Anaphylaxis Response." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535701847469787.

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Johnson, Lacey Nicole St George Clinical School UNSW. "Molecular regulation of Megakaryopoiesis: the role of Fli-1 and IFI16." Awarded by:University of New South Wales. St George Clinical School, 2006. http://handle.unsw.edu.au/1959.4/26819.

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Megakaryocytes (Mks) are unique bone marrow cells, which produce platelets. Dysregulated Mk development can lead to abnormal platelet number and the production of functionally defective platelets, causing bleeding, thrombotic events, and leukaemia. Understanding the molecular mechanisms driving megakaryopoiesis may yield insights into the molecular genetics and cellular pathophysiology of a diversity of disorders. The primary aim of this thesis was to gain insight into the molecular events required for normal Mk development. As transcription factors and cytokines play a central role in driving Mk development, both of these processes were investigated. Fli-1 and GATA-1 are key transcription factors regulating Mk-gene expression, alone and co-operatively. To understand the mechanism of transcriptional synergy exerted by Fli-1 and GATA-1, in vitro assays were carried out investigating the interactions between Fli-1, GATA-1 and DNA that mediate synergy. A novel mechanism of synergy was identified, where Fli-1 DNA binding is not required, although an interaction between Fli-1 and GATA-1, and GATA-1 DNA binding is required. Importantly, the results demonstrate that Fli-1 DNA binding is not essential for promoting Mk-gene expression in primary murine bone marrow cells. Thrombopoietin (TPO) is the primary cytokine responsible for Mk and platelet development. Identifying novel TPO gene-targets may provide invaluable information to aid the understanding of the complex and unique processes required for Mk development. Using microarray technology, IFI16 was identified as a TPO-responsive gene that has not previously been studied in the Mk lineage. This work demonstrated that IFI16 is expressed in CD34+ HSC-derived Mks, and that the Jak/STAT pathway is essential for the activation of IFI16 by both TPO and IFN-??. Of biological significance, IFI16 was found to regulate both the proliferation and differentiation of primary Mks, suggesting that IFI16 may control the balance between these two essential processes. In conclusion, the data in this thesis presents a novel mechanism through which Fli-1 and GATA-1 regulate the synergistic activation of Mk genes. The identification and functional characterisation of a novel TPO-inducible gene, IFI16, involved in regulating the proliferation and differentiation of Mks is also described. These findings have implications for several congenital and malignant conditions affecting Mk and platelet development, and possibly a mechanism for IFN-induced thrombocytopaenia.
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Books on the topic "GATA-1"

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(Japan), Nōrin Suisan Seisaku Kenkyūjo. Ajia Taiheiyō chiiki no bōeki kōzō to ASEAN + 1-gata FTA. Tōkyō: Nōrin Suisanshō Nōrin Suisan Seisaku Kenkyūjo, 2011.

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Kagaku Busshitsu Hyōka Kenkyū Kikō and Shin Enerugī Sangyō Gijutsu Sōgō Kaihatsu Kikō (Japan), eds. 4,4'-isopuropiridenjifenōru to 1-kuroro-2,3-epokishipuropan no jūshukugōbutsu (betsumei bisufenōru A-gata epokishi jushi) (ekijō no mono ni kagiru): Polymer of 4,4'-isopropylidenediphenol and 1-chloro-2,3-epoxypropane (liquid). Tōkyō: Seihin Hyōka Gijutsu Kiban Kikō Kagaku Busshitsu Hyōka Kenkyū Kikō, 2009.

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Bandai Namuko Gēmusu, Kabushiki Kaisha. Taburetto-gata jōhō tanmatsu o riyōshita tōkingu eido no kaihatsu (2-nen keikaku no 1-nenme): Heisei 22-nendo sōkatsu buntan hōkokusho. [Tokyo]: Bandai Namuko Gēmusu, 2011.

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Densei, Kabushiki Kaisha. Rimokon sōsa ni yoru hanzufurī-gata jinkō kōtō no seihinka (3-nen keikaku no 1-nenme): Shōgaisha jiritsu shien kiki tō kaihatsu sokushin jigyō : Heisei 22-nendo hōkokusho. [Ebetsu-shi]: Kabushiki Kaisha Densei, 2011.

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Kōki, Yasuhisa. Shōgaisha jiritsu shien kiki tō kaihatsu sokushin jigyō, shikaku shōgaishayō no pen "waiyaresu-gata shokuzu fude-pen" no shōhinka ni kansuru kaihatsu "2-nen keikaku no 1-nenme": Heisei 22-nendo sōkatsu buntan hōkokusho. [Tokyo]: Yasuhisa Kōki, 2011.

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Hsp. Over the gate, grade 1 take home book: Harcourt school publishers collections. [Place of publication not identified]: Holt Mcdougal, 2000.

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San Francisco (Calif.). Office of the Controller. Audits Division. Concession audit report: Golden Gate Bar, July 1, 1996 through June 30, 1998. San Francisco: Office of the Controller, 1999.

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International, Workshop on Gate Insulator (1st 2001 Tokyo Japan). Extended abstracts of International Workshop on Gate Insulator: IWGI 2001 : November 1-2, 2001, Tokyo, Japan. Tokyo: Business Center for Academic Societies Japan, 2001.

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1959-, Shiwakoti Shesh Raj, ed. Sarvocca Adālatadvārā pratipādita nayām̐ najīraharū: Sarvocca Adālatadvārā 2049 Vaiśākha 1 dekhi 2049 Mārga 30 gate sammamā pratipādita mahattvapūrṇa najīraharūko varṇānukramika vargīkr̥ta saṅgraha. Kāṭhamāḍauṃ: Jñānaguna Risarca Insṭicyūṭa, 1992.

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Nepal. Pradhānamantrī tathā Mantriparishadko Kāryālaya. Mantriparishad adhyaksha Khilarāja Regmīko netr̥tvamā gaṭhita vartamāna sarakārako 100 dinako pramukha kāma ra upalabdhiharu: 2069 Caitra 1 dekhi 2070 Asāra 7 gate samma. Kāṭhamāḍauṃ: Nepāla Sarakāra, Pradhānamantrī tathā Mantriparishadko Kāryālaya, 2013.

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Book chapters on the topic "GATA-1"

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Přibylová, Lenka, and Barbora Losová. "Symmetry Breaking for GATA-1/PU.1 Model." In Computational Methods in Systems Biology, 360–63. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-31304-3_27.

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Ray, Anuradha, Anupriya Khare, Nandini Krishnamoorthy, and Prabir Ray. "GATA-3." In Encyclopedia of Signaling Molecules, 1–14. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_29-1.

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Meigs, Thomas E., Alex Lyakhovich, Hoon Shim, Ching-Kang Chen, Denis J. Dupré, Terence E. Hébert, Joe B. Blumer, et al. "GATA-3 (GATA Binding Protein 3)." In Encyclopedia of Signaling Molecules, 760–69. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_29.

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Meigs, Thomas E., Alex Lyakhovich, Hoon Shim, Ching-Kang Chen, Denis J. Dupré, Terence E. Hébert, Joe B. Blumer, et al. "GATA-Binding Protein 3." In Encyclopedia of Signaling Molecules, 769. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_100525.

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Meigs, Thomas E., Alex Lyakhovich, Hoon Shim, Ching-Kang Chen, Denis J. Dupré, Terence E. Hébert, Joe B. Blumer, et al. "GAT-1." In Encyclopedia of Signaling Molecules, 760. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_100522.

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Imagawa, Shigehiko, Masayuki Yamamoto, and Yasusada Miura. "Gata Transcription Factors Negatively Regulate Erythropoietin Gene Expression." In Molecular Biology of Hematopoiesis 5, 501–13. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4613-0391-6_61.

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Ajitha, D., K. N. V. S. VijayaLakshmi, K. BhagyaLakshmi, and M. Mehetaj. "2:1 MUX Implementation Using NMV-Gate: NON MAJORITY GATE in QCA." In Lecture Notes in Electrical Engineering, 557–63. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-8942-9_46.

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Schwartz, Robert J., Jorge Sepulveda, and Narasimhaswamy S. Belaguli. "Molecular Regulation of Cardiac Myofibrillogenesis: Roles of Serum Response Factor, Nkx2-5, and GATA-4." In Myofibrillogenesis, 103–27. Boston, MA: Birkhäuser Boston, 2002. http://dx.doi.org/10.1007/978-1-4612-0199-1_7.

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Ip, S., David B. Wilson, Markku Heikinheimo, Jeffrey M. Leiden, and Michael S. Parmacek. "The GATA-4 Transcription Factor Transactivates the Cardiac-Specific Troponin C Promoter-Enhancer in Non-Muscle Cells." In Advances in Experimental Medicine and Biology, 117–24. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-1893-8_13.

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Shimoda, Tatsuya. "Thin-Film Oxide Transistor by Liquid Process (1): FGT (Ferroelectric Gate Thin-Film Transistor)." In Nanoliquid Processes for Electronic Devices, 417–39. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-2953-1_16.

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Conference papers on the topic "GATA-1"

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Shrestha, Eric, TianJiao Wang, Justin Saunders, and Janice E. Knepper. "Abstract 2197: Fliz-1 regulation of GATA-3 expression in mammary tumor cells." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-2197.

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Chen, JQ, J. Litton, L. Xiao, H.-Z. Zhang, CL Warneke, Y. Wu, X. Shen, et al. "Abstract P3-10-41: Quantitative Immunohistochemical Analysis and Prognostic Significance of TRPS-1, a New GATA Transcription Factor Family Member, in Breast Cancer." In Abstracts: Thirty-Third Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 8‐12, 2010; San Antonio, TX. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/0008-5472.sabcs10-p3-10-41.

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Lago, Bruno Corrêa do, Daniel Dias Wanderley, and Yani Neves Coelho. "HIPERPLASIA MAMÁRIA POR USO DE ANTICONCEPCIONAL EM FELINO FÊMEA." In I Congresso On-line Nacional de Clínica Veterinária de Pequenos Animais. Revista Multidisciplinar em Saúde, 2021. http://dx.doi.org/10.51161/rems/1857.

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Abstract:
Introdução: A hiperplasia mamária acomete principalmente a espécie felina, e é caracterizada pelo crescimento exagerado de uma ou mais glândulas mamárias devido a estímulos hormonais naturais ou sintéticos. É predominantemente incidente em animais jovens a partir do primeiro cio, devido à estimulação dos hormônios ovarianos que promovem o aumento do número das células do estroma mamário e ductos. Estatisticamente, acomete mais fêmeas que receberam progestágenos, ou seja, no início da gestação ou ciclando. Os sinais clínicos incluem aumento das glândulas mamárias, apatia, anorexia, febre e desidratação. O tratamento consiste na retirada do estímulo hormonal através de ováriosalpingoisterectomia (OSH) ou uso de antiprogestágenos. Objetivos: Objetivou-se relatar um caso sobre a hiperplasia mamária por uso de anticonceptivos em gata. Material e métodos: Uma fêmea, SRD, com 1 ano de idade e pesando 3,7 kg, com histórico de uso de anticoncepcional. A tutora relatou que há um mês o animal apresentava um pequeno crescimento em suas mamas, que foi ignorado até que se mostrasse de tamanho significativo e com ulcerações. Ao exame físico observou-se leve desidratação e mucosas hipocoradas, além de lesões nas mamas. Assim, sugeriu-se terapia à base de aglepristone (10mg/kg/dia/5 dias consecutivos) além de fazer uso de um protocolo a base de amoxicilina suspensão (50mg/animal a cada 12 horas, por 10 dias) e cetoprofeno gotas por 4 dias para dor e inflamação. Resultados: No terceiro dia de acompanhamento foi percebido uma regressão significativa de todas as cadeias mamárias do paciente, e consecutivamente a remissão quase que total da hiperplasia mamária com 23 dias após o uso do aglepristone. Entretanto, após o sucesso inicial do tratamento medicamentoso, a proprietária não se interessou em realizar a ovariossalpingohisterectomia. Conclusão: Relata-se caso de hiperplasia mamária por uso de anticoncepcional em gata, no qual o diagnóstico foi estabelecido pelo histórico e exame físico. O tratamento com aglepristone provou ser bastante eficaz e seguro no tratamento da hiperplasia mamária felina.
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Bao, Y., JQ Chen, Y. Wu, X.-H. Leng, E. Wang, F. Marincola, and LG Radvanyi. "Abstract P6-08-14: TRPS-1, a New GATA Family Transcription Factor, Regulates Epithelial-Mesenchymal Transition and Maintains an Estrogen Responsive, Claudin-Positive Phenotype in Breast Cancer Cells." In Abstracts: Thirty-Third Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 8‐12, 2010; San Antonio, TX. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/0008-5472.sabcs10-p6-08-14.

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Kesanakurti, Divya, Dilip Maddirela, Meena Gujrati, and Jasti S. Rao. "Abstract 420: Critical role of MMP-2 and GATA-1 nuclear interaction in the regulation of ionizing radiation (IR)-induced IL-10/Stat3-mediated invasion and migration in glioblastoma." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-420.

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Pereira, Andriely de Almeida, Andressa Francisca Silva Nogueira, Helcileia Dias Santos, and Nubia Elisa Montenegro Lima. "LEISHMANIOSE FELINA NO MUNICÍPIO DE ARAGUAÍNA-TO." In I Congresso On-line Nacional de Clínica Veterinária de Pequenos Animais. Revista Multidisciplinar em Saúde, 2021. http://dx.doi.org/10.51161/rems/1847.

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Abstract:
Introdução: A leishmaniose é uma zoonose que acomete gatos que, frequentemente, não manifestam sintomas, sugerindo que os felinos sejam mais refratários à doença, quando comparados aos caninos. Os sinais clínicos da leishmaniose felina são inespecíficos e incluem linfoadenomegalia local ou generalizada, perda de peso, lesões cutâneas como alopecia difusa e dermatite úlcero-crostosa; alterações oftálmicas; estomatite e gengivite. Objetivo: Relatar um caso de leishmaniose em um gato no município de Araguaína-TO. Metodologia: Foi encaminhado ao Laboratório de Patologia Clínica Veterinária da Clínica Veterinária Universitária da Universidade Federal do Norte do Tocantins (UFNT), uma gata, sem raça definida, para coleta e análise de exames laboratoriais, cuja suspeita era leishmaniose. Tratava-se de um animal errante que foi adotado há 1 ano, vive em um lar temporário para animais, tendo contato com animais sadios e doentes. Há 30 dias o animal apresentou uma massa na narina esquerda com crescimento contínuo e apatia, além de lesões em lábio superior e abaixo do lábio inferior. Durante a avaliação do paciente foi observado que a massa obstruía completamente a narina, provocando dificuldade respiratória, confirmou-se a presença das lesões e identificou-se que os linfonodos submandibulares, pré-escapulares e poplíteos encontravam-se aumentados. Foram coletadas amostras de sangue para hemograma, bioquímica sérica e citologia da massa nasal, lesões labial e linfonodos. A técnica utilizada para a coleta de material da massa nasal foi a de swab, enquanto para as demais foi realizada punção por agulha fina (PAF). Foram realizados hemograma, dosagens de ALT, ALB, PT, FA, ureia, creatinina e pesquisa de Leishmania spp.. Resultados: Não foi observada alteração no hemograma, na bioquímica observou-se hiperproteinemia com hipoalbuminemia e elevação das enzimas hepáticas. A pesquisa de leishmania spp. foi positiva evidenciando formas amastigotas do parasito. Conclusão: Felinos com sinais clínicos inespecíficos compatíveis para leishmaniose devem ser investigados. A citologia, por agulha fina e swab, foram eficazes para o diagnóstico de leishmania spp. em felinos. As alterações bioquímicas são compatíveis com o quadro de animais com leishmaniose.
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Thiele, Sebastian, and Frank Schwierz. "Simulation of 1-Nanometer Gate MoS2 MOSFETs." In 2018 14th IEEE International Conference on Solid-State and Integrated Circuit Technology (ICSICT). IEEE, 2018. http://dx.doi.org/10.1109/icsict.2018.8564849.

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Figueroa Toro, Dr. "1 Adaptive Systems in Floating-Gate CMOS Technology." In 2006 3rd International Conference on Electrical and Electronics Engineering. IEEE, 2006. http://dx.doi.org/10.1109/iceee.2006.251958.

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Yamamoto, Toyoji, Kazuya Uejima, and Tohru Mogami. "Impact of 1-2nm Gate Oxide for Sub-Quarter Micron Dual Gate CMOS." In 1999 International Conference on Solid State Devices and Materials. The Japan Society of Applied Physics, 1999. http://dx.doi.org/10.7567/ssdm.1999.a-3-2.

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Martinez, F. "Contributions of Channel Gate and Overlap Gate Currents on 1/f Gate Current Noise for Thin Oxide Gate p-MOSFETs." In NOISE AND FLUCTUATIONS: 18th International Conference on Noise and Fluctuations - ICNF 2005. AIP, 2005. http://dx.doi.org/10.1063/1.2036741.

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Reports on the topic "GATA-1"

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Chowdhury, Mostafiz R., Robert L. Hall, and Eileen Pesantes. Flow-Induced Vibration Experiments for a 1:25-Scale-Model Flat Wicket Gate. Fort Belvoir, VA: Defense Technical Information Center, August 1997. http://dx.doi.org/10.21236/ada329308.

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Ward, Daniel Robert. Option 1: Qubits in Gate-Defined Silicon Quantum Dots UW/Delft/Harvard/SNL Collaboration. Office of Scientific and Technical Information (OSTI), January 2020. http://dx.doi.org/10.2172/1596528.

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Engineering evaluation/cost analysis for the proposed removal of contaminated materials from Pad 1 at the Elza Gate site, Oak Ridge, Tennessee. Office of Scientific and Technical Information (OSTI), June 1990. http://dx.doi.org/10.2172/5666521.

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Engineering evaluation/cost analysis for the proposed removal of contaminated materials from pad 1 at the Elza Gate site, Oak Ridge, Tennessee. Office of Scientific and Technical Information (OSTI), September 1990. http://dx.doi.org/10.2172/6149022.

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