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Sample records for nuclear erythroid 2-related

  1. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders

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    Kim, Jiyoung [National Research Laboratory, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Cha, Young-Nam [Inha University College of Medicine, Incheon 382-751 (Korea, Republic of); Surh, Young-Joon, E-mail: surh@plaza.snu.ac.kr [National Research Laboratory, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul 110-799 (Korea, Republic of)

    2010-08-07

    Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress-response proteins. The 5'-flanking regions of genes encoding these cytoprotective proteins contain a specific consensus sequence termed antioxidant response element (ARE) to which Nrf2 binds. Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling causes enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.

  2. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders

    International Nuclear Information System (INIS)

    Kim, Jiyoung; Cha, Young-Nam; Surh, Young-Joon

    2010-01-01

    Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress-response proteins. The 5'-flanking regions of genes encoding these cytoprotective proteins contain a specific consensus sequence termed antioxidant response element (ARE) to which Nrf2 binds. Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling causes enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.

  3. DJ-1 Modulates Nuclear Erythroid 2-Related Factor-2-Mediated Protection in Human Primary Alveolar Type II Cells in Smokers.

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    Bahmed, Karim; Messier, Elise M; Zhou, Wenbo; Tuder, Rubin M; Freed, Curt R; Chu, Hong Wei; Kelsen, Steven G; Bowler, Russell P; Mason, Robert J; Kosmider, Beata

    2016-09-01

    Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2-related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases.

  4. Participation of nuclear factor (erythroid 2-related), factor 2 in ameliorating lithocholic acid-induced cholestatic liver injury in mice.

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    Tan, K P; Wood, G A; Yang, M; Ito, S

    2010-11-01

    Lithocholic acid (LCA), the most toxic bile acid, induces cholestatic liver injury in rodents. We previously showed that LCA activates the oxidative stress-responsive nuclear factor (erythroid-2 like), factor 2 (Nrf2) in cultured liver cells, triggering adaptive responses that reduce cell injury. In this study, we determined whether Nrf2 protects the liver against LCA-induced toxicity in vivo. Nrf2 disrupted (Nrf2(-/-) ) and wild-type mice were treated with LCA (125 mg·kg(-1) body weight) to induce liver injury. Levels of mRNA, protein and function of important Nrf2 target genes coupled with liver histology and injury biomarkers of mice were examined. In 4 day LCA treatments, we observed a significantly higher hepatic induction of Nrf2 target, cytoprotective genes including thioredoxin reductase 1, glutamate cysteine ligase subunits, glutathione S-transferases, haeme oxygenase-1 and multidrug resistance-associated proteins 3 and 4 in the wild type as compared with the Nrf2(-/-) mice. Moreover, basal and LCA-induced hepatic glutathione and activities of glutathione S-transferases and thioredoxin reductases were higher in wild-type than in Nrf2(-/-) mice. This reduced production of cytoprotective genes against LCA toxicity rendered Nrf2(-/-) mice more susceptible to severe liver damage with the presence of multifocal liver necrosis, inflamed bile ducts and elevation of lipid peroxidation and liver injury biomarkers, such as alanine aminotransferase and alkaline phosphatase. Nrf2 plays a crucial cytoprotective role against LCA-induced liver injury by orchestrating adaptive responses. The pharmacological potential of targeting liver Nrf2 in the management of cholestatic liver diseases is proposed. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

  5. Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation.

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    Barhwal, K; Hota, S K; Jain, V; Prasad, D; Singh, S B; Ilavazhagan, G

    2009-06-30

    Exposure to hypobaric hypoxia, a condition involving decreased availability of oxygen is known to be associated with oxidative stress, neurodegeneration and memory impairment. The multifactorial response of the brain and the complex signaling pathways involved therewith limits the therapeutic efficacy of several antioxidants in ameliorating hypobaric hypoxia-induced memory impairment. The present study was therefore aimed at investigating the potential of acetyl-l-carnitine (ALCAR), a known antioxidant that has been reported to augment neurotrophin-mediated survival mechanisms, in ameliorating hypoxia-induced neurodegeneration and memory impairment. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor involved in the cellular defense mechanism against oxidative stress related to brain injury and neurological disorders. The study was designed to understand the mechanisms involving Nrf2 stabilization following exposure to hypobaric hypoxia. The results displayed reference memory impairment in Sprague-Dawley rats exposed to hypobaric hypoxia (7620 m) for 14 consecutive days which however improved on administration of ALCAR during hypoxic exposure. The study also revealed Nrf2 regulated augmented antioxidant response on administration of ALCAR which was through a novel tyrosine kinase A (TrkA) receptor-mediated mechanism. A decrease in free radical generation, lipid peroxidation and protein oxidation was also observed along with a concomitant increase in thioredoxin and reduced glutathione levels on administration of ALCAR during exposure to hypobaric hypoxia. The present study therefore reveals the therapeutic potential of ALCAR under conditions of hypobaric hypoxia and elucidates a novel mechanism of action of the drug.

  6. Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5.

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    Ashino, Takashi; Ohkubo-Morita, Haruyo; Yamamoto, Masayuki; Yoshida, Takemi; Numazawa, Satoshi

    2014-01-01

    Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2)-deficient (Nrf2(-⧸-)) mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2(-⧸-) mouse livers were lower than that in wild-type mouse livers. Nrf2(-⧸-) mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression.

  7. Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5☆

    Science.gov (United States)

    Ashino, Takashi; Ohkubo-Morita, Haruyo; Yamamoto, Masayuki; Yoshida, Takemi; Numazawa, Satoshi

    2014-01-01

    Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2)–deficient (Nrf2−⧸−) mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2−⧸− mouse livers were lower than that in wild-type mouse livers. Nrf2−⧸− mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression. PMID:24494203

  8. Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5

    Directory of Open Access Journals (Sweden)

    Takashi Ashino

    2014-01-01

    Full Text Available Cytochrome P450 gene expression is altered by various chemical compounds. In this study, we used nuclear factor erythroid 2-related factor 2 (Nrf2–deficient (Nrf2−⧸− mice to investigate the involvement of Nrf2 in Cyp2b10 and Cyp2a5 gene expression. Phorone, an Nrf2 activator, strongly increased Cyp2b10 and Cyp2a5 mRNA as well as Nrf2 target genes, including NAD(PH-quinone oxidoreductase-1 and heme oxygenase-1, in wild-type mouse livers 8 h after treatment. The phorone-induced mRNA levels in Nrf2−⧸− mouse livers were lower than that in wild-type mouse livers. Nrf2−⧸− mice showed attenuated Cyp2b10 and Cyp2a5 induction by phenobarbital, a classical Cyp2b inducer. These findings suggest that the Nrf2 pathway is involved in Cyp2b10 and Cyp2a5 gene expression.

  9. Nuclear factor erythroid 2-related factor 2 antibody attenuates thermal hyperalgesia in the dorsal root ganglion: Neurochemical changes and behavioral studies after sciatic nerve-pinch injury.

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    Xiang, Qiong; Yu, Chao; Zhu, Yao-Feng; Li, Chun-Yan; Tian, Rong-Bo; Li, Xian-Hui

    2016-08-01

    Oxidative stress is generated in several peripheral nerve injury models.Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated to have a role in antioxidant effect. After nerve injury, the severely painful behavior is also performed. However, little has been explored regarding the function of Nrf2 in this painful process. Therefore, in this study, we compared the effects of Nrf2 antibody administration following sciatic nerve-pinch injury on painful behavior induced in young mice and neurochemical changes in dorsal root ganglion neurons. After pinch nerve injury, we found that the magnitude of the thermal allodynia was significantly decreased after application of Nrf2 antibody (5ul, 1mg/ml) in such injured animals and phosphorylated ERK(p-ERK) as well as the apoptotic protein (i.e., Bcl-6) in DRG neurons were also down-regulated in the anti-Nrf2-treated injured groups compared to the saline-treated groups. Taken collectively, these data suggested that the Nrf2 antibody reduced thermal hyperalgesia via ERK pathway and the down regulation of Bcl-6 protein from the apoptosis pathway might be protecting against the protein deletions caused by anti-Nrf2 effect and suggested the new therapeutic strategy with Nrf2 inhibitor following nerve injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Catalase overexpression prevents nuclear factor erythroid 2-related factor 2 stimulation of renal angiotensinogen gene expression, hypertension, and kidney injury in diabetic mice.

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    Abdo, Shaaban; Shi, Yixuan; Otoukesh, Abouzar; Ghosh, Anindya; Lo, Chao-Sheng; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao Ling; Chan, John S D

    2014-10-01

    This study investigated the impact of catalase (Cat) overexpression in renal proximal tubule cells (RPTCs) on nuclear factor erythroid 2-related factor 2 (Nrf2) stimulation of angiotensinogen (Agt) gene expression and the development of hypertension and renal injury in diabetic Akita transgenic mice. Additionally, adult male mice were treated with the Nrf2 activator oltipraz with or without the inhibitor trigonelline. Rat RPTCs, stably transfected with plasmid containing either rat Agt or Nrf2 gene promoter, were also studied. Cat overexpression normalized systolic BP, attenuated renal injury, and inhibited RPTC Nrf2, Agt, and heme oxygenase-1 (HO-1) gene expression in Akita Cat transgenic mice compared with Akita mice. In vitro, high glucose level, hydrogen peroxide, and oltipraz stimulated Nrf2 and Agt gene expression; these changes were blocked by trigonelline, small interfering RNAs of Nrf2, antioxidants, or pharmacological inhibitors of nuclear factor-κB and p38 mitogen-activated protein kinase. The deletion of Nrf2-responsive elements in the rat Agt gene promoter abolished the stimulatory effect of oltipraz. Oltipraz administration also augmented Agt, HO-1, and Nrf2 gene expression in mouse RPTCs and was reversed by trigonelline. These data identify a novel mechanism, Nrf2-mediated stimulation of intrarenal Agt gene expression and activation of the renin-angiotensin system, by which hyperglycemia induces hypertension and renal injury in diabetic mice. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. Role of nuclear factor erythroid 2-related factor 2 in the oxidative stress-dependent hypertension associated with the depletion of DJ-1.

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    Cuevas, Santiago; Yang, Yu; Konkalmatt, Prasad; Asico, Laureano D; Feranil, Jun; Jones, John; Villar, Van Anthony; Armando, Ines; Jose, Pedro A

    2015-06-01

    Renal dopamine 2 receptor dysfunction is associated with oxidative stress and high blood pressure (BP). We have reported that DJ-1, an oxidative stress response protein, is positively regulated by dopamine 2 receptor in the kidney. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of several antioxidant genes. We tested the hypothesis that Nrf2 is involved in the renal DJ-1-mediated inhibition of reactive oxygen species production. We have reported that silencing dopamine 2 receptor in mouse renal proximal tubule cells decreases the expression of DJ-1. We now report that silencing DJ-1 or dopamine 2 receptor in mouse proximal tubule cells and mouse kidneys decreases Nrf2 expression and activity and increases reactive oxygen species production; BP is also increased in mice in which renal DJ-1 or dopamine 2 receptor is silenced. DJ-1(-/-) mice have decreased renal Nrf2 expression and activity and increased nitro-tyrosine levels and BP. Silencing Nrf2 in mouse proximal tubule cells does not alter the expression of DJ-1 or dopamine 2 receptor, indicating that Nrf2 is downstream of dopamine 2 receptor and DJ-1. An Nrf2 inducer, bardoxolone, normalizes the systolic BP and renal malondialdehyde levels in DJ-1(-/-) mice without affecting them in their wild-type littermates. Because Nrf2 ubiquitination is increased in DJ-1(-/-) mice, we conclude that the protective effect of DJ-1 on renal oxidative stress is mediated, in part, by preventing Nrf2 degradation. Moreover, renal dopamine 2 receptor and DJ-1 are necessary for normal Nrf2 activity to keep a normal redox balance and BP. © 2015 American Heart Association, Inc.

  12. Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2 in burn patient immune cells and monocytes.

    Directory of Open Access Journals (Sweden)

    Timothy K Eitas

    Full Text Available Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA injury have elevated levels of the innate immune cytokines Interleukin-6 (IL-6 and Monocyte Chemoattractant Protein-1 (MCP-1/CC-motif Chemokine Ligand 2(CCL2 early after hospital admission (0-48 Hours Post-hospital Admission (HPA. Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs revealed that burn shock patients (≥15% TBSA produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2 agonist, CDDO-Me(bardoxolone methyl, reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10 secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA. Hence, our findings with CDDO-Me(bardoxolone methyl and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells.

  13. The effect of ex vivo CDDO-Me activation on nuclear factor erythroid 2-related factor 2 pathway in white blood cells from patients with septic shock.

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    Noel, Sanjeev; Zheng, Laura; Navas-Acien, Ana; Fuchs, Ralph J

    2014-11-01

    Nuclear factor erythroid 2-related factor 2 (NRF2) has been shown to protect against experimental sepsis in mice and lipopolysaccharide (LPS)-induced inflammation in ex vivo white blood cells from healthy subjects by upregulating cellular antioxidant genes. The objective of this study was to test the hypothesis that ex vivo methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate (CDDO-Me) activates NRF2-regulated antioxidant genes in white blood cells from patients with septic shock and protects against LPS-induced inflammation and reactive oxidative species production. Peripheral blood was collected from 18 patients with septic shock who were being treated in medical and surgical intensive care units. Real-time polymerase chain reaction was used to quantify the expression of NRF2 target genes (NQO1, HO-1, GCLM, and FTL) and IL-6 in peripheral blood mononuclear cells (PBMCs), monocytes, and neutrophils after CDDO-Me treatment alone or after subsequent LPS exposure. Superoxide anion (O2) was measured to assess the effect of CDDO-Me pretreatment on subsequent LPS exposure. Treatment with CDDO-Me increased the gene expression of NQO1 (P = 0.04) and decreased the expression of HO-1 (P = 0.03) in PBMCs from patients with septic shock. Purified monocytes exhibited significant increases in the expression of NQO1 (P = 0.01) and GCLM (P = 0.003) after CDDO-Me treatment. Levels of other NRF2 target genes (HO-1 and FTL) remained similar to those of vehicle-treated cells. Peripheral blood mononuclear cells showed a trend toward increased IL-6 gene expression after CDDO-Me treatment, whereas purified monocytes showed a trend toward decreased IL-6. There was no discernible trend in the IL-6 expression subsequent to LPS treatment in either vehicle-treated or CDDO-Me-treated PBMCs and monocytes. Treatment with CDDO-Me significantly increased O2 production in PBMCs (P = 0.04). Although CDDO-Me pretreatment significantly attenuated O2 production to subsequent LPS exposure (P = 0.03), the

  14. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

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    Lo, Raymond; Matthews, Jason, E-mail: jason.matthews@utoronto.ca

    2013-07-15

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  15. Impaired nuclear factor erythroid 2-related factor 2 expression increases apoptosis of airway epithelial cells in patients with chronic obstructive pulmonary disease due to cigarette smoking.

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    Yamada, Kazuhiro; Asai, Kazuhisa; Nagayasu, Fumihiro; Sato, Kanako; Ijiri, Naoki; Yoshii, Naoko; Imahashi, Yumiko; Watanabe, Tetsuya; Tochino, Yoshihiro; Kanazawa, Hiroshi; Hirata, Kazuto

    2016-02-09

    Cigarette smoking-induced oxidative stress is known to be a key mechanism in COPD pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a central transcription factor that regulates the antioxidant defense system. The aim of this study was to compare Nrf2 expression in COPD subjects and control subjects, and to determine the role of Nrf2 in protecting against oxidative stress-induced apoptosis. We enrolled 8 COPD subjects and 7 control subjects in this study. We performed bronchial brushing by bronchoscopy and obtained bronchial epithelial cells from the airways. Nrf2 expression in bronchial epithelial cells was evaluated by real-time PCR and Western blotting. We examined the effect of 10 or 15 % cigarette smoke extract (CSE) induced A549 cells apoptosis using a time-lapse cell imaging assay with caspase-3/7 activation detecting reagent and performed Terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling assay for confirming A549 cells apoptosis. We also examined the effects of Nrf2 knockdown and, 0.1, 0.5, and 1.0 mM N-acetyl cysteine on CSE-induced apoptosis. Statistical analyses were performed using t-test, paired t-test or an analysis of variance followed by the Tukey-Kramer method. Nrf2 mRNA expression in COPD subjects was significantly lower than that in control subjects and Nrf2 mRNA were negatively correlated with pack year. Nrf2 protein in COPD subjects was significantly lower than that in control subjects. CSE-induced A549 cells apoptosis was increased in a time-, concentration-dependent manner, and was significantly increased by Nrf2 knockdown. N-acetyl cysteine significantly ameliorated CSE-induced apoptosis. Nrf2 expression was lower in COPD patients than in control subjects. Nrf2 might have a protective role against apoptosis caused by CSE-induced oxidative stress. These results suggest an involvement of Nrf2 in COPD and administration of antioxidants to patients with COPD might be a basic therapeutic option.

  16. Nuclear factor erythroid 2-related factor 2 antioxidant response element pathways protect bovine mammary epithelial cells against H2O2-induced oxidative damage in vitro.

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    Ma, Y F; Wu, Z H; Gao, M; Loor, J J

    2018-03-21

    The experiment was conducted to determine the role of nuclear factor (erythroid-derived 2)-like factor 2 (NFE2L2, formerly Nrf2) antioxidant response element (ARE) pathway in protecting bovine mammary epithelial cells (BMEC) against H 2 O 2 -induced oxidative stress injury. An NFE2L2 small interfering RNA (siRNA) interference or a pCMV6-XL5-NFE2L2 plasmid fragment was transfected to independently downregulate or upregulate expression of NFE2L2. Isolated BMEC in triplicate were exposed to H 2 O 2 (600 μM) for 6 h to induce oxidative stress before transient transfection with scrambled siRNA, NFE2L2-siRNA, pCMV6-XL5, and pCMV6-XL5-NFE2L2. Cell proliferation, apoptosis and necrosis rates, antioxidant enzyme activities, reactive oxygen species (ROS) and malondialdehyde (MDA) production, protein and mRNA expression of NFE2L2 and downstream target genes, and fluorescence activity of ARE were measured. The results revealed that compared with the control, BMEC transfected with NFE2L2-siRNA3 had proliferation rates that were 9 or 65% lower without or with H 2 O 2 , respectively. These cells also had apoptosis and necrosis rates that were 27 and 3.5 times greater with H 2 O 2 compared with the control group, respectively. In contrast, transfected pCMV6-XL5-NFE2L2 had proliferation rates that were 64.3% greater or 17% lower without or with H 2 O 2 compared with the control group, respectively. Apoptosis rates were 1.8 times lower with H 2 O 2 compared with the control. In addition, compared with the control, production of ROS and MDA and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione-S-transferase (GST) increased markedly in cells transfected with pCMV6-XL5-NFE2L2 and without H 2 O 2 . However, compared with the control, production of ROS and MDA and activity of CAT and GSH-Px increased markedly, whereas activities of SOD and GST decreased in cells transfected with pCMV6-XL5-NFE2L2 and incubated with H 2 O 2

  17. Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) and inhibits pro-survival function of Nrf1

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    Biswas, Madhurima; Kwong, Erick K.; Park, Eujean; Nagra, Parminder; Chan, Jefferson Y., E-mail: jchan@uci.edu

    2013-08-01

    Nuclear factor E2-related factor-1 (Nrf1) is a basic leucine zipper transcription factor that is known to regulate antioxidant and cytoprotective gene expression. It was recently shown that Nrf1 is regulated by SCF–Fbw7 ubiquitin ligase. However our knowledge of upstream signals that targets Nrf1 for degradation by the UPS is not known. We report here that Nrf1 expression is negatively regulated by glycogen synthase kinase 3 (GSK3) in Fbw7-dependent manner. We show that GSK3 interacts with Nrf1 and phosphorylates the Cdc4 phosphodegron domain (CPD) in Nrf1. Mutation of serine residue in the CPD of Nrf1 to alanine (S350A), blocks Nrf1 from phosphorylation by GSK3, and stabilizes Nrf1. Knockdown of Nrf1 and expression of a constitutively active form of GSK3 results in increased apoptosis in neuronal cells in response to ER stress, while expression of the GSK3 phosphorylation resistant S350A–Nrf1 attenuates apoptotic cell death. Together these data suggest that GSK3 regulates Nrf1 expression and cell survival function in response to stress activation. Highlights: • The effect of GSK3 on Nrf1 expression was examined. • GSK3 destabilizes Nrf1 protein via Fbw7 ubiquitin ligase. • GSK3 binds and phosphorylates Nrf1. • Protection from stress-induced apoptosis by Nrf1 is inhibited by GSK3.

  18. The Cytoprotective Effect of Petalonia binghamiae Methanol Extract against Oxidative Stress in C2C12 Myoblasts: Mediation by Upregulation of Heme Oxygenase-1 and Nuclear Factor-Erythroid 2 Related Factor 2

    Directory of Open Access Journals (Sweden)

    Ji Sook Kang

    2015-04-01

    Full Text Available This study was designed to examine the protective effects of the marine brown algae Petalonia binghamiae against oxidative stress-induced cellular damage and to elucidate the underlying mechanisms. P. binghamiae methanol extract (PBME prevented hydrogen peroxide (H2O2-induced growth inhibition and exhibited scavenging activity against intracellular reactive oxygen species (ROS induced by H2O2 in mouse-derived C2C12 myoblasts. PBME also significantly attenuated H2O2-induced comet tail formation in a comet assay, histone γH2A.X phosphorylation, and annexin V-positive cells, suggesting that PBME prevented H2O2-induced cellular DNA damage and apoptotic cell death. Furthermore, PBME increased the levels of heme oxygenase-1 (HO-1, a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2 related factor 2 (Nrf2. However, zinc protoporphyrin IX, a HO-1 competitive inhibitor, significantly abolished the protective effects of PBME on H2O2-induced ROS generation, growth inhibition, and apoptosis. Collectively, these results demonstrate that PBME augments the antioxidant defense capacity through activation of the Nrf2/HO-1 pathway.

  19. Andrographolide stimulates p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 signaling in primary cerebral endothelial cells for definite protection against ischemic stroke in rats.

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    Yen, Ting-Lin; Chen, Ray-Jade; Jayakumar, Thanasekaran; Lu, Wan-Jung; Hsieh, Cheng-Ying; Hsu, Ming-Jen; Yang, Chih-Hao; Chang, Chao-Chien; Lin, Yen-Kuang; Lin, Kuan-Hung; Sheu, Joen-Rong

    2016-04-01

    Stroke pathogenesis involves complex oxidative stress-related pathways. The nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) pathways have been considered molecular targets in pharmacologic intervention for ischemic diseases. Andrographolide, a labdane diterpene, has received increasing attention in recent years because of its various pharmacologic activities. We determined that andrographolide modulates the mitogen-activated protein kinase (MAPK)-Nrf2-HO-1 signaling cascade in primary cerebral endothelial cells (CECs) to provide positive protection against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in rats. In the present study, andrographolide (10 μM) increased HO-1 protein and messenger RNA expressions, Nrf2 phosphorylation, and nuclear translocation in CECs, and these activities were disrupted by a p38 MAPK inhibitor, SB203580, but not by the extracellular signal-regulated kinase inhibitor PD98059 or c-Jun amino-terminal kinase inhibitor SP600125. Similar results were observed in confocal microscopy analysis. Moreover, andrographolide-induced Nrf2 and HO-1 protein expressions were significantly inhibited by Nrf2 small interfering RNA. Moreover, HO-1 knockdown attenuated the protective effect of andrographolide against oxygen-glucose deprivation-induced CEC death. Andrographolide (0.1 mg/kg) significantly suppressed free radical formation, blood-brain barrier disruption, and brain infarction in MCAO-insulted rats, and these effects were reversed by the HO-1 inhibitor zinc protoporphyrin IX. The mechanism is attributable to HO-1 activation, as directly evidenced by andrographolide-induced pronounced HO-1 expression in brain tissues, which was highly localized in the cerebral capillary. In conclusion, andrographolide increased Nrf2-HO-1 expression through p38 MAPK regulation, confirming that it provides protection against MCAO-induced brain injury. These findings provide strong evidence that andrographolide could

  20. Nuclear RNA sequencing of the mouse erythroid cell transcriptome.

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    Jennifer A Mitchell

    Full Text Available In addition to protein coding genes a substantial proportion of mammalian genomes are transcribed. However, most transcriptome studies investigate steady-state mRNA levels, ignoring a considerable fraction of the transcribed genome. In addition, steady-state mRNA levels are influenced by both transcriptional and posttranscriptional mechanisms, and thus do not provide a clear picture of transcriptional output. Here, using deep sequencing of nuclear RNAs (nucRNA-Seq in parallel with chromatin immunoprecipitation sequencing (ChIP-Seq of active RNA polymerase II, we compared the nuclear transcriptome of mouse anemic spleen erythroid cells with polymerase occupancy on a genome-wide scale. We demonstrate that unspliced transcripts quantified by nucRNA-seq correlate with primary transcript frequencies measured by RNA FISH, but differ from steady-state mRNA levels measured by poly(A-enriched RNA-seq. Highly expressed protein coding genes showed good correlation between RNAPII occupancy and transcriptional output; however, genome-wide we observed a poor correlation between transcriptional output and RNAPII association. This poor correlation is due to intergenic regions associated with RNAPII which correspond with transcription factor bound regulatory regions and a group of stable, nuclear-retained long non-coding transcripts. In conclusion, sequencing the nuclear transcriptome provides an opportunity to investigate the transcriptional landscape in a given cell type through quantification of unspliced primary transcripts and the identification of nuclear-retained long non-coding RNAs.

  1. Nuclear RNA Sequencing of the Mouse Erythroid Cell Transcriptome

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    Umlauf, David; Chen, Chih-yu; Moir, Catherine A.; Eskiw, Christopher H.; Schoenfelder, Stefan; Chakalova, Lyubomira; Nagano, Takashi; Fraser, Peter

    2012-01-01

    In addition to protein coding genes a substantial proportion of mammalian genomes are transcribed. However, most transcriptome studies investigate steady-state mRNA levels, ignoring a considerable fraction of the transcribed genome. In addition, steady-state mRNA levels are influenced by both transcriptional and posttranscriptional mechanisms, and thus do not provide a clear picture of transcriptional output. Here, using deep sequencing of nuclear RNAs (nucRNA-Seq) in parallel with chromatin immunoprecipitation sequencing (ChIP-Seq) of active RNA polymerase II, we compared the nuclear transcriptome of mouse anemic spleen erythroid cells with polymerase occupancy on a genome-wide scale. We demonstrate that unspliced transcripts quantified by nucRNA-seq correlate with primary transcript frequencies measured by RNA FISH, but differ from steady-state mRNA levels measured by poly(A)-enriched RNA-seq. Highly expressed protein coding genes showed good correlation between RNAPII occupancy and transcriptional output; however, genome-wide we observed a poor correlation between transcriptional output and RNAPII association. This poor correlation is due to intergenic regions associated with RNAPII which correspond with transcription factor bound regulatory regions and a group of stable, nuclear-retained long non-coding transcripts. In conclusion, sequencing the nuclear transcriptome provides an opportunity to investigate the transcriptional landscape in a given cell type through quantification of unspliced primary transcripts and the identification of nuclear-retained long non-coding RNAs. PMID:23209567

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

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    Gullberg Urban

    2010-05-01

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

  3. Pharmacological stimulation of nuclear factor (erythroid-derived 2)-like 2 translation activates antioxidant responses.

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    Perez-Leal, Oscar; Barrero, Carlos Alberto; Merali, Salim

    2017-08-25

    Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of the antioxidant response, and its function is tightly regulated at the transcriptional, translational, and post-translational levels. It is well-known that Nrf2 is regulated at the protein level by proteasomal degradation via Kelch-like ECH-associated protein 1 (Keap1), but how Nrf2 is regulated at the translational level is less clear. Here, we show that pharmacological stimulation increases Nrf2 levels by overcoming basal translational repression. We developed a novel reporter assay that enabled identification of natural compounds that induce Nrf2 translation by a mechanism independent of Keap1-mediated degradation. Apigenin, resveratrol, and piceatannol all induced Nrf2 translation. More importantly, the pharmacologically induced Nrf2 overcomes Keap1 regulation, translocates to the nucleus, and activates the antioxidant response. We conclude that translational regulation controls physiological levels of Nrf2, and this can be modulated by apigenin, resveratrol, and piceatannol. Also, targeting this mechanism with novel compounds could provide new insights into prevention and treatment of multiple diseases in which oxidative stress plays a significant role. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Nuclear Factor Erythroid 2 Regulates Human HSC Self-Renewal and T Cell Differentiation by Preventing NOTCH1 Activation

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    Alessandro Di Tullio

    2017-07-01

    Full Text Available Nuclear factor erythroid-derived 2 (NF-E2 has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG mice. This phenotype is likely to be related to both increased cell proliferation (p21-mediated and reduced Notch1 protein expression, which favors HSPC differentiation over self-renewal. Strikingly, although NF-E2 silencing in HSPCs did not affect their myeloid and B cell differentiation in vivo, it almost abrogated T cell production in primary hosts, as confirmed by in vitro studies. This effect is at least partly due to Notch1 downregulation in NF-E2-silenced HSPCs. Together these data reveal that NF-E2 is an important driver of human hematopoietic stem cell maintenance and T lineage differentiation.

  5. Nuclear Factor Erythroid 2 Regulates Human HSC Self-Renewal and T Cell Differentiation by Preventing NOTCH1 Activation.

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    Di Tullio, Alessandro; Passaro, Diana; Rouault-Pierre, Kevin; Purewal, Sukhveer; Bonnet, Dominique

    2017-07-11

    Nuclear factor erythroid-derived 2 (NF-E2) has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs) not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG) mice. This phenotype is likely to be related to both increased cell proliferation (p21-mediated) and reduced Notch1 protein expression, which favors HSPC differentiation over self-renewal. Strikingly, although NF-E2 silencing in HSPCs did not affect their myeloid and B cell differentiation in vivo, it almost abrogated T cell production in primary hosts, as confirmed by in vitro studies. This effect is at least partly due to Notch1 downregulation in NF-E2-silenced HSPCs. Together these data reveal that NF-E2 is an important driver of human hematopoietic stem cell maintenance and T lineage differentiation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Nuclear translocation of PKC-α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs).

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    Poli, Alessandro; Ratti, Stefano; Finelli, Carlo; Mongiorgi, Sara; Clissa, Cristina; Lonetti, Annalisa; Cappellini, Alessandra; Catozzi, Alessia; Barraco, Marilena; Suh, Pann-Ghill; Manzoli, Lucia; McCubrey, James A; Cocco, Lucio; Follo, Matilde Y

    2018-02-01

    PI-PLCβ1 is involved in cell proliferation, differentiation, and myelodysplastic syndrome (MDS) pathogenesis. Moreover, the increased activity of PI-PLCβ1 reduces the expression of PKC-α, which, in turn, delays the cell proliferation and is linked to erythropoiesis. Lenalidomide is currently used in low-risk patients with MDS and del(5q), where it can suppress the del(5q) clone and restore normal erythropoiesis. In this study, we analyzed the effect of lenalidomide on 16 patients with low-risk del(5q) MDS, as well as del(5q) and non-del(5q) hematopoietic cell lines, mainly focusing on erythropoiesis, cell cycle, and PI-PLCβ1/PKC-α signaling. Overall, 11 patients were evaluated clinically, and 10 (90%) had favorable responses; the remaining case had a stable disease. At a molecular level, both responder patients and del(5q) cells showed a specific induction of erythropoiesis, with a reduced γ/β-globin ratio, an increase in glycophorin A, and a nuclear translocation of PKC-α. Moreover, lenalidomide could induce a selective G 0 /G 1 arrest of the cell cycle in del(5q) cells, slowing down the rate proliferation in those cells. Altogether, our results could not only better explain the role of PI-PLCβ1/PKC-α signaling in erythropoiesis but also lead to a better comprehension of the lenalidomide effect on del(5q) MDS and pave the way to innovative, targeted therapies.-Poli, A., Ratti, S., Finelli, C., Mongiorgi, S., Clissa, C., Lonetti, A., Cappellini, A., Catozzi, A., Barraco, M., Suh, P.-G., Manzoli, L., McCubrey, J. A., Cocco, L., Follo, M. Y. Nuclear translocation of PKC-α is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs).

  7. Calcium Signaling Is Required for Erythroid Enucleation.

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    Christina B Wölwer

    Full Text Available Although erythroid enucleation, the property of erythroblasts to expel their nucleus, has been known for 7ore than a century, surprisingly little is known regarding the molecular mechanisms governing this unique developmental process. Here we show that similar to cytokinesis, nuclear extrusion requires intracellular calcium signaling and signal transduction through the calmodulin (CaM pathway. However, in contrast to cytokinesis we found that orthochromatic erythroblasts require uptake of extracellular calcium to enucleate. Together these functional studies highlight a critical role for calcium signaling in the regulation of erythroid enucleation.

  8. 4-Methylthio-3-butenyl isothiocyanate mediates nuclear factor (erythroid-derived 2)-like 2 activation by regulating reactive oxygen species production in human esophageal epithelial cells.

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    Hirata, Tadashi; Cho, Young-Man; Suzuki, Isamu; Toyoda, Takeshi; Akagi, Jun-Ichi; Nakamura, Yasushi; Numazawa, Satoshi; Ogawa, Kumiko

    2018-01-01

    4-Methylthio-3-butenyl isothiocyanate (MTBITC) extracted from daikon (Raphanus sativus), which shows antimutagenicity, may have applications as an effective chemopreventive agent in several cancers; however, few reports have described the associated mechanisms. We investigated whether MTBITC induced cytoprotective genes, including phase II enzymes, in Het-1A human esophageal epithelial cells. HMOX1, NQO1, and GCLC mRNA levels and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein levels were increased in Het-1A cells treated with 10 μM MTBITC. Reactive oxygen species (ROS) tended to increase when Het-1A cells were treated with MTBITC, and the increases in ROS and Nrf2 expression in the cells treated with MTBITC were completely abolished by treatment with N-acetyl-l-cysteine. We also examined the relationships between Nrf2 activation and mitogen-activated protein kinase (MAPK) signaling by western blot analysis. MTBITC induced extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 phosphorylation in Het-1A cells; however, MTBITC did not affect the relationship between Nrf2 activation and MAPK responses. In the present study, we found that MTBITC induced Nrf2 activation and cytoprotective genes via ROS production in Het-1A cells. These results suggest that MTBITC may have the potential for preventing esophageal carcinogenesis through modification of carcinogen metabolism by phase II enzyme induction via ROS production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. DJ-1 Modulates Nuclear Erythroid 2–Related Factor-2–Mediated Protection in Human Primary Alveolar Type II Cells in Smokers

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    Bahmed, Karim; Messier, Elise M.; Zhou, Wenbo; Tuder, Rubin M.; Freed, Curt R.; Chu, Hong Wei; Kelsen, Steven G.; Bowler, Russell P.; Mason, Robert J.

    2016-01-01

    Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2–related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases. PMID:27093578

  10. Molecular Evolution of the Nuclear Factor (Erythroid-Derived 2)-Like 2 Gene Nrf2 in Old World Fruit Bats (Chiroptera: Pteropodidae).

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    Yin, Qiuyuan; Zhu, Lei; Liu, Di; Irwin, David M; Zhang, Shuyi; Pan, Yi-Hsuan

    2016-01-01

    Mammals developed antioxidant systems to defend against oxidative damage in their daily life. Enzymatic antioxidants and low molecular weight antioxidants (LMWAs) constitute major parts of the antioxidant systems. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2, encoded by the Nrf2 gene) is a central transcriptional regulator, regulating transcription, of many antioxidant enzymes. Frugivorous bats eat large amounts of fruits that contain high levels of LMWAs such as vitamin C, thus, a reliance on LMWAs might greatly reduce the need for antioxidant enzymes in comparison to insectivorous bats. Therefore, it is possible that frugivorous bats have a reduced need for Nrf2 function due to their substantial intake of diet-antioxidants. To test whether the Nrf2 gene has undergone relaxed evolution in fruit-eating bats, we obtained Nrf2 sequences from 16 species of bats, including four Old World fruit bats (Pteropodidae) and one New World fruit bat (Phyllostomidae). Our molecular evolutionary analyses revealed changes in the selection pressure acting on Nrf2 gene and identified seven specific amino acid substitutions that occurred on the ancestral lineage leading to Old World fruit bats. Biochemical experiments were conducted to examine Nrf2 in Old World fruit bats and showed that the amount of catalase, which is regulated by Nrf2, was significantly lower in the brain, heart and liver of Old World fruit bats despite higher levels of Nrf2 protein in Old World fruit bats. Computational predictions suggest that three of these seven amino acid replacements might be deleterious to Nrf2 function. Therefore, the results suggest that Nrf2 gene might have experienced relaxed constraint in Old World fruit bats, however, we cannot rule out the possibility of positive selection. Our study provides the first data on the molecular adaptation of Nrf2 gene in frugivorous bats in compensation to the increased levels of LWMAs from their fruit-diet.

  11. Competition of nuclear factor-erythroid 2 factors related transcription factor isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction

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    Nikolai L. Chepelev

    2013-01-01

    Full Text Available Although the Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2 regulated expression of multiple antioxidant and cytoprotective genes through the electrophile responsive element (EpRE is well established, interaction of Nrf2/EpRE with Nrf1, a closely-related transcription factor, is less well understood. Due to either proteolysis or alternative translation, Nrf1 has been found as proteins of varying size, p120, p95, and p65, which have been described as either activators of EpRE or competitive inhibitors of Nrf2. We investigated the effect of Nrf1 on EpRE-regulated gene expression using the catalytic and modifier subunits of glutamate cysteine ligase (GCLC and GCLM as models and explored the potential role of Nrf1 in altering their expression in aging and upon chronic exposure to airborne nano-sized particulate matter (nPM. Nrf1 knockout resulted in the increased expression of GCLC and GCLM in human bronchial epithelial (HBE1 cells. Overexpression Nrf2 in combination with either p120 or p65 diminished or failed to further increase the GCLC- and GLCM-EpRE luciferase activity. All known forms of Nrf1 protein, remained unchanged in the lungs of mice with age or in response to nPM. Our study shows that Nrf1 could inhibit EpRE activity in vitro, whereas the precise role of Nrf1 in vivo requires further investigations. We conclude that Nrf1 may not be directly responsible for the loss of Nrf2-dependent inducibility of antioxidant and cytoprotective genes observed in aged animals.

  12. Sofalcone upregulates the nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 pathway, reduces soluble fms-like tyrosine kinase-1, and quenches endothelial dysfunction: potential therapeutic for preeclampsia.

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    Onda, Kenji; Tong, Stephen; Nakahara, Anzu; Kondo, Mei; Monchusho, Hideaki; Hirano, Toshihiko; Kaitu'u-Lino, Tu'uhevaha; Beard, Sally; Binder, Natalie; Tuohey, Laura; Brownfoot, Fiona; Hannan, Natalie J

    2015-04-01

    Preeclampsia is a severe complication of pregnancy, characterized by hypertension, oxidative stress, and severe endothelial dysfunction. Antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, play key pathophysiological roles in preeclampsia. Heme oxygenase-1 (HO-1) is a cytoprotective, antioxidant enzyme reported to be downregulated in preeclampsia. Studies propose that inducing HO-1 may also decrease sFlt-1 production. Sofalcone, a gastric antiulcer agent in clinical use, is known to induce HO-1 in gastric epithelium. We aimed to investigate whether sofalcone induces HO-1 and reduces sFlt-1 release from primary human placental and endothelial cells and blocks endothelial dysfunction in vitro. We isolated human trophoblasts and endothelial cells (human umbilical vein endothelial cells) and also used uterine microvascular cells. We investigated the effects of sofalcone on (1) HO-1 production, (2) activation of the nuclear factor (erythroid-derived 2)-like 2 pathway, (3) sFlt-1 and soluble endoglin release, (4) tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule upregulation, and (5) endothelial tubule formation. Sofalcone potently increased HO-1 mRNA and protein in both primary trophoblasts and human umbilical vein endothelial cells. Furthermore, sofalcone treatment caused nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 and transactivation of other nuclear factor (erythroid-derived 2)-like 2 responsive genes (NQO1, TXN, and GCLC). Importantly, sofalcone significantly decreased the secretion of sFlt-1 from primary human trophoblasts. Sofalcone potently suppressed endothelial dysfunction in 2 in vitro models, blocking tumor necrosis factor α-induced monocyte adhesion and vascular cell adhesion molecule 1 expression in human umbilical vein endothelial cells. These results indicate that in primary human tissues, sofalcone can potently activate antioxidant nuclear factor

  13. Increased Energy Expenditure, Ucp1 Expression, and Resistance to Diet-induced Obesity in Mice Lacking Nuclear Factor-Erythroid-2-related Transcription Factor-2 (Nrf2).

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    Schneider, Kevin; Valdez, Joshua; Nguyen, Janice; Vawter, Marquis; Galke, Brandi; Kurtz, Theodore W; Chan, Jefferson Y

    2016-04-01

    The NRF2 (also known as NFE2L2) transcription factor is a critical regulator of genes involved in defense against oxidative stress. Previous studies suggest thatNrf2plays a role in adipogenesisin vitro, and deletion of theNrf2gene protects against diet-induced obesity in mice. Here, we demonstrate that resistance to diet-induced obesity inNrf2(-/-)mice is associated with a 20-30% increase in energy expenditure. Analysis of bioenergetics revealed thatNrf2(-/-)white adipose tissues exhibit greater oxygen consumption. White adipose tissue showed a >2-fold increase inUcp1gene expression. Oxygen consumption is also increased nearly 2.5-fold inNrf2-deficient fibroblasts. Oxidative stress induced by glucose oxidase resulted in increasedUcp1expression. Conversely, antioxidant chemicals (such asN-acetylcysteine and Mn(III)tetrakis(4-benzoic acid)porphyrin chloride) and SB203580 (a known suppressor ofUcp1expression) decreasedUcp1and oxygen consumption inNrf2-deficient fibroblasts. These findings suggest that increasing oxidative stress by limitingNrf2function in white adipocytes may be a novel means to modulate energy balance as a treatment of obesity and related clinical disorders. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Transcriptional regulation of Hb-α and Hb-β through nuclear factor E2-related factor-2 (Nrf2) activation in human vaginal cells: A novel mechanism of cellular adaptability to oxidative stress.

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    Saha, Debarchana; Koli, Swanand; Reddy, Kudumula Venkata Rami

    2017-06-01

    Hemoglobin (Hb), a major protein involved in transport of oxygen (O 2 ), is expressed by erythroid lineages. Until recently, it was not known whether non-erythroid cells express Hb. The objective was to evaluate the expression and functional significance of Hb-α and Hb-β in human primary vaginal epithelial cells (hPVECs) and decipher downstream signaling. RT-PCR, qRT-PCR, flow cytometry, Western blot, immunofluorescence were used to evaluate the expression of Hb-α, Hb-β, and nuclear factor E2-related factor-2(Nrf2) after hydrogen peroxide (H 2 O 2 ) induction. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay were used to determine the binding efficiency of Nrf2 on the Hb-α promoter. Stimulation of hPVECs and human vaginal epithelial cell line, VK2/E6E7 with H 2 O 2 augmented the expression of Hb-α, Hb-β, Nrf2, heme oxygenase-1 (HO-1), and reactive oxygen species (ROS). Treatment of these cells with Nrf2 inhibitor, trigonelline (Trig) inhibited Hb-α and Hb-β expressions. Hb-α and Hb-β overexpression downregulated H 2 O 2 -induced ROS. The presence of Nrf2 binding domain was demonstrated within Hb-α promoter. The results revealed for the first time that Hb-α and Hb-β were induced by oxidative stress through the activation of Nrf2. Overexpression of Hb-α and Hb-β ameliorated H 2 O 2 -induced oxidative stress, indicating one of the possible mechanism(s) to protect hPVECS from oxidative stress. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

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    Ghosh, Debolina; LeVault, Kelsey R; Brewer, Gregory J

    2014-01-01

    To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. The transcription factor, Nuclear factor, erythroid 2 (Nfe2), is a regulator of the oxidative stress response during Danio rerio development

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Larissa M., E-mail: lwillia2@bates.edu [Biology Department, Bates College, 44 Campus Avenue, Lewiston, ME 04240 (United States); The MDI Biological Laboratory, 159 Old Bar Harbor Road, Bar Harbor, ME 04609 USA (United States); Lago, Briony A., E-mail: lagoba@mcmaster.ca [M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, Hamilton, ON L8S 4K1 (Canada); McArthur, Andrew G., E-mail: mcarthua@mcmaster.ca [M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, Hamilton, ON L8S 4K1 (Canada); Raphenya, Amogelang R., E-mail: raphenar@mcmaster.ca [M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, Hamilton, ON L8S 4K1 (Canada); Pray, Nicholas, E-mail: pray.nicholas@gmail.com [Biology Department, Bates College, 44 Campus Avenue, Lewiston, ME 04240 (United States); Saleem, Nabil, E-mail: nabilsaleem@gmail.com [Biology Department, Bates College, 44 Campus Avenue, Lewiston, ME 04240 (United States); The MDI Biological Laboratory, 159 Old Bar Harbor Road, Bar Harbor, ME 04609 USA (United States); Salas, Sophia, E-mail: sophia.salas2@gmail.com [Biology Department, Bates College, 44 Campus Avenue, Lewiston, ME 04240 (United States); The MDI Biological Laboratory, 159 Old Bar Harbor Road, Bar Harbor, ME 04609 USA (United States); Paulson, Katherine, E-mail: krpaulson@gmail.com [Biology Department, Bates College, 44 Campus Avenue, Lewiston, ME 04240 (United States); The MDI Biological Laboratory, 159 Old Bar Harbor Road, Bar Harbor, ME 04609 USA (United States); Mangar, Roshni S., E-mail: rmangar@coa.edu [The MDI Biological Laboratory, 159 Old Bar Harbor Road, Bar Harbor, ME 04609 USA (United States); College of the Atlantic, 105 Eden Street, Bar Harbor, ME 04609 (United States); and others

    2016-11-15

    Highlights: • Nfe2 is involved in erythropoiesis in zebrafish. • Nfe2 is a novel regulator of pro-oxidant induced oxidative stress. • Embryos mount a molecularly unique oxidative stress response compared to larvae. • Nfe2 regulates a wide-variety of genes beyond erythropoiesis. - Abstract: Development is a complex and well-defined process characterized by rapid cell proliferation and apoptosis. At this stage in life, a developmentally young organism is more sensitive to toxicants as compared to an adult. In response to pro-oxidant exposure, members of the Cap’n’Collar (CNC) basic leucine zipper (b-ZIP) transcription factor family (including Nfe2 and Nfe2-related factors, Nrfs) activate the expression of genes whose protein products contribute to reduced toxicity. Here, we studied the role of the CNC protein, Nfe2, in the developmental response to pro-oxidant exposure in the zebrafish (Danio rerio). Following acute waterborne exposures to diquat or tert-buytlhydroperoxide (tBOOH) at one of three developmental stages, wildtype (WT) and nfe2 knockout (KO) embryos and larvae were morphologically scored and their transcriptomes sequenced. Early in development, KO animals suffered from hypochromia that was made more severe through exposure to pro-oxidants; this phenotype in the KO may be linked to decreased expression of alas2, a gene involved in heme synthesis. WT and KO eleutheroembryos and larvae were phenotypically equally affected by exposure to pro-oxidants, where tBOOH caused more pronounced phenotypes as compared to diquat. Comparing diquat and tBOOH exposed embryos relative to the WT untreated control, a greater number of genes were up-regulated in the tBOOH condition as compared to diquat (tBOOH: 304 vs diquat: 148), including those commonly found to be differentially regulated in the vertebrate oxidative stress response (OSR) (e.g. hsp70.2, txn1, and gsr). When comparing WT and KO across all treatments and times, there were 1170 genes that were

  17. Regulated expression of the overlapping ubiquitous and erythroid transcription units of the human porphobilinogen deaminase (PBG-D) gene introduced into non-erythroid and erythroid cells.

    Science.gov (United States)

    Raich, N; Mignotte, V; Dubart, A; Beaupain, D; Leboulch, P; Romana, M; Chabret, C; Charnay, P; Papayannopoulou, T; Goossens, M

    1989-06-15

    The human gene coding for porphobilinogen deaminase (PBG-D) is transcribed into two distinct transcription units giving two mRNAs. These units originate from two adjacent promoters distant of 3 kilobase pairs. The upstream promoter is active in all cell types, whereas the downstream promoter is active only in erythroid cells. We have studied the expression of this gene either after introduction of the corresponding human chromosome into murine erythroid cells using somatic hybrids or after transfection into both erythroid and non-erythroid cells. Using somatic hybrids, we showed that activation of the erythroid-specific promoter of the PBG-D gene did not reduce the rate of initiation of the ubiquitous promoter. Transfection experiments in erythroid cells showed that the PBG-D erythroid transcription unit, controlled by the PBG-D erythroid promoter, was correctly transcribed and regulated. Furthermore, we found that the PBG-D erythroid promoter alone was sufficient for correct expression and regulation of a reporter gene during erythroid differentiation. When the human PBG-D gene was transfected into non-erythroid cells, only the ubiquitous promoter was active. Deletion of the ubiquitous promoter did not lead to any activation of the erythroid promoter, suggesting that its inactivity in non-erythroid cells was not due to promoter occlusion but to a strict erythroid specificity.

  18. Nuclear factor E2-related factor 2 knockdown enhances glucose uptake and alters glucose metabolism in AML12 hepatocytes.

    Science.gov (United States)

    Yuan, Xiaoyang; Huang, Huijing; Huang, Yi; Wang, Jinli; Yan, Jinhua; Ding, Ling; Zhang, Cuntai; Zhang, Le

    2017-05-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce the expression of a variety of antioxidant and detoxification genes. Recently, increasing evidence has revealed roles for Nrf2 in glucose, lipid, and energy metabolism; however, the exact functions of Nrf2 in hepatocyte biology are largely unclear. In the current study, the transient knockdown of Nrf2 via siRNA transfection enhanced the glucose uptake of fasting AML12 hepatocytes to 325.3 ± 11.1% ( P glucose metabolism were then examined in AML12 cells under both high-glucose (33 mmol/L) and low-glucose (4.5 mmol/L) conditions. NK lowered the gene and protein expression of the anti-oxidases heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 and increased p-eukaryotic initiation factor-2α S51 , p-nuclear factor-κB p65 S276 , and its downstream proinflammatory factors, including interleukin-1 beta, tumor necrosis factor-α, matrix metalloproteinase 2, and matrix metalloproteinase 9, at the protein level. NK also altered the protein expression of fibroblast growth factor 21, glucose transporter type 4, insulin-like growth factor 1, forkhead box protein O1, p-AKT S473 , and p-GSK3α/β Y279/Y216 , which are involved in glucose uptake, glycogenesis, and gluconeogenesis in AML12 cells. Our results provide a comprehensive understanding of the central role of Nrf2 in the regulation of glucose metabolism in AML12 hepatocytes, in addition to its classical roles in the regulation of redox signaling, endoplasmic reticulum stress and proinflammatory responses, and support the potential of Nrf2 as a therapeutic target for the prevention and treatment of obesity and other associated metabolic syndromes. Impact statement Increasing evidence supports the complexity of Nrf2 functions beyond the antioxidant and detoxification response. Previous in vivo studies employing either Nrf2-knockout or Nrf2-activated mice have achieved a similar endpoint: protection against an obese and

  19. Centella asiatica Fraction-3 Suppresses the Nuclear Factor Erythroid 2-Related Factor 2 Anti-Oxidant Pathway and Enhances Reactive Oxygen Species-Mediated Cell Death in Cancerous Lung A549 Cells.

    Science.gov (United States)

    Naidoo, Dhaneshree Bestinee; Phulukdaree, Alisa; Anand, Krishnan; Sewram, Vikash; Chuturgoon, Anil Amichund

    2017-10-01

    Centella asiatica is a tropical medicinal plant that is commonly used in traditional medicine. Medicinal properties of C. asiatica include anti-oxidant, anti-inflammatory, and anti-cancer activity. We investigated the anti-oxidant and anti-proliferative/cytotoxic effects of a semi-purified fraction of C. asiatica ethanolic leaf extract (C3) in cancerous lung A549 cells. C3 was obtained by silica column fractionation and identified by using thin-layer chromatography and gas chromatography mass spectrometry. Cytotoxicity of C3 in A549 cells was evaluated (cell viability assay-WST-1; 24 h; [0.2-3 mg/mL]) to determine an inhibitory concentration (IC 50 ). Intracellular reactive oxygen species (IROS), mitochondrial membrane potential (flow cytometry), malondialdehyde (MDA), lactate dehydrogenase (LDH) (spectrophotometry), glutathione (GSH), oxidised glutathione (GSSG), adenosine triphosphate levels, caspase activity (luminometry), and DNA damage (comet assay) were evaluated. Protein expression (Nrf-2, p53, Bax, Bcl-2, and HSP-70) and gene expression (Nrf-2, GPx, SOD, CAT, c-myc, and OGG-1) were quantified by western blotting and quantitative polymerase chain reaction (qPCR), respectively. C3 dose dependently decreased A549 cell viability. The IC 50 of C3 increased MDA, IROS, mitochondrial depolarization, LDH, caspase (-8, -9, -3/7) activity, DNA damage, GSH levels, Nrf-2 protein expression, HSP-70 protein expression, and OGG-1 gene expression (P < .05). GSSG levels, anti-oxidant (Nrf-2, GPx, SOD) gene expression, p53, Bax, and Bcl-2 protein expression were decreased by C3 (P < .02). C3 diminished the anti-oxidant gene expression and induced anti-proliferative/cytotoxic effects in A549 cells.

  20. PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis.

    Science.gov (United States)

    Ryu, Moon-Suhn; Zhang, Deliang; Protchenko, Olga; Shakoury-Elizeh, Minoo; Philpott, Caroline C

    2017-05-01

    Developing erythrocytes take up exceptionally large amounts of iron, which must be transferred to mitochondria for incorporation into heme. This massive iron flux must be precisely controlled to permit the coordinated synthesis of heme and hemoglobin while avoiding the toxic effects of chemically reactive iron. In cultured animal cells, iron chaperones poly rC-binding protein 1 (PCBP1) and PCBP2 deliver iron to ferritin, the sole cytosolic iron storage protein, and nuclear receptor coactivator 4 (NCOA4) mediates the autophagic turnover of ferritin. The roles of PCBP, ferritin, and NCOA4 in erythroid development remain unclear. Here, we show that PCBP1, NCOA4, and ferritin are critical for murine red cell development. Using a cultured cell model of erythroid differentiation, depletion of PCBP1 or NCOA4 impaired iron trafficking through ferritin, which resulted in reduced heme synthesis, reduced hemoglobin formation, and perturbation of erythroid regulatory systems. Mice lacking Pcbp1 exhibited microcytic anemia and activation of compensatory erythropoiesis via the regulators erythropoietin and erythroferrone. Ex vivo differentiation of erythroid precursors from Pcbp1-deficient mice confirmed defects in ferritin iron flux and heme synthesis. These studies demonstrate the importance of ferritin for the vectorial transfer of imported iron to mitochondria in developing red cells and of PCBP1 and NCOA4 in mediating iron flux through ferritin.

  1. The role of nuclear factor E2-Related factor 2 and uncoupling protein 2 in glutathione metabolism: Evidence from an in vivo gene knockout study

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yanyan [The First Affiliated Hospital, China Medical University, Shenyang, Liaoning (China); The Hamner Institutes for Health Sciences, Research Triangle Park, NC (United States); Xu, Yuanyuan, E-mail: yyxu@cmu.edu.cn [School of Public Health, China Medical University, Shenyang, Liaoning (China); Zheng, Hongzhi [The First Affiliated Hospital, China Medical University, Shenyang, Liaoning (China); The Hamner Institutes for Health Sciences, Research Triangle Park, NC (United States); Fu, Jingqi; Hou, Yongyong; Wang, Huihui [School of Public Health, China Medical University, Shenyang, Liaoning (China); Zhang, Qiang [Rollins School of Public Health, Emory University, Atlanta, GA (United States); Yamamoto, Masayuki [Graduate School of Medicine, Tohoku University, Sendai (Japan); Pi, Jingbo, E-mail: jbpi@cmu.edu.cn [School of Public Health, China Medical University, Shenyang, Liaoning (China); The Hamner Institutes for Health Sciences, Research Triangle Park, NC (United States)

    2016-09-09

    Nuclear factor E2-related factor 2 (NRF2) and uncoupling protein 2 (UCP2) are indicated to protect from oxidative stress. They also play roles in the homeostasis of glutathione. However, the detailed mechanisms are not well understood. In the present study, we found Nrf2-knockout (Nrf2-KO) mice exhibited altered glutathione homeostasis and reduced expression of various genes involved in GSH biosynthesis, regeneration, utilization and transport in the liver. Ucp2-knockout (Ucp2-KO) mice exhibited altered glutathione homeostasis in the liver, spleen and blood, as well as increased transcript of cystic fibrosis transmembrane conductance regulator in the liver, a protein capable of mediating glutathione efflux. Nrf2-Ucp2-double knockout (DKO) mice showed characteristics of both Nrf2-KO and Ucp2-KO mice. But no significant difference was observed in DKO mice when compared with Nrf2-KO or Ucp2-KO mice, except in blood glutathione levels. These data suggest that ablation of Nrf2 and Ucp2 leads to disrupted GSH balance, which could result from altered expression of genes involved in GSH metabolism. DKO may not evoke more severe oxidative stress than the single gene knockout. - Highlights: • Nrf2/Ucp2 deficiency leads to alteration of glutathione homeostasis. • Nrf2 regulates expression of genes in glutathione generation and utilization. • Ucp2 affects glutathione metabolism by regulating hepatic efflux of glutathione. • Nrf2 deficiency may not aggravate oxidative stress in Ucp2-deficient mice.

  2. The role of nuclear factor E2-Related factor 2 and uncoupling protein 2 in glutathione metabolism: Evidence from an in vivo gene knockout study

    International Nuclear Information System (INIS)

    Chen, Yanyan; Xu, Yuanyuan; Zheng, Hongzhi; Fu, Jingqi; Hou, Yongyong; Wang, Huihui; Zhang, Qiang; Yamamoto, Masayuki; Pi, Jingbo

    2016-01-01

    Nuclear factor E2-related factor 2 (NRF2) and uncoupling protein 2 (UCP2) are indicated to protect from oxidative stress. They also play roles in the homeostasis of glutathione. However, the detailed mechanisms are not well understood. In the present study, we found Nrf2-knockout (Nrf2-KO) mice exhibited altered glutathione homeostasis and reduced expression of various genes involved in GSH biosynthesis, regeneration, utilization and transport in the liver. Ucp2-knockout (Ucp2-KO) mice exhibited altered glutathione homeostasis in the liver, spleen and blood, as well as increased transcript of cystic fibrosis transmembrane conductance regulator in the liver, a protein capable of mediating glutathione efflux. Nrf2-Ucp2-double knockout (DKO) mice showed characteristics of both Nrf2-KO and Ucp2-KO mice. But no significant difference was observed in DKO mice when compared with Nrf2-KO or Ucp2-KO mice, except in blood glutathione levels. These data suggest that ablation of Nrf2 and Ucp2 leads to disrupted GSH balance, which could result from altered expression of genes involved in GSH metabolism. DKO may not evoke more severe oxidative stress than the single gene knockout. - Highlights: • Nrf2/Ucp2 deficiency leads to alteration of glutathione homeostasis. • Nrf2 regulates expression of genes in glutathione generation and utilization. • Ucp2 affects glutathione metabolism by regulating hepatic efflux of glutathione. • Nrf2 deficiency may not aggravate oxidative stress in Ucp2-deficient mice.

  3. Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

    Science.gov (United States)

    Kulkarni, Supriya R.; Donepudi, Ajay C.; Xu, Jialin; Wei, Wei; Cheng, Qiuqiong C.; Driscoll, Maureen V.; Johnson, Delinda A.; Johnson, Jeffrey A.; Li, Xiaoling

    2014-01-01

    Abstract Aims: The purpose of this study was to determine whether 3′-5′-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2–4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2- and SIRT1–dependent mechanisms. In intact mouse liver, fasting induces NRF2 target gene expression by at least 1.5 to 5-fold. In mouse and human hepatocytes, treatment with 8-Bromoadenosine-cAMP, a cAMP analogue, increased NRF2 target gene expression and antioxidant response element activity, which was decreased by the PKA inhibitor, H-89. Moreover, fasting induced NRF2 target gene expression was decreased in liver and hepatocytes of SIRT1 liver-specific null mice and NRF2-null mice. Lastly, NRF2 and SIRT1 were recruited to MAREs and Antioxidant Response Elements (AREs) in the human ABCC2 promoter. Innovation: Oxidative stress mediated NRF2 activation is well described, yet the influence of basic metabolic processes on NRF2 activation is just emerging. Conclusion: The current data point toward a novel role of nutrient status in regulation of NRF2 activity and the antioxidant response, and indicates that cAMP/PKA and SIRT1 are upstream regulators for fasting-induced activation of the NRF2-ARE pathway. Antioxid. Redox Signal. 20, 15–30. PMID:23725046

  4. Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative Stress-Induced Pancreatic β-Cell Damage

    Directory of Open Access Journals (Sweden)

    Jingqi Fu

    2015-01-01

    Full Text Available Oxidative stress is implicated in the pathogenesis of pancreatic β-cell dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2-related factor 2 (NRF2 is a master regulator in the cellular adaptive response to oxidative stress. The present study found that MIN6 β-cells with stable knockdown of Nrf2 (Nrf2-KD and islets isolated from Nrf2-knockout mice expressed substantially reduced levels of antioxidant enzymes in response to a variety of stressors. In scramble MIN6 cells or wild-type islets, acute exposure to oxidative stressors, including hydrogen peroxide (H2O2 and S-nitroso-N-acetylpenicillamine, resulted in cell damage as determined by decrease in cell viability, reduced ATP content, morphology changes of islets, and/or alterations of apoptotic biomarkers in a concentration- and/or time-dependent manner. In contrast, silencing of Nrf2 sensitized MIN6 cells or islets to the damage. In addition, pretreatment of MIN6 β-cells with NRF2 activators, including CDDO-Im, dimethyl fumarate (DMF, and tert-butylhydroquinone (tBHQ, protected the cells from high levels of H2O2-induced cell damage. Given that reactive oxygen species (ROS are involved in regulating glucose-stimulated insulin secretion (GSIS and persistent activation of NRF2 blunts glucose-triggered ROS signaling and GSIS, the present study highlights the distinct roles that NRF2 may play in pancreatic β-cell dysfunction that occurs in different stages of diabetes.

  5. Nuclear Factor E2-Related Factor-2 Negatively Regulates NLRP3 Inflammasome Activity by Inhibiting Reactive Oxygen Species-Induced NLRP3 Priming.

    Science.gov (United States)

    Liu, Xiuting; Zhang, Xin; Ding, Yang; Zhou, Wei; Tao, Lei; Lu, Ping; Wang, Yajing; Hu, Rong

    2017-01-01

    The NLRP3 inflammasome is a multiprotein complex that protects hosts against a variety of pathogens. However, the molecular mechanisms of modulating NLRP3 inflammasome activation, especially at the priming step, are still poorly understood. This study was designed to elucidate the negative regulation of nuclear factor E2-related factor-2 (Nrf2) on the activation of NLRP3 inflammasome. We reported that Nrf2 activation inhibited NLRP3 expression, caspase-1 cleavage, and subsequent IL-1β generation. Compared with normal cells, Nrf2-deficient cells showed upregulated cleaved caspase-1, which were attributed to the increased transcription of NLRP3 caused by excess reactive oxygen species (ROS). Furthermore, priming of the NLRP3 inflammasome was sensitive to the exogenous ROS levels induced by H 2 O 2 or rotenone. Combined with adenosine triphosphate, rotenone triggered higher activity of the NLRP3 inflammasome compared with lipopolysaccharide, suggesting that ROS promoted the priming step. In addition, Nrf2-induced NQO1 was involved in the inhibition of the NLRP3 inflammasome. In an in vivo alum-induced peritonitis mouse model, Nrf2 activation suppressed typical IL-1 signaling-dependent inflammation, whereas Nrf2 -/- mice exhibited a significant increase in the recruitment of immune cell and the generation of IL-1β compared with wild-type mice. We elucidated the effects and possible mechanisms of Nrf2 activation-induced NQO1 expression on NLRP3 inflammasome inactivation and established a novel regulatory role of the Nrf2 pathway in ROS-induced NLRP3 priming. We demonstrated Nrf2 negatively regulating NLRP3 inflammasome activity by inhibiting the priming step and suggested that Nrf2 could be a potential target for some uncontrolled inflammasome activation-associated diseases. Antioxid. Redox Signal. 26, 28-43.

  6. Nuclear factor E2-related factor 2’s activation in transgenic mice fed with high dosage of fish oil.

    Directory of Open Access Journals (Sweden)

    Elena Mariani

    2016-06-01

    Full Text Available Some fatty acids, such as CLA (conjugated linoleic acid and n-3 fatty acids modulate immune and inflammatory response in ruminants and monogastrics; their supplementation alters fatty acids profile of meat and milk, enhancing their nutritional quality. However, it is still unclear if their addition causes oxidative damage to animals. Nuclear factor E2-related factor 2 (Nrf2 plays an important role in cellular defenses against oxidative stress, indeed it produces a rapid induction of its target genes involved in antioxidant response. The aim of the project is to investigate the activation of Nrf2 in luciferase reporter mice fed different amount of n-3 PUFA in the diet (7,5% lard, 7,5% tuna oil, 20 % lard and 20%tuna oil. Forty-eight reporter mice are divided into three groups: male, intact female and ovariectomized female. Each group is split in four subgroups fed different diets. Oxidative status will be studied monitoring Nrf2’s activation with in vivo bioluminescent imaging. The inflammatory and immune response will be assessed using calprotectin and lactoferrin levels in faecal samples that are non-invasive techniques. The trial is still in progress: on the 62nd day, animals will be sacrificed after a challenge in order to measure the different effects of diets and +/- oestrogen on stress response. Finally, the post mortem analysis will be carried on extract organs. Data obtained will be analysed using statistical procedures and results will improve the knowledge about interaction between omega-3 fatty acids and animals’ oxidative status.

  7. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bei [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Department of Histology and Embryology, College of Basic Medical Sciences, China Medical University, Shenyang 110001 (China); Fu, Jingqi; Zheng, Hongzhi; Xue, Peng; Yarborough, Kathy; Woods, Courtney G.; Hou, Yongyong; Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2012-11-01

    Chronic human exposure to inorganic arsenic (iAs), a potent environmental oxidative stressor, is associated with increased prevalence of type 2 diabetes, where impairment of pancreatic β-cell function is a key pathogenic factor. Nuclear factor E2-related factor 2 (Nrf2) is a central transcription factor regulating cellular adaptive response to oxidative stress. However, persistent activation of Nrf2 in response to chronic oxidative stress, including inorganic arsenite (iAs{sup 3+}) exposure, blunts glucose-triggered reactive oxygen species (ROS) signaling and impairs glucose-stimulated insulin secretion (GSIS). In the current study, we found that MIN6 pancreatic β-cells with stable knockdown of Nrf2 (Nrf2-KD) by lentiviral shRNA and pancreatic islets isolated from Nrf2-knockout (Nrf2−/−) mice exhibited reduced expression of several antioxidant and detoxification enzymes in response to acute iAs{sup 3+} exposure. As a result, Nrf2-KD MIN6 cells and Nrf2−/− islets were more susceptible to iAs{sup 3+} and monomethylarsonous acid (MMA{sup 3+})-induced cell damage, as measured by decreased cell viability, augmented apoptosis and morphological change. Pretreatment of MIN6 cells with Nrf2 activator tert-butylhydroquinone protected the cells from iAs{sup 3+}-induced cell damage in an Nrf2-dependent fashion. In contrast, antioxidant N‐acetyl cysteine protected Nrf2-KD MIN6 cells against acute cytotoxicity of iAs{sup 3+}. The present study demonstrates that Nrf2-mediated antioxidant response is critical in the pancreatic β-cell defense mechanism against acute cytotoxicity by arsenic. The findings here, combined with our previous results on the inhibitory effect of antioxidants on ROS signaling and GSIS, suggest that Nrf2 plays paradoxical roles in pancreatic β-cell dysfunction induced by environmental arsenic exposure. -- Highlights: ► Lack of Nrf2 reduced expression of antioxidant genes induced by iAs{sup 3+} in β-cells. ► Deficiency of Nrf2 in

  8. Nuclear factor E2-related factor 2’s activation in transgenic mice fed with dosage of saturated or unsaturated fatty acids using in vivo bioluminescent imaging

    Directory of Open Access Journals (Sweden)

    Elena Mariani

    2017-05-01

    Full Text Available To counteract oxidative stress cells developed several mechanisms, including the transcription factor Nuclear Factor E2-related factor 2 (Nrf2. The aim of the study was to evaluate the activation of Nrf2 in transgenic mice fed saturated or polyunsaturated fatty acids and the anti-inflammatory effect of estrogens on organism. Forty-eight ARE CRE OMO reporter mice were divided into 3 groups, consisting of 16 animals, based on presence/absence of estrogens (ovariectomized or sham female, OVX - SH; male, MA. Each group was further split in 4 subgroups of 4 animals each and fed different diets (7.5% lard, 7.5% tuna oil, 20.0 % lard and 20.0% tuna oil. Two times a week animals were anaesthetized and injected i.p. with 100µL luciferin 15 min before the imaging session. Using the Living Image Software, photon emission was mapped for selected body areas. On day 70, animals were sacrificed after a challenge with Sodium Arsenite. Specific organs were dissected and immediately subjected to ex vivo imaging session. MIXED and GLM procedures of SAS software were used for statistical analysis. Dietary treatments did not affect body weight and feed intake as well as Nrf2 expression in both pre- and post-challenge phases, with the exception of the abdominal region (P=0.031 pre-challenge; in this area, during the pre-challenge phase, OVX showed lower Nrf2 activation (P<0.001. Ex vivo results outlined a significant effect of the challenge on all the considered organs (P<0.001, while OVX subjects had higher Nrf2 expression on urinary bladder and kidney (P<0.05 and high fat diet increased Nrf2 in urinary bladder (P<0.05. The present trial shows how saturated or polyunsaturated fatty acids supplementation in the diet do not exert significant effects on oxidative stress in mice, but confirms the protective role of estrogens under physiological condition.

  9. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) drug discovery: Biochemical toolbox to develop NRF2 activators by reversible binding of Kelch-like ECH-associated protein 1 (KEAP1).

    Science.gov (United States)

    Bresciani, Alberto; Missineo, Antonino; Gallo, Mariana; Cerretani, Mauro; Fezzardi, Paola; Tomei, Licia; Cicero, Daniel Oscar; Altamura, Sergio; Santoprete, Alessia; Ingenito, Raffaele; Bianchi, Elisabetta; Pacifici, Robert; Dominguez, Celia; Munoz-Sanjuan, Ignacio; Harper, Steven; Toledo-Sherman, Leticia; Park, Larry C

    2017-10-01

    Mechanisms that activate innate antioxidant responses, as a way to mitigate oxidative stress at the site of action, hold much therapeutic potential in diseases, such as Parkinson's disease, Alzheimer's disease and Huntington's disease, where the use of antioxidants as monotherapy has not yielded positive results. The nuclear factor NRF2 is a transcription factor whose activity upregulates the expression of cell detoxifying enzymes in response to oxidative stress. NRF2 levels are modulated by KEAP1, a sensor of oxidative stress. KEAP1 binds NRF2 and facilitates its ubiquitination and subsequent degradation. Recently, compounds that reversibly disrupt the NRF2-KEAP1 interaction have been described, opening the field to a new era of safer NRF2 activators. This paper describes a set of new, robust and informative biochemical assays that enable the selection and optimization of non-covalent KEAP1 binders. These include a time-resolved fluorescence resonance energy transfer (TR-FRET) primary assay with high modularity and robustness, a surface plasmon resonance (SPR) based KEAP1 direct binding assay that enables the quantification and analysis of full kinetic binding parameters and finally a 1 H- 15 N heteronuclear single quantum coherence (HSQC) NMR assay suited to study the interaction surface of KEAP1 with residue-specific information to validate the interaction of ligands in the KEAP1 binding site. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Enhancement of erythroid colony growth in culture by hemin

    International Nuclear Information System (INIS)

    Porter, P.N.; Meints, R.H.; Mesner, K.

    1979-01-01

    Hemin was found to enhance the growth of murine erythroid colonies in culture. In the presence of 100 mU/ml erythropoietin (EPO), the addition of hemin (0.05-0.2 mM) resulted in the growth of twice as many colonies as were obtained with EPO alone. Hemin also significantly increased erythroid colony formation in culture in the absence of added EPO. Hemoblobin synthesis as measured by the incorporation of 59 Fe into cyclohexanone extractable heme was augmented in culture by hemin. Neither Δ-aminolevulinic acid, a hemin precursor, nor FeCl 3 increased colony number. (author)

  11. Circulating granulocytic and erythroid progenitor cells in chronic granulocytic leukaemia.

    Science.gov (United States)

    Goldman, J M; Shiota, F; Th'ng, K H; Orchard, K H

    1980-09-01

    We used a standard methyl cellulose method to assay erythroid progenitor cells in the blood of 35 patients with untreated CGL and of 18 normal controls. In 28 patients we simultaneously assayed granulocyte/monocyte committed progenitor cells (CFU-c) by an agar method. Circulating erythroid burst-forming units (BFU-e) in CGL were increased above normal by a factor of about 180; CFU-c were increased by a factor of about 9000. Both BFU-e and CFU-c numbers were linearly related to the total leucocyte count in individual patients but not to numbers of circulating blast cells. There was a positive correlation in individual patients between CFU-c and BFU-e numbers. Circulating BFU-e and erythroid colony-forming cells (CFU-e) were unable to proliferate in vitro in the absence of erythropoietin. We conclude that erythroid progenitor cells are involved in the 'clonal expansion' that characterizes CGL, but apparently to a lesser extent than are granulocyte/moonocyte progenitor cells.

  12. TMEM14C is required for erythroid mitochondrial heme metabolism.

    Science.gov (United States)

    Yien, Yvette Y; Robledo, Raymond F; Schultz, Iman J; Takahashi-Makise, Naoko; Gwynn, Babette; Bauer, Daniel E; Dass, Abhishek; Yi, Gloria; Li, Liangtao; Hildick-Smith, Gordon J; Cooney, Jeffrey D; Pierce, Eric L; Mohler, Kyla; Dailey, Tamara A; Miyata, Non; Kingsley, Paul D; Garone, Caterina; Hattangadi, Shilpa M; Huang, Hui; Chen, Wen; Keenan, Ellen M; Shah, Dhvanit I; Schlaeger, Thorsten M; DiMauro, Salvatore; Orkin, Stuart H; Cantor, Alan B; Palis, James; Koehler, Carla M; Lodish, Harvey F; Kaplan, Jerry; Ward, Diane M; Dailey, Harry A; Phillips, John D; Peters, Luanne L; Paw, Barry H

    2014-10-01

    The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias.

  13. Acute erythroid leukemia: autopsy report of a rare disease

    Directory of Open Access Journals (Sweden)

    Cristiane Rúbia Ferreira

    2011-12-01

    Full Text Available Acute erythroid leukemia (AEL is a rare subtype of acute myeloid leukemia(AML, characterized by predominant erythroid proliferation. The 2008 WorldHealth Organization (WHO classification of AML defined two AEL subtypes:erythroleukaemia (EL, in which erythroid precursors account for 50% or moreof all nucleated bone marrow cells and myeloblasts account for 20% or more ofthe nonerythroid cell population; and pure erythroid leukemia (PEL, in whicherythroid precursors account for 80% or more of all nucleated bone marrowcells. We report the case of an elderly female patient with wasting syndromeand pancytopenia without evidence of blasts in peripheral blood. A diagnosisof PEL was established on the basis of bone marrow biopsy findings. Thepatient died on postadmission day 20, and an autopsy was performed. Wereclassified the disease as EL on the basis of the autopsy findings, whichincluded myeloblasts accounting for more than 20% of the nonerythroid cellsin the bone marrow, as well as leukemic infiltration and myeloid metaplasia insolid organs, such as the liver, spleen, kidneys, adrenal glands, and abdominallymph nodes. A rare disease, AEL accounts for less than 5% of all AMLs and ispractically a diagnosis of exclusion. Autopsy reports of AEL are extremely rarein the literature. We demonstrate that in the case reported here, leukemia cellstended to infiltrate solid organs with myeloid metaplasia. Our findings alsoshow that a larger neoplastic bone marrow sample is crucial to the correctdiagnosis of EL, which is based on morphological and quantitative criteria.

  14. The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiao-Fei; Wu, Xiao-Rong; Xue, Ming; Wang, Yan; Wang, Jie; Li, Yang; Suriguga,; Zhang, Guang-Yao; Yi, Zong-Chun, E-mail: yizc@buaa.edu.cn

    2012-11-15

    Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes. -- Highlights: ► Catechol enhanced hemin-induced hemoglobin accumulation. ► Exposure to catechol resulted in up-regulated expression of erythroid genes. ► Catechol reduced methylation levels at some CpG sites in erythroid genes.

  15. The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells

    International Nuclear Information System (INIS)

    Li, Xiao-Fei; Wu, Xiao-Rong; Xue, Ming; Wang, Yan; Wang, Jie; Li, Yang; Suriguga,; Zhang, Guang-Yao; Yi, Zong-Chun

    2012-01-01

    Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes. -- Highlights: ► Catechol enhanced hemin-induced hemoglobin accumulation. ► Exposure to catechol resulted in up-regulated expression of erythroid genes. ► Catechol reduced methylation levels at some CpG sites in erythroid genes.

  16. TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells

    Directory of Open Access Journals (Sweden)

    Ashley C. Kramer

    2017-02-01

    Full Text Available Metabolism of oxidative stress is necessary for cellular survival. We have previously utilized the zebrafish as a model of the oxidative stress response. In this study, we found that gata1-expressing erythroid cells contributed to a significant proportion of total-body oxidative stress when animals were exposed to a strong pro-oxidant. RNA-seq of zebrafish under oxidative stress revealed the induction of tp53. Zebrafish carrying tp53 with a mutation in its DNA-binding domain were acutely sensitive to pro-oxidant exposure and displayed significant reactive oxygen species (ROS and tp53-independent erythroid cell death resulting in an edematous phenotype. We found that a major contributing factor to ROS was increased basal mitochondrial respiratory rate without reserve. These data add to the concept that tp53, while classically a tumor suppressor and cell-cycle regulator, has additional roles in controlling cellular oxidative stress.

  17. Development and differentiation of the erythroid lineage in mammals

    OpenAIRE

    Barminko, Jeffrey; Reinholt, Brad; Baron, Margaret H.

    2015-01-01

    The red blood cell (RBC) is responsible for performing the highly specialized function of oxygen transport, making it essential for survival during gestation and postnatal life. Establishment of sufficient RBC numbers, therefore, has evolved to be a major priority of the postimplantation embryo. The “primitive” erythroid lineage is the first to be specified in the developing embryo proper. Significant resources are dedicated to producing RBCs throughout gestation. Two transient and morphologi...

  18. LAMA2-related myopathy

    DEFF Research Database (Denmark)

    Løkken, Nicoline; Born, Alfred Peter; Duno, Morten

    2015-01-01

    INTRODUCTION: Muscular dystrophy caused by LAMA2-gene mutations is an autosomal recessive disease typically presenting as a severe, early-onset congenital muscular dystrophy (CMD). However, milder cases with a limb-girdle type muscular dystrophy (LGMD) have been described. METHODS: In this study......, we assessed the frequency and phenotypic spectrum of LAMA2-related muscular dystrophy in CMD (n = 18) and LGMD2 (n = 128) cohorts identified in the last 15 years in eastern Denmark. The medical history, brain-MRI, muscle pathology, muscle laminin-α2 expression, and genetic analyses were assessed....... RESULTS: Molecular genetics revealed 2 pathogenic LAMA2 mutations in 5 of 18 CMD and 3 of 128 LGMD patients, corresponding to a LAMA2-mutation frequency of 28% in the CMD and 2.3% in the LGMD cohorts, respectively. CONCLUSIONS: This study demonstrates a wide clinical spectrum of LAMA2-related muscular...

  19. The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells.

    Science.gov (United States)

    Li, Xiao-Fei; Wu, Xiao-Rong; Xue, Ming; Wang, Yan; Wang, Jie; Li, Yang; Suriguga; Zhang, Guang-Yao; Yi, Zong-Chun

    2012-11-15

    Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. The uniqueness of morphological features of pure erythroid leukemia in myeloid neoplasm with erythroid predominance: A reassessment using criteria revised in the 2016 World Health Organization classification

    OpenAIRE

    Ko, Po-Shen; Liu, Yao-Chung; Yeh, Chiu-Mei; Gau, Jyh-Pyng; Yu, Yuan-Bin; Hsiao, Liang-Tsai; Tzeng, Cheng-Hwai; Chen, Po-Min; Chiou, Tzeon-Jye; Liu, Chia-Jen; Liu, Jin-Hwang

    2017-01-01

    We reviewed 97 consecutive cases of myeloid neoplasm with erythroid predominance (MN-EP) between 2000 and 2015. Following 2016 WHO classification, MN-EP patients were classified into four groups. Eight pure erythroid leukemia (PEL) (including t-MN and AML-MRC morphologically fulfilled criteria for PEL) patients had dismal outcomes (median OS: 1 month) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis than the other gr...

  1. A reevaluation of erythroid predominance in Acute Myeloid Leukemia using the updated WHO 2016 Criteria.

    Science.gov (United States)

    Margolskee, Elizabeth; Mikita, Geoff; Rea, Bryan; Bagg, Adam; Zuo, Zhuang; Sun, Yi; Goswami, Maitrayee; Wang, Sa A; Oak, Jean; Arber, Daniel A; Allen, M Brandon; George, Tracy I; Rogers, Heesun J; Hsi, Eric; Hasserjian, Robert P; Orazi, Attilio

    2018-02-05

    The 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO. We retrospectively identified patients with ≥50% erythroid precursors and either ≥20% bone marrow blasts or ≥20% peripheral blood blasts at the time of initial diagnosis at seven major academic centers. Laboratory and clinical data were obtained. Patients were then reclassified according to 2016 WHO guidelines. A matched control group was also obtained. We identified 146 patients with acute myeloid leukemia with erythroid predominance (62% M, average age: 62 y, range: 5-93 y). Of these, 91 were acute myeloid leukemia with myelodysplasia-related changes, 20 (14%) were therapy-related myeloid neoplasm, 23 (16%) acute myeloid leukemia, not otherwise specified, and ten acute myeloid leukemia with recurrent cytogenetic/molecular abnormalities. The bone marrow blast count ranged from 9-41%. There was no difference in survival for patients with erythroid predominance compared to patients with acute myeloid leukemia without erythroid proliferations. In a multivariable analysis, cytogenetic risk was the only significant predictor of survival. We find a significantly lower rate of FLT3 and RAS pathway alterations in acute myeloid leukemia with erythroid predominance compared to controls. Our study is one of the first to apply the 2016 WHO guidelines for classification of acute myeloid leukemia. We find acute myeloid leukemia with erythroid

  2. Expression of assayable residual stem cell damage in erythroid differentiation

    International Nuclear Information System (INIS)

    Huebner, G.E.; Miller, M.E.; Cronkite, E.P.

    1985-01-01

    In rodents, residual damage is inducible in hematopoietic stem cells by exposure to ionizing radiation or alkylating agents. This damage can b e assayed in mice by transferring bone marrow into lethally irradiated syngeneic recipients and subsequently measuring the incremental increase of-( 125 I)iodo-2'-deoxyuridine incorporation in spleens. In this study, bone marrow from mice treated 3 weeks previously with Methylnitrosourea (50 mg/kg) or 450 rad was injected into recipients in order to determine possible residual effects of treatment of erythroid cell differentiation following stem cell seeding. Such effects were detected by a reduced amount of 59 Fe incorporation into spleens, thus indicatin g transfer of residual stem cell damage to differentiating cells. (orig.)

  3. Reduction of erythroid progenitors in protein-energy malnutrition.

    Science.gov (United States)

    Borelli, Primavera; Blatt, Solange; Pereira, Juliana; de Maurino, Beatriz Beutler; Tsujita, Maristela; de Souza, Ana Cristina; Xavier, José Guilherme; Fock, Ricardo Ambrósio

    2007-02-01

    Protein-energy malnutrition is a syndrome in which anaemia together with multivitamin and mineral deficiency may be present. The pathophysiological mechanisms involved have not, however, yet been completely elucidated. The aim of the present study was to evaluate the pathophysiological processes that occur in this anaemia in animals that were submitted to protein-energy malnutrition, in particular with respect to Fe concentration and the proliferative activity of haemopoietic cells. For this, histological, histochemical, cell culture and immunophenotyping techniques were used. Two-month-old male Swiss mice were submitted to protein-energy malnutrition with a low-protein diet (20 g/kg) compared with control diet (400 g/kg). When the experimental group had attained a 20 % loss of their original body weight, the animals from both groups received, intravenously, 20 IU erythropoietin every other day for 14 d. Malnourished animals showed a decrease in red blood cells, Hb concentration and reticulocytopenia, as well as severe bone marrow and splenic atrophy. The results for serum Fe, total Fe-binding capacity, transferrin and erythropoietin in malnourished animals were no different from those of the control animals. Fe reserves in the spleen, liver and bone marrow were found to be greater in the malnourished animals. The mixed colony-forming unit assays revealed a smaller production of granulocyte-macrophage colony-forming units, erythroid burst-forming units, erythroid colony-forming units and CD45, CD117, CD119 and CD71 expression in the bone marrow and spleen cells of malnourished animals. These findings suggest that, in this protein-energy malnutrition model, anaemia is not caused by Fe deficiency or erythropoietin deficiency, but is a result of ineffective erythropoiesis.

  4. Re-evaluation of acute erythroid leukemia according to the 2016 WHO classification.

    Science.gov (United States)

    Chen, Yan; Pourabdollah, Maryam; Atenafu, Eshetu G; Tierens, Anne; Schimmer, Aaron; Chang, Hong

    2017-10-01

    In the recent update of WHO classification, the definition of myeloid neoplasms with erythroid predominance has been modified shifting the main criteria for calculating blast percentage from non-erythroid cells (NEC) to all nucleated marrow cells (ANC). Thus, the cases previously classified as erythroid/myeloid subtype of acute erythroid leukemia (AEL) based on the 2008 WHO will now be categorized either as myelodysplastic syndrome with excess blasts (MDS-EB) or acute myeloid leukemia, not otherwise specified (AML-NOS). However, the clinical significance of this new classification has not been demonstrated. Thus, we reviewed a leukemia database and reclassified 38 cases previously diagnosed as AEL, erythroid/myeloid subtype, with the consideration of 2016 revision criteria. Twenty seven (71%) of them had >20% blasts in NEC but less than 20% blasts in ANC, and 11 (29%) had >20% in both NEC and ANC. There was no significant difference in overall survivals (OS) among AEL, MDS-EB, and AML-NOS (non-erythroid predominance, NEP). However, AML with myelodysplasia-related changes showed significant shorter OS than AEL, MDS-EB and AML-NOS (NEP). Our results indicate that in myeloid neoplasm with erythroid predominance, patients with >20% blasts, of either NEC or ANC, share similar clinical laboratory features and survival outcomes with AML-NOS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. DNA of Erythroid Origin Is Present in Human Plasma and Informs the Types of Anemia.

    Science.gov (United States)

    Lam, W K Jacky; Gai, Wanxia; Sun, Kun; Wong, Raymond S M; Chan, Rebecca W Y; Jiang, Peiyong; Chan, Natalie P H; Hui, Winnie W I; Chan, Anthony W H; Szeto, Cheuk-Chun; Ng, Siew C; Law, Man-Fai; Chan, K C Allen; Chiu, Rossa W K; Lo, Y M Dennis

    2017-10-01

    There is much interest in the tissue of origin of circulating DNA in plasma. Data generated using DNA methylation markers have suggested that hematopoietic cells of white cell lineages are important contributors to the circulating DNA pool. However, it is not known whether cells of the erythroid lineage would also release DNA into the plasma. Using high-resolution methylation profiles of erythroblasts and other tissue types, 3 genomic loci were found to be hypomethylated in erythroblasts but hypermethylated in other cell types. We developed digital PCR assays for measuring erythroid DNA using the differentially methylated region for each locus. Based on the methylation marker in the ferrochelatase gene, erythroid DNA represented a median of 30.1% of the plasma DNA of healthy subjects. In subjects with anemia of different etiologies, quantitative analysis of circulating erythroid DNA could reflect the erythropoietic activity in the bone marrow. For patients with reduced erythropoietic activity, as exemplified by aplastic anemia, the percentage of circulating erythroid DNA was decreased. For patients with increased but ineffective erythropoiesis, as exemplified by β-thalassemia major, the percentage was increased. In addition, the plasma concentration of erythroid DNA was found to correlate with treatment response in aplastic anemia and iron deficiency anemia. Plasma DNA analysis using digital PCR assays targeting the other 2 differentially methylated regions showed similar findings. Erythroid DNA is a hitherto unrecognized major component of the circulating DNA pool and is a noninvasive biomarker for differential diagnosis and monitoring of anemia. © 2017 American Association for Clinical Chemistry.

  6. Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae-Ryung, E-mail: heaven@umich.edu; Loch-Caruso, Rita

    2014-11-15

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants, and BDE-47 is a prevalent PBDE congener detected in human tissues. Exposure to PBDEs has been linked to adverse pregnancy outcomes in humans. Although the underlying mechanisms of adverse birth outcomes are poorly understood, critical roles for oxidative stress and inflammation are implicated. The present study investigated antioxidant responses in a human extravillous trophoblast cell line, HTR-8/SVneo, and examined the role of nuclear factor E2-related factor 2 (Nrf2), an antioxidative transcription factor, in BDE-47-induced inflammatory responses in the cells. Treatment of HTR-8/SVneo cells with 5, 10, 15, and 20 μM BDE-47 for 24 h increased intracellular glutathione (GSH) levels compared to solvent control. Treatment of HTR-8/SVneo cells with 20 μM BDE-47 for 24 h induced the antioxidant response element (ARE) activity, indicating Nrf2 transactivation by BDE-47 treatment, and resulted in differential expression of redox-sensitive genes compared to solvent control. Pretreatment with tert-butyl hydroquinone (tBHQ) or sulforaphane, known Nrf2 inducers, reduced BDE-47-stimulated IL-6 release with increased ARE reporter activity, reduced nuclear factor kappa B (NF-κB) reporter activity, increased GSH production, and stimulated expression of antioxidant genes compared to non-Nrf2 inducer pretreated groups, suggesting that Nrf2 may play a protective role against BDE-47-mediated inflammatory responses in HTR-8/SVneo cells. These results suggest that Nrf2 activation significantly attenuated BDE-47-induced IL-6 release by augmentation of cellular antioxidative system via upregulation of Nrf2 signaling pathways, and that Nrf2 induction may be a potential therapeutic target to reduce adverse pregnancy outcomes associated with toxicant-induced oxidative stress and inflammation. - Highlights: • BDE-47 stimulated ARE reporter activity and GSH production. • BDE-47 resulted in differential

  7. [Update on the biology of heme synthesis in erythroid cells].

    Science.gov (United States)

    Fujiwara, Tohru; Harigae, Hideo

    2015-02-01

    Heme is a prosthetic group of hemoproteins playing important roles in oxygen transport, detoxification, circadian rhythm, microRNA processing, regulation of transcription, and translation. The majority of heme (-85%) is synthesized in red blood cells mainly for hemoglobin production, whereas hepatocytes account for most of the rest, functioning primarily in the synthesis of cytochrome P450 enzymes and mitochondrial respiratory enzymes. Thus, failure of heme biosynthesis causes severe inherited or acquired disorders in humans, including porphyria and sideroblastic anemia. The heme biosynthetic pathway is composed of eight enzymes that work in either mitochondria or the cytoplasm, which have been extensively researched and frequently reviewed. On the other hand, the mechanisms governing transport and intracellular trafficking of heme intermediates, as well as their potential links to human diseases, are poorly understood. Herein, we focus on recent understanding of the heme biosynthetic pathway and on human disorders due to defective heme synthesis in erythroid cells, such as X-linked sideroblastic anemia and erythropoietic protoporphyria.

  8. Force Dependent Changes in Non-Erythroid Spectrin and Ankyrins

    Science.gov (United States)

    Degaga, Eleni; Forstner, Martin

    2012-02-01

    Mechanotransduction in cells describes the process by which external physical stimuli are converted into biochemical activity and plays an important role in many biological functions on both the cell and tissue level. However, the specific mechanisms by which mechanical forces lead to particular molecular and cellular responses are much less understood. We investigate the changes in non-erythroid spectrin and ankyrins as a result of equi-biaxial strain application to live cells in culture. Specifically, we focus on the spectrins' role in the ubiquitination process - a vital process in the regulation of protein degradation- of spectrin and ankyrins. We utilize immune-fluorescence staining and fluorescent fusion proteins for quantitative fluorescence imaging as well as biochemical methods to measure changes in of cell's spectrin and ankyrin content. Protein expression levels and localization between cells exposed to mechanical stimuli of different temporal and spatial profiles are compared. In addition, the threshold behavior of cell proliferation - as measured by number densities - of a variety of cell types as a function of mechano-stimulation is investigated.

  9. Recombinant human parvovirus B19 vectors: erythroid cell-specific delivery and expression of transduced genes.

    Science.gov (United States)

    Ponnazhagan, S; Weigel, K A; Raikwar, S P; Mukherjee, P; Yoder, M C; Srivastava, A

    1998-06-01

    A novel packaging strategy combining the salient features of two human parvoviruses, namely the pathogenic parvovirus B19 and the nonpathogenic adeno-associated virus type 2 (AAV), was developed to achieve erythroid cell-specific delivery as well as expression of the transduced gene. The development of such a chimeric vector system was accomplished by packaging heterologous DNA sequences cloned within the inverted terminal repeats of AAV and subsequently packaging the DNA inside the capsid structure of B19 virus. Recombinant B19 virus particles were assembled, as evidenced by electron microscopy as well as DNA slot blot analyses. The hybrid vector failed to transduce nonerythroid human cells, such as 293 cells, as expected. However, MB-02 cells, a human megakaryocytic leukemia cell line which can be infected by B19 virus following erythroid differentiation with erythropoietin (N. C. Munshi, S. Z. Zhou, M. J. Woody, D. A. Morgan, and A. Srivastava, J. Virol. 67:562-566, 1993) but lacks the putative receptor for AAV (S. Ponnazhagan, X.-S. Wang, M. J. Woody, F. Luo, L. Y. Kang, M. L. Nallari, N. C. Munshi, S. Z. Zhou, and A. Srivastava, J. Gen. Virol. 77:1111-1122, 1996), were readily transduced by this vector. The hybrid vector was also found to specifically target the erythroid population in primary human bone marrow cells as well as more immature hematopoietic progenitor cells following erythroid differentiation, as evidenced by selective expression of the transduced gene in these target cells. Preincubation with anticapsid antibodies against B19 virus, but not anticapsid antibodies against AAV, inhibited transduction of primary human erythroid cells. The efficiency of transduction of primary human erythroid cells by the recombinant B19 virus vector was significantly higher than that by the recombinant AAV vector. Further development of the AAV-B19 virus hybrid vector system should prove beneficial in gene therapy protocols aimed at the correction of inherited and

  10. Melatonin Attenuates Memory Impairment Induced by Klotho Gene Deficiency Via Interactive Signaling Between MT2 Receptor, ERK, and Nrf2-Related Antioxidant Potential

    Science.gov (United States)

    Shin, Eun-Joo; Chung, Yoon Hee; Le, Hoang-Lan Thi; Jeong, Ji Hoon; Dang, Duy-Khanh; Nam, Yunsung; Wie, Myung Bok; Nah, Seung-Yeol; Nabeshima, Yo-Ichi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2015-01-01

    Background: We demonstrated that oxidative stress plays a crucial role in cognitive impairment in klotho mutant mice, a genetic model of aging. Since down-regulation of melatonin due to aging is well documented, we used this genetic model to determine whether the antioxidant property of melatonin affects memory impairment. Methods: First, we examined the effects of melatonin on hippocampal oxidative parameters and the glutathione/oxidized glutathione (GSH/GSSG) ratio and memory dysfunction of klotho mutant mice. Second, we investigated whether a specific melatonin receptor is involved in the melatonin-mediated pharmacological response by application with melatonin receptor antagonists. Third, we examined phospho-extracellular-signal-regulated kinase (ERK) expression, nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, Nrf2 DNA binding activity, and glutamate-cysteine ligase (GCL) mRNA expression. Finally, we examined effects of the ERK inhibitor SL327 in response to antioxidant efficacy and memory enhancement mediated by melatonin. Results: Treatment with melatonin resulted in significant attenuations of oxidative damage, a decrease in the GSH/GSSG ratio, and a significant amelioration of memory impairment in this aging model. These effects of melatonin were significantly counteracted by the selective MT2 receptor antagonist 4-P-PDOT. Importantly, 4-P-PDOT or SL327 also counteracted melatonin-mediated attenuation in response to the decreases in phospho-ERK expression, Nrf2 nuclear translocation, Nrf2 DNA-binding activity, and GCL mRNA expression in the hippocampi of klotho mutant mice. SL327 also counteracted the up-regulation of the GSH/GSSG ratio and the memory enhancement mediated by melatonin in klotho mutant mice. Conclusions: Melatonin attenuates oxidative stress and the associated memory impairment induced by klotho deficiency via signaling interaction between the MT2 receptor and ERK- and Nrf2-related antioxidant potential. PMID

  11. JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny

    Directory of Open Access Journals (Sweden)

    Cokic Vladan P

    2012-06-01

    Full Text Available Abstract Background It has been reported that the phosphatidylinositol 3-kinase (PI3K-AKT signaling pathway regulates erythropoietin (EPO-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival have also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the function of EPO activation of JAK-STAT and PI3K/AKT pathways in the development of erythroid progenitors from hematopoietic CD34+ progenitor cells, as well as to distinguish early EPO target genes in human erythroid progenitors during ontogeny. Methods Hematopoietic CD34+ progenitor cells, isolated from fetal and adult hematopoietic tissues, were differentiated into erythroid progenitor cells. We have used microarray analysis to examine JAK-STAT and PI3K/AKT related genes, as well as broad gene expression modulation in these human erythroid progenitor cells. Results In microarray studies, a total of 1755 genes were expressed in fetal liver, 3844 in cord blood, 1770 in adult bone marrow, and 1325 genes in peripheral blood-derived erythroid progenitor cells. The erythroid progenitor cells shared 1011 common genes. Using the Ingenuity Pathways Analysis software, we evaluated the network pathways of genes linked to hematological system development, cellular growth and proliferation. The KITLG, EPO, GATA1, PIM1 and STAT3 genes represent the major connection points in the hematological system development linked genes. Some JAK-STAT signaling pathway-linked genes were steadily upregulated throughout ontogeny (PIM1, SOCS2, MYC, PTPN11, while others were downregulated (PTPN6, PIAS, SPRED2. In addition, some JAK-STAT pathway related genes are differentially expressed only in some stages of ontogeny (STATs, GRB2, CREBB. Beside the continuously upregulated (AKT1, PPP2CA, CHUK, NFKB1 and downregulated (FOXO1, PDPK1, PIK3CG genes in the PI3K-AKT signaling pathway, we also observed intermittently

  12. Unravelling pathways downstream Sox6 induction in K562 erythroid cells by proteomic analysis

    KAUST Repository

    Barbarani, Gloria

    2017-10-20

    The Sox6 transcription factor is crucial for terminal maturation of definitive red blood cells. Sox6-null mouse fetuses present misshapen and nucleated erythrocytes, due to impaired actin assembly and cytoskeleton stability. These defects are accompanied with a reduced survival of Sox6-/- red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark of erythroid maturation. To obtain an overview on processes downstream to Sox6 expression, we performed a differential proteomic analysis on human erythroid K562 cells overexpressing Sox6. Sox6-overexpression induces dysregulation of 64 proteins, involved in cytoskeleton remodeling and in protein synthesis, folding and trafficking, key processes for erythroid maturation. Moreover, 43 out of 64 genes encoding for differentially expressed proteins contain within their proximal regulatory regions sites that are bound by SOX6 according to ENCODE ChIP-seq datasets and are possible direct SOX6 targets. SAR1B, one of the most induced proteins upon Sox6 overexpression, shares a conserved regulatory module, composed by a double SOX6 binding site and a GATA1 consensus, with the adjacent SEC24 A gene. Since both genes encode for COPII components, this element could concur to the coordinated expression of these proteins during erythropoiesis.

  13. Human Cord Blood and Bone Marrow CD34+ Cells Generate Macrophages That Support Erythroid Islands.

    Directory of Open Access Journals (Sweden)

    Eyayu Belay

    Full Text Available Recently, we developed a small molecule responsive hyperactive Mpl-based Cell Growth Switch (CGS that drives erythropoiesis associated with macrophages in the absence of exogenous cytokines. Here, we compare the physical, cellular and molecular interaction between the macrophages and erythroid cells in CGS expanded CD34+ cells harvested from cord blood, marrow or G-CSF-mobilized peripheral blood. Results indicated that macrophage based erythroid islands could be generated from cord blood and marrow CD34+ cells but not from G-CSF-mobilized CD34+ cells. Additional studies suggest that the deficiency resides with the G-CSF-mobilized CD34+ derived monocytes. Gene expression and proteomics studies of the in vitro generated erythroid islands detected the expression of erythroblast macrophage protein (EMP, intercellular adhesion molecule 4 (ICAM-4, CD163 and DNASE2. 78% of the erythroblasts in contact with macrophages reached the pre reticulocyte orthochromatic stage of differentiation within 14 days of culture. The addition of conditioned medium from cultures of CD146+ marrow fibroblasts resulted in a 700-fold increase in total cell number and a 90-fold increase in erythroid cell number. This novel CD34+ cell derived erythroid island may serve as a platform to explore the molecular basis of red cell maturation and production under normal, stress and pathological conditions.

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

    Directory of Open Access Journals (Sweden)

    Deepti Jain

    2015-06-01

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

  15. Erythroid Krüppel-like factor (EKLF) is active in primitive and definitive erythroid cells and is required for the function of 5'HS3 of the beta-globin locus control region

    NARCIS (Netherlands)

    Tewari, R.; Gillemans, N.; Wijgerde, M.; Nuez, B.; von Lindern, M.; Grosveld, F.; Philipsen, S.

    1998-01-01

    Disruption of the gene for transcription factor EKLF (erythroid Krüppel-like factor) results in fatal anaemia caused by severely reduced expression of the adult beta-globin gene, while other erythroid-specific genes, including the embryonic epsilon- and fetal gamma-globin genes, are expressed

  16. Erythroid progenitors from patients with low-risk myelodysplastic syndromes are dependent on the surrounding micro environment for their survival

    NARCIS (Netherlands)

    Folkerts, Hendrik; Hazenberg, Carin L. E.; Houwerzijl, Ewout J.; van den Heuvel, Fiona A. J.; Mulder, Andre B.; van der Want, Johannes J. L.; Vellenga, Edo

    To investigate whether the type of programmed cell death of myelodysplastic erythroid cells depends on their cellular context, we performed studies on cells from patients with low-risk myelodysplastic syndromes. We compared erythroid cells (and their precursor cells) from the mononuclear cell

  17. Acute myeloid leukemia (AML with erythroid predominance exhibits clinical and molecular characteristics that differ from other types of AML.

    Directory of Open Access Journals (Sweden)

    Zhuang Zuo

    Full Text Available The clinical importance of erythroid predominance in bone marrow of patients with acute myeloid leukemia (AML is controversial. These cases represent a heterogeneous group of diseases that historically have been classified into different categories. We studied 313 AML patients and specifically compared the clinical, cytogenetic, and molecular features of cases of AML with erythroid predominance, arbitrarily defined as ≥50% erythroid precursors, to AML cases without erythroid predominance. We also assessed 51 patients with a high-grade myelodysplastic syndrome (MDS, refractory anemia with excess blasts (RAEB. All neoplasms were classified according to the World Health Organization classification. With the exception of therapy-related AML/MDS, the presence of erythroid predominance in variously classified categories of AML was associated with a survival advantage. In addition, AML with erythroid predominance had a lower frequency of cytogenetic abnormalities as well as a lower frequency of mutations involving NPM1, NRAS and FLT3 as compared with AML without erythroid predominance. We conclude that the clinical, cytogenetic, and molecular features of AML with erythroid predominance in the non-therapy-related setting are much closer to those of a high-grade myelodysplastic syndrome than they are to other types of AML.

  18. Erythroid progenitors from patients with low-risk myelodysplastic syndromes are dependent on the surrounding micro environment for their survival.

    Science.gov (United States)

    Folkerts, Hendrik; Hazenberg, Carin L E; Houwerzijl, Ewout J; van den Heuvel, Fiona A J; Mulder, André B; van der Want, Johannes J L; Vellenga, Edo

    2015-03-01

    To investigate whether the type of programmed cell death of myelodysplastic erythroid cells depends on their cellular context, we performed studies on cells from patients with low-risk myelodysplastic syndromes. We compared erythroid cells (and their precursor cells) from the mononuclear cell fraction with those from the hematon fraction, which are compacted complexes of hematopoietic cells surrounded by their own micro-environment. In directly fixed materials, erythroblasts exhibited signs of autophagy with limited apoptosis (micro-environment was noted for immature erythroid progenitor cells. Myelodysplastic hematons exhibited distinct numbers of erythroid burst-forming units in association with an extensive network of stromal cells, whereas small numbers of erythroid burst-forming units were generated from the myelodysplastic mononuclear cells compared with normal mononuclear cells (10.2 ± 9 vs. 162 ± 125, p micro-environment. Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  19. Monomethylfumarate induces γ-globin expression and fetal hemoglobin production in cultured human retinal pigment epithelial (RPE) and erythroid cells, and in intact retina.

    Science.gov (United States)

    Promsote, Wanwisa; Makala, Levi; Li, Biaoru; Smith, Sylvia B; Singh, Nagendra; Ganapathy, Vadivel; Pace, Betty S; Martin, Pamela M

    2014-05-13

    Sickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina. Human globin gene expression was evaluated by RT-quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase-qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous β(s) mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed. Retinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation. The production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  20. Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells.

    Directory of Open Access Journals (Sweden)

    Ryo Kurita

    Full Text Available Transfusion of red blood cells (RBCs is a standard and indispensable therapy in current clinical practice. In vitro production of RBCs offers a potential means to overcome a shortage of transfusable RBCs in some clinical situations and also to provide a source of cells free from possible infection or contamination by microorganisms. Thus, in vitro production of RBCs may become a standard procedure in the future. We previously reported the successful establishment of immortalized mouse erythroid progenitor cell lines that were able to produce mature RBCs very efficiently. Here, we have developed a reliable protocol for establishing immortalized human erythroid progenitor cell lines that are able to produce enucleated RBCs. These immortalized cell lines produce functional hemoglobin and express erythroid-specific markers, and these markers are upregulated following induction of differentiation in vitro. Most importantly, these immortalized cell lines all produce enucleated RBCs after induction of differentiation in vitro, although the efficiency of producing enucleated RBCs remains to be improved further. To the best of our knowledge, this is the first demonstration of the feasibility of using immortalized human erythroid progenitor cell lines as an ex vivo source for production of enucleated RBCs.

  1. Cytotoxicity of quantum dots and graphene oxide to erythroid cells and macrophages

    Science.gov (United States)

    Qu, Guangbo; Wang, Xiaoyan; Wang, Zhe; Liu, Sijin; Jiang, Guibing

    2013-04-01

    Great concerns have been raised about the exposure and possible adverse influence of nanomaterials due to their wide applications in a variety of fields, such as biomedicine and daily lives. The blood circulation system and blood cells form an important barrier against invaders, including nanomaterials. However, studies of the biological effects of nanomaterials on blood cells have been limited and without clear conclusions thus far. In the current study, the biological influence of quantum dots (QDs) with various surface coating on erythroid cells and graphene oxide (GO) on macrophages was closely investigated. We found that QDs posed great damage to macrophages through intracellular accumulation of QDs coupled with reactive oxygen species generation, particularly for QDs coated with PEG-NH2. QD modified with polyethylene glycol-conjugated amine particles exerted robust inhibition on cell proliferation of J744A.1 macrophages, irrespective of apoptosis. Additionally, to the best of our knowledge, our study is the first to have demonstrated that GO could provoke apoptosis of erythroid cells through oxidative stress in E14.5 fetal liver erythroid cells and in vivo administration of GO-diminished erythroid population in spleen, associated with disordered erythropoiesis in mice.

  2. A genome-based approach for the study of erythroid biology and disease.

    Science.gov (United States)

    Miller, Jeffery L

    2004-01-01

    The human genome contains all elements of the erythroid transcriptome with the exception of those genes encoded in mitochondrial DNA. The concept of a "genome-based" approach for the study of erythroid biology and disease was envisioned in the mid-1990s as a logical offshoot of efforts to map the human genome. Although a completed human genome map was not expected until 2005 [Science 279 (1998) 23], the idea of creating a robust and retrievable description of erythroid gene activity was both encouraged and supported on the NIDDK Bethesda campus of the National Institutes of Health. The 5-10-year goals were organized into three parts. The initial project goal involved the collection of sequence data derived from mRNA expressed in developmentally staged erythroblasts. Those cells were isolated prospectively by flow cytometry monitoring of CD71 and glycophorin A expression patterns. Next, the sequence data was organized into a database and integrated with related information available in the public domain. The paramount goal of the project continues to be clinical application. As discussed in this paper, progress already made in each of these areas suggests that genome-based approaches will greatly facilitate future studies of erythroid biology and disease.

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

    Science.gov (United States)

    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.

  4. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Ya-Yun [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Tseng, Yu-Ting [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Lo, Yi-Ching, E-mail: yichlo@kmu.edu.tw [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2013-11-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H{sub 2}O{sub 2} neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS

  5. The role of catechol-O-methyltransferase in catechol-enhanced erythroid differentiation of K562 cells

    Energy Technology Data Exchange (ETDEWEB)

    Suriguga,; Li, Xiao-Fei; Li, Yang; Yu, Chun-Hong; Li, Yi-Ran; Yi, Zong-Chun, E-mail: yizc@buaa.edu.cn

    2013-12-15

    Catechol is widely used in pharmaceutical and chemical industries. Catechol is also one of phenolic metabolites of benzene in vivo. Our previous study showed that catechol improved erythroid differentiation potency of K562 cells, which was associated with decreased DNA methylation in erythroid specific genes. Catechol is a substrate for the catechol-O-methyltransferase (COMT)-mediated methylation. In the present study, the role of COMT in catechol-enhanced erythroid differentiation of K562 cells was investigated. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation and induced mRNA expression of erythroid specific genes in K562 cells. Treatment with catechol caused a time- and concentration-dependent increase in guaiacol concentration in the medium of cultured K562 cells. When COMT expression was knocked down by COMT shRNA expression in K562 cells, the production of guaiacol significantly reduced, and the sensitivity of K562 cells to cytotoxicity of catechol significantly increased. Knockdown of COMT expression by COMT shRNA expression also eliminated catechol-enhanced erythroid differentiation of K562 cells. In addition, the pre-treatment with methyl donor S-adenosyl-L-methionine or its demethylated product S-adenosyl-L-homocysteine induced a significant increase in hemin-induced Hb synthesis in K562 cells and the mRNA expression of erythroid specific genes. These findings indicated that O-methylation catalyzed by COMT acted as detoxication of catechol and involved in catechol-enhanced erythroid differentiation of K562 cells, and the production of S-adenosyl-L-homocysteine partly explained catechol-enhanced erythroid differentiation. - Highlights: • Catechol enhanced hemin-induced hemoglobin accumulation. • COMT-catalyzed methylation acted as detoxication of catechol. • COMT involved in catechol-enhanced erythroid differentiation.

  6. Structural characterization of a noncovalent complex between ubiquitin and the transactivation domain of the erythroid-specific factor EKLF.

    Science.gov (United States)

    Raiola, Luca; Lussier-Price, Mathieu; Gagnon, David; Lafrance-Vanasse, Julien; Mascle, Xavier; Arseneault, Genevieve; Legault, Pascale; Archambault, Jacques; Omichinski, James G

    2013-11-05

    Like other acidic transactivation domains (TAD), the minimal TAD from the erythroid-specific transcription factor EKLF (EKLFTAD) has been shown to contribute both to its transcriptional activity as well as to its ubiquitin(UBI)-mediated degradation. In this article, we examine the activation-degradation role of the acidic TAD of EKLF and demonstrate that the first 40 residues (EKLFTAD1) within this region form a noncovalent interaction with UBI. Nuclear magnetic resonance (NMR) structural studies of an EKLFTAD1-UBI complex show that EKLFTAD1 adopts a 14-residue α helix that forms the recognition interface with UBI in a similar manner as the UBI-interacting helix of Rabex5. We also identify a similar interaction between UBI and the activation-degradation region of SREBP1a, but not with the activation-degradation regions of p53, GAL4, and VP16. These results suggest that select activation-degradation regions like the ones found in EKLF and SREBP1a function in part through their ability to form noncovalent interactions with UBI. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria

    NARCIS (Netherlands)

    Houwerzijl, E. J.; Pol, H-W D.; Blom, N. R.; van der Want, J. J. L.; de Wolf, J. Thm; Vellenga, E.

    Recent studies in erythroid cells have shown that autophagy is an important process for the physiological clearance of mitochondria during terminal differentiation. However, autophagy also plays an important role in removing damaged and dysfunctional mitochondria. Defective mitochondria and impaired

  8. The uniqueness of morphological features of pure erythroid leukemia in myeloid neoplasm with erythroid predominance: A reassessment using criteria revised in the 2016 World Health Organization classification.

    Science.gov (United States)

    Ko, Po-Shen; Liu, Yao-Chung; Yeh, Chiu-Mei; Gau, Jyh-Pyng; Yu, Yuan-Bin; Hsiao, Liang-Tsai; Tzeng, Cheng-Hwai; Chen, Po-Min; Chiou, Tzeon-Jye; Liu, Chia-Jen; Liu, Jin-Hwang

    2017-01-01

    We reviewed 97 consecutive cases of myeloid neoplasm with erythroid predominance (MN-EP) between 2000 and 2015. Following 2016 WHO classification, MN-EP patients were classified into four groups. Eight pure erythroid leukemia (PEL) (including t-MN and AML-MRC morphologically fulfilled criteria for PEL) patients had dismal outcomes (median OS: 1 month) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis than the other groups. In the univariate analysis, risks of death in MN-EP patients included the morphologic features of PEL, very poor cytogenetic risk by IPSS-R, bone marrow fibrosis, leukocytosis, anemia, hypoalbuminemia, high LDH, and poor PS. In the multivariate analysis, independent predictors of death were morphologic features of PEL (adjusted hazards ratio [HR] 3.48, 95% confidence interval [CI] 1.24-9.74, p = 0.018), very poor cytogenetic risk by IPSS-R (adjusted HR 2.73, 95% CI 1.22-6.10, p = 0.015), hypoalbuminemia (< 3.7 g/dl) (adjusted HR 2.33, 95% CI 1.10-4.91, p = 0.026) and high serum LDH (≥ 250 U/L) (adjusted HR 2.36, 95% CI 1.28-4.36, p = 0.006). Poor or unfavorable risk in different cytogenetic risk systems independently predicted death and UKMRC-R was the best model.

  9. Hematopoiesis and aging. IV. Mass and distribution of erythroid marrow in aged mice

    International Nuclear Information System (INIS)

    Boggs, D.R.

    1985-01-01

    Aged mice are ''anemic,'' i.e., they have a lower hematocrit than young adult mice, but this appears to be a ''dilutional'' anemia; the red cell mass is normal. Other observations have supported the hypothesis that basal erythropoiesis does not change as mice grow old. In the present study, the percentage of injected 59 Fe found in the skeleton and spleen, 59 Fe distribution between various bones and bone groups, and the number of nucleated erythroid cells per humerus were studied and the total mass of erythroid precursors was calculated. There was no significant difference in any of these values between mice aged 3-27 months. The variability of 59 Fe distribution within various skeletal parts was no greater in aged than in young mice. Thus, these data further strengthen the case for normal basal rates of erythropoiesis in aged mice

  10. Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion

    DEFF Research Database (Denmark)

    Falchi, Mario; Varricchio, Lilian; Martelli, Fabrizio

    2015-01-01

    Cultures of human CD34(pos) cells stimulated with erythroid growth factors plus dexamethasone, a model for stress erythropoiesis, generate numerous erythroid cells plus a few macrophages (approx. 3%; 3:1 positive and negative for CD169). Interactions occurring between erythroblasts and macrophages...... in these cultures and the biological effects associated with these interactions were documented by live phase-contrast videomicroscopy. Macrophages expressed high motility interacting with hundreds/thousands of erythroblasts per hour. CD169(pos) macrophages established multiple rapid 'loose' interactions...... with proerythroblasts leading to formation of transient erythroblastic island-like structures. By contrast, CD169(neg) macrophages established 'tight' interactions with mature erythroblasts and phagocytosed these cells. 'Loose' interactions of CD169(pos) macrophages were associated with proerythroblast cytokinesis (the...

  11. RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development.

    Science.gov (United States)

    Verma, Rakesh; Su, Su; McCrann, Donald J; Green, Jennifer M; Leu, Karen; Young, Peter R; Schatz, Peter J; Silva, Jeffrey C; Stokes, Matthew P; Wojchowski, Don M

    2014-08-25

    Ligation of erythropoietin (EPO) receptor (EPOR) JAK2 kinase complexes propagates signals within erythroid progenitor cells (EPCs) that are essential for red blood cell production. To reveal hypothesized novel EPOR/JAK2 targets, a phosphotyrosine (PY) phosphoproteomics approach was applied. Beyond known signal transduction factors, 32 new targets of EPO-modulated tyrosine phosphorylation were defined. Molecular adaptors comprised one major set including growth factor receptor-bound protein 2 (GRB2)-associated binding proteins 1-3 (GAB1-3), insulin receptor substrate 2 (IRS2), docking protein 1 (DOK1), Src homology 2 domain containing transforming protein 1 (SHC1), and sprouty homologue 1 (SPRY1) as validating targets, and SPRY2, SH2 domain containing 2A (SH2D2A), and signal transducing adaptor molecule 2 (STAM2) as novel candidate adaptors together with an ORF factor designated as regulator of human erythroid cell expansion (RHEX). RHEX is well conserved in Homo sapiens and primates but absent from mouse, rat, and lower vertebrate genomes. Among tissues and lineages, RHEX was elevated in EPCs, occurred as a plasma membrane protein, was rapidly PY-phosphorylated >20-fold upon EPO exposure, and coimmunoprecipitated with the EPOR. In UT7epo cells, knockdown of RHEX inhibited EPO-dependent growth. This was associated with extracellular signal-regulated kinase 1,2 (ERK1,2) modulation, and RHEX coupling to GRB2. In primary human EPCs, shRNA knockdown studies confirmed RHEX regulation of erythroid progenitor expansion and further revealed roles in promoting the formation of hemoglobinizing erythroblasts. RHEX therefore comprises a new EPO/EPOR target and regulator of human erythroid cell expansion that additionally acts to support late-stage erythroblast development. © 2014 Verma et al.

  12. RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development

    OpenAIRE

    Verma, Rakesh; Su, Su; McCrann, Donald J.; Green, Jennifer M.; Leu, Karen; Young, Peter R.; Schatz, Peter J.; Silva, Jeffrey C.; Stokes, Matthew P.; Wojchowski, Don M.

    2014-01-01

    Ligation of erythropoietin (EPO) receptor (EPOR) JAK2 kinase complexes propagates signals within erythroid progenitor cells (EPCs) that are essential for red blood cell production. To reveal hypothesized novel EPOR/JAK2 targets, a phosphotyrosine (PY) phosphoproteomics approach was applied. Beyond known signal transduction factors, 32 new targets of EPO-modulated tyrosine phosphorylation were defined. Molecular adaptors comprised one major set including growth factor receptor-bound protein 2 ...

  13. Umbilical cord CD71+ erythroid cells are reduced in neonates born to women in spontaneous preterm labor.

    Science.gov (United States)

    Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Miller, Derek; Unkel, Ronald; C MacKenzie, Tippi; Frascoli, Michela; Hassan, Sonia S

    2016-10-01

    Preterm neonates are highly susceptible to infection. Neonatal host defense against infection seems to be maintained by the temporal presence of immunosuppressive CD71+ erythroid cells. The aim of this study was to investigate whether umbilical cord CD71+ erythroid cells are reduced in neonates born to women who undergo spontaneous preterm labor/birth. Umbilical cord blood samples (n=155) were collected from neonates born to women who delivered preterm with (n=39) and without (n=12) spontaneous labor or at term with (n=82) and without (n=22) spontaneous labor. Time-matched maternal peripheral blood samples were also included (n=111). Mononuclear cells were isolated from these samples, and CD71+ erythroid cells were identified and quantified as CD3-CD235a+CD71+ cells by flow cytometry. (i) The proportion of CD71+ erythroid cells was 50-fold higher in cord blood than in maternal blood; (ii) a reduced number and frequency of umbilical cord CD71+ erythroid cells were found in neonates born to women who underwent spontaneous preterm labor compared to those born to women who delivered preterm without labor; (iii) umbilical cord CD71+ erythroid cells were fewer in neonates born to term pregnancies, regardless of the process of labor, than in those born to women who delivered preterm without labor; and (iv) no differences were seen in umbilical cord CD71+ erythroid cells between neonates born to women who underwent spontaneous preterm labor and those born to women who delivered at term with labor. Umbilical cord CD71+ erythroid cells are reduced in neonates born to women who had undergone spontaneous preterm labor. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  14. Dynamic changes in transcription factor complexes during erythroid differentiation revealed by quantitative proteomics.

    Science.gov (United States)

    Brand, Marjorie; Ranish, Jeffrey A; Kummer, Nicolas T; Hamilton, Joan; Igarashi, Kazuhiko; Francastel, Claire; Chi, Tian H; Crabtree, Gerald R; Aebersold, Ruedi; Groudine, Mark

    2004-01-01

    During erythroid differentiation, beta-globin gene expression is regulated by the locus control region (LCR). The transcription factor NF-E2p18/MafK binds within this region and is essential for beta-globin expression in murine erythroleukemia (MEL) cells. Here we use the isotope-coded affinity tag (ICAT) technique of quantitative mass spectrometry to compare proteins interacting with NF-E2p18/MafK during differentiation. Our results define MafK as a 'dual-function' molecule that shifts from a repressive to an activating mode during erythroid differentiation. The exchange of MafK dimerization partner from Bach1 to NF-E2p45 is a key step in the switch from the repressed to the active state. This shift is associated with changes in the interaction of MafK with co-repressors and co-activators. Thus, our results suggest that in addition to its role as a cis-acting activator of beta-globin gene expression in differentiated erythroid cells, the LCR also promotes an active repression of beta-globin transcription in committed cells before terminal differentiation.

  15. Robust reprogramming of Ataxia-Telangiectasia patient and carrier erythroid cells to induced pluripotent stem cells.

    Science.gov (United States)

    Bhatt, Niraj; Ghosh, Rajib; Roy, Sanchita; Gao, Yongxing; Armanios, Mary; Cheng, Linzhao; Franco, Sonia

    2016-09-01

    Biallelic mutations in ATM result in the neurodegenerative syndrome Ataxia-Telangiectasia, while ATM haploinsufficiency increases the risk of cancer and other diseases. Previous studies revealed low reprogramming efficiency from A-T and carrier fibroblasts, a barrier to iPS cell-based modeling and regeneration. Here, we tested the feasibility of employing circulating erythroid cells, a compartment no or minimally affected in A-T, for the generation of A-T and carrier iPS cells. Our results indicate that episomal expression of Yamanaka factors plus BCL-xL in erythroid cells results in highly efficient iPS cell production in feeder-free, xeno-free conditions. Moreover, A-T iPS cells generated with this protocol maintain long-term replicative potential, stable karyotypes, re-elongated telomeres and capability to differentiate along the neural lineage in vitro and to form teratomas in vivo. Finally, we find that haploinsufficiency for ATM does not limit reprogramming from human erythroid cells or in vivo teratoma formation in the mouse. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Polyherbal EMSA ERITIN Promotes Erythroid Lineages and Lymphocyte Migration in Irradiated Mice

    Directory of Open Access Journals (Sweden)

    Ibrahim Mansur

    2016-01-01

    Full Text Available Radiotherapy is commonly used to kill malignant cells, but it can significantly deplete hematopoietic and splenic erythroblasts. Radioprotective agents are therefore very important in clinical radiotherapy. We examined the effect of poly-herbal EMSA ERITIN on immunological responses when administered to sublethally irradiated mice with the aim of highlighting promotes erythroid lineages and lymphocytes migration in irradiated mice with the parameter are TER119+CD123+in bone marrow and SDF-1 in bone marrow and spleen organ. Normal BALB/c mice were sublethally irradiated with 600 rad. EMSA ERITIN was administered orally at different doses:(1.04, 3.125 and 9.375 mg/g body weight for 15 days. On day 16 erythroid lineages (TER-119+CD123+ were observed in bone marrow and lymphocytes migration by the production of SDF-1 in spleen and bone marrow. Lymphocytes migration was indicated by the production of SDF-1 in spleen and bone marrow using flow cytometry analysis. EMSA ERITIN increased the generation of erythroid lineage cells marked by TER119+CD123+ and promoted lymphocyte migration by increasing SDF-1 production in bone marrow and spleen. EMSA ERITIN appears to be a powerful medicinal herb with potential as a food supplement to normalize homeostasis and erythropoiesis after radiation.

  17. Changes in DNA methylation of erythroid-specific genes in K562 cells exposed to catechol in long term.

    Science.gov (United States)

    Yu, Chun-Hong; Cui, Ning-Xuan; Wang, Yan; Wang, Ying; Liu, Wen-Juan; Gong, Meng; Zhao, Xiao; Rong, Long; Yi, Zong-Chun

    2017-09-01

    Catechol is one of phenolic metabolites of benzene that is a general occupational hazard and a ubiquitous environmental air pollutant. Catechol also occurs naturally in fruits, vegetables and cigarettes. Previous studies have revealed that 72h exposure to catechol improved hemin-induced erythroid differentiation of K562 cells accompanied with elevated methylation in erythroid specific genes. In present study, K562 cells were treated with 0, 10 or 20μM catechol for 1-4weeks, hemin-induced hemoglobin synthesis increased in a concentration- and time-dependent manner and the enhanced hemoglobin synthesis was relatively stable. The mRNA expression of α-, β- and γ-globin genes, erythroid heme synthesis enzymes PBGD and ALAS2, transcription factor GATA-1 and NF-E2 showed a significant increase in K562 cells exposed to 20μM catechol for 3w, and catechol enhanced hemin-induced mRNA expression of these genes. Quantitative MassARRAY methylation analysis also confirmed that the exposure to catechol changed DNA methylation levels at several CpG sites in several erythroid-specific genes and their far upstream of regulatory elements. These results demonstrated that long-term exposure to low concentration of catechol enhanced the hemin-induced erythroid differentiation of K562 cells, in which DNA methylation played a role by up-regulating erythroid specific genes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. SOD2 deficient erythroid cells up-regulate transferrin receptor and down-regulate mitochondrial biogenesis and metabolism.

    Directory of Open Access Journals (Sweden)

    Florent M Martin

    2011-02-01

    Full Text Available Mice irradiated and reconstituted with hematopoietic cells lacking manganese superoxide dismutase (SOD2 show a persistent hemolytic anemia similar to human sideroblastic anemia (SA, including characteristic intra-mitochondrial iron deposition. SA is primarily an acquired, clonal marrow disorder occurring in individuals over 60 years of age with uncertain etiology.To define early events in the pathogenesis of this murine model of SA, we compared erythroid differentiation of Sod2⁻/⁻ and normal bone marrow cells using flow cytometry and gene expression profiling of erythroblasts. The predominant transcriptional differences observed include widespread down-regulation of mitochondrial metabolic pathways and mitochondrial biogenesis. Multiple nuclear encoded subunits of complexes I-IV of the electron transport chain, ATP synthase (complex V, TCA cycle and mitochondrial ribosomal proteins were coordinately down-regulated in Sod2⁻/⁻ erythroblasts. Despite iron accumulation within mitochondria, we found increased expression of transferrin receptor, Tfrc, at both the transcript and protein level in SOD2 deficient cells, suggesting deregulation of iron delivery. Interestingly, there was decreased expression of ABCb7, the gene responsible for X-linked hereditary SA with ataxia, a component required for iron-sulfur cluster biogenesis.These results indicate that in erythroblasts, mitochondrial oxidative stress reduces expression of multiple nuclear genes encoding components of the respiratory chain, TCA cycle and mitochondrial protein synthesis. An additional target of particular relevance for SA is iron:sulfur cluster biosynthesis. By decreasing transcription of components of cluster synthesis machinery, both iron utilization and regulation of iron uptake are impacted, contributing to the sideroblastic phenotype.

  19. Exploring the use of expanded erythroid cells for autologous transfusion for anemia of prematurity.

    Science.gov (United States)

    Khodabux, Chantal M; van Hensbergen, Yvette; Slot, Manon C; Bakker-Verweij, Margreet; Giordano, Piero C; Brand, Anneke

    2013-12-01

    Autologous cord blood (CB) red blood cells (RBCs) can partly substitute transfusion needs in premature infants suffering from anemia. To explore whether expanded CB cells could provide additional autologous cells suitable for transfusion, we set up a simple one-step protocol to expand premature CB cells. CB buffy coat cells and isolated CD34-positive (CD34(pos) ) cells from premature and full-term CB and adult blood were tested with several combinations of growth factors while omitting xenogeneic proteins from the culture medium. Cell differentiation was analyzed serially during 21 days using flow cytometry, progenitor assays, and high-performance liquid chromatography. Expanded CB buffy coat cells resulted in a threefold higher number of erythroblasts than the isolated CD34(pos) cells. However, the RBCs contaminating the buffy coat remained present during the culture with uncertain quality. Premature and full-term CB CD34(pos) cells had similar fold expansion capacity and erythroid differentiation. With the use of interleukin-3, stem cell factor, and erythropoietin, the fold increases of all CD34(pos) cell sources were similar: CB 3942 ± 1554, adult peripheral mobilized blood 4702 ± 1826, and bone marrow (BM) 4143 ± 1908. The proportion of CD235a expression indicating erythroblast presence on Day 21 was slightly higher in the adult CD34(pos) cell sources: peripheral blood stem cells (96.7 ± 0.8%) and BM (98.9 ± 0.5%) compared to CB (87.7 ± 2.7%; p = 0.002). We were not able to induce further erythroid maturation in vitro. This explorative study showed that fairly pure autologous erythroid-expanded cell populations could be obtained by a simple culture method, which should be optimized. Future challenges comprise obtaining ex vivo enucleation of RBCs with the use of a minimal manipulating approach, which can add up to autologous RBCs derived from CB in the treatment of anemia of prematurity. © 2013 American Association of Blood Banks.

  20. Daughter Cells and Erythroid Cells Budding from PGCCs and Their Clinicopathological Significances in Colorectal Cancer.

    Science.gov (United States)

    Zhang, Dan; Yang, Xiaoyun; Yang, Zhengduo; Fei, Fei; Li, Shuyuan; Qu, Jie; Zhang, Mingqing; Li, Yuwei; Zhang, Xipeng; Zhang, Shiwu

    2017-01-01

    Purpose: We previously reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride (CoCl 2 ) exhibit cancer stem cell properties. Daughter cells generated by PGCCs possess epithelial mesenchymal transition (EMT) phenotype changes and EMT plays an important role in cancer development and progression. This study investigated the characteristics of PGCCs from LoVo and HCT116 induced by CoCl 2 and the clinicopathological significances of PGCCs in colorectal cancer (CRC). Materials and Methods: Western blotting and immunocytochemical staining were used to compare the expression levels of EMT-related proteins between PGCCs with budding daughter cells and the control cells. In addition, tissue samples were collected from 159 patients with CRC for analysis of PGCCs, vasculogenic mimicry (VM), and single stromal PGCCs with budding, as well as immunohistochemical staining for cathepsin B, vimentin, and hemoglobin A. Results: Single PGCCs induced by CoCl 2 formed spheroids in vitro . Poorly differentiated CRCs showed the highest numbers of PGCCs and VM, and expression of cathepsin B. There was greater expression of EMT-related proteins in PGCCs with budding daughter cells than in control cells. The expression of vimentin located in PGCC nuclei. Single stomal PGCCs with budding were detected in 27.45% of well differentiated, 50% of moderately differentiated, and 90.20% of poorly differentiated CRC samples. PGCCs can generate erythroid cells that express delta-hemoglobin to form VM. Erythroid cells generated by PGCCs were positive for hemoglobin A immunocytochemical staining. Conclusion: PGCCs from LoVo and HCT116 treated by CoCl 2 exhibited cancer stem cell properties. The number of PGCCs and VM were associated with CRC differentiation and daughter cells budded from PGCCs may promote the lymph node metastasis via expression of EMT-related proteins. PGCCs and their newly generated erythroid cells form VM structures.

  1. Gamma-interferon alters globin gene expression in neonatal and adult erythroid cells

    International Nuclear Information System (INIS)

    Miller, B.A.; Perrine, S.P.; Antognetti, G.; Perlmutter, D.H.; Emerson, S.G.; Sieff, C.; Faller, D.V.

    1987-01-01

    The effect of gamma-interferon on fetal hemoglobin synthesis by purified cord blood, fetal liver, and adult bone marrow erythroid progenitors was studied with a radioligand assay to measure hemoglobin production by BFU-E-derived erythroblasts. Coculture with recombinant gamma-interferon resulted in a significant and dose-dependent decrease in fetal hemoglobin production by neonatal and adult, but not fetal, BFU-E-derived erythroblasts. Accumulation of fetal hemoglobin by cord blood BFU-E-derived erythroblasts decreased up to 38.1% of control cultures (erythropoietin only). Synthesis of both G gamma/A gamma globin was decreased, since the G gamma/A gamma ratio was unchanged. Picograms fetal hemoglobin per cell was decreased by gamma-interferon addition, but picograms total hemoglobin was unchanged, demonstrating that a reciprocal increase in beta-globin production occurred in cultures treated with gamma-interferon. No toxic effect of gamma-interferon on colony growth was noted. The addition of gamma-interferon to cultures resulted in a decrease in the percentage of HbF produced by adult BFU-E-derived cells to 45.6% of control. Fetal hemoglobin production by cord blood, fetal liver, and adult bone marrow erythroid progenitors, was not significantly affected by the addition of recombinant GM-CSF, recombinant interleukin 1 (IL-1), recombinant IL-2, or recombinant alpha-interferon. Although fetal progenitor cells appear unable to alter their fetal hemoglobin program in response to any of the growth factors added here, the interaction of neonatal and adult erythroid progenitors with gamma-interferon results in an altered expression of globin genes

  2. Induction of erythroid differentiation in human erythroleukemia cells by depletion of malic enzyme 2.

    Directory of Open Access Journals (Sweden)

    Jian-Guo Ren

    2010-09-01

    Full Text Available Malic enzyme 2 (ME2 is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and CO2 and uses NAD as a cofactor. Higher expression of this enzyme correlates with the degree of cell de-differentiation. We found that ME2 is expressed in K562 erythroleukemia cells, in which a number of agents have been found to induce differentiation either along the erythroid or the myeloid lineage. We found that knockdown of ME2 led to diminished proliferation of tumor cells and increased apoptosis in vitro. These findings were accompanied by differentiation of K562 cells along the erythroid lineage, as confirmed by staining for glycophorin A and hemoglobin production. ME2 knockdown also totally abolished growth of K562 cells in nude mice. Increased ROS levels, likely reflecting increased mitochondrial production, and a decreased NADPH/NADP+ ratio were noted but use of a free radical scavenger to decrease inhibition of ROS levels did not reverse the differentiation or apoptotic phenotype, suggesting that ROS production is not causally involved in the resultant phenotype. As might be expected, depletion of ME2 induced an increase in the NAD+/NADH ratio and ATP levels fell significantly. Inhibition of the malate-aspartate shuttle was insufficient to induce K562 differentiation. We also examined several intracellular signaling pathways and expression of transcription factors and intermediate filament proteins whose expression is known to be modulated during erythroid differentiation in K562 cells. We found that silencing of ME2 leads to phospho-ERK1/2 inhibition, phospho-AKT activation, increased GATA-1 expression and diminished vimentin expression. Metabolomic analysis, conducted to gain insight into intermediary metabolic pathways that ME2 knockdown might affect, showed that ME2 depletion resulted in high orotate levels, suggesting potential impairment of pyrimidine metabolism. Collectively our data point to ME2 as a potentially novel

  3. Generation of erythroid cells from polyploid giant cancer cells: re-thinking about tumor blood supply.

    Science.gov (United States)

    Yang, Zhigang; Yao, Hong; Fei, Fei; Li, Yuwei; Qu, Jie; Li, Chunyuan; Zhang, Shiwu

    2018-04-01

    During development and tumor progression, cells need a sufficient blood supply to maintain development and rapid growth. It is reported that there are three patterns of blood supply for tumor growth: endothelium-dependent vessels, mosaic vessels, and vasculogenic mimicry (VM). VM was first reported in highly aggressive uveal melanomas, with tumor cells mimicking the presence and function of endothelial cells forming the walls of VM vessels. The walls of mosaic vessels are randomly lined with both endothelial cells and tumor cells. We previously proposed a three-stage process, beginning with VM, progressing to mosaic vessels, and eventually leading to endothelium-dependent vessels. However, many phenomena unique to VM channel formation remain to be elucidated, such as the origin of erythrocytes before VM vessels connect with endothelium-dependent vessels. In adults, erythroid cells are generally believed to be generated from hematopoietic stem cells in the bone marrow. In contrast, embryonic tissue obtains oxygen through formation of blood islands, which are largely composed of embryonic hemoglobin with a higher affinity with oxygen, in the absence of mature erythrocytes. Recent data from our laboratory suggest that embryonic blood-forming mechanisms also exist in cancer tissue, particularly when these tissues are under environmental stress such as hypoxia. We review the evidence from induced pluripotent stem cells in vitro and in vivo to support this previously underappreciated cell functionality in normal and cancer cells, including the ability to generate erythroid cells. We will also summarize the current understanding of tumor angiogenesis, VM, and our recent work on polyploid giant cancer cells, with emphasis on their ability to generate erythroid cells and their association with tumor growth under hypoxia. An alternative embryonic pathway to obtain oxygen in cancer cells exists, particularly when they are under hypoxic conditions.

  4. Eos negatively regulates human γ-globin gene transcription during erythroid differentiation.

    Directory of Open Access Journals (Sweden)

    Hai-Chuan Yu

    Full Text Available BACKGROUND: Human globin gene expression is precisely regulated by a complicated network of transcription factors and chromatin modifying activities during development and erythropoiesis. Eos (Ikaros family zinc finger 4, IKZF4, a member of the zinc finger transcription factor Ikaros family, plays a pivotal role as a repressor of gene expression. The aim of this study was to examine the role of Eos in globin gene regulation. METHODOLOGY/PRINCIPAL FINDINGS: Western blot and quantitative real-time PCR detected a gradual decrease in Eos expression during erythroid differentiation of hemin-induced K562 cells and Epo-induced CD34+ hematopoietic stem/progenitor cells (HPCs. DNA transfection and lentivirus-mediated gene transfer demonstrated that the enforced expression of Eos significantly represses the expression of γ-globin, but not other globin genes, in K562 cells and CD34+ HPCs. Consistent with a direct role of Eos in globin gene regulation, chromatin immunoprecipitaion and dual-luciferase reporter assays identified three discrete sites located in the DNase I hypersensitivity site 3 (HS3 of the β-globin locus control region (LCR, the promoter regions of the Gγ- and Aγ- globin genes, as functional binding sites of Eos protein. A chromosome conformation capture (3C assay indicated that Eos may repress the interaction between the LCR and the γ-globin gene promoter. In addition, erythroid differentiation was inhibited by enforced expression of Eos in K562 cells and CD34+ HPCs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Eos plays an important role in the transcriptional regulation of the γ-globin gene during erythroid differentiation.

  5. Induction of foetal haemoglobin synthesis in erythroid progenitor stem cells: mediated by water-soluble components of Terminalia catappa.

    Science.gov (United States)

    Aimola, I A; Inuwa, H M; Nok, A J; Mamman, A I

    2014-06-01

    Current novel therapeutic agents for the treatment of sickle cell anaemia (SCA) focus on increasing foetal haemoglobin (HbF) levels in SCA patients. Unfortunately, the only approved HbF-inducing agent, hydroxyurea, has long-term unpredictable side effects. Studies have shown the potential of plant compounds to modulate HbF synthesis in primary erythroid progenitor stem cells. We isolated a novel HbF-inducing Terminalia catappa distilled water active fraction (TCDWF) from Terminalia catappa leaves that induced the commitment of erythroid progenitor stem cells to the erythroid lineage and relatively higher HbF synthesis of 9.2- and 6.8-fold increases in both erythropoietin (EPO)-independent and EPO-dependent progenitor stem cells respectively. TCDWF was differentially cytotoxic to EPO-dependent and EPO-independent erythroid progenitor stem cell cultures as revealed by lactate dehydrogenase release from the cells. TCDWF demonstrated a protective effect on EPO-dependent and not EPO-independent progenitor cells. TCDWF induced a modest increase in caspase 3 activity in EPO-independent erythroid progenitor stem cell cultures compared with a significantly higher (P˂0.05) caspase 3 activity in EPO-dependent ones. The results demonstrate that TCDWF may hold promising HbF-inducing compounds, which work synergistically, and suggest a dual modulatory effect on erythropoiesis inherent in this active fraction. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Fusion of ZMYND8 and RELA genes in acute erythroid leukemia

    DEFF Research Database (Denmark)

    Panagopoulos, Ioannis; Micci, Francesca; Thorsen, Jim

    2013-01-01

    Acute erythroid leukemia was diagnosed in a 4-month-old boy. Cytogenetic analysis of bone marrow (BM) cells showed a t(11;20)(p11;q11) translocation. RNA extracted from the BM was sequenced and analyzed for fusion transcripts using the software FusionMap. A ZMYND8-RELA fusion was ranked first. RT...... the translocation. The putative ZMYND8-RELA fusion protein contains the Zinc-PHD finger domain, a bromodomain, a PWWP domain, a MYND type of zinc finger of ZMYND8, and the entire RELA protein, indicating that it might act leukemogenically by influencing several cellular processes including the NF-kappa-B pathway....

  7. Proteomic analysis of erythroid differentiation induced by hexamethylene bisacetamide in murine erythroleukemia cells

    Czech Academy of Sciences Publication Activity Database

    Petrák, J.; Myslivcová, D.; Man, Petr; Čmejlová, J.; Čmejla, R.; Vyoral, D.

    2007-01-01

    Roč. 35, - (2007), s. 193-202 ISSN 0301-472X R&D Projects: GA MŠk LC545 Grant - others:CZ(CZ) 023736; GA ČR(CZ) GA303/04/0003; GA MŠk(CZ) LC06044 Institutional research plan: CEZ:AV0Z50200510 Source of funding: V - iné verejné zdroje ; V - iné verejné zdroje ; V - iné verejné zdroje Keywords : murine erythroleukemia cells * erythroid differentiation * hexamethylene bisacetamide Subject RIV: EE - Microbiology, Virology Impact factor: 3.147, year: 2007

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

    Directory of Open Access Journals (Sweden)

    Guo Y

    2015-06-01

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

  9. Protection of zidovudine-induced toxicity against murine erythroid progenitor cells by vitamin E.

    Science.gov (United States)

    Gogu, S R; Lertora, J J; George, W J; Hyslop, N E; Agrawal, K C

    1991-08-01

    The ability of vitamin E (alpha-tocopherol) to stimulate erythroid progenitor cells was investigated in an attempt to identify ways to ameliorate zidovudine (azidothymidine, AZT)-induced anemia. In vitro, alpha-tocopherol acid succinate (ATS), upon incubation with murine bone marrow cells at concentrations of up to 4 micrograms/ml, caused a dose-dependent increase in erythroid colony-forming unit (CFU-E)-derived colonies. This increase was equivalent to the effect demonstrated by 50 mU of recombinant human erythropoietin (rhEpo) or 200 U of recombinant interleukin 3 (rIL-3). For in vivo studies, anemia was produced in CD-1 male mice by administering AZT in drinking water (1.5 mg/ml). Treatment with vitamin E (50 mg/kg body weight) or Epo (0.4 U per mouse) was initiated 24 h later and continued for five consecutive days. Seventh day bone marrow cells from femurs were assayed for CFU-E-derived colonies. Both vitamin E and Epo significantly increased the number of CFU-E-derived colonies by 75% and 86% of control, respectively, indicating that these agents were approximately similar in protecting the bone marrow from AZT-induced toxicity.

  10. Characterization of human erythroid burst-promoting activity derived from bone marrow conditioned media

    International Nuclear Information System (INIS)

    Porter, P.N.; Ogawa, M.

    1982-01-01

    Bone marrow conditioned media (BMCM) increases burst number and the incorporation of 59 Fe into heme by bursts when peripheral blood or bone marrow cells are cultured at limiting serum concentrations. Burst-promoting activity (BPA) has now been purified approximately 300-fold from this source by ion-exchange chromatography on DEAE-Sephadex and absorption chromatography on hydroxyapatite agarose gel. Marrow BPA increased burst number and hemoglobin (Hb) synthesis in a dose-dependent manner. A larger increase in Hb synthesis than in burst number was consistently observed, which was probably a consequence of the increase in the number of cells per burst that occurs in the presence of BPA. The role of BPA in culture could be distinguished from erythropoietin (Ep), since no bursts grew in the absence of Ep, whether or not BPA was present, and since it had no effect on the growth of erythroid colonies scored at day 5 of culture. Our purified fraction did not support the growth of CFU-C in culture. Activity was stable at temperatures of 70 degrees C or lower for 10 min; exposure to 80 degrees C resulted in approximately 50% loss of activity. BPA was completely inactivated by treatment at 100 degrees C for 10 min. Thus, human bone marrow cells produce a heat-sensitive factor that specifically promotes the growth of early erythroid progenitors in culture

  11. Functional plasticity of the N-methyl-d-aspartate receptor in differentiating human erythroid precursor cells.

    Science.gov (United States)

    Hänggi, Pascal; Telezhkin, Vsevolod; Kemp, Paul J; Schmugge, Markus; Gassmann, Max; Goede, Jeroen S; Speer, Oliver; Bogdanova, Anna

    2015-06-15

    Calcium signaling is essential to support erythroid proliferation and differentiation. Precise control of the intracellular Ca(2+) levels in erythroid precursor cells (EPCs) is afforded by coordinated expression and function of several cation channels, including the recently identified N-methyl-d-aspartate receptor (NMDAR). Here, we characterized the changes in Ca(2+) uptake and electric currents mediated by the NMDARs occurring during EPC differentiation using flow cytometry and patch clamp. During erythropoietic maturation, subunit composition and properties of the receptor changed; in proerythroblasts and basophilic erythroblasts, fast deactivating currents with high amplitudes were mediated by the GluN2A subunit-dominated receptors, while at the polychromatic and orthochromatic erythroblast stages, the GluN2C subunit was getting more abundant, overriding the expression of GluN2A. At these stages, the currents mediated by the NMDARs carried the features characteristic of the GluN2C-containing receptors, such as prolonged decay time and lower conductance. Kinetics of this switch in NMDAR properties and abundance varied markedly from donor to donor. Despite this variability, NMDARs were essential for survival of EPCs in any subject tested. Our findings indicate that NMDARs have a dual role during erythropoiesis, supporting survival of polychromatic erythroblasts and contributing to the Ca(2+) homeostasis from the orthochromatic erythroblast stage to circulating red blood cells. Copyright © 2015 the American Physiological Society.

  12. Parvovirus B19 integration into human CD36+ erythroid progenitor cells.

    Science.gov (United States)

    Janovitz, Tyler; Wong, Susan; Young, Neal S; Oliveira, Thiago; Falck-Pedersen, Erik

    2017-11-01

    The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome. Computational analysis of integration patterns revealed strong correlations with gene intronic regions, H3K9me3 sites, and the identification of 41 base pair consensus sequence with an octanucleotide core motif. The octanucleotide core has homology to a single region of B19V, adjacent to the P6 promoter TATA box. We present the first direct evidence that B19V infection of erythroid progenitor cells disrupts the human genome and facilitates viral DNA integration. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex.

    Science.gov (United States)

    Ganaie, Safder S; Zou, Wei; Xu, Peng; Deng, Xuefeng; Kleiboeker, Steve; Qiu, Jianming

    2017-05-01

    Productive infection of human parvovirus B19 (B19V) exhibits high tropism for burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) progenitor cells in human bone marrow and fetal liver. This exclusive restriction of the virus replication to human erythroid progenitor cells is partly due to the intracellular factors that are essential for viral DNA replication, including erythropoietin signaling. Efficient B19V replication also requires hypoxic conditions, which upregulate the signal transducer and activator of transcription 5 (STAT5) pathway, and phosphorylated STAT5 is essential for virus replication. In this study, our results revealed direct involvement of STAT5 in B19V DNA replication. Consensus STAT5-binding elements were identified adjacent to the NS1-binding element within the minimal origins of viral DNA replication in the B19V genome. Phosphorylated STAT5 specifically interacted with viral DNA replication origins both in vivo and in vitro, and was actively recruited within the viral DNA replication centers. Notably, STAT5 interacted with minichromosome maintenance (MCM) complex, suggesting that STAT5 directly facilitates viral DNA replication by recruiting the helicase complex of the cellular DNA replication machinery to viral DNA replication centers. The FDA-approved drug pimozide dephosphorylates STAT5, and it inhibited B19V replication in ex vivo expanded human erythroid progenitors. Our results demonstrated that pimozide could be a promising antiviral drug for treatment of B19V-related diseases.

  14. Enhancement of erythroid colony formation in vitro by spleen extract from irradiated rats

    International Nuclear Information System (INIS)

    Kasai, Shiro; Terasawa, Waka; Kodama, Hiroaki; Terasawa, Takashi

    1980-01-01

    The effect of spleen extract from irradiated rats on CFU-e and BFU-e colony formation of rat bone marrow cells was investigated by using modified plasma clot culture media. In the presence of erythropoietin (Ep), CFU-e colony formation peaked at 48 hr of culture, and the Ep-induced increase of CFU-e colonies was dose-dependent. The addition of spleen extract enhanced the colony formation more than two-fold in the Ep-containing culture. BFU-e colony formation was also enhanced by the addition of spleen extract. These results indicate that spleen extract from irradiated rats contains factor(s) which stimulates the proliferation of erythroid progenitors. (author)

  15. Erythroid cell mitochondria receive endosomal iron by a "kiss-and-run" mechanism.

    Science.gov (United States)

    Hamdi, Amel; Roshan, Tariq M; Kahawita, Tanya M; Mason, Anne B; Sheftel, Alex D; Ponka, Prem

    2016-12-01

    In erythroid cells, more than 90% of transferrin-derived iron enters mitochondria where ferrochelatase inserts Fe 2+ into protoporphyrin IX. However, the path of iron from endosomes to mitochondrial ferrochelatase remains elusive. The prevailing opinion is that, after its export from endosomes, the redox-active metal spreads into the cytosol and mysteriously finds its way into mitochondria through passive diffusion. In contrast, this study supports the hypothesis that the highly efficient transport of iron toward ferrochelatase in erythroid cells requires a direct interaction between transferrin-endosomes and mitochondria (the "kiss-and-run" hypothesis). Using a novel method (flow sub-cytometry), we analyze lysates of reticulocytes after labeling these organelles with different fluorophores. We have identified a double-labeled population definitively representing endosomes interacting with mitochondria, as demonstrated by confocal microscopy. Moreover, we conclude that this endosome-mitochondrion association is reversible, since a "chase" with unlabeled holotransferrin causes a time-dependent decrease in the size of the double-labeled population. Importantly, the dissociation of endosomes from mitochondria does not occur in the absence of holotransferrin. Additionally, mutated recombinant holotransferrin, that cannot release iron, significantly decreases the uptake of 59 Fe by reticulocytes and diminishes 59 Fe incorporation into heme. This suggests that endosomes, which are unable to provide iron to mitochondria, cause a "traffic jam" leading to decreased endocytosis of holotransferrin. Altogether, our results suggest that a molecular mechanism exists to coordinate the iron status of endosomal transferrin with its trafficking. Besides its contribution to the field of iron metabolism, this study provides evidence for a new intracellular trafficking pathway of organelles. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Computational modeling of the hematopoietic erythroid-myeloid switch reveals insights into cooperativity, priming, and irreversibility.

    Directory of Open Access Journals (Sweden)

    Vijay Chickarmane

    2009-01-01

    Full Text Available Hematopoietic stem cell lineage choices are decided by genetic networks that are turned ON/OFF in a switch-like manner. However, prior to lineage commitment, genes are primed at low expression levels. Understanding the underlying molecular circuitry in terms of how it governs both a primed state and, at the other extreme, a committed state is of relevance not only to hematopoiesis but also to developmental systems in general. We develop a computational model for the hematopoietic erythroid-myeloid lineage decision, which is determined by a genetic switch involving the genes PU.1 and GATA-1. Dynamical models based upon known interactions between these master genes, such as mutual antagonism and autoregulation, fail to make the system bistable, a desired feature for robust lineage determination. We therefore suggest a new mechanism involving a cofactor that is regulated as well as recruited by one of the master genes to bind to the antagonistic partner that is necessary for bistability and hence switch-like behavior. An interesting fallout from this architecture is that suppression of the cofactor through external means can lead to a loss of cooperativity, and hence to a primed state for PU.1 and GATA-1. The PU.1-GATA-1 switch also interacts with another mutually antagonistic pair, C/EBPalpha-FOG-1. The latter pair inherits the state of its upstream master genes and further reinforces the decision due to several feedback loops, thereby leading to irreversible commitment. The genetic switch, which handles the erythroid-myeloid lineage decision, is an example of a network that implements both a primed and a committed state by regulating cooperativity through recruitment of cofactors. Perturbing the feedback between the master regulators and downstream targets suggests potential reprogramming strategies. The approach points to a framework for lineage commitment studies in general and could aid the search for lineage-determining genes.

  17. Dihydroartemisinin inhibits the human erythroid cell differentiation by altering the cell cycle

    International Nuclear Information System (INIS)

    Finaurini, Sara; Basilico, Nicoletta; Corbett, Yolanda; D’Alessandro, Sarah; Parapini, Silvia; Olliaro, Piero; Haynes, Richard K.; Taramelli, Donatella

    2012-01-01

    Artemisinin derivatives such as dihydroartemisinin (DHA) induce significant depletion of early embryonic erythroblasts in animal models. We have reported previously that DHA specifically targets pro-erythroblasts and basophilic erythroblasts, when human CD34+ stem cells are differentiated toward the erythroid lineage, indicating that a window of susceptibility to artemisinins may exist also in human developmental erythropoiesis during pregnancy. To better investigate the toxicity of artemisinin derivatives, the structure–activity relationship was evaluated against the K562 leukaemia cell line, used as a model for differentiating early human erythroblasts. All artemisinins derivatives, except deoxyartemisinin, inhibited both spontaneous and induced erythroid differentiation, confirming that the peroxide bridge is responsible for the erythro-toxicity. On the contrary, cell growth was markedly reduced by DHA, artemisone and artesunate but not by artemisinin, 10-deoxoartemisinin or deoxy-artemisinin. The substituent at position C-10 is responsible only for the anti-proliferative effect, since 10-deoxoartemisinin did not reduce cell growth but arrested the differentiation of K562 cells. In particular, the results showed that DHA resulted the most potent and rapidly acting compound of the drug family, causing (i) the decreased expression of GpA surface receptors and the down regulation the γ-globin gene; (ii) the alteration of S phase of cell cycle and (iii) the induction of programmed cell death of early erythroblasts in a dose dependent manner within 24 h. In conclusion, these findings confirm that the active metabolite DHA is responsible for the erythro-toxicity of most of artemisinins used in therapy. Thus, as long as no further clinical data are available, current WHO recommendations of avoiding malaria treatment with artemisinins during the first trimester of pregnancy remain valid.

  18. The role of the epigenetic signal, DNA methylation, in gene regulation during erythroid development.

    Science.gov (United States)

    Ginder, Gordon D; Gnanapragasam, Merlin N; Mian, Omar Y

    2008-01-01

    The sequence complexity of the known vertebrate genomes alone is insufficient to account for the diversity between individuals of a species. Although our knowledge of vertebrate biology has evolved substantially with the growing compilation of sequenced genomes, understanding the temporal and spatial regulation of genes remains fundamental to fully exploiting this information. The importance of epigenetic factors in gene regulation was first hypothesized decades ago when biologists posited that methylation of DNA could heritably alter gene expression [Holliday and Pugh, 1975. Science 187(4173), 226-232; Riggs, 1975. Cytogenet. and Cell Genet.14(1), 9-25; Scarano et al., 1967. Proc. Natl. Acad. Sci. USA 57(5), 1394-1400)]. It was subsequently shown that vertebrate DNA methylation, almost exclusively at the 5' position of cytosine in the dinucleotide CpG, played a role in a number of processes including embryonic development, genetic imprinting, cell differentiation, and tumorigenesis. At the time of this writing, a large and growing list of genes is known to exhibit DNA methylation-dependent regulation, and we understand in some detail the mechanisms employed by cells in using methylation as a regulatory modality. In this context, we revisit one of the original systems in which the role of DNA methylation in vertebrate gene regulation during development was described and studied: erythroid cells. We briefly review the recent advances in our understanding of DNA methylation and, in particular, its regulatory role in red blood cells during differentiation and development. We also address DNA methylation as a component of erythroid chromatin architecture, and the interdependence of CpG methylation and histone modification.

  19. CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells.

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    Laurie A Steiner

    Full Text Available CTCF and cohesinSA-1 are regulatory proteins involved in a number of critical cellular processes including transcription, maintenance of chromatin domain architecture, and insulator function. To assess changes in the CTCF and cohesinSA-1 interactomes during erythropoiesis, chromatin immunoprecipitation coupled with high throughput sequencing and mRNA transcriptome analyses via RNA-seq were performed in primary human hematopoietic stem and progenitor cells (HSPC and primary human erythroid cells from single donors.Sites of CTCF and cohesinSA-1 co-occupancy were enriched in gene promoters in HSPC and erythroid cells compared to single CTCF or cohesin sites. Cell type-specific CTCF sites in erythroid cells were linked to highly expressed genes, with the opposite pattern observed in HSPCs. Chromatin domains were identified by ChIP-seq with antibodies against trimethylated lysine 27 histone H3, a modification associated with repressive chromatin. Repressive chromatin domains increased in both number and size during hematopoiesis, with many more repressive domains in erythroid cells than HSPCs. CTCF and cohesinSA-1 marked the boundaries of these repressive chromatin domains in a cell-type specific manner.These genome wide data, changes in sites of protein occupancy, chromatin architecture, and related gene expression, support the hypothesis that CTCF and cohesinSA-1 have multiple roles in the regulation of gene expression during erythropoiesis including transcriptional regulation at gene promoters and maintenance of chromatin architecture. These data from primary human erythroid cells provide a resource for studies of normal and perturbed erythropoiesis.

  20. Carbon monoxide induced erythroid differentiation of K562 cells mimics the central macrophage milieu in erythroblastic islands.

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    Shlomi Toobiak

    Full Text Available Growing evidence supports the role of erythroblastic islands (EI as microenvironmental niches within bone marrow (BM, where cell-cell attachments are suggested as crucial for erythroid maturation. The inducible form of the enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in erythroblasts where hemoglobin (Hb is synthesized. Yet, the central macrophage, which retains high HO-1 activity, might be suitable to take over degradation of extra, harmful, Hb heme. Of these enzymatic products, only the hydrophobic gas molecule--CO can transfer from the macrophage to surrounding erythroblasts directly via their tightly attached membranes in the terminal differentiation stage.Based on the above, the study hypothesized CO to have a role in erythroid maturation. Thus, the effect of CO gas as a potential erythroid differentiation inducer on the common model for erythroid progenitors, K562 cells, was explored. Cells were kept under oxygen lacking environment to mimic BM conditions. Nitrogen anaerobic atmosphere (N₂A served as control for CO atmosphere (COA. Under both atmospheres cells proliferation ceased: in N₂A due to cell death, while in COA as a result of erythroid differentiation. Maturation was evaluated by increased glycophorin A expression and Hb concentration. Addition of 1%CO only to N₂A, was adequate for maintaining cell viability. Yet, the average Hb concentration was low as compared to COA. This was validated to be the outcome of diversified maturation stages of the progenitor's population.In fact, the above scenario mimics the in vivo EI conditions, where at any given moment only a minute portion of the progenitors proceeds into terminal differentiation. Hence, this model might provide a basis for further molecular investigations of the EI structure/function relationship.

  1. Molecular pathways of early CD105-positive erythroid cells as compared with CD34-positive common precursor cells by flow cytometric cell-sorting and gene expression profiling

    International Nuclear Information System (INIS)

    Machherndl-Spandl, S; Suessner, S; Danzer, M; Proell, J; Gabriel, C; Lauf, J; Sylie, R; Klein, H-U; Béné, M C; Weltermann, A; Bettelheim, P

    2013-01-01

    Special attention has recently been drawn to the molecular network of different genes that are responsible for the development of erythroid cells. The aim of the present study was to establish in detail the immunophenotype of early erythroid cells and to compare the gene expression profile of freshly isolated early erythroid precursors with that of the CD34-positive (CD34 + ) compartment. Multiparameter flow cytometric analyses of human bone marrow mononuclear cell fractions (n=20) defined three distinct early erythroid stages. The gene expression profile of sorted early erythroid cells was analyzed by Affymetrix array technology. For 4524 genes, a differential regulation was found in CD105-positive erythroid cells as compared with the CD34 + progenitor compartment (2362 upregulated genes). A highly significant difference was observed in the expression level of genes involved in transcription, heme synthesis, iron and mitochondrial metabolism and transforming growth factor-β signaling. A comparison with recently published data showed over 1000 genes that as yet have not been reported to be upregulated in the early erythroid lineage. The gene expression level within distinct pathways could be illustrated directly by applying the Ingenuity software program. The results of gene expression analyses can be seen at the Gene Expression Omnibus repository

  2. MiR-27a Promotes Hemin-Induced Erythroid Differentiation of K562 Cells by Targeting CDC25B

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    Dongsheng Wang

    2018-03-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs play a crucial role in erythropoiesis. MiR-23a∼27a∼24-2 clusters have been proven to take part in erythropoiesis via some proteins. CDC25B (cell division control Cdc2 phosphostase B is also the target of mir-27a; whether it regulates erythropoiesis and its mechanism are unknown. Methods: To evaluate the potential role of miR-27a during erythroid differentiation, we performed miR-27a gain- and loss-of-function experiments on hemin-induced K562 cells. We detected miR-27a expression after hemin stimulation at different time points. At the same time, the γ-globin gene also was measured via real-time PCR. According to the results of the chips, we screened the target protein of miR-27a through a dual-luciferase reporter assay and identified it via Western blot analyses. To evaluate the function of CDC25B, benzidine staining and flow cytometry were employed to detect the cell differentiation and cell cycle. Results: We found that miR-27a promotes hemin-induced erythroid differentiation of human K562 cells by targeting cell division cycle 25 B (CDC25B. Overexpression of miR-27a promotes the differentiation of hemin-induced K562 cells, as demonstrated by γ-globin overexpression. The inhibition of miR-27a expression suppresses erythroid differentiation, thus leading to a reduction in the γ-globin gene. CDC25B was identified as a new target of miR-27a during erythroid differentiation. Overexpression of miR-27a led to decreased CDC25B expression after hemin treatment, and CDC25B was up-regulated when miR-27a expression was inhibited. Moreover, the inhibition of CDC25B affected erythroid differentiation, as assessed by γ-globin expression. Conclusion: This study is the first report of the interaction between miR-27a and CDC25B, and it improves the understanding of miRNA functions during erythroid differentiation.

  3. Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch.

    Science.gov (United States)

    Hwang, Yung; Futran, Melinda; Hidalgo, Daniel; Pop, Ramona; Iyer, Divya Ramalingam; Scully, Ralph; Rhind, Nicholas; Socolovsky, Merav

    2017-05-01

    Cell cycle regulators are increasingly implicated in cell fate decisions, such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. We studied an S phase-dependent cell fate switch, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. We found that progenitors are dependent on p57 KIP2 -mediated slowing of replication forks for self-renewal, a novel function for cyclin-dependent kinase inhibitors. The switch to differentiation entails rapid down-regulation of p57 KIP2 with a consequent global increase in replication fork speed and an abruptly shorter S phase. Our work suggests that cell cycles with specialized global DNA replication dynamics are integral to the maintenance of specific cell states and to cell fate decisions.

  4. Biosynthesis of heme in immature erythroid cells. The regulatory step for heme formation in the human erythron

    International Nuclear Information System (INIS)

    Gardner, L.C.; Cox, T.M.

    1988-01-01

    Heme formation in reticulocytes from rabbits and rodents is subject to end product negative feedback regulation: intracellular free heme has been shown to control acquisition of transferrin iron for heme synthesis. To identify the site of control of heme biosynthesis in the human erythron, immature erythroid cells were obtained from peripheral blood and aspirated bone marrow. After incubation with human 59Fe transferrin, 2-[14C]glycine, or 4-[14C]delta-aminolevulinate, isotopic incorporation into extracted heme was determined. Addition of cycloheximide to increase endogenous free heme, reduced incorporation of labeled glycine and iron but not delta-aminolevulinate into cell heme. Incorporation of glycine and iron was also sensitive to inhibition by exogenous hematin (Ki, 30 and 45 microM, respectively) i.e. at concentrations in the range which affect cell-free protein synthesis in reticulocyte lysates. Hematin treatment rapidly diminished incorporation of intracellular 59Fe into heme by human erythroid cells but assimilation of 4-[14C]delta-aminolevulinate into heme was insensitive to inhibition by hematin (Ki greater than 100 microM). In human reticulocytes (unlike those from rabbits), addition of ferric salicylaldehyde isonicotinoylhydrazone, to increase the pre-heme iron pool independently of the transferrin cycle, failed to promote heme synthesis or modify feedback inhibition induced by hematin. In human erythroid cells (but not rabbit reticulocytes) pre-incubation with unlabeled delta-aminolevulinate or protoporphyrin IX greatly stimulated utilization of cell 59Fe for heme synthesis and also attenuated end product inhibition. In human erythroid cells heme biosynthesis is thus primarily regulated by feedback inhibition at one or more steps which lead to delta-aminolevulinate formation

  5. Therapeutic Effects of Erythroid Differentiation Regulator 1 on Imiquimod-Induced Psoriasis-Like Skin Inflammation

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    Kyung Eun Kim

    2016-02-01

    Full Text Available Psoriasis is a common skin disease accompanied by chronic inflammation. In previous studies, erythroid differentiation regulator 1 (ERDR1 was shown to have a negative correlation with proinflammatory cytokine IL-18. However, the role of ERDR1 in the inflammatory skin disease psoriasis has not been evaluated. In this study, to investigate the role of ERDR1 in psoriasis, recombinant ERDR1 was injected intraperitoneally into a psoriasis mouse model. Recombinant ERDR1 (rERDR1 significantly alleviated the symptoms of psoriasis-like skin inflammation and reduced the mRNA of various psoriasis-related markers, including keratin 14, S100A8, and Th17-related cytokines IL-17 and IL-22, suggesting that rERDR1 exerts therapeutic effects on psoriasis via the regulation of Th17 functions. Additionally, the expression of CCL20, a well-known Th17 attracting chemokine, was determined. CCL20 expression significantly decreased in the rERDR1-injected group compared with the vehicle (PBS-injected group. CCR6 expression in the psoriatic lesional skin was also decreased by rERDR1 administration, implying the inhibition of CCR6-expressing Th17 cell chemotaxis via the downregulation of CCL20. Taken together, this study provides the first evidence that ERDR1 may be a potential therapeutic target for psoriasis.

  6. FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia

    International Nuclear Information System (INIS)

    Pašaliç, Z; Greif, P A; Jurinoviç, V; Mulaw, M; Kakadia, P M; Tizazu, B; Fröhlich-Archangelo, L; Krause, A; Bohlander, S K

    2011-01-01

    The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294–335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6

  7. Characterization of erythroid and granulocyte monocyte progenitors in human cord blood.

    Science.gov (United States)

    Issaragrisil, S; Grilli, G; Nothdurft, W; Fliedner, T M

    1984-09-01

    Some characteristics of both erythroid and granulocyte monocyte progenitors in human cord blood were compared to those in adult blood and bone marrow. The number of progenitors in cord blood was higher than that in adult blood and bone marrow. Most colonies in cord blood culture were monocyte-macrophage, whereas those from adult blood were largely eosinophilic. Cord blood progenitors had a slower sedimentation velocity than that reported for marrow, but sedimented faster than that for adult blood. A significant proportion of progenitors in cord blood as well as adult marrow was found to be in the DNA synthetic phase of the cell cycle whereas progenitors in adult blood were not. Cord blood BFU-E were more resistant than adult blood BFU-E but cord blood CFU-GM were not different from adult blood CFU-GM with regard to radiation sensitivity. Cord blood CFU-GM appeared to be more radio-resistant than adult marrow GFU-GM. From these results is seems clear that progenitors in cord blood differ in some aspects from those in adult blood and bone marrow.

  8. Human primary erythroid cells as a more sensitive alternative in vitro hematological model for nanotoxicity studies: Toxicological effects of silver nanoparticles.

    Science.gov (United States)

    Rujanapun, Narawadee; Aueviriyavit, Sasitorn; Boonrungsiman, Suwimon; Rosena, Apiwan; Phummiratch, Duangkamol; Riolueang, Suchada; Chalaow, Nipon; Viprakasit, Vip; Maniratanachote, Rawiwan

    2015-12-01

    Although immortalized cells established from cancerous cells have been widely used for studies in nanotoxicology studies, the reliability of the results derived from immortalized cells has been questioned because of their different characteristics from normal cells. In the present study, human primary erythroid cells in liquid culture were used as an in vitro hematological cell model for investigation of the nanotoxicity of silver nanoparticles (AgNPs) and comparing the results to the immortalized hematological cell lines HL60 and K562. The AgNPs caused significant cytotoxic effects in the primary erythroid cells, as shown by the decreased cell viability and induction of intracellular ROS generation and apoptosis, whereas they showed much lower cytotoxic and apoptotic effects in HL60 and K562 cells and did not induced ROS generation in these cell lines. Scanning electron microcopy revealed an interaction of AgNPs to the cell membrane in both primary erythroid and immortalized cells. In addition, AgNPs induced hemolysis in the primary erythroid cells in a dose-dependent manner, and transmission electron microcopy analysis revealed that AgNPs damaged the erythroid cell membrane. Taken together, these results suggest that human primary erythroid cells in liquid culture are a more sensitive alternative in vitro hematological model for nanotoxicology studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression.

    Science.gov (United States)

    Zolea, Fabiana; Battaglia, Anna Martina; Chiarella, Emanuela; Malanga, Donatella; De Marco, Carmela; Bond, Heather Mandy; Morrone, Giovanni; Costanzo, Francesco; Biamonte, Flavia

    2017-10-17

    Erythroid differentiation is a complex and multistep process during which an adequate supply of iron for hemoglobinization is required. The role of ferritin heavy subunit, in this process, has been mainly attributed to its capacity to maintain iron in a non-toxic form. We propose a new role for ferritin heavy subunit (FHC) in controlling the erythroid commitment of K562 erythro-myeloid cells. FHC knockdown induces a change in the balance of GATA transcription factors and significantly reduces the expression of a repertoire of erythroid-specific genes, including α- and γ-globins, as well as CD71 and CD235a surface markers, in the absence of differentiation stimuli. These molecular changes are also reflected at the morphological level. Moreover, the ability of FHC-silenced K562 cells to respond to the erythroid-specific inducer hemin is almost completely abolished. Interestingly, we found that this new role for FHC is largely mediated via regulation of miR-150, one of the main microRNA implicated in the cell-fate choice of common erythroid/megakaryocytic progenitors. These findings shed further insight into the biological properties of FHCand delineate a role in erythroid differentiation where this protein does not act as a mere iron metabolism-related factor but also as a critical regulator of the expression of genes of central relevance for erythropoiesis.

  10. No changes in heme synthesis in human Friedreich´s ataxia erythroid progenitor cells.

    Science.gov (United States)

    Steinkellner, Hannes; Singh, Himanshu Narayan; Muckenthaler, Martina U; Goldenberg, Hans; Moganty, Rajeswari R; Scheiber-Mojdehkar, Barbara; Sturm, Brigitte

    2017-07-20

    Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the protein frataxin. Frataxin is thought to play a role in iron-sulfur cluster biogenesis and heme synthesis. In this study, we used erythroid progenitor stem cells obtained from FRDA patients and healthy donors to investigate the putative role, if any, of frataxin deficiency in heme synthesis. We used electrochemiluminescence and qRT-PCR for frataxin protein and mRNA quantification. We used atomic absorption spectrophotometry for iron levels and a photometric assay for hemoglobin levels. Protoporphyrin IX and Ferrochelatase were analyzed using auto-fluorescence. An "IronChip" microarray analysis followed by a protein-protein interaction analysis was performed. FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis. The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Recombinant erythroid differentiation regulator 1 inhibits both inflammation and angiogenesis in a mouse model of rosacea.

    Science.gov (United States)

    Kim, Miri; Kim, Kyung-Eun; Jung, Haw Young; Jo, Hyunmu; Jeong, Seo-Won; Lee, Jahyung; Kim, Chang Han; Kim, Heejong; Cho, Daeho; Park, Hyun Jeong

    2015-09-01

    The erythroid differentiation regulator 1 (Erdr1), which is a novel and highly conserved factor, was recently reported to be negatively regulated by IL-18 and to play a crucial role as an antimetastatic factor. IL-18 is a proinflammatory cytokine that functions as an angiogenic mediator in inflammation. Rosacea is a chronic inflammatory skin disorder that is characterized by abnormal inflammation and vascular hyperactivity of the facial skin. To determine whether Erdr1 contributes to the regulation of the chronic inflammatory process in the development of rosacea, an immunohistochemical analysis was performed in healthy donors and patients with rosacea. In this study, we showed that Erdr1 was downregulated, whereas IL-18 was upregulated, in patients with rosacea, which led us to question the role of Erdr1 in this disorder. Moreover, a rosacea-like BALB/c mouse model was used to determine the role of Erdr1 in rosacea in vivo. LL-37 injection induced typical rosacea features, including erythema, telangiectasia and inflammation. Treatment with recombinant Erdr1 (rErdr1) resulted in a significant reduction of erythema, inflammatory cell infiltration (including CD4(+) and CD8(+) T cells), and microvessel density with vascular endothelial growth factor (VEGF). Taken together, our findings suggest that rErdr1 may be involved in attenuating the inflammation and angiogenesis associated with the pathogenesis of rosacea. Thus, these results provide new insight into the mechanism involved in this condition and indicate that rErdr1 could be a potential target for therapeutic intervention of rosacea. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection

    Science.gov (United States)

    Elahi, Shokrollah; Ertelt, James M.; Kinder, Jeremy M.; Jiang, Tony T.; Zhang, Xuzhe; Xin, Lijun; Chaturvedi, Vandana; Strong, Beverly S.; Qualls, Joseph E.; Steinbrecher, Kris A.; Kalfa, Theodosia A.; Shaaban, Aimen F.; Way, Sing Sing

    2013-12-01

    Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71+ cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with L-arginine overrides immunosuppression. In addition, the ablation of CD71+ cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli. However, CD71+ cell-mediated susceptibility to infection is counterbalanced by CD71+ cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition. Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71+ cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these

  13. Erythroid Krüppel-like factor (EKLF) is active in primitive and definitive erythroid cells and is required for the function of 5'HS3 of the beta-globin locus control region.

    Science.gov (United States)

    Tewari, R; Gillemans, N; Wijgerde, M; Nuez, B; von Lindern, M; Grosveld, F; Philipsen, S

    1998-04-15

    Disruption of the gene for transcription factor EKLF (erythroid Krüppel-like factor) results in fatal anaemia caused by severely reduced expression of the adult beta-globin gene, while other erythroid-specific genes, including the embryonic epsilon- and fetal gamma-globin genes, are expressed normally. Thus, EKLF is thought to be a stage-specific factor acting through the CACC box in the beta-gene promoter, even though it is already present in embryonic red cells. Here, we show that a beta-globin gene linked directly to the locus control region (LCR) is expressed at embryonic stages, and that this is only modestly reduced in EKLF-/- embryos. Thus, embryonic beta-globin expression is not intrinsically dependent on EKLF. To investigate whether EKLF functions in the locus control region, we analysed the expression of LCR-driven lacZ reporters. This shows that EKLF is not required for reporter activation by the complete LCR. However, embryonic expression of reporters driven by 5'HS3 of the LCR requires EKLF. This suggests that EKLF interacts directly with the CACC motifs in 5'HS3 and demonstrates that EKLF is also a transcriptional activator in embryonic erythropoiesis. Finally, we show that overexpression of EKLF results in an earlier switch from gamma- to beta-globin expression. Adult mice with the EKLF transgene have reduced platelet counts, suggesting that EKLF levels affect the balance between the megakaryocytic and erythroid lineages. Interestingly, the EKLF transgene rescues the lethal phenotype of EKLF null mice, setting the stage for future studies aimed at the analysis of the EKLF protein and its role in beta-globin gene activation.

  14. PI3 kinase is important for Ras, MEK and Erk activation of Epo-stimulated human erythroid progenitors

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    Schmidt Enrico K

    2004-05-01

    Full Text Available Abstract Background Erythropoietin is a multifunctional cytokine which regulates the number of erythrocytes circulating in mammalian blood. This is crucial in order to maintain an appropriate oxygen supply throughout the body. Stimulation of primary human erythroid progenitors (PEPs with erythropoietin (Epo leads to the activation of the mitogenic kinases (MEKs and Erks. How this is accomplished mechanistically remained unclear. Results Biochemical studies with human cord blood-derived PEPs now show that Ras and the class Ib enzyme of the phosphatidylinositol-3 kinase (PI3K family, PI3K gamma, are activated in response to minimal Epo concentrations. Surprisingly, three structurally different PI3K inhibitors block Ras, MEK and Erk activation in PEPs by Epo. Furthermore, Erk activation in PEPs is insensitive to the inhibition of Raf kinases but suppressed upon PKC inhibition. In contrast, Erk activation induced by stem cell factor, which activates c-Kit in the same cells, is sensitive to Raf inhibition and insensitive to PI3K and PKC inhibitors. Conclusions These unexpected findings contrast with previous results in human primary cells using Epo at supraphysiological concentrations and open new doors to eventually understanding how low Epo concentrations mediate the moderate proliferation of erythroid progenitors under homeostatic blood oxygen levels. They indicate that the basal activation of MEKs and Erks in PEPs by minimal concentrations of Epo does not occur through the classical cascade Shc/Grb2/Sos/Ras/Raf/MEK/Erk. Instead, MEKs and Erks are signal mediators of PI3K, probably the recently described PI3K gamma, through a Raf-independent signaling pathway which requires PKC activity. It is likely that higher concentrations of Epo that are induced by hypoxia, for example, following blood loss, lead to additional mitogenic signals which greatly accelerate erythroid progenitor proliferation.

  15. The MNS glycophorin variant GP.Mur affects differential erythroid expression of Rh/RhAG transcripts.

    Science.gov (United States)

    Hsu, K; Kuo, M-S; Yao, C-C; Cheng, H-C; Lin, H-J; Chan, Y-S; Lin, M

    2017-10-01

    The band 3 macrocomplex (also known as the ankyrin-associated complex) on the red cell membrane comprises two interacting subcomplexes: a band 3/glycophorin A subcomplex, and a Rh/RhAG subcomplex. Glycophorin B (GPB) is a component of the Rh/RhAG subcomplex that is also structurally associated with glycophorin A (GPA). Expression of glycophorin B-A-B hybrid GP.Mur enhances band 3 expression and is associated with lower levels of Rh-associated glycoprotein (RhAG) and Rh polypeptides. The goal of this study was to determine whether GP.Mur influenced erythroid Rh/RhAG expression at the transcript level. GP.Mur was serologically determined in healthy participants from Taitung County, Taiwan. RNA was extracted from the reticulocyte-enriched fraction of peripheral blood, followed by reverse transcription and quantitative PCR for RhAG, RhD and RhCcEe. Quantification by real-time PCR revealed significantly fewer RhAG and RhCcEe transcripts in the reticulocytes from subjects with homozygous GYP*Mur. Independent from GYP.Mur, both RhAG and RhD transcript levels were threefold or higher than that of RhCcEe. Also, in GYP.Mur and the control samples alike, direct quantitative associations were observed between the transcript levels of RhAG and RhD, but not between that of RhAG and RhCcEe. Erythroid RhD and RhCcEe were differentially expressed at the transcript levels, which could be related to their different degrees of interaction or sensitivity to RhAG. Further, the reduction or absence of glycophorin B in GYP.Mur erythroid cells affected transcript expressions of RhAG and RhCcEe. Thus, GPB and GP.Mur differentially influenced Rh/RhAG expressions prior to protein translation. © 2017 International Society of Blood Transfusion.

  16. Human parvovirus B19 infection causes cell cycle arrest of human erythroid progenitors at late S phase that favors viral DNA replication.

    Science.gov (United States)

    Luo, Yong; Kleiboeker, Steve; Deng, Xuefeng; Qiu, Jianming

    2013-12-01

    Human parvovirus B19 (B19V) infection has a unique tropism to human erythroid progenitor cells (EPCs) in human bone marrow and the fetal liver. It has been reported that both B19V infection and expression of the large nonstructural protein NS1 arrested EPCs at a cell cycle status with a 4 N DNA content, which was previously claimed to be "G2/M arrest." However, a B19V mutant infectious DNA (M20(mTAD2)) replicated well in B19V-semipermissive UT7/Epo-S1 cells but did not induce G2/M arrest (S. Lou, Y. Luo, F. Cheng, Q. Huang, W. Shen, S. Kleiboeker, J. F. Tisdale, Z. Liu, and J. Qiu, J. Virol. 86:10748-10758, 2012). To further characterize cell cycle arrest during B19V infection of EPCs, we analyzed the cell cycle change using 5-bromo-2'-deoxyuridine (BrdU) pulse-labeling and DAPI (4',6-diamidino-2-phenylindole) staining, which precisely establishes the cell cycle pattern based on both cellular DNA replication and nuclear DNA content. We found that although both B19V NS1 transduction and infection immediately arrested cells at a status of 4 N DNA content, B19V-infected 4 N cells still incorporated BrdU, indicating active DNA synthesis. Notably, the BrdU incorporation was caused neither by viral DNA replication nor by cellular DNA repair that could be initiated by B19V infection-induced cellular DNA damage. Moreover, several S phase regulators were abundantly expressed and colocalized within the B19V replication centers. More importantly, replication of the B19V wild-type infectious DNA, as well as the M20(mTAD2) mutant, arrested cells at S phase. Taken together, our results confirmed that B19V infection triggers late S phase arrest, which presumably provides cellular S phase factors for viral DNA replication.

  17. The hypomorphic Gata1low mutation alters the proliferation/differentiation potential of the common megakaryocytic-erythroid progenitor

    Science.gov (United States)

    Ghinassi, Barbara; Sanchez, Massimo; Martelli, Fabrizio; Amabile, Giovanni; Vannucchi, Alessandro Maria; Migliaccio, Giovanni; Orkin, Stuart H.; Migliaccio, Anna Rita

    2007-01-01

    Recent evidence suggests that mutations in the Gata1 gene may alter the proliferation/differentiation potential of hemopoietic progenitors. By single-cell cloning and sequential replating experiments of prospectively isolated progenitor cells, we demonstrate here that the hypomorphic Gata1low mutation increases the proliferation potential of a unique class of progenitor cells, similar in phenotype to adult common erythroid/megakaryocytic progenitors (MEPs), but with the “unique” capacity to generate erythroblasts, megakaryocytes, and mast cells in vitro. Conversely, progenitor cells phenotypically similar to mast cell progenitors (MCPs) are not detectable in the marrow from these mutants. At the single-cell level, about 11% of Gata1low progenitor cells, including MEPs, generate cells that will continue to proliferate in cultures for up to 4 months. In agreement with these results, trilineage (erythroid, megakaryocytic, and mastocytic) cell lines are consistently isolated from bone marrow and spleen cells of Gata1low mice. These results confirm the crucial role played by Gata1 in hematopoietic commitment and identify, as a new target for the Gata1 action, the restriction point at which common myeloid progenitors become either MEPs or MCPs. PMID:17038527

  18. The Potential Role of Cell Penetrating Peptides in the Intracellular Delivery of Proteins for Therapy of Erythroid Related Disorders

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    Lefkothea C. Papadopoulou

    2013-01-01

    Full Text Available The erythroid related disorders (ERDs represent a large group of hematological diseases, which in most cases are attributed either to the deficiency or malfunction of biosynthetic enzymes or oxygen transport proteins. Current treatments for these disorders include histo-compatible erythrocyte transfusions or allogeneic hematopoietic stem cell (HSC transplantation. Gene therapy delivered via suitable viral vectors or genetically modified HSCs have been under way. Protein Transduction Domain (PTD technology has allowed the production and intracellular delivery of recombinant therapeutic proteins, bearing Cell Penetrating Peptides (CPPs, into a variety of mammalian cells. Remarkable progress in the field of protein transduction leads to the development of novel protein therapeutics (CPP-mediated PTs for the treatment of monogenetic and/or metabolic disorders. The “concept” developed in this paper is the intracellular protein delivery made possible via the PTD technology as a novel therapeutic intervention for treatment of ERDs. This can be achieved via four stages including: (i the production of genetically engineered human CPP-mediated PT of interest, since the corresponding native protein either is missing or is mutated in the erythroid progenitor cell (ErPCs or mature erythrocytes of patients; (ii isolation of target cells from the peripheral blood of the selected patients; (iii ex vivo transduction of cells with the CPP-mediated PT of interest; and (iv re-administration of the successfully transduced cells back into the same patients.

  19. Role of the mitochondrial amino acid pool in the differential sensitivity of erythroid and myeloid cells to chloramphenicol

    International Nuclear Information System (INIS)

    Abou-Khalil, S.; Abou-Khalil, W.H.; Whitney, P.L.; Yunis, A.A.

    1986-01-01

    Previous studies in the authors laboratory have suggested that mitochondrial amino acid (AA) pool is involved in the differential sensitivity of erythroid and myeloid cells to chloramphenicol (CAP). The present study examines the role of AA pool by analysis of its composition and testing the effects of its major components. The endogenous AA composition of isolated mitochondria protein was determined using a JEOL 5AH AA analyzer. L-( 14 C) leucine incorporation into mitochondrial protein was used to measure the rate of protein synthesis. Analysis of the endogenous pool in erythroleukemia (EM) and chloroleukemia (CM) mitochrondria showed similar total amount of AAs. However, some AAs were present in significantly higher or lower quantity within EM and CM (i.e. EM had about 2-fold higher glycine content). When compensating for each low AA addition of that particular acid to the reaction medium, only glycine and serine had significant effect. Thus, the addition of increasing concentrations of glycine or serine enhanced the sensitivity to CAP from 14% to 49-51% in CM but not in EM. Other AAs gave little or no effect. Since glycine is one of the first reactants in heme biosynthesis within mitochondria and is interconvertible with serine, it would appear that erythroid cells sensitivity to CAP is determined by the mitochondrial glycine-serine pool and may be somehow related of the pathway to heme biosynthesis in these cells

  20. Delayed Mesoderm and Erythroid Differentiation of Murine Embryonic Stem Cells in the Absence of the Transcriptional Regulator FUBP1

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    Josephine Wesely

    2017-01-01

    Full Text Available The transcriptional regulator far upstream binding protein 1 (FUBP1 is essential for fetal and adult hematopoietic stem cell (HSC self-renewal, and the constitutive absence of FUBP1 activity during early development leads to embryonic lethality in homozygous mutant mice. To investigate the role of FUBP1 in murine embryonic stem cells (ESCs and in particular during differentiation into hematopoietic lineages, we generated Fubp1 knockout (KO ESC clones using CRISPR/Cas9 technology. Although FUBP1 is expressed in undifferentiated ESCs and during spontaneous differentiation following aggregation into embryoid bodies (EBs, absence of FUBP1 did not affect ESC maintenance. Interestingly, we observed a delayed differentiation of FUBP1-deficient ESCs into the mesoderm germ layer, as indicated by impaired expression of several mesoderm markers including Brachyury at an early time point of ESC differentiation upon aggregation to EBs. Coculture experiments with OP9 cells in the presence of erythropoietin revealed a diminished differentiation capacity of Fubp1 KO ESCs into the erythroid lineage. Our data showed that FUBP1 is important for the onset of mesoderm differentiation and maturation of hematopoietic progenitor cells into the erythroid lineage, a finding that is supported by the phenotype of FUBP1-deficient mice.

  1. Inhibition of MEK/ERK signalling pathway promotes erythroid differentiation and reduces HSCs engraftment in ex vivo expanded haematopoietic stem cells.

    Science.gov (United States)

    Zarrabi, Morteza; Afzal, Elaheh; Asghari, Mohammad Hossein; Mohammad, Monireh; Es, Hamidreza Aboulkheyr; Ebrahimi, Marzieh

    2018-03-01

    The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self-renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34 + cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway-PD0325901 (PD)-significantly reduces the expansion of CD34 + and CD34 +  CD38 - cells, while there is no change in the expression of stemness-related genes (HOXB4, BMI1). Moreover, in vivo analysis demonstrates that PD reduces engraftment capacity of ex vivo expanded CD34 + cells. Notably, when ERK pathway is blocked in UCB-MNCs, spontaneous erythroid differentiation is promoted, found in concomitant with increasing number of burst-forming unit-erythroid colony (BFU-E) as well as enhancement of erythroid glycophorin-A marker. These results are in total conformity with up-regulation of some erythroid enhancer genes (TAL1, GATA2, LMO2) and down-regulation of some erythroid repressor genes (JUN, PU1) as well. Taken together, our results support the idea that MEK/ERK pathway has a critical role in achieving the correct balance between self-renewal and differentiation of UCB cells. Also, we suggest that inhibition of ERK signalling could likely be a new key for erythroid induction of UCB-haematopoietic progenitor cells. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains.

    Science.gov (United States)

    Kim, J-H; Yu, S; Chen, J D; Kong, A N

    2013-01-24

    Nuclear factor erythroid 2-related factor 2 (Nrf2, NM 006164, 605 AA) is essential for the antioxidant responsive element (ARE)-mediated expression of a group of detoxifying antioxidant genes that detoxify carcinogens and protect against oxidative stress. Several proteins have been identified as Nrf2-interacting molecules. In this study, we found that the overexpression of receptor-associated coactivator 3 (RAC3)/AIB-1/steroid receptor coactivator-3, a nuclear coregulator and oncogene frequently amplified in human breast cancers, induced heme oxygenase-1 (HO-1) through Nrf2 transactivation in HeLa cells. Next, we determined the interaction between RAC3 and Nrf2 proteins using a co-immunoprecipitation assay and fluorescence resonance energy transfer analysis. The results showed that RAC3 bound directly to the Nrf2 protein in the nucleus. Subsequently, we identified the interacting domains of Nrf2 and RAC3 using a glutathione S-transferase pull-down assay. The results showed that both the N-terminal RAC3-pasB and C-terminal RAC3-R3B3 domains were tightly bound to the Neh4 and Neh5 transactivation domains. Furthermore, chromatin immunoprecipitation showed that RAC3 bound tightly to the ARE enhancer region of the HO-1 promoter via Nrf2 binding. These data suggest that Nrf2 activation is modulated and directly controlled through interactions with the RAC3 protein in HeLa cells.

  3. Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway

    NARCIS (Netherlands)

    Wierenga, Albertus T.J.; Vogelzang, Irma; Eggen, BJL; Vellenga, E

    Objective. Erythropoietin (EPO) is a key regulator of erythropoiesis, playing a role in both the proliferation and differentiation of erythroid cells. One of the signal transduction molecules activated upon EPO stimulation is signal transducer and activator of transcription (STAT) 3. Besides

  4. Generation and Characterization of Erythroid Cells from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells: An Overview

    Directory of Open Access Journals (Sweden)

    Kai-Hsin Chang

    2011-01-01

    Full Text Available Because of the imbalance in the supply and demand of red blood cells (RBCs, especially for alloimmunized patients or patients with rare blood phenotypes, extensive research has been done to generate therapeutic quantities of mature RBCs from hematopoietic stem cells of various sources, such as bone marrow, peripheral blood, and cord blood. Since human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs can be maintained indefinitely in vitro, they represent potentially inexhaustible sources of donor-free RBCs. In contrast to other ex vivo stem-cell-derived cellular therapeutics, tumorigenesis is not a concern, as RBCs can be irradiated without marked adverse effects on in vivo function. Here, we provide a comprehensive review of the recent publications relevant to the generation and characterization of hESC- and iPSC-derived erythroid cells and discuss challenges to be met before the eventual realization of clinical usage of these cells.

  5. Pathogenic mitochondrial DNA-induced respiration defects in hematopoietic cells result in anemia by suppressing erythroid differentiation.

    Science.gov (United States)

    Inoue, Shin-Ichi; Yokota, Mutsumi; Nakada, Kazuto; Miyoshi, Hiroyuki; Hayashi, Jun-Ichi

    2007-05-01

    Anemia is a symptom in patients with Pearson syndrome caused by the accumulation of mutated mitochondrial DNA (mtDNA). Such mutated mtDNAs have been detected in patients with anemia. This suggested that respiration defects due to mutated mtDNA are responsible for the anemia. However, there has been no convincing experimental evidence to confirm the pathophysiological relation between respiration defects in hematopoietic cells and expression of anemia. We address this issue by transplanting bone marrow cells carrying pathogenic mtDNA with a large-scale deletion (DeltamtDNA) into normal mice. The bone marrow-transplanted mice carried high proportion of DeltamtDNA only in hematopoietic cells, and resultant the mice suffered from macrocytic anemia. They show abnormalities of erythroid differentiation and weak erythropoietic response to a stressful condition. These observations suggest that hematopoietic cell-specific respiration defects caused by mtDNAs with pathogenic mutations are responsible for anemia by inducing abnormalities in erythropoiesis.

  6. Multiple cis elements regulate an alternative splicing event at 4.1R pre-mRNA during erythroid differentiation.

    Science.gov (United States)

    Deguillien, M; Huang, S C; Morinière, M; Dreumont, N; Benz, E J; Baklouti, F

    2001-12-15

    The inclusion of exon 16 in the mature protein 4.1R messenger RNA (mRNA) is a critical event in red blood cell membrane biogenesis. It occurs during late erythroid development and results in inclusion of the 10-kd domain needed for stabilization of the spectrin/actin lattice. In this study, an experimental model was established in murine erythroleukemia cells that reproduces the endogenous exon 16 splicing patterns from a transfected minigene. Exon 16 was excluded in predifferentiated and predominantly included after induction. This suggests that the minigene contained exon and abutting intronic sequences sufficient for splicing regulation. A systematic analysis of the cis-acting regulatory sequences that reside within the exon and flanking introns was performed. Results showed that (1) the upstream intron of 4.1R pre-mRNA is required for exon recognition and it displays 2 enhancer elements, a distal element acting in differentiating cells and a proximal constitutive enhancer that resides within the 25 nucleotides preceding the acceptor site; (2) the exon itself contains a strong constitutive splicing silencer; (3) the exon has a weak 5' splice site; and (4) the downstream intron contains at least 2 splicing enhancer elements acting in differentiating cells, a proximal element at the vicinity of the 5' splice site, and a distal element containing 3 copies of the UGCAUG motif. These results suggest that the interplay between negative and positive elements may determine the inclusion or exclusion of exon 16. The activation of the enhancer elements in late erythroid differentiation may play an important role in the retention of exon 16.

  7. H-Ferritin Is Preferentially Incorporated by Human Erythroid Cells through Transferrin Receptor 1 in a Threshold-Dependent Manner.

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    Soichiro Sakamoto

    Full Text Available Ferritin is an iron-storage protein composed of different ratios of 24 light (L and heavy (H subunits. The serum level of ferritin is a clinical marker of the body's iron level. Transferrin receptor (TFR1 is the receptor not only for transferrin but also for H-ferritin, but how it binds two different ligands and the blood cell types that preferentially incorporate H-ferritin remain unknown. To address these questions, we investigated hematopoietic cell-specific ferritin uptake by flow cytometry. Alexa Fluor 488-labeled H-ferritin was preferentially incorporated by erythroid cells among various hematopoietic cell lines examined, and was almost exclusively incorporated by bone marrow erythroblasts among human primary hematopoietic cells of various lineages. H-ferritin uptake by erythroid cells was strongly inhibited by unlabeled H-ferritin but was only partially inhibited by a large excess of holo-transferrin. On the other hand, internalization of labeled holo-transferrin by these cells was not inhibited by H-ferritin. Chinese hamster ovary cells lacking functional endogenous TFR1 but expressing human TFR1 with a mutated RGD sequence, which is required for transferrin binding, efficiently incorporated H-ferritin, indicating that TFR1 has distinct binding sites for H-ferritin and holo-transferrin. H-ferritin uptake by these cells required a threshold level of cell surface TFR1 expression, whereas there was no threshold for holo-transferrin uptake. The requirement for a threshold level of TFR1 expression can explain why among primary human hematopoietic cells, only erythroblasts efficiently take up H-ferritin.

  8. Protein: FBB1 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available FBB1 CNC family transcription factors NFE2L1 HBZ17, NRF1, TCF11 NFE2L1 Nuclear factor erythro...id 2-related factor 1 Locus control region-factor 1, Nuclear factor, erythroid derived 2, like 1,

  9. A common signaling pathway is activated in erythroid cells expressing high levels of fetal hemoglobin: a potential role for cAMP-elevating agents in β-globin disorders

    Directory of Open Access Journals (Sweden)

    Ikuta T

    2013-12-01

    Full Text Available Tohru Ikuta,1 Yuichi Kuroyanagi,1 Nadine Odo,1 Siyang Liu21Department of Anesthesiology and Perioperative Medicine, 2Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, GA, USABackground: Although erythroid cells prepared from fetal liver, cord blood, or blood from β-thalassemia patients are known to express fetal hemoglobin at high levels, the underlying mechanisms remain elusive. We previously showed that cyclic nucleotides such as cAMP and cGMP induce fetal hemoglobin expression in primary erythroid cells. Here we report that cAMP signaling contributes to high-level fetal hemoglobin expression in erythroid cells prepared from cord blood and β-thalassemia.Methods: The status of the cAMP signaling pathway was investigated using primary erythroid cells prepared from cord blood and the mononuclear cells of patients with β-thalassemia; erythroid cells from adult bone marrow mononuclear cells served as the control.Results: We found that intracellular cAMP levels were higher in erythroid cells from cord blood and β-thalassemia than from adult bone marrow. Protein kinase A activity levels and cAMP-response element binding protein phosphorylation were higher in erythroid cells from cord blood or β-thalassemia than in adult bone marrow progenitors. Mitogen-activated protein kinase pathways, which play a role in fetal hemoglobin expression, were not consistently activated in cord blood or β-thalassemia erythroid cells. When cAMP signaling was activated in adult erythroid cells, fetal hemoglobin was induced at high levels and associated with reduced expression of BCL11A, a silencer of the β-globin gene.Conclusion: These results suggest that activated cAMP signaling may be a common mechanism among erythroid cells with high fetal hemoglobin levels, in part because of downregulation of BCL11A. Activation of the cAMP signaling pathway with cAMP-elevating agents may prove to be an important signaling mechanism to

  10. p53-Independent cell cycle and erythroid differentiation defects in murine embryonic stem cells haploinsufficient for Diamond Blackfan anemia-proteins: RPS19 versus RPL5.

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    Sharon A Singh

    Full Text Available Diamond Blackfan anemia (DBA is a rare inherited bone marrow failure syndrome caused by ribosomal protein haploinsufficiency. DBA exhibits marked phenotypic variability, commonly presenting with erythroid hypoplasia, less consistently with non-erythroid features. The p53 pathway, activated by abortive ribosome assembly, is hypothesized to contribute to the erythroid failure of DBA. We studied murine embryonic stem (ES cell lines harboring a gene trap mutation in a ribosomal protein gene, either Rps19 or Rpl5. Both mutants exhibited ribosomal protein haploinsufficiency and polysome defects. Rps19 mutant ES cells showed significant increase in p53 protein expression, however, there was no similar increase in the Rpl5 mutant cells. Embryoid body formation was diminished in both mutants but nonspecifically rescued by knockdown of p53. When embryoid bodies were further differentiated to primitive erythroid colonies, both mutants exhibited a marked reduction in colony formation, which was again nonspecifically rescued by p53 inhibition. Cell cycle analyses were normal in Rps19 mutant ES cells, but there was a significant delay in the G2/M phase in the Rpl5 mutant cells, which was unaffected by p53 knockdown. Concordantly, Rpl5 mutant ES cells had a more pronounced growth defect in liquid culture compared to the Rps19 mutant cells. We conclude that the defects in our RPS19 and RPL5 haploinsufficient mouse ES cells are not adequately explained by p53 stabilization, as p53 knockdown appears to increase the growth and differentiation potential of both parental and mutant cells. Our studies demonstrate that gene trap mouse ES cells are useful tools to study the pathogenesis of DBA.

  11. The Locus Control Region Is Necessary for Gene Expression in the Human β-Globin Locus but Not the Maintenance of an Open Chromatin Structure in Erythroid Cells

    Science.gov (United States)

    Reik, Andreas; Telling, Agnes; Zitnik, Galynn; Cimbora, Daniel; Epner, Elliot; Groudine, Mark

    1998-01-01

    Studies in many systems have led to the model that the human β-globin locus control region (LCR) regulates the transcription, chromatin structure, and replication properties of the β-globin locus. However the precise mechanisms of this regulation are unknown. We have developed strategies to use homologous recombination in a tissue culture system to examine how the LCR regulates the locus in its natural chromosomal environment. Our results show that when the functional components of the LCR, as defined by transfection and transgenic studies, are deleted from the endogenous β-globin locus in an erythroid background, transcription of all β-globin genes is abolished in every cell. However, formation of the remaining hypersensitive site(s) of the LCR and the presence of a DNase I-sensitive structure of the β-globin locus are not affected by the deletion. In contrast, deletion of 5′HS5 of the LCR, which has been suggested to serve as an insulator, has only a minor effect on β-globin transcription and does not influence the chromatin structure of the locus. These results show that the LCR as currently defined is not necessary to keep the locus in an “open” conformation in erythroid cells and that even in an erythroid environment an open locus is not sufficient to permit transcription of the β-like globin genes. PMID:9742116

  12. The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

    Energy Technology Data Exchange (ETDEWEB)

    Uziel, Orit, E-mail: Oritu@clalit.org.il [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Kanfer, Gil [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Beery, Einat [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Yelin, Dana; Shepshelovich, Daniel [Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Bakhanashvili, Mary [Unit of Infectious Diseases, Sheba Medical Center, Tel-Hashomer (Israel); Nordenberg, Jardena [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Dep. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Endocrinology Laboratory, Beilinson Medical Center, Petah-Tikva (Israel); Lahav, Meir [Felsenstein Medical Research Center, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel); Medicine A, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv (Israel)

    2014-07-18

    Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway.

  13. The effects of erythropoietin signaling on telomerase regulation in non-erythroid malignant and non-malignant cells

    International Nuclear Information System (INIS)

    Uziel, Orit; Kanfer, Gil; Beery, Einat; Yelin, Dana; Shepshelovich, Daniel; Bakhanashvili, Mary; Nordenberg, Jardena; Lahav, Meir

    2014-01-01

    Highlights: • We assumed that some of erythropoietin adverse effects may be mediated by telomerase activity. • EPO administration increased telomerase activity, cells proliferation and migration. • The inhibition of telomerase modestly repressed the proliferative effect of erythropoietin. • Telomere shortening caused by long term inhibition of the enzyme totally abolished that effect. • This effect was mediated via the Lyn–AKT axis and not by the canonical JAK2–STAT pathway. - Abstract: Treatment with erythropoietin (EPO) in several cancers is associated with decreased survival due to cancer progression. Due to the major importance of telomerase in cancer biology we hypothesized that some of these effects may be mediated through EPO effect on telomerase. For this aim we explored the possible effects of EPO on telomerase regulation, cell migration and chemosensitivity in non-erythroid malignant and non-malignant cells. Cell proliferation, telomerase activity (TA) and cell migration increased in response to EPO. EPO had no effect on cancer cells sensitivity to cisplatinum and on the cell cycle status. The inhibition of telomerase modestly repressed the proliferative effect of EPO. Telomere shortening caused by long term inhibition of the enzyme abolished the effect of EPO, suggesting that EPO effects on cancer cells are related to telomere dynamics. TA was correlated with the levels of Epo-R. The increase in TA was mediated post-translationally through the Lyn-Src and not the canonical JAK2 pathway

  14. Modification in oxidative stress, inflammation, and lipoprotein assembly in response to hepatocyte nuclear factor 4alpha knockdown in intestinal epithelial cells.

    Science.gov (United States)

    Marcil, Valérie; Seidman, Ernest; Sinnett, Daniel; Boudreau, François; Gendron, Fernand-Pierre; Beaulieu, Jean-François; Ménard, Daniel; Precourt, Louis-Philippe; Amre, Devendra; Levy, Emile

    2010-12-24

    Hepatocyte nuclear factor 4α (HNF4α) is a nuclear transcription factor mainly expressed in the liver, intestine, kidney, and pancreas. Many of its hepatic and pancreatic functions have been described, but limited information is available on its role in the gastrointestinal tract. The objectives of this study were to evaluate the anti-inflammatory and antioxidant functions of HNF4α as well as its implication in intestinal lipid transport and metabolism. To this end, the HNF4A gene was knocked down by transfecting Caco-2 cells with a pGFP-V-RS lentiviral vector containing an shRNA against HNF4α. Inactivation of HNF4α in Caco-2 cells resulted in the following: (a) an increase in oxidative stress as demonstrated by the levels of malondialdehyde and conjugated dienes; (b) a reduction in secondary endogenous antioxidants (catalase, glutathione peroxidase, and heme oxygenase-1); (c) a lower protein expression of nuclear factor erythroid 2-related factor that controls the antioxidant response elements-regulated antioxidant enzymes; (d) an accentuation of cellular inflammatory activation as shown by levels of nuclear factor-κB, interleukin-6, interleukin-8, and leukotriene B4; (e) a decrease in the output of high density lipoproteins and of their anti-inflammatory and anti-oxidative components apolipoproteins (apo) A-I and A-IV; (f) a diminution in cellular lipid transport revealed by a lower cellular secretion of chylomicrons and their apoB-48 moiety; and (g) alterations in the transcription factors sterol regulatory element-binding protein 2, peroxisome proliferator-activated receptor α, and liver X receptor α and β. In conclusion, HNF4α appears to play a key role in intestinal lipid metabolism as well as intestinal anti-oxidative and anti-inflammatory defense mechanisms.

  15. The negative impact of Wnt signaling on megakaryocyte and primitive erythroid progenitors derived from human embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Prasuna Paluru

    2014-03-01

    Full Text Available The Wnt gene family consists of structurally related genes encoding secreted signaling molecules that have been implicated in many developmental processes, including regulation of cell fate and patterning during embryogenesis. Previously, we found that Wnt signaling is required for primitive or yolk sac-derived-erythropoiesis using the murine embryonic stem cell (ESC system. Here, we examine the effect of Wnt signaling on the formation of early hematopoietic progenitors derived from human ESCs. The first hematopoietic progenitor cells in the human ESC system express the pan-hematopoietic marker CD41 and the erythrocyte marker, glycophorin A or CD235. We have developed a novel serum-free, feeder-free, adherent differentiation system that can efficiently generate large numbers of CD41 + CD235+ cells. We demonstrate that this cell population contains progenitors not just for primitive erythroid and megakaryocyte cells but for the myeloid lineage as well and term this population the primitive common myeloid progenitor (CMP. Treatment of mesoderm-specified cells with Wnt3a led to a loss of hematopoietic colony-forming ability while the inhibition of canonical Wnt signaling with DKK1 led to an increase in the number of primitive CMPs. Canonical Wnt signaling also inhibits the expansion and/or survival of primitive erythrocytes and megakaryocytes, but not myeloid cells, derived from this progenitor population. These findings are in contrast to the role of Wnt signaling during mouse ESC differentiation and demonstrate the importance of the human ESC system in studying species-specific differences in development.

  16. Asn-150 of Murine Erythroid 5-Aminolevulinate Synthase Modulates the Catalytic Balance between the Rates of the Reversible Reaction.

    Science.gov (United States)

    Stojanovski, Bosko M; Ferreira, Gloria C

    2015-12-25

    5-Aminolevulinate synthase (ALAS) catalyzes the first step in mammalian heme biosynthesis, the pyridoxal 5'-phosphate (PLP)-dependent and reversible reaction between glycine and succinyl-CoA to generate CoA, CO2, and 5-aminolevulinate (ALA). Apart from coordinating the positioning of succinyl-CoA, Rhodobacter capsulatus ALAS Asn-85 has a proposed role in regulating the opening of an active site channel. Here, we constructed a library of murine erythroid ALAS variants with substitutions at the position occupied by the analogous bacterial asparagine, screened for ALAS function, and characterized the catalytic properties of the N150H and N150F variants. Quinonoid intermediate formation occurred with a significantly reduced rate for either the N150H- or N150F-catalyzed condensation of glycine with succinyl-CoA during a single turnover. The introduced mutations caused modifications in the ALAS active site such that the resulting variants tipped the balance between the forward- and reverse-catalyzed reactions. Although wild-type ALAS catalyzes the conversion of ALA into the quinonoid intermediate at a rate 6.3-fold slower than the formation of the same quinonoid intermediate from glycine and succinyl-CoA, the N150F variant catalyzes the forward reaction at a mere 1.2-fold faster rate than that of the reverse reaction, and the N150H variant reverses the rate values with a 1.7-fold faster rate for the reverse reaction than that for the forward reaction. We conclude that the evolutionary selection of Asn-150 was significant for optimizing the forward enzymatic reaction at the expense of the reverse, thus ensuring that ALA is predominantly available for heme biosynthesis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through Nrf2-Related Inflammatory Response.

    Science.gov (United States)

    Seo, Ji Yeon; Pyo, Euisun; An, Jin-Pyo; Kim, Jinwoong; Sung, Sang Hyun; Oh, Won Keun

    2017-01-01

    Therapeutic approach of Alzheimer's disease (AD) has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata , and focused on the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase (HO)-1-inducing effects and the inhibitory activity of amyloid beta (A β ) 42 -induced microglial activation related to Nrf2 and nuclear factor κ B (NF- κ B)-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE) gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular A β 42 in BV-2 cells and decreased the production of interleukin (IL)-6, IL-1 β , prostaglandin (PG)E 2 , and nitric oxide (NO) because of artificial phagocytic A β 42 . It decreased pNF- κ B accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS) and cyclooxygenase II (COX-II) in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits A β 42 -overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

  18. Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through Nrf2-Related Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Ji Yeon Seo

    2017-01-01

    Full Text Available Therapeutic approach of Alzheimer’s disease (AD has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata, and focused on the Kelch-like ECH-associated protein 1 (Keap1/nuclear factor (erythroid-derived 2-like 2 (Nrf2-mediated heme oxygenase (HO-1-inducing effects and the inhibitory activity of amyloid beta (Aβ42-induced microglial activation related to Nrf2 and nuclear factor κB (NF-κB-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular Aβ42 in BV-2 cells and decreased the production of interleukin (IL-6, IL-1β, prostaglandin (PGE2, and nitric oxide (NO because of artificial phagocytic Aβ42. It decreased pNF-κB accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS and cyclooxygenase II (COX-II in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits Aβ42-overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

  19. Identification of Stages of Erythroid Differentiation in Bone Marrow and Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in Autoimmune Hemolytic Anemia in Mouse

    Science.gov (United States)

    Chatterjee, Sreoshi; Bhardwaj, Nitin; Saxena, Rajiv K.

    2016-01-01

    Repeated weekly injections of rat erythrocytes produced autoimmune hemolytic anemia (AIHA) in C57BL/6 mice after 5–6 weeks. Using the double in vivo biotinylation (DIB) technique, recently developed in our laboratory, turnover of erythrocyte cohorts of different age groups during AIHA was monitored. Results indicate a significant decline in the proportion of reticulocytes, young and intermediate age groups of erythrocytes, but a significant increase in the proportion of old erythrocytes in blood circulation. Binding of the autoantibody was relatively higher to the young erythrocytes and higher levels of intracellular reactive oxygen species (ROS) were also seen in these cells. Erythropoietic activity in the bone marrows and the spleen of AIHA induced mice was examined by monitoring the relative proportion of erythroid cells at various stages of differentiation in these organs. Cells at different stages of differentiation were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Erythroid cells in bone marrow declined significantly in AIHA induced mice, erythroblast C being most affected (50% decline). Erythroblast C also recorded high intracellular ROS level along with increased levels of membrane-bound autoantibody. No such decline was observed in spleen. A model of AIHA has been proposed indicating that binding of autoantibodies may not be a sufficient condition for destruction of erythroid cells in bone marrow and in blood circulation. Last stage of erythropoietic differentiation in bone marrow and early stages of erythrocytes in blood circulation are specifically susceptible to removal in AIHA. PMID:27870894

  20. Acute leukaemia with a pure erythroid phenotype: under-recognized morphological and cytogenetic signatures associated universally with primary refractory disease and a dismal clinical outcome.

    Science.gov (United States)

    Park, David C; Ozkaya, Neval; Lovitch, Scott B

    2017-08-01

    Pure erythroid leukaemia (PEL) is an extremely rare and aggressive subtype of acute myeloid leukaemia defined by the World Health Organization (WHO) as a neoplastic proliferation of immature cells committed exclusively to the erythroid lineage, comprising >80% of bone marrow cells and not meeting the criteria of other well-defined myeloid neoplasms. The aim of this study was to describe the clinicopathological features of acute leukaemias with a pure erythroid phenotype (ALPEP) irrespective of their WHO classification and to determine if ALPEP represents a distinct clinicopathological entity. We identified seven cases of ALPEP, in which immature cells fulfilled WHO morphological and immunophenotypical criteria for PEL. All patients except one were male, with a median age of 60 years. Three cases represented de novo PEL, three were therapy-related myeloid neoplasms and one was a blast phase of a myeloproliferative neoplasm. Extensive tumour necrosis was present in five cases (71%). Five cases with available modal karyotypes all demonstrated a complex karyotype involving the TP53 gene locus, with three cases (60%) also showing a monosomy 5 or deletion 5q and additional material on chromosome 19q13. All patients died of their disease, with a mean overall survival of 189 and 64.7 days in cases without and with necrosis on the initial biopsy, respectively. We describe previously unreported but relatively common findings of extensive tumour necrosis and recurring cytogenetic abnormalities in ALPEP. Our findings suggest strongly that ALPEP represents a distinct clinicopathological entity regardless of its WHO classification. © 2017 John Wiley & Sons Ltd.

  1. Identification of Stages of Erythroid Differentiation in Bone Marrow and Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in Autoimmune Hemolytic Anemia in Mouse.

    Directory of Open Access Journals (Sweden)

    Sreoshi Chatterjee

    Full Text Available Repeated weekly injections of rat erythrocytes produced autoimmune hemolytic anemia (AIHA in C57BL/6 mice after 5-6 weeks. Using the double in vivo biotinylation (DIB technique, recently developed in our laboratory, turnover of erythrocyte cohorts of different age groups during AIHA was monitored. Results indicate a significant decline in the proportion of reticulocytes, young and intermediate age groups of erythrocytes, but a significant increase in the proportion of old erythrocytes in blood circulation. Binding of the autoantibody was relatively higher to the young erythrocytes and higher levels of intracellular reactive oxygen species (ROS were also seen in these cells. Erythropoietic activity in the bone marrows and the spleen of AIHA induced mice was examined by monitoring the relative proportion of erythroid cells at various stages of differentiation in these organs. Cells at different stages of differentiation were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71 monoclonal antibodies. Erythroid cells in bone marrow declined significantly in AIHA induced mice, erythroblast C being most affected (50% decline. Erythroblast C also recorded high intracellular ROS level along with increased levels of membrane-bound autoantibody. No such decline was observed in spleen. A model of AIHA has been proposed indicating that binding of autoantibodies may not be a sufficient condition for destruction of erythroid cells in bone marrow and in blood circulation. Last stage of erythropoietic differentiation in bone marrow and early stages of erythrocytes in blood circulation are specifically susceptible to removal in AIHA.

  2. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease

    DEFF Research Database (Denmark)

    de Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul

    2013-01-01

    Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown....

  3. Antisense myb inhibition of purified erythroid progenitors in development and differentiation is linked to cycling activity and expression of DNA polymerase alpha

    International Nuclear Information System (INIS)

    Valtieri, M.; Venturelli, D.; Care, A.; Fossati, C.; Pelosi, E.; Labbaye, C.; Mattia, G.; Gewirtz, A.M.; Calabretta, B.; Peschle, C.

    1991-01-01

    These studies aimed to determine the expression and functional role of c-myb in erythroid progenitors with different cycling activities. In the first series of experiments the erythroid burst-forming unit (BFU-E) and colony-forming unit (CFU-E) populations from adult peripheral blood (PB), bone marrow (BM), and embryonic-fetal liver (FL) were treated with either c-myb antisense oligomers or 3H-thymidine (3H-TdR). A direct correlation was always observed between the inhibitory effect of anti-myb oligomers and the level of cycling activity. Thus, the inhibitory effect of antisense c-myb on the number of BFU-E colonies was 28.3% +/- 15.8% in PB, 53.4% +/- 9.3% in BM, and 68.2% +/- 24.5% in FL. Both adult and embryonic CFU-E were markedly inhibited. Using purified PB progenitors, we observed a similar pattern, although with slightly lower inhibitory effects. In the 3H-TdR suicide assay the killing index of BFU-E was 8.9% +/- 4.2% in PB, 29.4% +/- 6.5% in BM, and 40.1% +/- 9.6% in FL. The values for adult and embryonic CFU-E were 55.7% +/- 7.9% and 60.98% +/- 6.6%, respectively. We then investigated the kinetics of c-myb mRNA level during the erythroid differentiation of purified adult PB and FL BFU-E, as evaluated in liquid-phase culture by reverse transcription-polymerase chain reaction. Adult erythroid precursors showed a gradual increase of c-myb mRNA from day 4 through day 8 of culture and a sharp decrease at later times, whereas the expression of c-myb mRNA and protein in differentiation embryonic precursors peaked 2 days earlier. In both cases, c-myb mRNA level peaked at the CFU-E stage of differentiation. Finally, highly purified adult PB BFU-E were stimulated into cycling by a 3-day treatment with interleukin-3 in liquid phase: both the sensitivity to c-myb antisense oligomers and the 3H-TdR suicide index showed a gradual, strictly parallel increase

  4. Interlaboratory trial of the rat Pig-a mutation assay using an erythroid marker HIS49 antibody.

    Science.gov (United States)

    Kimoto, Takafumi; Horibata, Katsuyoshi; Chikura, Satsuki; Hashimoto, Kazuyuki; Itoh, Satoru; Sanada, Hisakazu; Muto, Shigeharu; Uno, Yoshifumi; Yamada, Masami; Honma, Masamitsu

    2013-08-15

    The peripheral blood Pig-a assay has shown promise as a tool for evaluating in vivo mutagenicity. In this study five laboratories participated in a collaborative trial that evaluated the transferability and reproducibility of a rat Pig-a assay that uses a HIS49 antibody reacts with an antigen found on erythrocytes and erythroid progenitors. In preliminary work, flow cytometry methods were established that enabled all laboratories to detect CD59-negative erythrocyte frequencies (Pig-a mutant frequencies) of laboratories (the in-life labs) then treated male rats with a single oral dose of N-nitroso-N-ethylurea, 7,12-dimethylbenz[a]anthracene (DMBA), or 4-nitroquinoline-1-oxide (4NQO). Blood samples were collected up to 4 weeks after the treatments and analyzed by flow cytometry for the frequency of CD59-negative cells among total red blood cells (RBCs; RBC Pig-a assay). RBC Pig-a assays were conducted in the four in-life laboratories, plus a fifth laboratory that received blood samples from the other laboratories. In addition, three of the five laboratories performed a Pig-a assay on reticulocytes (RETs; PIGRET assay), using blood from the rats treated with DMBA and 4NQO. The four in-life laboratories detected consistent, time- and dose-related increases in RBC Pig-a mutant frequency (MF) for all three test articles. Furthermore, comparable results were obtained in the fifth laboratory that received blood samples from other laboratories. The three laboratories conducting the PIGRET assay also detected consistent, time- and dose-related increases in Pig-a MF, with the RET MFs increasing more rapidly with time than RBC MFs. These results indicate that rat Pig-a assays using a HIS49 antibody were transferable between laboratories and that data generated by the assays were reproducible. The findings also suggest that the PIGRET assay may detect the in vivo mutagenicity of test compounds earlier than the RBC Pig-a assay. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage

    DEFF Research Database (Denmark)

    Järås, Marcus; Johnels, Petra; Agerstam, Helena

    2009-01-01

    OBJECTIVE: The P190 and P210 BCR/ABL1 fusion genes are mainly associated with different types of hematologic malignancies, but it is presently unclear whether they are functionally different following expression in primitive human hematopoietic cells. MATERIALS AND METHODS: We investigated...... and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. RESULTS: Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells...... and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under...

  6. Natural killer cells recognize friend retrovirus-infected erythroid progenitor cells through NKG2D-RAE-1 interactions In Vivo.

    Science.gov (United States)

    Ogawa, Tatsuya; Tsuji-Kawahara, Sachiyo; Yuasa, Takae; Kinoshita, Saori; Chikaishi, Tomomi; Takamura, Shiki; Matsumura, Haruo; Seya, Tsukasa; Saga, Toshihiko; Miyazawa, Masaaki

    2011-06-01

    Natural killer (NK) cells function as early effector cells in the innate immune defense against viral infections and also participate in the regulation of normal and malignant hematopoiesis. NK cell activities have been associated with early clearance of viremia in experimental simian immunodeficiency virus and clinical human immunodeficiency virus type 1 (HIV-1) infections. We have previously shown that NK cells function as major cytotoxic effector cells in vaccine-induced immune protection against Friend virus (FV)-induced leukemia, and NK cell depletion totally abrogates the above protective immunity. However, how NK cells recognize retrovirus-infected cells remains largely unclear. The present study demonstrates a correlation between the expression of the products of retinoic acid early transcript-1 (RAE-1) genes in target cells and their susceptibility to killing by NK cells isolated from FV-infected animals. This killing was abrogated by antibodies blocking the NKG2D receptor in vitro. Further, the expression of RAE-1 proteins on erythroblast surfaces increased early after FV inoculation, and administration of an RAE-1-blocking antibody resulted in increased spleen infectious centers and exaggerated pathology, indicating that FV-infected erythroid cells are recognized by NK cells mainly through the NKG2D-RAE-1 interactions in vivo. Enhanced retroviral replication due to host gene-targeting resulted in markedly increased RAE-1 expression in the absence of massive erythroid cell proliferation, indicating a direct role of retroviral replication in RAE-1 upregulation.

  7. Dual role for the methyltransferase G9a in the maintenance of beta-globin gene transcription in adult erythroid cells.

    Science.gov (United States)

    Chaturvedi, Chandra-Prakash; Hosey, Alison M; Palii, Carmen; Perez-Iratxeta, Carolina; Nakatani, Yoshihiro; Ranish, Jeffrey A; Dilworth, F Jeffrey; Brand, Marjorie

    2009-10-27

    Using a proteomics screen, we have identified the methyltransferase G9a as an interacting partner of the hematopoietic activator NF-E2. We show that G9a is recruited to the beta-globin locus in a NF-E2-dependent manner and spreads over the entire locus. While G9a is often regarded as a corepressor, knocking down this protein in differentiating adult erythroid cells leads to repression of the adult beta(maj) globin gene and aberrant reactivation of the embryonic beta-like globin gene E(y). While in adult cells G9a maintains E(y) in a repressed state via dimethylation of histone H3 at lysines 9 and 27, it activates beta(maj) transcription in a methyltransferase-independent manner. Interestingly, the demethylase UTX is recruited to the beta(maj) (but not the E(y)) promoter where it antagonizes G9a-dependent H3K27 dimethylation. Collectively, these results reveal a dual role for G9a in maintaining proper expression (both repression and activation) of the beta-globin genes in differentiating adult erythroid cells.

  8. Cis-vaccenic acid induces differentiation and up-regulates gamma globin synthesis in K562, JK1 and transgenic mice erythroid progenitor stem cells

    Science.gov (United States)

    Aimola, Idowu A.; Inuwa, Hajiya M.; Nok, Andrew J.; Mamman, Aisha I.; Bieker, James J.

    2017-01-01

    Gamma globin induction remains a promising pharmacological therapeutic treatment mode for sickle cell anemia and beta thalassemia, however Hydroxyurea remains the only FDA approved drug which works via this mechanism. In this regard, we assayed the γ-globin inducing capacity of Cis-vaccenic acid (CVA). CVA induced differentiation of K562, JK1 and transgenic mice primary bone marrow hematopoietic progenitor stem cells. CVA also significantly up-regulated γ-globin gene expression in JK-1 and transgenic mice bone marrow erythroid progenitor stem cells (TMbmEPSCs) but not K562 cells without altering cell viability. Increased γ-globin expression was accompanied by KLF1 suppression in CVA induced JK-1 cells. Erythropoietin induced differentiation of JK-1 cells 24 h before CVA induction did not significantly alter CVA induced differentiation and γ-globin expression in JK-1 cells. Inhibition of JK-1 and Transgenic mice bone marrow erythroid progenitor stem cells Fatty acid elongase 5 (Elovl5) and Δ9 desaturase suppressed the γ-globin inductive effects of CVA. CVA treatment failed to rescue γ-globin expression in Elovl5 and Δ9-desaturase inhibited cells 48 h post inhibition in JK-1 cells. The data suggests that CVA directly modulates differentiation of JK-1 and TMbmEPSCs, and indirectly modulates γ-globin gene expression in these cells. Our findings provide important clues for further evaluations of CVA as a potential fetal hemoglobin therapeutic inducer PMID:26879870

  9. Nuclear law - Nuclear safety

    International Nuclear Information System (INIS)

    Pontier, Jean-Marie; Roux, Emmanuel; Leger, Marc; Deguergue, Maryse; Vallar, Christian; Pissaloux, Jean-Luc; Bernie-Boissard, Catherine; Thireau, Veronique; Takahashi, Nobuyuki; Spencer, Mary; Zhang, Li; Park, Kyun Sung; Artus, J.C.

    2012-01-01

    This book contains the contributions presented during a one-day seminar. The authors propose a framework for a legal approach to nuclear safety, a discussion of the 2009/71/EURATOM directive which establishes a European framework for nuclear safety in nuclear installations, a comment on nuclear safety and environmental governance, a discussion of the relationship between citizenship and nuclear, some thoughts about the Nuclear Safety Authority, an overview of the situation regarding the safety in nuclear waste burying, a comment on the Nome law with respect to electricity price and nuclear safety, a comment on the legal consequences of the Fukushima accident on nuclear safety in the Japanese law, a presentation of the USA nuclear regulation, an overview of nuclear safety in China, and a discussion of nuclear safety in the medical sector

  10. Hemolytic disease of the fetus and newborn due to anti-Ge3: combined antibody-dependent hemolysis and erythroid precursor cell growth inhibition.

    Science.gov (United States)

    Blackall, Douglas P; Pesek, Gina D; Montgomery, Matthew M; Oza, Krishna K; Arndt, Patricia A; Garratty, George; Shahcheraghi, Ali; Denomme, Gregory A

    2008-10-01

    The Gerbich (Ge) antigens are a collection of high-incidence antigens carried on the red blood cell membrane glycoproteins, glycophorins C and D. Antibodies against these antigens are uncommon, and there have been only rare case reports of hemolytic disease of the fetus and newborn due to anti-Ge. In this case report, we present a neonate with severe anemia and hyperbilirubinemia due to anti-Ge3. Routine and special laboratory studies undertaken in this case suggested two mechanisms for the patient's hemolysis and persistent anemia. Antibody-dependent hemolysis was associated with early-onset hyperbilirubinemia, anemia, and a mild reticulocytosis, and inhibition of erythroid progenitor cell growth was associated with late anemia and normal bilirubin and reticulocyte values. Though rare, anti-Ge3 can be a dangerous antibody in pregnancy. Affected neonates may require intensive initial therapy and close follow-up for at least several weeks after delivery.

  11. Erythroid progenitor cells (CFU-E*) from Friend virus-infected mice undergo 55Fe suicide in vitro in the absence of added erythropoietin

    International Nuclear Information System (INIS)

    Del Rizzo, D.F.; Axelrad, A.A.

    1985-01-01

    The authors have investigated the effect of 55 Fe on the survival in suspension of erythropoietin (epo)-independent erythroid progenitor cells (CFU-E*) induced by Friend polycythemia virus (FV). Spleen cells from C3Hf/Bi mice previously infected with FV were exposed to carrier-free 55 Fe, and the survival of CFU-E* as a function of time in liquid medium was determined from the number of erythroid colonies that developed from these cells seeded in plasma cultures without added epo. The results showed that spleen CFU-E* were highly vulnerable to 55 Fe. Marrow CFU-E* behaved in a similar manner. The 55 Fe responsible for their suicide had been presented to the progenitor cells only during the 4-h period of incubation, after which they were washed and plated in excess nonradioactive iron. They therefore conclude that CFU-E* themselves, and not only their progeny, are capable of actively incorporating iron. Under the same conditions in the absence of added epo, the effect of 55 Fe on the survival of normal spleen or marrow CFU-E could not be assessed because two few normal CFU-E survived the incubation period. Normal bone marrow cells incubated in complete medium containing epo retained their capacity for erythrocytic colony formation, and CFU-E could then be shown to be vulnerable to 55 Fe. Thus, either the iron-incorporating system of normal CFU-E was inducible by epo, or else epo permitted survival of the CFU-E so that the activity of a constitutive iron-incorporating system could be recognized

  12. An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification.

    Science.gov (United States)

    Qiu, Shaowei; Jiang, Erlie; Wei, Hui; Lin, Dong; Zhang, Guangji; Wei, Shuning; Zhou, Chunlin; Liu, Kaiqi; Wang, Ying; Liu, Bingcheng; Liu, Yuntao; Gong, Benfa; Gong, Xiaoyuan; Feng, Sizhou; Mi, Yingchang; Han, Mingzhe; Wang, Jianxiang

    2017-08-09

    The incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria. We respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared. Statistical analyses were performed by SPSS software version 18.0. The median age was 37 years-old, the two-thirds of previous AEL cases were diagnosed as MDS, and there was no obvious difference between two subtypes except for male/female ratio and age. Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. When the cytogenetic risk of patients belonged to MRC intermediate category and age were below 40 years-old in previous AEL cases, the patients who received induction chemotherapy without transplantation had a similar survival compared with the patients who underwent transplantation (3-year OS: 67.2% vs 68.5%). Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. Transplantation was a better choice for those whose cytogenetic category was unfavorable.

  13. The nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo-inducing phenol monobenzone.

    Science.gov (United States)

    Arowojolu, Omotayo A; Orlow, Seth J; Elbuluk, Nada; Manga, Prashiela

    2017-07-01

    Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Zebrafish as a Model to Investigate Dynamin 2-Related Diseases.

    Science.gov (United States)

    Bragato, Cinzia; Gaudenzi, Germano; Blasevich, Flavia; Pavesi, Giulio; Maggi, Lorenzo; Giunta, Michele; Cotelli, Franco; Mora, Marina

    2016-02-04

    Mutations in the dynamin-2 gene (DNM2) cause autosomal dominant centronuclear myopathy (CNM) and dominant intermediate Charcot-Marie-Tooth (CMT) neuropathy type B (CMTDIB). As the relation between these DNM2-related diseases is poorly understood, we used zebrafish to investigate the effects of two different DNM2 mutations. First we identified a new alternatively spliced zebrafish dynamin-2a mRNA (dnm2a-v2) with greater similarity to human DNM2 than the deposited sequence. Then we knocked-down the zebrafish dnm2a, producing defects in muscle morphology. Finally, we expressed two mutated DNM2 mRNA by injecting zebrafish embryos with human mRNAs carrying the R522H mutation, causing CNM, or the G537C mutation, causing CMT. Defects arose especially in secondary motor neuron formation, with incorrect branching in embryos injected with CNM-mutated mRNA, and total absence of branching in those injected with CMT-mutated mRNA. Muscle morphology in embryos injected with CMT-mutated mRNA appeared less regularly organized than in those injected with CNM-mutated mRNA. Our results showing, a continuum between CNM and CMTDIB phenotypes in zebrafish, similarly to the human conditions, confirm this animal model to be a powerful tool to investigate mutations of DNM2 in vivo.

  15. MeCP2-Related Diseases and Animal Models

    Directory of Open Access Journals (Sweden)

    Chinelo D. Ezeonwuka

    2014-01-01

    Full Text Available The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2. MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.

  16. Nuclear Medicine

    Science.gov (United States)

    ... Parents/Teachers Resource Links for Students Glossary Nuclear Medicine What is nuclear medicine? What are radioactive tracers? ... funded researchers advancing nuclear medicine? What is nuclear medicine? Nuclear medicine is a medical specialty that uses ...

  17. Invisible nuclear; converting nuclear

    International Nuclear Information System (INIS)

    Park, Jongmoon

    1993-03-01

    This book consists of 14 chapters which are CNN era and big science, from East and West to North and South, illusory nuclear strategy, UN and nuclear arms reduction, management of armaments, advent of petroleum period, the track of nuclear power generation, view of energy, internationalization of environment, the war over water in the Middle East, influence of radiation and an isotope technology transfer and transfer armament into civilian industry, the end of nuclear period and the nuclear Nonproliferation, national scientific and technological power and political organ and executive organ.

  18. Nuclear substructure reorganization during late stageerythropoiesis is selective and does not involve caspase cleavage ofmajor nuclear substructural proteins

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, Sharon Wald; Lo, Annie J.; Short, Sarah A.; Koury, MarkJ.; Mohandas, Narla; Chasis, Joel Anne

    2005-04-06

    Enucleation, a rare feature of mammalian differentiation, occurs in three cell types: erythroblasts, lens epithelium and keratinocytes. Previous investigations suggest that caspase activation functions in lens epithelial and keratinocyte enucleation, as well as in early erythropoiesis encompassing BFU-E differentiation to proerythroblast. To determine whether caspase activation contributes to later erythropoiesis and whether nuclear substructures other than chromatin reorganize, we analyzed distributions of nuclear subcompartment proteins and assayed for caspase-induced cleavage of subcompartmental target proteins in mouse erythroblasts. We found that patterns of lamin B in the filamentous network interacting with both the nuclear envelope and DNA, nuclear matrix protein NuMA, and splicing factors Sm and SC35 persisted during nuclear condensation, consistent with effective transcription of genes expressed late in differentiation. Thus nuclear reorganization prior to enucleation is selective, allowing maintenance of critical transcriptional processes independent of extensive chromosomal reorganization. Consistent with these data, we found no evidence for caspase-induced cleavage of major nuclear subcompartment proteins during late erythropoiesis, in contrast to what has been observed in early erythropoiesis and in lens epithelial and keratinocyte differentiation. These findings imply that nuclear condensation and extrusion during terminal erythroid differentiation involve novel mechanisms that do not entail major activation of apoptotic machinery.

  19. Nuclear liability - nuclear insurance

    International Nuclear Information System (INIS)

    Roesch, H.

    1981-01-01

    In the fourth concluding article on this subject (following articles in VW 1981 pp. 483, 552 and 629), the author explains procedures, duties and obligations according to the Para. Para. 5, 6 and 7 of the AHBKA. These obligations are to be observed before or after the occurrence of damages. In addition, legal consequences following violations of duties - loss of right - joint, insurance, transfer ban, period for filing suit, duty to notify, 'The German Nuclear Reactor Insurance and Reinsurance Community', the insurance according to the 'General terms and conditions governing the liability insurance of licensed activities involving nuclear fuels and other radioactive substances outside nuclear installations (AHBStr.)', object, beginning and exclusion of coverage, 'Special conditions governing the transport of nuclear fuels according to Para. 25 (2) of the Atomic Energy Law' are attached to the General Terms and Conditions governing the liability insurance of licenced activities involving nuclear fuels and other radioactive substances outside nuclear installations. (HSCH) [de

  20. [Nuclear theory

    International Nuclear Information System (INIS)

    Haxton, W.

    1990-01-01

    This report discusses research in nuclear physics. Topics covered in this paper are: symmetry principles; nuclear astrophysics; nuclear structure; quark-gluon plasma; quantum chromodynamics; symmetry breaking; nuclear deformation; and cold fusion

  1. Production of β-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous β039 thalassemia patients

    Science.gov (United States)

    Salvatori, Francesca; Breveglieri, Giulia; Zuccato, Cristina; Finotti, Alessia; Bianchi, Nicoletta; Borgatti, Monica; Feriotto, Giordana; Destro, Federica; Canella, Alessandro; Brognara, Eleonora; Lampronti, Ilaria; Breda, Laura; Rivella, Stefano; Gambari, Roberto

    2013-01-01

    In several types of thalassemia (including β039-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying β-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the β039- thalassemia globin gene under control of the β-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of β-globin by K562 cell clones expressing the β039-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from β039-thalassemia patients were demonstrated to be able to produce β-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of β0-thalassemia caused by stop codon mutations. PMID:19810011

  2. Nuclear power and nuclear weapons

    International Nuclear Information System (INIS)

    Vaughen, V.C.A.

    1983-01-01

    The proliferation of nuclear weapons and the expanded use of nuclear energy for the production of electricity and other peaceful uses are compared. The difference in technologies associated with nuclear weapons and nuclear power plants are described

  3. Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphatidylinositol 3-kinase/Akt-dependent mechanism.

    Science.gov (United States)

    Zhang, Xiuli; Liang, Dan; Lian, Xu; Jiang, Yan; He, Hui; Liang, Wei; Zhao, Yue; Chi, Zhi-Hong

    2016-06-01

    Apoptosis of tubular epithelial cells is a major feature of diabetic kidney disease, and hyperglycemia triggers the generation of free radicals and oxidant stress in tubular cells. Berberine (BBR) is identified as a potential anti-diabetic herbal medicine due to its beneficial effects on insulin sensitivity, glucose metabolism and glycolysis. In this study, the underlying mechanisms involved in the protective effects of BBR on high glucose-induced apoptosis were explored using cultured renal tubular epithelial cells (NRK-52E cells) and human kidney proximal tubular cell line (HK-2 cells). We identified the pivotal role of phosphatidylinositol 3-kinase (PI3K)/Akt in BBR cellular defense mechanisms and revealed the novel effect of BBR on nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2) and heme oxygenase (HO)-1 in NRK-52E and HK-2 cells. BBR attenuated reactive oxygen species production, antioxidant defense (GSH and SOD) and oxidant-sensitive proteins (Nrf2 and HO-1), which also were blocked by LY294002 (an inhibitor of PI3K) in HG-treated NRK-52E and HK-2 cells. Furthermore, BBR improved mitochondrial function by increasing mitochondrial membrane potential. BBR-induced anti-apoptotic function was demonstrated by decreasing apoptotic proteins (cytochrome c, Bax, caspase3 and caspase9). All these findings suggest that BBR exerts the anti-apoptosis effects through activation of PI3K/Akt signal pathways and leads to activation of Nrf2 and induction of Nrf2 target genes, and consequently protecting the renal tubular epithelial cells from HG-induced apoptosis.

  4. Nuclear rights - nuclear wrongs

    Energy Technology Data Exchange (ETDEWEB)

    Paul, E.F.; Miller, F.D.; Paul, J.; Ahrens, J.

    1986-01-01

    This book contains 11 selections. The titles are: Three Ways to Kill Innocent Bystanders: Some Conundrums Concerning the Morality of War; The International Defense of Liberty; Two Concepts of Deterrence; Nuclear Deterrence and Arms Control; Ethical Issues for the 1980s; The Moral Status of Nuclear Deterrent Threats; Optimal Deterrence; Morality and Paradoxical Deterrence; Immoral Risks: A Deontological Critique of Nuclear Deterrence; No War Without Dictatorship, No Peace Without Democracy: Foreign Policy as Domestic Politics; Marxism-Leninism and its Strategic Implications for the United States; Tocqueveille War.

  5. Nuclear moments

    CERN Document Server

    Kopferman, H; Massey, H S W

    1958-01-01

    Nuclear Moments focuses on the processes, methodologies, reactions, and transformations of molecules and atoms, including magnetic resonance and nuclear moments. The book first offers information on nuclear moments in free atoms and molecules, including theoretical foundations of hyperfine structure, isotope shift, spectra of diatomic molecules, and vector model of molecules. The manuscript then takes a look at nuclear moments in liquids and crystals. Discussions focus on nuclear paramagnetic and magnetic resonance and nuclear quadrupole resonance. The text discusses nuclear moments and nucl

  6. Nuclear power

    OpenAIRE

    2005-01-01

    David Waller and Alan McDonald ask whether a nuclear renaissance can be predicted; Judith M. Greenwald discusses keeping the nuclear power option open; Paul Mobbs considers the availability of uranium and the future of nuclear energy.

  7. Nuclear Medicine.

    Science.gov (United States)

    Badawi, Ramsey D.

    2001-01-01

    Describes the use of nuclear medicine techniques in diagnosis and therapy. Describes instrumentation in diagnostic nuclear medicine and predicts future trends in nuclear medicine imaging technology. (Author/MM)

  8. Induction of Mkp-1 and Nuclear Translocation of Nrf2 by Limonoids from Khaya grandifoliola C.DC Protect L-02 Hepatocytes against Acetaminophen-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Arnaud F. Kouam

    2017-09-01

    Full Text Available Drug-induced liver injury (DILI is a major clinical problem where natural compounds hold promise for its abrogation. Khaya grandifoliola (Meliaceae is used in Cameroonian traditional medicine for the treatment of liver related diseases and has been studied for its hepatoprotective properties. Till date, reports showing the hepatoprotective molecular mechanism of the plant are lacking. The aim of this study was therefore to identify compounds from the plant bearing hepatoprotective activity and the related molecular mechanism by assessing their effects against acetaminophen (APAP-induced hepatotoxicity in normal human liver L-02 cells line. The cells were exposed to APAP (10 mM or co-treated with phytochemical compounds (40 μM over a period of 36 h and, biochemical and molecular parameters assessed. Three known limonoids namely 17-epi-methyl-6-hydroxylangolensate, 7-deacetoxy-7-oxogedunin and deacetoxy-7R-hydroxygedunin were identified. The results of cells viability and membrane integrity, reactive oxygen species generation and lipid membrane peroxidation assays, cellular glutathione content determination as well as expression of cytochrome P450 2E1 demonstrated the protective action of the limonoids. Immunoblotting analysis revealed that limonoids inhibited APAP-induced c-Jun N-terminal Kinase phosphorylation (p-JNK, mitochondrial translocation of p-JNK and Bcl2-associated X Protein, and the release of Apoptosis-inducing Factor into the cytosol. Interestingly, limonoids increased the expression of Mitogen-activated Protein Kinase Phosphatase (Mkp-1, an endogenous inhibitor of JNK phosphorylation and, induced the nuclear translocation of Nuclear Factor Erythroid 2-related Factor-2 (Nrf2 and decreased the expression of Kelch-like ECH-associated Protein-1. The limonoids also reversed the APAP-induced decreased mRNA levels of Catalase, Superoxide Dismutase-1, Glutathione-S-Transferase and Methionine Adenosyltransferase-1A. The obtained results

  9. Nuclear medicine

    International Nuclear Information System (INIS)

    Lentle, B.C.

    1986-01-01

    Several growth areas for nuclear medicine were defined. Among them were: cardiac nuclear medicine, neuro-psychiatric nuclear medicine, and cancer diagnosis through direct tumor imaging. A powerful new tool, Positron Emission Tomography (PET) was lauded as the impetus for new developments in nuclear medicine. The political environment (funding, degree of autonomy) was discussed, as were the economic and scientific environments

  10. Nuclear links

    International Nuclear Information System (INIS)

    1981-01-01

    The subject is dealt with in sections: introduction; energy and the third world; world energy consumption 1978; oil -the energy dilemma; nuclear chains - introduction; uranium; Namibia; enrichment and reprocessing; countries with enrichment and reprocessing facilities; waste; conclusion; why take the nuclear option; third world countries with nuclear reactors; the arms connection; government spending and human resources 1977 (by countries); nuclear power - the final solution; the fascists; world bank; campaigns; community action in Plogoff; Australian labour movement; NUM against nuclear power; Scottish campaign; students against nuclear energy; anti-nuclear campaign; partizans; 3W1 disarmament and development; campaign ATOM; CANUC; 3W1; SANE. (U.K.)

  11. Nuclear terrorism

    OpenAIRE

    RUTIC SRDJAN Z.

    2016-01-01

    The paper has analyzed different manifestations of terrorism with nuclear weapons and ionizing radiation as a special kind of terrorism. Possibilities that terrorist groups come into possession of nuclear weapons and apply them for terrorist purposes have been analysed. The forms and methods of terrorist activities with nuclear means have been given as well. It has been concluded that nuclear terrorism includes various forms of threats, including not only nuclear weapons but also the sources ...

  12. Nuclear safeguards and nuclear shutdowns

    International Nuclear Information System (INIS)

    Worthington, J.D.

    1976-01-01

    The issues involved in the California nuclear initiative (Proposition 15) are described. Some of the characteristics of the anti-nuclear lobby are outlined. Some do's and don'ts for the nuclear group are listed. The nuclear shutdown effort was concentrated on the safeguards and high-level waste disposal issues

  13. New Methods of Determining Two-Phase CO2 Relative Permeability and Temperature and Pressure Dependence of CO2 Relative Permeability in Water-Wet Rocks

    Science.gov (United States)

    Chen, X.; Kianinejad, A.; Gao, S.; DiCarlo, D. A.

    2017-12-01

    The prediction of CO2 geological sequestration requires CO2 relative permeability as a key input. However, due to the low viscosity of CO2, experimental measurements often encounter capillary end effects and give lower CO2 relative permeability data than actual values. Previous work shows that using a long core and pressure taps, capillary end effects can be minimized during steady-state CO2-brine two-phase corefloods and accurate CO2 relative permeability data can be obtained. This is achieved by using X-ray CT to measure in situ saturation profile versus time and multiple pressure transducers to measure pressure drops of individual sections. In particular, the core exit section's pressure drop is not used. Based on Buckley Leverett theory, we outline a new method to calculate in situ water fractional flows along the core using measured in situ water saturation profiles. Along with pressure drop and saturation measurements, the water fractional flows can be used to directly calculate unsteady-state CO2-brine relative permeability for each section (excluding the exit section) of the core using Darcy-Buckingham equation. On the other hand, the fractional flows, pressure drops and saturations can be used to extend the conventional JBN method to calculate unsteady-state CO2-brine relative permeability at each pressure tap locations of the core. Both unsteady-state methods give consistent CO2-brine relative permeability data with the steady-state methods and give more data points. Since the core exit section is not used, CO2 relative permeability is obtained with minimized capillary end effect. Compared with the conventional JBN, the extended JBN gives more data points and more accurate data. Furthermore, we find steady-state CO2 relative permeability does not depend on temperature or pressure within 20-60°C and 8-12 MPa in Berea sandstones. This is because CO2 is always the non-wetting phase and flowing inside pores in water-wet rocks and small changes in contact

  14. JPRS Report, Nuclear Developments

    National Research Council Canada - National Science Library

    1989-01-01

    Partial Contents: Nuclear Weapons, Nuclear Development, Nuclear Power Plant, Uranium, Missiles, Space Firm Protested, Satellite, Rocket Launching, Nuclear Submarine, Environmental, Radioactivity, Nuclear Plant...

  15. Nuclear forensics

    International Nuclear Information System (INIS)

    Venugopal, V.

    2010-01-01

    Nuclear forensics is the analysis of nuclear materials recovered from either the capture of unused materials, or from the radioactive debris following a nuclear explosion and can contribute significantly to the identification of the sources of the materials and the industrial processes used to obtain them. In the case of an explosion, nuclear forensics can also reconstruct key features of the nuclear device. Nuclear forensic analysis works best in conjunction with other law enforcement, radiological protection dosimetry, traditional forensics, and intelligence work to provide the basis for attributing the materials and/or nuclear device to its originators. Nuclear forensics is a piece of the overall attribution process, not a stand-alone activity

  16. Nuclear Scans

    Science.gov (United States)

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  17. Nuclear structure

    International Nuclear Information System (INIS)

    Eastham, D.A.; Joy, T.

    1986-01-01

    The paper on 'nuclear structure' is the Appendix to the Daresbury (United Kingdom) Annual Report 1985/86, and contains the research work carried out at the Nuclear Structure Facility, Daresbury, within that period. During the year a total of 74 experiments were scheduled covering the main areas of activity including: nuclear collective motion, nuclei far from stability, and nuclear collisions. The Appendix contains brief reports on these experiments and associated theory. (U.K.)

  18. Nuclear electronics

    International Nuclear Information System (INIS)

    Friese, T.

    1981-09-01

    A short survey is given on nuclear radiation detectors and nuclear electronics. It is written for newcomers and those, who are not very familiar with this technique. Some additional information is given on typical failures in nuclear measurement systems. (orig.) [de

  19. Nuclear power

    International Nuclear Information System (INIS)

    d'Easum, Lille.

    1976-03-01

    An environmentalist's criticism of nuclear energy is given, on a layman's level. Such subjects as conflict of interest in controlling bodies, low-level radiation, reactor safety, liability insurance, thermal pollution, economics, heavy water production, export of nuclear technology, and the history of the anti-nuclear movement are discussed in a sensationalistic tone. (E.C.B.)

  20. Nuclear terrorism

    International Nuclear Information System (INIS)

    2002-01-01

    Recent reports of alleged terrorist plans to build a 'dirty bomb' have heightened longstanding concerns about nuclear terrorism. This briefing outlines possible forms of attack, such as: detonation of a nuclear weapon; attacks involving radioactive materials; attacks on nuclear facilities. Legislation addressing these risks and the UK's strategy for coping with them are also considered

  1. Nuclear weapons, nuclear effects, nuclear war

    Energy Technology Data Exchange (ETDEWEB)

    Bing, G.F.

    1991-08-20

    This paper provides a brief and mostly non-technical description of the militarily important features of nuclear weapons, of the physical phenomena associated with individual explosions, and of the expected or possible results of the use of many weapons in a nuclear war. Most emphasis is on the effects of so-called ``strategic exchanges.``

  2. Effects of montelukast on M2-related cytokine and chemokine in M2 macrophages

    Directory of Open Access Journals (Sweden)

    Yi-Ching Lin

    2018-02-01

    Conclusion: Montelukast suppressed LPS-induced M2-related cytokines and chemokines in alternatively activated macrophages, and the effects might be mediated through the MAPK-p38 and NF-κB-p65 pathways.

  3. Nuclear energy

    International Nuclear Information System (INIS)

    2007-01-01

    This digest document was written by members of the union of associations of ex-members and retired people of the Areva group (UARGA). It gives a comprehensive overview of the nuclear industry world, starting from radioactivity and its applications, and going on with the fuel cycle (front-end, back-end, fuel reprocessing, transports), the nuclear reactors (PWR, BWR, Candu, HTR, generation 4 systems), the effluents from nuclear facilities, the nuclear wastes (processing, disposal), and the management and safety of nuclear activities. (J.S.)

  4. Nuclear physics

    International Nuclear Information System (INIS)

    Kamal, Anwar

    2014-01-01

    Explains the concepts in detail and in depth. Provides step-by-step derivations. Contains numerous tables and diagrams. Supports learning and teaching with numerous worked examples, questions and problems with answers. Sketches also the historical development of the subject. This textbook explains the experimental basics, effects and theory of nuclear physics. It supports learning and teaching with numerous worked examples, questions and problems with answers. Numerous tables and diagrams help to better understand the explanations. A better feeling to the subject of the book is given with sketches about the historical development of nuclear physics. The main topics of this book include the phenomena associated with passage of charged particles and radiation through matter which are related to nuclear resonance fluorescence and the Moessbauer effect., Gamov's theory of alpha decay, Fermi theory of beta decay, electron capture and gamma decay. The discussion of general properties of nuclei covers nuclear sizes and nuclear force, nuclear spin, magnetic dipole moment and electric quadrupole moment. Nuclear instability against various modes of decay and Yukawa theory are explained. Nuclear models such as Fermi Gas Model, Shell Model, Liquid Drop Model, Collective Model and Optical Model are outlined to explain various experimental facts related to nuclear structure. Heavy ion reactions, including nuclear fusion, are explained. Nuclear fission and fusion power production is treated elaborately.

  5. Nuclear power

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    The committee concludes that the nature of the proliferation problem is such that even stopping nuclear power completely could not stop proliferation completely. Countries can acquire nuclear weapons by means independent of commercial nuclear power. It is reasonable to suppose if a country is strongly motivated to acquire nuclear weapons, it will have them by 2010, or soon thereafter, no matter how nuclear power is managed in the meantime. Unilateral and international diplomatic measures to reduce the motivations that lead to proliferation should be high on the foreign policy agenda of the United States. A mimimum antiproliferation prescription for the management of nuclear power is to try to raise the political barriers against proliferation through misuse of nuclear power by strengthening the Non-Proliferation Treaty, and to seek to raise the technological barriers by placing fuel-cycle operations involving weapons-usable material under international control. Any such measures should be considered tactics to slow the spread of nuclear weapons and thus earn time for the exercise of statesmanship. The committee concludes the following about technical factors that should be considered in formulating nuclear policy: (1) rate of growth of electricity use is a primary factor; (2) growth of conventional nuclear power will be limited by producibility of domestic uranium sources; (3) greater contribution of nuclear power beyond 400 GWe past the year 2000 can only be supported by advanced reactor systems; and (4) several different breeder reactors could serve in principle as candidates for an indefinitely sustainable source of energy

  6. Nuclear forensics

    International Nuclear Information System (INIS)

    Karadeniz, O.; Guenalp, G.

    2010-01-01

    This review discusses the methodology of nuclear forensics and illicit trafficking of nuclear materials. Nuclear forensics is relatively new scientific branch whose aim it is to read out material inherent from nuclear material. Nuclear forensics investigations have to be considered as part of a comprehensive set of measures for detection,interception, categorization and characterization of illicitly trafficking nuclear material. Prevention, detection and response are the main elements in combating illicit trafficking. Forensics is a key element in the response process. Forensic science is defined as the application of a broad spectrum of sciences to answer questions of interest to the legal system. Besides, in this study we will explain age determination of nuclear materials.

  7. Nuclear fuels

    International Nuclear Information System (INIS)

    Gangwani, Saloni; Chakrabortty, Sumita

    2011-01-01

    Nuclear fuel is a material that can be consumed to derive nuclear energy, by analogy to chemical fuel that is burned for energy. Nuclear fuels are the most dense sources of energy available. Nuclear fuel in a nuclear fuel cycle can refer to the fuel itself, or to physical objects (for example bundles composed of fuel rods) composed of the fuel material, mixed with structural, neutron moderating, or neutron reflecting materials. Long-lived radioactive waste from the back end of the fuel cycle is especially relevant when designing a complete waste management plan for SNF. When looking at long-term radioactive decay, the actinides in the SNF have a significant influence due to their characteristically long half-lives. Depending on what a nuclear reactor is fueled with, the actinide composition in the SNF will be different. The following paper will also include the uses. advancements, advantages, disadvantages, various processes and behavior of nuclear fuels

  8. Nuclear networking.

    Science.gov (United States)

    Xie, Wei; Burke, Brian

    2017-07-04

    Nuclear lamins are intermediate filament proteins that represent important structural components of metazoan nuclear envelopes (NEs). By combining proteomics and superresolution microscopy, we recently reported that both A- and B-type nuclear lamins form spatially distinct filament networks at the nuclear periphery of mouse fibroblasts. In particular, A-type lamins exhibit differential association with nuclear pore complexes (NPCs). Our studies reveal that the nuclear lamina network in mammalian somatic cells is less ordered and more complex than that of amphibian oocytes, the only other system in which the lamina has been visualized at high resolution. In addition, the NPC component Tpr likely links NPCs to the A-type lamin network, an association that appears to be regulated by C-terminal modification of various A-type lamin isoforms. Many questions remain, however, concerning the structure and assembly of lamin filaments, as well as with their mode of association with other nuclear components such as peripheral chromatin.

  9. Nuclear chemistry

    International Nuclear Information System (INIS)

    Vertes, A.; Kiss, I.

    1987-01-01

    This book is an introduction to the application of nuclear science in modern chemistry. The first group of chapters discuss the basic phenomena and concepts of nuclear physics with emphasis on their relation to chemical problems, including the main properties and the composition of atomic nuclei, nuclear reactions, radioactive decay and interactions of radiation with matter. These chapters provide the basis for understanding the following chapters which encompass the wide scope of nuclear chemistry. The methods of the investigation of chemical structure based on the interaction of nuclear radiation with matter including positronium chemistry and other exotic atoms is elaborated in particular detail. Separate chapters are devoted to the use of radioactive tracers, the chemical consequences of nuclear processes (i.e. hot atom chemistry), radiation chemistry, isotope effects and their applications, and the operation of nuclear reactors. (Auth.)

  10. Nuclear chemistry

    International Nuclear Information System (INIS)

    Vertes, A.; Kiss, I.

    1987-01-01

    This book is an introduction to the application of nuclear science in modern chemistry. The first group of chapters discuss the basic phenomena and concepts of nuclear physics with emphasis on their relation to chemical problems, including the main properties and the composition of atomic nuclei, nuclear reactions, radioactive decay and interactions of radiation with matter. These chapters provide the basis for understanding the following chapters which encompass the wide scope of nuclear chemistry. The methods of the investigation of chemical structure based on the interaction of nuclear radiation with matter including positronium chemistry and other exotic atoms is elaborated in particular detail. Separate chapters are devoted to the use of radioactive tracers, the chemical consequences of nuclear processes (i.e. hot atom chemistry), radiation chemistry, isotope effects and their applications, and the operation of nuclear reactors

  11. Nuclear renaissance and nuclear nonproliferation

    International Nuclear Information System (INIS)

    Kuno, Yusuke

    2010-01-01

    Nuclear energy would grow in response to climate change and the need for a stable energy supply even in an unstable global non-proliferation regime. Some emerging countries probably will try to acquire nuclear fuel cycle as a part of the peaceful use of nuclear energy. How to avoid the risk of proliferation of sensitive technologies is a crucial challenge for the international community. This paper describes the direction to peaceful use of nuclear technology, particularly nuclear fuel cycle, with appropriate non-proliferation measures. (author)

  12. Nuclear blackmail and nuclear balance

    International Nuclear Information System (INIS)

    Betts, R.K.

    1987-01-01

    This book raises pointed questions about nuclear saber rattling. More than a dozen cases since the bombing of Hiroshima and Magasaki in which some sort of nuclear threat was used as a sparring technique in tense confrontations are cited. Each incident is described and analyzed. Two theories offered to explain America's use of nuclear threats, the balance of interest theory and the balance of power theory, are contrasted throughout the book. This book helps to fill the gap in the understanding of nuclear weapons and their uses, while pointing out that nuclear bravado could lead to an unintended unleashing of these weapons

  13. Nuclear energy and nuclear weapons

    International Nuclear Information System (INIS)

    Robertson, J.A.L.

    1983-06-01

    We all want to prevent the use of nuclear weapons. The issue before us is how best to achieve this objective; more specifically, whether the peaceful applications of nuclear energy help or hinder, and to what extent. Many of us in the nuclear industry are working on these applications from a conviction that without peaceful nuclear energy the risk of nuclear war would be appreciably greater. Others, however, hold the opposite view. In discussing the subject, a necessary step in allaying fears is understanding some facts, and indeed facing up to some unpalatable facts. When the facts are assessed, and a balance struck, the conclusion is that peaceful nuclear energy is much more part of the solution to preventing nuclear war than it is part of the problem

  14. Nuclear power

    International Nuclear Information System (INIS)

    King, P.

    1990-01-01

    Written from the basis of neutrality, neither for nor against nuclear power this book considers whether there are special features of nuclear power which mean that its development should be either promoted or restrained by the State. The author makes it dear that there are no easy answers to the questions raised by the intervention of nuclear power but calls for openness in the nuclear decision making process. First, the need for energy is considered; most people agree that energy is the power to progress. Then the historicalzed background to the current position of nuclear power is given. Further chapters consider the fuel cycle, environmental impacts including carbon dioxide emission and the greenhouse effect, the costs, safety and risks and waste disposal. No conclusion either for or against nuclear power is made. The various shades of opinion are outlined and the arguments presented so that readers can come to their own conclusions. (UK)

  15. Nuclear power

    International Nuclear Information System (INIS)

    Porter, Arthur.

    1980-01-01

    This chapter of the final report of the Royal Commission on Electric Power Planning in Ontario updates its interim report on nuclear power in Ontario (1978) in the light of the Three Mile Island accident and presents the commission's general conclusions and recommendations relating to nuclear power. The risks of nuclear power, reactor safety with special reference to Three Mile Island and incidents at the Bruce generating station, the environmental effects of uranium mining and milling, waste management, nuclear power economics, uranium supplies, socio-political issues, and the regulation of nuclear power are discussed. Specific recommendations are made concerning the organization and public control of Ontario Hydro, but the commission concluded that nuclear power is acceptable in Ontario as long as satisfactory progress is made in the disposal of uranium mill tailings and spent fuel wastes. (LL)

  16. Leukemic transformation by the v-ErbA oncoprotein entails constitutive binding to and repression of an erythroid enhancer in vivo

    NARCIS (Netherlands)

    Ciana, P.; Braliou, G. G.; Demay, F. G.; von Lindern, M.; Barettino, D.; Beug, H.; Stunnenberg, H. G.

    1998-01-01

    v-ErbA, a mutated thyroid hormone receptor alpha (TRalpha), is thought to contribute to avian erythroblastosis virus (AEV)-induced leukemic transformation by constitutively repressing transcription of target genes. However, the binding of v-ErbA or any unliganded nuclear receptor to a

  17. Nuclear physics

    International Nuclear Information System (INIS)

    Patel, S.B.

    1991-01-01

    This book is a simple and direct introduction to the tools of modern nuclear physics, both experimental and mathematical. Emphasizes physical intuition and illuminating analogies, rather than formal mathematics. Topics covered include particle accelerators, radioactive series, types of nuclear reactions, detection of the neutrino, nuclear isomerism, binding energy of nuclei, fission chain reactions, and predictions of the shell model. Each chapter contains problems and illustrative examples. Pre-requisites are calculus and elementary vector analysis

  18. Nuclear astrophysics

    International Nuclear Information System (INIS)

    Haxton, W.C.

    1992-01-01

    The problem of core-collapse supernovae is used to illustrate the many connections between nuclear astrophysics and the problems nuclear physicists study in terrestrial laboratories. Efforts to better understand the collapse and mantle ejection are also motivated by a variety of interdisciplinary issues in nuclear, particle, and astrophysics, including galactic chemical evolution, neutrino masses and mixing, and stellar cooling by the emission of new particles. The current status of theory and observations is summarized

  19. Nuclear safety

    International Nuclear Information System (INIS)

    1991-01-01

    This document brings together a series of articles illustrating the way nuclear safety is conceived organised and applied in France. It also deals with foreign experts contributions related to the safety of future nuclear power plants and the impact of probabilistic studies. The opinion of a french Deputy, pleading for nuclear transparency, is sustained by the final conclusions analysing the lessons learned from the past and the current priorities [fr

  20. Nuclear Asia

    National Research Council Canada - National Science Library

    Ferguson, Joseph; Tarleton, Gael

    2004-01-01

    .... This event was an opportunity for policy makers, security analysts, nuclear scientists and engineers, regional experts, and military planners to share perspectives and identify those issues requiring...

  1. Nuclear medicine

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The area of nuclear medicine, the development of artificially produced radioactive isotopes for medical applications, is relatively recent. Among the subjects covered in a lengthy discussion are the following: history of development; impact of nuclear medicine; understanding the most effective use of radioisotopes; most significant uses of nuclear medicine radioimmunoassays; description of equipment designed for use in the field of nuclear medicine (counters, scanning system, display systems, gamma camera); description of radioisotopes used and their purposes; quality control. Numerous historical photographs are included. 52 refs

  2. Nuclear Safety

    Energy Technology Data Exchange (ETDEWEB)

    Silver, E G [ed.

    1989-01-01

    This document is a review journal that covers significant developments in the field of nuclear safety. Its scope includes the analysis and control of hazards associated with nuclear energy, operations involving fissionable materials, and the products of nuclear fission and their effects on the environment. Primary emphasis is on safety in reactor design, construction, and operation; however, the safety aspects of the entire fuel cycle, including fuel fabrication, spent-fuel processing, nuclear waste disposal, handling of radioisotopes, and environmental effects of these operations, are also treated.

  3. Clinical Correlations With Lewy Body Pathology in LRRK2-Related Parkinson Disease

    Science.gov (United States)

    Kalia, Lorraine V.; Lang, Anthony E.; Hazrati, Lili-Naz; Fujioka, Shinsuke; Wszolek, Zbigniew K.; Dickson, Dennis W.; Ross, Owen A.; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Hurtig, Howard I.; Alcalay, Roy N.; Marder, Karen S.; Clark, Lorraine N.; Gaig, Carles; Tolosa, Eduardo; Ruiz-Martínez, Javier; Marti-Masso, Jose F.; Ferrer, Isidre; de Munain, Adolfo López; Goldman, Samuel M.; Schüle, Birgitt; Langston, J. William; Aasly, Jan O.; Giordana, Maria T.; Bonifati, Vincenzo; Puschmann, Andreas; Canesi, Margherita; Pezzoli, Gianni; De Paula, Andre Maues; Hasegawa, Kazuko; Duyckaerts, Charles; Brice, Alexis; Stoessl, A. Jon; Marras, Connie

    2015-01-01

    IMPORTANCE Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD. OBSERVATIONS We describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013. Among the different mutations, the LRRK2 p.G2019S mutation was most frequently associated with LB pathology. Nonmotor features of cognitive impairment/dementia, anxiety, and orthostatic hypotension were correlated with the presence of LBs. In contrast, a primarily motor phenotype was associated with a lack of LBs. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of clinicopathological correlations in a series of LRRK2-related PD cases. Findings from this selected group of patients with PD demonstrated that parkinsonian motor features can occur in the absence of LBs. However, LB pathology in LRRK2-related PD may be a marker for a broader parkinsonian symptom complex including cognitive impairment. PMID:25401511

  4. 27 CFR 447.2 - Relation to other laws and regulations.

    Science.gov (United States)

    2010-04-01

    ... IMPLEMENTS OF WAR Scope § 447.2 Relation to other laws and regulations. (a) All of those items on the U.S... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Relation to other laws and regulations. 447.2 Section 447.2 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS...

  5. Nuclear lifetimes

    International Nuclear Information System (INIS)

    Caraca, J.M.G.

    1976-01-01

    The importance of the results obtained in experiments of measurement of lifetimes for a detailed knowledge of nuclear structure is referred. Direct methods of measurement of nuclear lifetimes are described, namely, electronic methods, recoil-distance method, doppler shift atenuation method and blocking-method. A brief reference is made to indirect methods for measurement of life-times

  6. Nuclear energy

    International Nuclear Information System (INIS)

    1978-01-01

    This brochure is intended as a contribution to a better and more general understanding of one of the most urgent problems of present society. Emphasis is laid on three issues that are always raised in the nuclear debate: 1) Fuel cycle, 2) environmental effects of nuclear power plants, 3) waste disposal problems. (GL) [de

  7. Nuclear safety

    International Nuclear Information System (INIS)

    1991-02-01

    This book reviews the accomplishments, operations, and problems faced by the defense Nuclear Facilities Safety Board. Specifically, it discusses the recommendations that the Safety Board made to improve safety and health conditions at the Department of Energy's defense nuclear facilities, problems the Safety Board has encountered in hiring technical staff, and management problems that could affect the Safety Board's independence and credibility

  8. Nuclear energy

    International Nuclear Information System (INIS)

    Collier, J.G.

    1984-01-01

    The achievements in commercial nuclear power plants over the past 30 years since the first one was commissioned in 1954 are described. By 1982 there were 297 commercial nuclear units in operation world-wide with a capacity of 173GWe and a further 216 units (205GWe) were under construction. The number and performance of the different types of reactors is examined and the experience in different countries is considered. In particular, nuclear power in France and the USA are compared. Uranium production and demand and the attitude to fuel reprocessing in different countries is considered. It is concluded that with increasing demands for energy, nuclear power must be developed to the full. If the conditions are right it can be the most economically advantageous method of energy production. However public acceptance of nuclear power must be sought as this influences the political will for a nuclear power programme. Winning the public's trust and confidence is thus an important part of the nuclear industry's job. The future place of nuclear power in the developing countries is also an issue which must be tackled. (U.K.)

  9. Nuclear violence

    International Nuclear Information System (INIS)

    Mullen, R.K.

    1987-01-01

    A great deal of attention has been paid in the past decade or so to the characteristics of terrorists and their apparent goals and objectives, capabilities, and evolving strategy and tactics with respect to nuclear terrorism. In contrast, little has been said about the procedural aspects of nuclear terrorism, and even less about the way in which such endeavors can fail. This latter omission is important because it bears directly on the ability to evaluate credibly the potential for nuclear terrorism. Here, the author addresses the requirements inherent in acquiring a nuclear explosive capability by three routes: separation of plutonium from irradiated light or heavy water reactor (LWR or HWR) fuel, processing, or use of separated fissile material, and theft of a nuclear weapon. In addition, he deals with other potential acts of nuclear terrorism: sabotage of power reactors, uranium enrichment facilities and spent nuclear fuel in transport, and dispersal of radioactive materials, in particular, plutonium. He specifically does not look at the design or production of a nuclear weapon. Finally, the discussion here assumes that the terrorist is subnational; that is, a nation is not involved. Also, the discussion of subnational participation does not address the possibility of collusion with insiders

  10. Nuclear pollution

    International Nuclear Information System (INIS)

    Ramade, Francois

    1979-01-01

    In this chapter devoted to nuclear pollution the following topics were studied: fundamentals of radiobiology (ecological importance of the various radioisotopes, biological effects of ionizing radiations); ecological effects of radioactive fallout (contamination of atmosphere, terrestrial ecosystems, oceans). The electronuclear industry and its environmental impact. PWR type reactors, fuel reprocessing plants, contamination of trophic chains by radionuclides released in the environment from nuclear installations [fr

  11. Nuclear installations

    International Nuclear Information System (INIS)

    1998-01-01

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 2 of the document contains some details about the existing Brazilian nuclear installations. Also, safety improvements at Angra 1 and aspects of Angra 2 and 3 are reported

  12. Nuclear power

    International Nuclear Information System (INIS)

    Abd Khalik Wood

    2003-01-01

    This chapter discuss on nuclear power and its advantages. The concept of nucleus fission, fusion, electric generation are discussed in this chapter. Nuclear power has big potential to become alternative energy to substitute current conventional energy from coal, oil and gas

  13. Nuclear facts

    International Nuclear Information System (INIS)

    1982-01-01

    The subject is discussed as follows: the case for using nuclear energy (Britain's energy needs; energy policy); safety; transport of spent fuel; radiation (natural radioactivity); environment (land use of nuclear power plants; storage and disposal of radioactive wastes). (U.K.)

  14. Atypical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress.

    Science.gov (United States)

    Numazawa, Satoshi; Ishikawa, Makie; Yoshida, Aya; Tanaka, Sachiko; Yoshida, Takemi

    2003-08-01

    Transcription factor NF-E2-related factor 2 (Nrf2) regulates the induction of antioxidative proteins, including heme oxygenase-1 (HO-1). Nrf2 is sequestered in the cytoplasm by Keap1 under unstimulated conditions but translocates into the nucleus and transactivates the antioxidant responsive element (ARE) upon exposure to oxidative insults. It has recently been demonstrated that in vitro phosphorylation of Nrf2 on Ser40 by protein kinase C (PKC) facilitates the dissociation of Nrf2 from the Keap1 complex (Huang HC, Nguyen T, and Pickett CB. J Biol Chem 277: 42769-42774, 2002). The present study was designed to examine whether PKC is involved in oxidative stress-mediated nuclear translocation of Nrf2 in vivo and, if so, which PKC isoforms are involved. Induction of HO-1 gene expression by phorone, a glutathione depletor, and 4-hydroxy-2,3-nonenal (4-HNE), an end product of lipid peroxidation, was suppressed by a specific PKC inhibitor, Ro-31-8220, at concentrations that inhibit all isoforms in WI-38 cells. The induction of HO-1 was not affected by prolonged exposure of the cells to 12-O-tetradecanoylphorbol-13 acetate (TPA), suggesting that TPA-insensitive atypical PKC (aPKC) isoforms are involved. An immunocomplex kinase assay revealed that phorone and 4-HNE increased aPKCiota activity. In COS-7 cells, 4-HNE induced nuclear translocation of the Nrf2-green fluorescent protein (GFP) fusion protein, but not the Nrf2(S40A)-GFP mutant. In the absence of oxidative insults, the Nrf2(S40E)-GFP mutant was distributed in the nucleus. The Nrf2-GFP accumulation in the nucleus was induced by coexpression of aPKCiota, but not by a kinase inactive mutant aPKCiota(K274W). The activity of an ARE-driven reporter was increased by coexpression of aPKCiota, and this effect was eliminated by Ro-31-8220 in HepG2 cells. The reporter activity induced by 4-HNE was inhibited by coexpression of aPKCiota(K274W). These results suggest that phosphorylation of Nrf2 Ser40 by aPKC(s) is involved in

  15. Isolating a cytoprotective compound from Ganoderma tsugae: effects on induction of Nrf-2-related genes in endothelial cells.

    Science.gov (United States)

    Wei, Yu-Shan; Wung, Being-Sun; Lin, Yuan-Chun; Hsieh, Chia-Wen

    2009-08-01

    Ganoderma tsugae is a medicinal fungus with several biological activities. It has long been used as a folk remedy for the promotion of health and longevity in China and other oriental countries. Here, a bioactive fraction of G. tsugae was progressively purified to be enriched in the activity of cytoprotective enzymes. The highest bioactivity was detected in the 20% EtOH-precipitated fraction, which was prepared from submerged fermentation filtrate of G. tsugae. Following further purification by gel filtration chromatography and acetone extraction, the most bioactive fraction, F5-2, was identified as a peptidoglycan-like compound. Extracts of G. tsugae (F5-2) induced heme oxygenase-1 (HO-1) and thioredoxin reductase-1 (TrxR1) expression in endothelial cells by increasing NF-E2-related factor-2 (Nrf2) nuclear translocation. Pretreatment with F5-2 increased intracellular glutathione (GSH) and protected against H(2)O(2), suggesting that induction of these antioxidant enzymes is important in protection against oxidative stress. Hence the bioactive peptidoglycan-like compound from G. tsugae might protect endothelial cells.

  16. Nuclear proliferation

    International Nuclear Information System (INIS)

    Stencel, S.

    1978-01-01

    The terms and reactions to President Carter's nuclear policy, culminating in the 1978 Nuclear Non-Proliferation Act, are reviewed and analyzed. The new law increases restrictions on nuclear exports, encourages continued use of light water reactors in preference to plutonium-fueled reactors, and emphasizes technical solutions to proliferation problems. Critics of the law point out that it will hurt U.S. trade unfairly, that other countries do not have as many fuel options as the U.S. has, and that nuclear sales have as many political and economic as technical solutions. Compromise areas include new international safety guidelines, the possibility of an international nuclear fuel bank, and a willingness to consider each case on its merits. 21 references

  17. Nuclear haematology

    International Nuclear Information System (INIS)

    Masjhur, J.S.

    1992-01-01

    Nuclear techniques have been applied to study diagnose and treat various haematological disorders for more than five decades. Two scientists are regarded as pioneers in this field, i.e. John Lawrence who in 1938 used 32 P to treat chronic myeloid leukaemia and George Hevessy who used 32 P labelled erythrocytes to measure blood volume in 1939. At present, many nuclear medicine procedures are available for diagnosis and therapy of a variety of haematological disorders. Although nuclear techniques are somewhat complex, they give direct and quantitative assessment of the kinetics of blood elements as compared to other non-isotopic haematological tests. Basically, equipment required for nuclear haematology is very simple such as well scintillation counters to measure radioactivity in blood samples. More sophisticated equipment like rectilinear scanner or gamma camera is required when imaging is necessary. An overview of the basic principles and clinical applications of nuclear haematology is given

  18. Nuclear Safety

    International Nuclear Information System (INIS)

    1978-09-01

    In this short paper it has only been possible to deal in a rather general way with the standards of safety used in the UK nuclear industry. The record of the industry extending over at least twenty years is impressive and, indeed, unique. No other industry has been so painstaking in protection of its workers and in its avoidance of damage to the environment. Headings are: introduction; how a nuclear power station works; radiation and its effects (including reference to ICRP, the UK National Radiological Protection Board, and safety standards); typical radiation doses (natural radiation, therapy, nuclear power programme and other sources); safety of nuclear reactors - design; key questions (matters of concern which arise in the public mind); safety of operators; safety of people in the vicinity of a nuclear power station; safety of the general public; safety bodies. (U.K.)

  19. Nuclear questions

    Energy Technology Data Exchange (ETDEWEB)

    Durrani, M. [Physics World (United Kingdom)

    2006-01-01

    The future of nuclear power has returned to centre stage. Freezing weather on both sides of the Atlantic and last month's climate-change talks in Montreal have helped to put energy and the future of nuclear power right back on the political agenda. The issue is particularly pressing for those countries where existing nuclear stations are reaching the end of their lives. In the UK, prime minister Tony Blair has commissioned a review of energy, with a view to deciding later this year whether to build new nuclear power plants. The review comes just four years after the Labour government published a White Paper on energy that said the country should keep the nuclear option open but did not follow this up with any concrete action. In Germany, new chancellor and former physicist Angela Merkel is a fan of nuclear energy and had said she would extend the lifetime of its nuclear plants beyond 2020, when they are due to close. However, that commitment has had to be abandoned, at least for the time being, following negotiations with her left-wing coalition partners. The arguments in favour of nuclear power will be familiar to all physicists - it emits almost no carbon dioxide and can play a vital role in maintaining a diverse energy supply. To over-rely on imported supplies of oil and gas can leave a nation hostage to fortune. The arguments against are equally easy to list - the public is scared of nuclear power, it generates dangerous waste with potentially huge clean-up costs, and it is not necessarily cheap. Nuclear plants could also be a target for terrorist attacks. Given political will, many of these problems can be resolved, or at least tackled. China certainly sees the benefits of nuclear power, as does Finland, which is building a new 1600 MW station - the world's most powerful - that is set to open in 2009. Physicists, of course, are essential to such developments. They play a vital role in ensuring the safety of such plants and developing new types of

  20. Nuclear war and nuclear peace

    Energy Technology Data Exchange (ETDEWEB)

    Segal, G.; Moreton, E.; Freedman, L.; Baylis, J.

    1983-01-01

    This book is an in-depth examination of East-West tactical and strategic nuclear weapons policy. The contributors explore such issues as the history and implications of tactical weapons in Europe, the general conflicts that have characterized US and Soviet interaction, the development of British nuclear weapons policy, and arms control including SALT I and II and the START talks.

  1. Nuclear energy

    International Nuclear Information System (INIS)

    Rippon, S.

    1984-01-01

    Do we need nuclear energy. Is it safe. What are the risks. Will it lead to proliferation. The questions are endless, the answers often confused. In the vigorous debates that surround the siting and operation of nuclear power plants, it is all too easy to lose sight of the central issues amid the mass of arguments and counter-arguments put forward. And there remains the doubt, who do we believe. This book presents the facts, simply, straightforwardly, and comprehensibly. It describes the different types of nuclear reactor, how they work, how energy is produced and transformed into usable power, how nuclear waste is handled, what safeguards are built in to prevent accident, contamination and misuse. More important, it does this in the context of the real world, examining the benefits as well as the dangers of a nuclear power programme, quantifying the risks, and providing an authoritative account of the nuclear industry worldwide. Technically complex and politically controversial, the contribution of nuclear energy to our future energy requirements is a crucial topic of our time. (author)

  2. Nuclear inheritance

    International Nuclear Information System (INIS)

    Delpech, Therese

    1997-01-01

    Since the end of the East-West confronting, the nuclear weapon issue has been focused in an international debate with obvious repercussions in Europe, because it is the European continent which indicated first the significance of nuclear deterrence. This debate refers first upon the past, as the German unification allowed capturing numerous documents of Warsaw treaty which revealed the intentions and the plans of Soviet Union during the cold war, and secondly concerns the future, since the role of nuclear weapons must be re-thought in a new context. This is the subject of this book, which refers also to the problem of the nuclear proliferation in the world and evolution of different countries in a political and regional context. The extension of the non-proliferation treaty for an undefined duration, in May 1995, is a incontestable victory because this treaty rules the renouncement to nuclear weapons of 185 countries. However, it does not solve most sensible problems like the Iraq case, for which a specific inspection regime has been instituted, or the case of Iran, which is suspected to acquire the bomb, although no clear evidence has been provided up to now. This is also the case of Israel, India and Pakistan which allege plainly their willingness of keeping open, from security reasons, their nuclear option. The content is displayed in five chapters: 1. Introduction; 2. The role of the nuclear weapons after the cold war; 3. The nuclear proliferation at crossroads; 4. Undefined extension of the NPT, a striking but fragile victory; 5. Conclusions. An appendix containing the text of the Nuclear Weapon Non-Proliferation Treaty and a chronology are added

  3. Rotterdam Nuclear

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    In 1965 Rotterdam Nuclear received an order for the design, supply of materials, manufacture, testing, inspection and preparation for shipment of one 450MW Boiling Water Reactor pressure vessel. This was one of the first orders for a reactor pressure vessel, ever obtained by a European Manufacturer. The Company has since supplied 19 reactor pressure vessels for nuclear power stations, having a total weight of about 10,000,000kg. The nuclear power stations in which these are installed represent an electrical output of about 15,000MW and they are located in seven different countries (USA, Spain, Switzerland, Argentina, Sweden, Germany and the Netherlands). (Auth.)

  4. Nuclear questions

    International Nuclear Information System (INIS)

    Hohlfeld, W.

    1977-01-01

    This brochure 'nuclear problems' deals with the attitude of the protestant church in the region around the northern Elbe towards further quantitative economic growth, esp. nuclear energy, with the following essays: preaching the Gospel in an environment in danger: the Christian occident and the problems of the third world, facing the problems of exhausted supplies, the role of the prophet, problem of environment - a problem of theology, the political dimension, against ATW, signal Brokdorf, strange effects (defense of the church from unqualified teachings by non-professionals), Christian liberty, church and nuclear energy, violence and robes. (HP) [de

  5. Nuclear electronics

    International Nuclear Information System (INIS)

    Lucero B, E.

    1989-01-01

    The rapid technical development of Colombia over the past years, resulted among others, a considerable increase in the number of measuring instrumentation and testing laboratories, scientific research and metrology centers, in industry, agriculture, public health, education on the nuclear field, etc. IAN is a well organized institution with qualified management, trained staff and reasonably equipped laboratories to carry out tasks as: Metrology, standardization, quality control and maintenance and repair of nuclear instruments. The government of Colombia has adopted a policy to establish and operate through the country maintenance and repair facilities for nuclear instrumentation. This policy is reflected in the organization of electronic laboratories in Bogota-IAN

  6. Nuclear energy

    International Nuclear Information System (INIS)

    Wethe, Per Ivar

    2009-01-01

    Today we know two forms of nuclear energy: fission and fusion. Fission is the decomposition of heavy nuclei, while fusion is the melting together of light nuclei. Both processes create a large surplus of energy. Technologically, we can currently only use fission to produce energy in today's nuclear power plants, but there is intense research worldwide in order to realize a controlled fusion process. In a practical context, today's nuclear energy is a sustained source of energy since the resource base is virtually unlimited. When fusion technology is realized, the resource supply will be a marginal problem. (AG)

  7. Nuclear constants

    International Nuclear Information System (INIS)

    Foos, J.

    1999-01-01

    This paper is written in two tables. The first one describes the different particles (bosons and fermions). The second one gives the isotopes nuclear constants of the different elements, for Z = 1 to 56. (A.L.B.)

  8. Nuclear constants

    International Nuclear Information System (INIS)

    Foos, J.

    2000-01-01

    This paper is written in two tables. The first one describes the different particles (bosons and fermions). The second one gives the isotopes nuclear constants of the different elements, for Z = 56 to 68. (A.L.B.)

  9. Nuclear constants

    International Nuclear Information System (INIS)

    Foos, J.

    1998-01-01

    This paper is made of two tables. The first table describes the different particles (bosons and fermions) while the second one gives the nuclear constants of isotopes from the different elements with Z = 1 to 25. (J.S.)

  10. Nuclear constants

    International Nuclear Information System (INIS)

    Foos, J.

    1999-01-01

    This paper is written in two tables. The first one describes the different particles (bosons and fermions). The second one gives the isotopes nuclear constants of the different elements, for Z = 56 to 68. (A.L.B.)

  11. Nuclear reaction

    CERN Multimedia

    Penwarden, C

    2001-01-01

    At the European Research Organization for Nuclear Research, Nobel laureates delve into the mysteries of particle physics. But when they invited artists from across the continent to visit their site in Geneva, they wanted a new kind of experiment.

  12. Nuclear Engineering

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    The Nuclear Engineering Division is engaged in both teaching and research. Staff members teach both graduate and undergraduate courses at the UPR Mayaguez Campus and direct the thesis work of nuclear engineering students. They do research on their own projects and assist the staff of other PRNC divisions as the need arises. The scientists on the Division's staff all hold joint appointments at PRNC and UPR, and they make up the faculty of the UPR Nuclear Engineering Department, the Head of the PRNC Division being also the Chairman of the UPR Department. The Division provides the classrooms, offices, laboratories and equipment, and most of the administrative personnel required for the education and training of the graduate students at the UPR Nuclear Engineering Department

  13. Nuclear honeymoon

    International Nuclear Information System (INIS)

    2009-01-01

    Full text: The Australian National University (ANU) and the Australian Nuclear Science and Technology Organisation (ANSTO) have signed a Memorandum of Understanding (MoU) to collaborate across research fields including key accelerator facilities, future energy sources and nuclear non-proliferation. T he potential of this partnership demonstrates the value of Commonwealth institutions working together for the betterment of all Australians,' says ANY vice-chancellor Professor Ian Chubb who believes that both organisations have infrastructure and facilities available that if shared could bring greater benefit to the nation. The partnership will develop a national strategy to coordinate use and development of a heavy-ion accelerator and ion source technology, he says. In addition, it will undertake collaborative activities that enhance educational programs in nuclear physics, nuclear engineering and materials science.

  14. Nuclear shields

    International Nuclear Information System (INIS)

    Linares, R.C.; Nienart, L.F.; Toelcke, G.A.

    1976-01-01

    A process is described for preparing melt-processable nuclear shielding compositions from chloro-fluoro substituted ethylene polymers, particularly PCTFE and E-CTFE, containing 1 to 75 percent by weight of a gadolinium compound. 13 claims, no drawings

  15. Nuclear waste

    International Nuclear Information System (INIS)

    1992-05-01

    The Nuclear Waste Policy Act of 1982, as amended in 1987, directed the Secretary of Energy to, among other things, investigate Yucca Mountain, Nevada, as a potential site for permanently disposing of highly radioactive wastes in an underground repository. In April 1991, the authors testified on Yucca Mountain project expenditures before your Subcommittee. Because of the significance of the authors findings regrading DOE's program management and expenditures, you asked the authors to continue reviewing program expenditures in depth. As agreed with your office, the authors reviewed the expenditures of project funds made available to the Department of Energy's (DOE) Lawrence Livermore National Laboratory, which is the lead project contractor for developing a nuclear waste package that wold be used for disposing of nuclear waste at Yucca Mountain. This report discusses the laboratory's use of nuclear waste funds to support independent research projects and to manage Yucca Mountain project activities. It also discusses the laboratory's project contracting practices

  16. Nuclear safety

    International Nuclear Information System (INIS)

    Tarride, Bruno

    2015-10-01

    The author proposes an overview of methods and concepts used in the nuclear industry, at the design level as well as at the exploitation level, to ensure an acceptable safety level, notably in the case of nuclear reactors. He first addresses the general objectives of nuclear safety and the notion of acceptable risk: definition and organisation of nuclear safety (relationships between safety authorities and operators), notion of acceptable risk, deterministic safety approach and main safety principles (safety functions and confinement barriers, concept of defence in depth). Then, the author addresses the safety approach at the design level: studies of operational situations, studies of internal and external aggressions, safety report, design principles for important-for-safety systems (failure criterion, redundancy, failure prevention, safety classification). The next part addresses safety during exploitation and general exploitation rules: definition of the operation domain and of its limits, periodic controls and tests, management in case of incidents, accidents or aggressions

  17. Nuclear astrophysics

    International Nuclear Information System (INIS)

    Lehoucq, Roland; Klotz, Gregory

    2015-11-01

    Astronomy deals with the position and observation of the objects in our Universe, from planets to galaxies. It is the oldest of the sciences. Astrophysics is the study of the physical properties of these objects. It dates from the start of the 20. century. Nuclear astrophysics is the marriage of nuclear physics, a laboratory science concerned with the infinitely small, and astrophysics, the science of what is far away and infinitely large. Its aim is to explain the origin, evolution and abundance of the elements in the Universe. It was born in 1938 with the work of Hans Bethe, an American physicist who won the Nobel Prize for physics in 1967, on the nuclear reactions that can occur at the center of stars. It explains where the incredible energy of the stars and the Sun comes from and enables us to understand how they are born, live and die. The matter all around us and from which we are made, is made up of ninety-two chemical elements that can be found in every corner of the Universe. Nuclear astrophysics explains the origin of these chemical elements by nucleosynthesis, which is the synthesis of atomic nuclei in different astrophysical environments such as stars. Nuclear astrophysics provides answers to fundamental questions: - Our Sun and the stars in general shine because nuclear reactions are taking place within them. - The stars follow a sequence of nuclear reaction cycles. Nucleosynthesis in the stars enables us to explain the origin and abundance of elements essential to life, such as carbon, oxygen, nitrogen and iron. - Star explosions, in the form of supernovae, disperse the nuclei formed by nucleosynthesis into space and explain the formation of the heaviest chemical elements such as gold, platinum and lead. Nuclear astrophysics is still a growing area of science. (authors)

  18. Nuclear medicine

    International Nuclear Information System (INIS)

    Chamberlain, M.J.

    1986-01-01

    Despite an aggressive, competitive diagnostic radiology department, the University Hospital, London, Ontario has seen a decline of 11% total (in vivo and in the laboratory) in the nuclear medicine workload between 1982 and 1985. The decline of in vivo work alone was 24%. This trend has already been noted in the U.S.. Nuclear medicine is no longer 'a large volume prosperous specialty of wide diagnostic application'

  19. Seguro Nuclear

    International Nuclear Information System (INIS)

    Oliveira, S.C.C. de.

    1978-04-01

    A description of the constitutive elements of insurance and its features in the field of law, and special legislation about the matter are given. The relationship between the liability of the nuclear power plant operator and the international conventions about civil liability on nuclear damage is discussed. Some considerations on damage reparing in the United States, Germany, France and Spain are presented. (A.L.S.L.) [pt

  20. Nuclear accidents

    International Nuclear Information System (INIS)

    1987-01-01

    On 27 May 1986 the Norwegian government appointed an inter-ministerial committee of senior officials to prepare a report on experiences in connection with the Chernobyl accident. The present second part of the committee's report describes proposals for measures to prevent and deal with similar accidents in the future. The committee's evaluations and proposals are grouped into four main sections: Safety and risk at nuclear power plants; the Norwegian contingency organization for dealing with nuclear accidents; compensation issues; and international cooperation

  1. Nuclear hadrodynamics

    International Nuclear Information System (INIS)

    Geesaman, D.F.

    1984-01-01

    The role of hadron dynamics in the nucleus is illustrated to show the importance of nuclear medium effects in hadron interactions. The low lying hadron spectrum is considered to provide the natural collective variables for nuclear systems. Recent studies of nucleon-nucleon and delta-nucleon interactions are reviewed, with emphasis on the type of experimental phenomena which signal the importance of the many-body dynamics. 28 references

  2. Nuclear medicine

    International Nuclear Information System (INIS)

    Blanquet, Paul; Blanc, Daniel.

    1976-01-01

    The applications of radioisotopes in medical diagnostics are briefly reviewed. Each organ system is considered and the Nuclear medicine procedures pertinent to that system are discussed. This includes, the principle of the test, the detector and the radiopharmaceutical used, the procedure followed and the clinical results obtained. The various types of radiation detectors presently employed in Nuclear Medicine are surveyed, including scanners, gamma cameras, positron cameras and procedures for obtaining tomographic presentation of radionuclide distributions [fr

  3. Nuclear education

    International Nuclear Information System (INIS)

    Kemeny, L.G.

    1987-01-01

    All scientists and technologists are agreed that the coal based fuel cycle is somewhere between 50 to 300 times more dangerous than the uranium fuel cycle. Under these circumstances it is not difficult to show that on a more quantitative basis, the nuclear industry, in all countries, has an unblemished safety record when compared with other energy sources. Various hazards and benefits of nuclear power are analyzed in this paper comparing with other energy sources. (Liu)

  4. Nuclear instrumentation

    International Nuclear Information System (INIS)

    Weill, Jacky; Fabre, Rene.

    1981-01-01

    This article sums up the Research and Development effort at present being carried out in the five following fields of applications: Health physics and Radioprospection, Control of nuclear reactors, Plant control (preparation and reprocessing of the fuel, testing of nuclear substances, etc.), Research laboratory instrumentation, Detectors. It also sets the place of French industrial activities by means of an estimate of the French market, production and flow of trading with other countries [fr

  5. Nuclear Data

    Energy Technology Data Exchange (ETDEWEB)

    White, Morgan C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-01-23

    PowerPoint presentation targeted for educational use. Nuclear data comes from a variety of sources and in many flavors. Understanding where the data you use comes from and what flavor it is can be essential to understand and interpret your results. This talk will discuss the nuclear data pipeline with particular emphasis on providing links to additional resources that can be used to explore the issues you will encounter.

  6. Nuclear astrophysics

    International Nuclear Information System (INIS)

    Arnould, M.; Takahashi, K.

    1999-01-01

    Nuclear astrophysics is that branch of astrophysics which helps understanding of the Universe, or at least some of its many faces, through the knowledge of the microcosm of the atomic nucleus. It attempts to find as many nuclear physics imprints as possible in the macrocosm, and to decipher what those messages are telling us about the varied constituent objects in the Universe at present and in the past. In the last decades much advance has been made in nuclear astrophysics thanks to the sometimes spectacular progress made in the modelling of the structure and evolution of the stars, in the quality and diversity of the astronomical observations, as well as in the experimental and theoretical understanding of the atomic nucleus and of its spontaneous or induced transformations. Developments in other subfields of physics and chemistry have also contributed to that advance. Notwithstanding the accomplishment, many long-standing problems remain to be solved, and the theoretical understanding of a large variety of observational facts needs to be put on safer grounds. In addition, new questions are continuously emerging, and new facts endangering old ideas. This review shows that astrophysics has been, and still is, highly demanding to nuclear physics in both its experimental and theoretical components. On top of the fact that large varieties of nuclei have to be dealt with, these nuclei are immersed in highly unusual environments which may have a significant impact on their static properties, the diversity of their transmutation modes, and on the probabilities of these modes. In order to have a chance of solving some of the problems nuclear astrophysics is facing, the astrophysicists and nuclear physicists are obviously bound to put their competence in common, and have sometimes to benefit from the help of other fields of physics, like particle physics, plasma physics or solid-state physics. Given the highly varied and complex aspects, we pick here some specific nuclear

  7. Nuclear technology

    International Nuclear Information System (INIS)

    Steele, L.E.

    1986-01-01

    This book has sixteen peer-reviewed papers divided into four sections that reflect changes in the nuclear power industry occurring since 1981, including escalating capital requirements and a growing worldwide dependence on nuclear power for electricity production. The four sections of this book are: Overview of National Programs; Surveillance and Other Radiation Embrittlement Studies; Pressure Vessel Integrity and Regulatory Considerations; and Mechanisms of Irradiation Embrittlement

  8. Nuclear safety

    International Nuclear Information System (INIS)

    Arnott, D.

    1981-01-01

    Dr Arnott, scientific consultant to PANDORA, emphasises our lack of knowledge of the behaviour of highly active radioactive wastes, particularly effluents, and their characteristics. He proposes that they should be stored, preferably in a solidified state, until our knowledge allows their safe disposal. Political aspects and government policies are discussed and human fallibility is stressed. The nuclear establishment and nuclear power programme are severely criticised. (U.K.)

  9. Nuclear technology

    International Nuclear Information System (INIS)

    1983-03-01

    This report examines nuclear technology in Canada, with emphasis on Quebec, as a means of revitilizing industry. The historical, present day, and future states of Atomic Energy of Canada Limited are examined. Future research programs are discussed in greatest detail. These range from disposal of porcine wastes to new applications for electricity to nuclear medical techniques (to cite only a few examples). The executive summary is written in English. (23 fig., 16 tab.)

  10. Nuclear safety

    International Nuclear Information System (INIS)

    2014-01-01

    The Program on Nuclear Safety comprehends Radioprotection, Radioactive Waste Management and Nuclear Material Control. These activities are developed at the Nuclear Safety Directory. The Radioactive Waste Management Department (GRR) was formally created in 1983, to promote research and development, teaching and service activities in the field of radioactive waste. Its mission is to develop and employ technologies to manage safely the radioactive wastes generated at IPEN and at its customer’s facilities all over the country, in order to protect the health and the environment of today's and future generations. The Radioprotection Service (GRP) aims primarily to establish requirements for the protection of people, as workers, contractors, students, members of the general public and the environment from harmful effects of ionizing radiation. Furthermore, it also aims to establish the primary criteria for the safety of radiation sources at IPEN and planning and preparing for response to nuclear and radiological emergencies. The procedures about the management and the control of exposures to ionizing radiation are in compliance with national standards and international recommendations. Research related to the main activities is also performed. The Nuclear Material Control has been performed by the Safeguard Service team, which manages the accountability and the control of nuclear material at IPEN facilities and provides information related to these activities to ABACC and IAEA. (author)

  11. Nuclear telemedicine

    Science.gov (United States)

    Morrison, R. T.; Szasz, I. J.

    1990-06-01

    Diagnostic nuclear medicine patient images have been transniitted for 8 years from a regional conununity hospital to a university teaching hospital 700 kiloinetres away employing slow scan TV and telephone. Transruission and interpretation were done at the end of each working day or as circumstances required in cases of emergencies. Referring physicians received the nuclear medicine procedure report at the end of the completion day or within few minutes of completion in case of emergency procedures. To date more than 25 patient studies have been transmitted for interpretation. Blinded reinterpretation of the original hard copy data of 350 patient studies resulted in 100 agreement with the interpretation of transmitted data. This technique provides high quality diagnostic and therapeutic nuclear medicine services in remote hospitals where the services of an on-site nuclear physician is not available. 2. HISTORY Eight years ago when the nuclear medicine physician at Trail Regional Hospital left the Trail area and an other could not be recruited we examined the feasibility of image transmission by phone for interpretation since closing the department would have imposed unacceptable physical and financial hardship and medical constraints on the patient population the nearest nuclear medicine facility was at some 8 hours drive away. In hospital patients would have to be treated either based purely on physical findings or flown to Vancouver at considerable cost to the health care system (estimated cost $1500.

  12. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging ... the limitations of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch ...

  13. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Physician Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses ... limitations of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of ...

  14. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small ... of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical ...

  15. Children's (Pediatric) Nuclear Medicine

    Science.gov (United States)

    ... Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small amounts ... Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  16. General Nuclear Medicine

    Science.gov (United States)

    ... Resources Professions Site Index A-Z General Nuclear Medicine Nuclear medicine imaging uses small amounts of radioactive ... of General Nuclear Medicine? What is General Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  17. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small amounts ... Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  18. Calycosin regulates glucocorticoid-induced apoptosis via Nrf2/ARE ...

    African Journals Online (AJOL)

    treatment decreased expression levels of caspase-3/-8/-9 and PARP. In addition, DEX treatment significantly suppressed the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) as well as its downstream targets, viz, heme oxygenase-1 and quinone oxidoreductase-1. Interestingly, CA treatment reversed this ...

  19. Protective Effects of Tetrahydrocurcumin and Curcumin against ...

    African Journals Online (AJOL)

    Purpose: To investigate the cytoprotective effect of tetrahydrocurcumin, (THC) and curcumin (CUR) on cytotoxicity induced by doxorubicin and cadmium in Chang liver cells. Methods: Cytotoxicity was determined by sulforhodamine B assay. The expression of nuclear factor- erythroid-2-related factor 2 (Nrf2) Nrf2 regulated ...

  20. Molecular Alterations in a Mouse Cardiac Model of Friedreich Ataxia

    DEFF Research Database (Denmark)

    Anzovino, Amy; Chiang, Shannon; Brown, Bronwyn E

    2017-01-01

    Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a master regulator of the antioxidant response. However, studies in models of Friedreich ataxia, a neurodegenerative and cardiodegenerative disease associated with oxidative stress, reported decreased Nrf2 expression attributable to unknown me...

  1. Attenuation of sepsis-induced rat liver injury by epigallocatechin ...

    African Journals Online (AJOL)

    Protein and mRNA expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor (Nrf2) were measured by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Results: Survival rates were significantly (p < 0.05) increased by EGCG (83.3 %) when ...

  2. Nuclear risk

    International Nuclear Information System (INIS)

    Levenson, M.

    1989-01-01

    The title of our session, Nuclear Risk Versus Other Power Options, is provocative. It is also a title with different meanings to different people. To the utility chief executive officer, nuclear power is a high-risk financial undertaking because of political and economic barriers to cost recovery. To the utility dispatcher, it is a high-risk future power source since plant completion and start-up dates can be delayed for very long times due to uncertain legal and political issues. To the environmentalist, concerned about global effects such as greenhouse and acid rain, nuclear power is a relatively low risk energy source. To the financial people, nuclear power is a cash cow turned sour because of uncertainties as to what new plants will cost and whether they will even be allowed to operate. The statistics on risk are known and the results of probability risk assessment calculations of risks are known. The challenge is not to make nuclear power safer, it is already one of the safest, if not the safest, source of power currently available. The challenge is to find a way to communicate this to the public

  3. Astaxanthin Activates Nuclear Factor Erythroid-Related Factor 2 and the Antioxidant Responsive Element (Nrf2-ARE Pathway in the Brain after Subarachnoid Hemorrhage in Rats and Attenuates Early Brain Injury

    Directory of Open Access Journals (Sweden)

    Qi Wu

    2014-12-01

    Full Text Available Astaxanthin (ATX has been proven to ameliorate early brain injury (EBI after experimental subarachnoid hemorrhage (SAH by modulating cerebral oxidative stress. This study was performed to assess the effect of ATX on the Nrf2-ARE pathway and to explore the underlying molecular mechanisms of antioxidant properties of ATX in EBI after SAH. A total of 96 male SD rats were randomly divided into four groups. Autologous blood was injected into the prechiasmatic cistern of the rat to induce an experimental SAH model. Rats in each group were sacrificed at 24 h after SAH. Expressions of Nrf2 and heme oxygenase-1 (HO-1 were measured by Western blot and immunohistochemistry analysis. The mRNA levels of HO-1, NAD (P H: quinone oxidoreductase 1 (NQO-1, and glutathione S-transferase-α1 (GST-α1 were determined by real-time polymerase chain reaction (PCR. It was observed that administration of ATX post-SAH could up-regulate the cortical expression of these agents, mediated in the Nrf2-ARE pathway at both pretranscriptional and posttranscriptional levels. Meanwhile, oxidative damage was reduced. Furthermore, ATX treatment significantly attenuated brain edema, blood–brain barrier (BBB disruption, cellular apoptosis, and neurological dysfunction in SAH models. This study demonstrated that ATX treatment alleviated EBI in SAH model, possibly through activating the Nrf2-ARE pathway by inducing antioxidant and detoxifying enzymes.

  4. Omeprazole induces NAD(P)H quinone oxidoreductase 1 via aryl hydrocarbon receptor-independent mechanisms: Role of the transcription factor nuclear factor erythroid 2–related factor 2

    International Nuclear Information System (INIS)

    Zhang, Shaojie; Patel, Ananddeep; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-01-01

    Activation of the aryl hydrocarbon receptor (AhR) transcriptionally induces phase I (cytochrome P450 (CYP) 1A1) and phase II (NAD(P)H quinone oxidoreductase 1 (NQO1) detoxifying enzymes. The effects of the classical and nonclassical AhR ligands on phase I and II enzymes are well studied in human hepatocytes. Additionally, we observed that the proton pump inhibitor, omeprazole (OM), transcriptionally induces CYP1A1 in the human adenocarcinoma cell line, H441 cells via AhR. Whether OM activates AhR and induces the phase II enzyme, NAD(P)H quinone oxidoreductase 1 (NQO1), in fetal primary human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce NQO1 in HPMEC via the AhR. The concentrations of OM used in our experiments did not result in cytotoxicity. OM activated AhR as evident by increased CYP1A1 mRNA expression. However, contrary to our hypothesis, OM increased NQO1 mRNA and protein via an AhR-independent mechanism as AhR knockdown failed to abrogate OM-mediated increase in NQO1 expression. Interestingly, OM activated Nrf2 as evident by increased phosphoNrf2 (S40) expression in OM-treated compared to vehicle-treated cells. Furthermore, Nrf2 knockdown abrogated OM-mediated increase in NQO1 expression. In conclusion, we provide evidence that OM induces NQO1 via AhR-independent, but Nrf2-dependent mechanisms. - Highlights: • We investigated whether omeprazole induces NQO1 in human fetal lung cells. • Omeprazole induces the phase II enzyme, NQO1, in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of NQO1. • Omeprazole increases phosphoNrf2 (S40) protein expression in human fetal lung cells. • Nrf2 knockdown abrogates the induction of NQO1 by omeprazole in human lung cells.

  5. Omeprazole induces NAD(P)H quinone oxidoreductase 1 via aryl hydrocarbon receptor-independent mechanisms: Role of the transcription factor nuclear factor erythroid 2–related factor 2

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shaojie; Patel, Ananddeep; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2015-11-13

    Activation of the aryl hydrocarbon receptor (AhR) transcriptionally induces phase I (cytochrome P450 (CYP) 1A1) and phase II (NAD(P)H quinone oxidoreductase 1 (NQO1) detoxifying enzymes. The effects of the classical and nonclassical AhR ligands on phase I and II enzymes are well studied in human hepatocytes. Additionally, we observed that the proton pump inhibitor, omeprazole (OM), transcriptionally induces CYP1A1 in the human adenocarcinoma cell line, H441 cells via AhR. Whether OM activates AhR and induces the phase II enzyme, NAD(P)H quinone oxidoreductase 1 (NQO1), in fetal primary human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce NQO1 in HPMEC via the AhR. The concentrations of OM used in our experiments did not result in cytotoxicity. OM activated AhR as evident by increased CYP1A1 mRNA expression. However, contrary to our hypothesis, OM increased NQO1 mRNA and protein via an AhR-independent mechanism as AhR knockdown failed to abrogate OM-mediated increase in NQO1 expression. Interestingly, OM activated Nrf2 as evident by increased phosphoNrf2 (S40) expression in OM-treated compared to vehicle-treated cells. Furthermore, Nrf2 knockdown abrogated OM-mediated increase in NQO1 expression. In conclusion, we provide evidence that OM induces NQO1 via AhR-independent, but Nrf2-dependent mechanisms. - Highlights: • We investigated whether omeprazole induces NQO1 in human fetal lung cells. • Omeprazole induces the phase II enzyme, NQO1, in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of NQO1. • Omeprazole increases phosphoNrf2 (S40) protein expression in human fetal lung cells. • Nrf2 knockdown abrogates the induction of NQO1 by omeprazole in human lung cells.

  6. Nuclear waste

    International Nuclear Information System (INIS)

    Anon.

    1996-01-01

    The NEA Nuclear Waste Bulletin has been prepared by the Radiation Protection and Waste Management Division of the OECD Nuclear Energy Agency to provide a means of communication amongst the various technical and policy groups within the waste management community. In particular, it is intended to provide timely and concise information on radioactive waste management activities, policies and programmes in Member countries and at the NEA. It is also intended that the Bulletin assists in the communication of recent developments in a variety of areas contributing to the development of acceptable technology for the management and disposal of nuclear waste (e.g., performance assessment, in-situ investigations, repository engineering, scientific data bases, regulatory developments, etc)

  7. Nuclear astrophysics

    Science.gov (United States)

    Penionzhkevich, Yu. E.

    2010-08-01

    The International Year of Astronomy 2009 (IYA2009) was declared by the 62nd General Assembly of the United Nations and was also endorsed by UNESCO. Investigations in the realms of particle and nuclear physicsmake a large contribution in the development of our ideas of the properties of the Universe. The present article discusses some problems of the evolution of the Universe, nucleosyntheses, and cosmochronology from the point of view of nuclear and particle physics. Processes occurring in the Universe are compared with the mechanisms of the production and decay of nuclei, as well as with the mechanisms of their interaction at high energies. Examples that demonstrate the potential of nuclearphysics methods for studying cosmic objects and the properties of the Universe are given. The results that come from investigations into nuclear reactions induced by beams of radioactive nuclei and which make it possible to take a fresh look at the nucleosynthesis scenario in the range at light nuclei are presented.

  8. Nuclear scales

    International Nuclear Information System (INIS)

    Friar, J.L.

    1998-01-01

    Nuclear scales are discussed from the nuclear physics viewpoint. The conventional nuclear potential is characterized as a black box that interpolates nucleon-nucleon (NN) data, while being constrained by the best possible theoretical input. The latter consists of the longer-range parts of the NN force (e.g., OPEP, TPEP, the π-γ force), which can be calculated using chiral perturbation theory and gauged using modern phase-shift analyses. The shorter-range parts of the force are effectively parameterized by moments of the interaction that are independent of the details of the force model, in analogy to chiral perturbation theory. Results of GFMC calculations in light nuclei are interpreted in terms of fundamental scales, which are in good agreement with expectations from chiral effective field theories. Problems with spin-orbit-type observables are noted

  9. Nuclear scales

    Energy Technology Data Exchange (ETDEWEB)

    Friar, J.L.

    1998-12-01

    Nuclear scales are discussed from the nuclear physics viewpoint. The conventional nuclear potential is characterized as a black box that interpolates nucleon-nucleon (NN) data, while being constrained by the best possible theoretical input. The latter consists of the longer-range parts of the NN force (e.g., OPEP, TPEP, the {pi}-{gamma} force), which can be calculated using chiral perturbation theory and gauged using modern phase-shift analyses. The shorter-range parts of the force are effectively parameterized by moments of the interaction that are independent of the details of the force model, in analogy to chiral perturbation theory. Results of GFMC calculations in light nuclei are interpreted in terms of fundamental scales, which are in good agreement with expectations from chiral effective field theories. Problems with spin-orbit-type observables are noted.

  10. Co-occurring Down syndrome and SUCLA2-related mitochondrial depletion syndrome.

    Science.gov (United States)

    Couser, Natario L; Marchuk, Daniel S; Smith, Laurie D; Arreola, Alexandra; Kaiser-Rogers, Kathleen A; Muenzer, Joseph; Pandya, Arti; Gucsavas-Calikoglu, Muge; Powell, Cynthia M

    2017-10-01

    Mitochondrial DNA depletion syndrome 5 (MIM 612073) is a rare autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the beta subunit of the succinate-CoA ligase gene located within the 13q14 band. We describe two siblings of Hispanic descent with SUCLA2-related mitochondrial depletion syndrome (encephalomyopathic form with methylmalonic aciduria); the older sibling is additionally affected with trisomy 21. SUCLA2 sequencing identified homozygous p.Arg284Cys pathogenic variants in both patients. This mutation has previously been identified in four individuals of Italian and Caucasian descent. The older sibling with concomitant disease has a more severe phenotype than what is typically described in patients with either SUCLA2-related mitochondrial depletion syndrome or Down syndrome alone. The younger sibling, who has a normal female chromosome complement, is significantly less affected compared to her brother. While the clinical and molecular findings have been reported in about 50 patients affected with a deficiency of succinate-CoA ligase caused by pathogenic variants in SUCLA2, this report describes the first known individual affected with both a mitochondrial depletion syndrome and trisomy 21. © 2017 Wiley Periodicals, Inc.

  11. Nuclear glutathione.

    Science.gov (United States)

    García-Giménez, José Luis; Markovic, Jelena; Dasí, Francisco; Queval, Guillaume; Schnaubelt, Daniel; Foyer, Christine H; Pallardó, Federico V

    2013-05-01

    Glutathione (GSH) is a linchpin of cellular defences in plants and animals with physiologically-important roles in the protection of cells from biotic and abiotic stresses. Moreover, glutathione participates in numerous metabolic and cell signalling processes including protein synthesis and amino acid transport, DNA repair and the control of cell division and cell suicide programmes. While it is has long been appreciated that cellular glutathione homeostasis is regulated by factors such as synthesis, degradation, transport, and redox turnover, relatively little attention has been paid to the influence of the intracellular partitioning on glutathione and its implications for the regulation of cell functions and signalling. We focus here on the functions of glutathione in the nucleus, particularly in relation to physiological processes such as the cell cycle and cell death. The sequestration of GSH in the nucleus of proliferating animal and plant cells suggests that common redox mechanisms exist for DNA regulation in G1 and mitosis in all eukaryotes. We propose that glutathione acts as "redox sensor" at the onset of DNA synthesis with roles in maintaining the nuclear architecture by providing the appropriate redox environment for the DNA replication and safeguarding DNA integrity. In addition, nuclear GSH may be involved in epigenetic phenomena and in the control of nuclear protein degradation by nuclear proteasome. Moreover, by increasing the nuclear GSH pool and reducing disulfide bonds on nuclear proteins at the onset of cell proliferation, an appropriate redox environment is generated for the stimulation of chromatin decompaction. This article is part of a Special Issue entitled Cellular functions of glutathione. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Nuclear dilemma

    Energy Technology Data Exchange (ETDEWEB)

    Penn, J.

    Declaring nuclear preparedness 'immoral' helps to recreate the pacifism of 50 years ago. War itself is a dilemma, not the weapons with which it is waged. We must ask of the anti-war proposals: whom do they benefit. On the whole people concerned are ordinary citizens who are fearful of nuclear incineration. But marching with them is a spectrum of forces with other motivations and purposes. In a real life situation of international tension or crises, numbers of weapons in combination with their particular charateristics could mean the difference between peace and outbreak of war.

  13. Nuclear reactions

    International Nuclear Information System (INIS)

    Lane, A.M.

    1980-01-01

    In reviewing work at Harwell over the past 25 years on nuclear reactions it is stated that a balance has to be struck in both experiment and theory between work on cross-sections of direct practical relevance to reactors and on those relevant to an overall understanding of reaction processes. The compound nucleus and direct process reactions are described. Having listed the contributions from AERE, Harwell to developments in nuclear reaction research in the period, work on the optical model, neutron capture theory, reactions at doorway states with fine structure, and sum-rules for spectroscopic factors are considered in more detail. (UK)

  14. Nuclear microprobe

    International Nuclear Information System (INIS)

    Engelmann, C.

    1989-01-01

    The nuclear microprobe allows punctual analysis and localization of detected elements inside the volume swept by the particle beam. Particularly well adapted for light elements (and their isotopes) determination. They are detected by nuclear reaction and selectivity is obtained by choice of particles and their energy. Other elements are analyzed by X-ray spectra obtained with the primary ion beam. In some cases concentration profils are obtained in few micrometers and are non-destructive. Operation principle, equipment, performance and examples of applications are reviewed. 71 refs [fr

  15. Nuclear energy

    CERN Document Server

    Marquardt, Meg

    2016-01-01

    A piece of nuclear fuel the size of your fingertip holds as much energy as 150 gallons (568 L) of oil. In Nuclear Energy, learn how scientists developed this amazing source of energy, how it works, and why it has attracted controversy. Easy-to-read text, vivid images, and helpful back matter give readers a clear look at this subject. Features include a table of contents, infographics, a glossary, additional resources, and an index. Aligned to Common Core Standards and correlated to state standards. Core Library is an imprint of Abdo Publishing, a division of ABDO.

  16. Nuclear Positioning

    Science.gov (United States)

    Gundersen, Gregg G.; Worman, Howard J.

    2013-01-01

    SUMMARY The nucleus is the largest organelle and is commonly depicted in the center of the cell. Yet during cell division, migration and differentiation, it frequently moves to an asymmetric position aligned with cell function. We consider the toolbox of proteins that move and anchor the nucleus within the cell and how forces generated by the cytoskeleton are coupled to the nucleus to move it. The significance of proper nuclear positioning is underscored by numerous diseases resulting from genetic alterations in the toolbox proteins. Finally, we discuss how nuclear position may influence cellular organization and signaling pathways. PMID:23498944

  17. Nuclear politics

    International Nuclear Information System (INIS)

    Hall, Tony.

    1986-01-01

    Written by an arts graduate journalist this is intended for a non-technical general readership. It chronicles the history of the nuclear power industry in Britain from its beginnings, which were inextricably tied to the development of the atomic bomb, to the Sellafield investigation and Sizewell public inquiry. In particular the government decisions which have influenced the present structure and state of the industry are criticised. With important decisions about to be made the author questions the accountability of the nuclear industry and the government's ability to understand the complex technical aspects of the industry. (U.K.)

  18. Nuclear fuel

    International Nuclear Information System (INIS)

    Azevedo, J.B.L. de.

    1980-01-01

    All stages of nuclear fuel cycle are analysed with respect to the present situation and future perspectives of supply and demand of services; the prices and the unitary cost estimation of these stages for the international fuel market are also mentioned. From the world resources and projections of uranium consumption, medium-and long term analyses are made of fuel availability for several strategies of use of different reactor types. Finally, the cost of nuclear fuel in the generation of electric energy is calculated to be used in the energetic planning of the electric sector. (M.A.) [pt

  19. Nuclear cardiology

    International Nuclear Information System (INIS)

    Bashore, T.M.; Shaffer, P.B.

    1985-01-01

    The birth of nuclear cardiology has generally been attributed to a 1927 experiment during which a radium salt was injected in one arm vein and the circulation time calculated by recording the arrival of the radioactivity in the opposite arm. This simple experiment lead to the radiocardiogram in the late 1940s that was used to measure left ventricular function and, later, cardiac output. This chapter provides a brief overview of nuclear cardiology. Methodology is presented when it is important for the understanding of test results. The use of these studies in the diagnosis and evaluation of patients with suspected cardiovascular disease is emphasized

  20. Nuclear law

    International Nuclear Information System (INIS)

    Zwam, H.J. van

    1985-01-01

    A description is given of international and Dutch-national atomic energy law. Attention is paid to regulations relevant to industry, as well as to relationships between national and international regulations. First, international law is considered, namely the Euratom Treaty, Euratom institutes and tasks of Euratom. Next, the Dutch-national legislation is discussed with respect to nuclear fuels, ores and security of State (Defence interests). Regulations concerning radioactive materials in working rooms and instruments, personnel dosimetry and safety measures are discussed. Finally, authority control on rule observance and penal uphold of nuclear law is considered. (G.J.P.)

  1. Two novel mutations (p.(Ser160Pro) and p.(Arg472Cys)) causing glucose-6-phosphate isomerase deficiency are associated with erythroid dysplasia and inappropriately suppressed hepcidin.

    Science.gov (United States)

    Mojzikova, Renata; Koralkova, Pavla; Holub, Dusan; Saxova, Zuzana; Pospisilova, Dagmar; Prochazkova, Daniela; Dzubak, Petr; Horvathova, Monika; Divoky, Vladimir

    2018-03-01

    Glucose-6-phosphate isomerase (GPI) deficiency, a genetic disorder responsible for chronic nonspherocytic hemolytic anemia, is the second most common red blood cell glycolytic enzymopathy. We report three patients from two unrelated families of Czech and Slovak origin with macrocytic hemolytic anemia due to GPI deficiency. The first patient had 15% of residual GPI activity resulting from two new heterozygous missense mutations c.478T>C and c.1414C>T leading to substitutions p.(Ser160Pro) and p.(Arg472Cys). Two other patients (siblings) inherited the same c.1414C>T p.(Arg472Cys) mutation in a homozygous constitution and lost approximately 89% of their GPI activity. Erythroid hyperplasia with dysplastic features was observed in the bone marrow of all three patients. Low hepcidin/ferritin ratio and elevated soluble transferrin receptor detected in our GPI-deficient patients suggest disturbed balance between erythropoiesis and iron metabolism contributing to iron overload. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Nuclear reactions

    International Nuclear Information System (INIS)

    Corner, J.; Richardson, K.; Fenton, N.

    1990-01-01

    Nuclear reactions' marks a new development in the study of television as an agency of public policy debate. During the Eighties, nuclear energy became a major international issue. The disasters at Three-mile Island and Chernobyl created a global anxiety about its risks and a new sensitivity to it among politicians and journalists. This book is a case-study into documentary depictions of nuclear energy in television and video programmes and into the interpretations and responses of viewers drawn from many different occupational groupings. How are the complex and specialist arguments about benefit, risk and proof conveyed through the different conventions of commentary, interview and film sequence? What symbolic associations does the visual language of television bring to portrayals of the issue? And how do viewers make sense of various and conflicting accounts, connecting what they see and hear on the screen with their pre-existing knowledge, experience and 'civic' expectations. The authors examine some of the contrasting forms and themes which have been used by programme makers to explain and persuade, and then give a sustained analysis of the nature and sources of viewers' own accounts. 'Nuclear Reactions' inquires into the public meanings surrounding energy and the environment, spelling out in its conclusion some of the implications for future media treatments of this issue. It is also a key contribution to the international literature on 'television knowledge' and the processes of active viewing. (author)

  3. Nuclear waste

    International Nuclear Information System (INIS)

    1990-06-01

    DOE estimates that disposing of radioactive waste from civilian nuclear power plants and its defense-related nuclear facilities could eventually end up costing $32 billion. To pay for this, DOE collects fees from utilities on electricity generated by nuclear power plants and makes payments from its defense appropriation. This report states that unless careful attention is given to its financial condition, the nuclear waste program is susceptible to future shortfalls. Without a fee increase, the civilian-waste part of the program may already be underfunded by at least $2.4 billion (in discounted 1988 dollars). Also, DOE has not paid its share of cost-about $480 million-nor has it disclosed this liability in its financial records. Indexing the civilian fee to the inflation rate would address one major cost uncertainty. However, while DOE intends to do this at an appropriate time, it does not use a realistic rate of inflation as its most probable scenario in assessing whether that time has arrived

  4. Nuclear imaging

    International Nuclear Information System (INIS)

    Miller, J.H.; Reid, B.S.

    1985-01-01

    Nuclear imaging, utilizing relatively low photon energy emitting isotopes, allows an assessment of anatomic configuration and organ function. This method of imaging is predicted on the utilization of physiologically active radioisotope-labeled compounds or biologically active radioisotopes. Localization of such isotopes in normal or abnormal concentrations may be due to varying physiological or pathological mechanisms

  5. Nuclear fragmentation

    International Nuclear Information System (INIS)

    Chung, K.C.

    1989-01-01

    An introduction to nuclear fragmentation, with emphasis in percolation ideas, is presented. The main theoretical models are discussed and as an application, the uniform expansion approximation is presented and the statistical multifragmentation model is used to calculate the fragment energy spectra. (L.C.)

  6. Nuclear Energy

    International Nuclear Information System (INIS)

    1982-11-01

    A brief indication is given of the United Kingdom nuclear power programme including descriptions of the fission process, the Magnox, AGR and PWR type reactors, the recycling process, waste management and decommissioning, safety precautions, the prototype fast reactor at Dounreay, and the JET fusion experiment. (U.K.)

  7. Nuclear physics

    International Nuclear Information System (INIS)

    1990-01-01

    This work describes the actual situation of nuclear physics in Brazil as well as its perspectives of developments and real needs in the next decade. It discusses the main projects and the financing of brazilian research groups and Universities. (A.C.A.S.)

  8. Nuclear films

    International Nuclear Information System (INIS)

    Malone, Peter.

    1985-01-01

    This booklet is a resource for the study of feature films that highlight the theme of nuclear war. It provides basic credits and brief indication of the theme, treatment, quality and particular notable aspects; and a series of questions raised by the film. Seventy feature films and thirty documentaries are examined

  9. Nuclear reactor

    International Nuclear Information System (INIS)

    Mysels, K.J.; Shenoy, A.S.

    1976-01-01

    A nuclear reactor is described in which the core consists of a number of fuel regions through each of which regulated coolant flows. The coolant from neighbouring fuel regions is combined in a manner which results in an averaging of the coolant temperature at the outlet of the core. By this method the presence of hot streaks in the reactor is reduced. (UK)

  10. On osp(2 | 2) -relative cohomology of the Lie superalgebra of contact vector fields and deformations

    Science.gov (United States)

    Nizar, Ben Fraj; Abdaoui, Meher; Hamza, Raouafi

    2018-02-01

    We consider the 1 | 2-dimensional real superspace R 1 | 2 endowed with its standard contact structure defined by the 1-form α. The conformal Lie superalgebra K(2) acts on R 1 | 2 as the Lie superalgebra of contact vector fields; it contains the Möbius superalgebra osp(2 | 2) . We classify osp(2 | 2) -invariant superskew-symmetric binary differential operators from K(2) ∧ K(2) to Dλ,μ vanishing on osp(2 | 2) , where Dλ,μ is the superspace of linear differential operators between the superspaces of weighted densities. This result allows us to compute the second differential osp(2 | 2) -relative cohomology of K(2) with coefficients in Dλ,μ. We study generic formal osp(2 | 2) -trivial deformations of the K(2) -module structure on the direct sum of the superspaces of weighted densities. This work is the simplest superization of a result by Bouarroudj (2007).

  11. Nuclear safety culture and nuclear safety supervision

    International Nuclear Information System (INIS)

    Chai Jianshe

    2013-01-01

    In this paper, the author reviews systematically and summarizes up the development process and stage characteristics of nuclear safety culture, analysis the connotation and characteristics of nuclear safety culture, sums up the achievements of our country's nuclear safety supervision, dissects the challenges and problems of nuclear safety supervision. This thesis focused on the relationship between nuclear safety culture and nuclear safety supervision, they are essential differences, but there is a close relationship. Nuclear safety supervision needs to introduce some concepts of nuclear safety culture, lays emphasis on humanistic care and improves its level and efficiency. Nuclear safety supervision authorities must strengthen nuclear safety culture training, conduct the development of nuclear safety culture, make sure that nuclear safety culture can play significant roles. (author)

  12. Institute for Nuclear Research and Nuclear Energy and Nuclear Science

    International Nuclear Information System (INIS)

    Stamenov, J.

    2004-01-01

    The Institute for Nuclear Research and Nuclear Energy (INRNE) of the Bulgarian Academy of Sciences is the leading Bulgarian Institute for scientific investigations and applications of nuclear science. The main Institute's activities in the field of elementary particles and nuclear physics, high energy physics and nuclear energy, radiochemistry, radioecology, radioactive wastes treatment, monitoring of the environment, nuclear instruments development ect. are briefly described. Several examples for: environmental radiation monitoring; monitoring of the radioactivity and heavy metals in aerosols, 99m Tc clinical use, Boron Neutron Capture Therapy application of IRT-2000 Research Reactor, neutron fluence for reactor vessel embrittlement, NPP safety analysis, nuclear fuel modelling are also presented

  13. Nuclear power plants

    International Nuclear Information System (INIS)

    1985-01-01

    Data concerning the existing nuclear power plants in the world are presented. The data was retrieved from the SIEN (Nuclear and Energetic Information System) data bank. The information are organized in table forms as follows: nuclear plants, its status and type; installed nuclear power plants by country; nuclear power plants under construction by country; planned nuclear power plants by country; cancelled nuclear power plants by country; shut-down nuclear power plants by country. (E.G.) [pt

  14. Nuclear power of Korea

    International Nuclear Information System (INIS)

    Chun Bee-Ho

    2011-01-01

    National nuclear is presented. Nuclear energy safety after Fukushima, international cooperation in nuclear energy is discussed. Nuclear projects with the United Arab Emirates have been developed to build 4 nuclear power plants in the UAE - APR 1400. At the Korea-Bulgaria Industrial Committee Meeting in Sofia (March 2011) Korean side proposed Nuclear Safety Training Program in Korea for Bulgarian government officials and experts transfer of know-how and profound expertise on world-class nuclear technology and nuclear safety

  15. A nuclear proliferation antigen in chronic lymphoproliferative disease

    International Nuclear Information System (INIS)

    Hassab, A.H.; Nafae, M.H.

    1998-01-01

    To determine whether the proliferation rates of tumour cells, in chronic lymphoproliferative disorders may reflect disease activity and relate to prognosis, we studied the expression of Ki-67% (a nuclear proliferation marker) by alkaline phosphatase anti-alkaline phosphatase technique (APAAP), in peripheral blood and bone marrow mononuclear cells (separated on ficoll-hypaque) and in lymph-node biopsies, from patients with chronic lymphatic leukemia (Cll), chronic lymphatic leukemia/prolymphocytic leukemia (CLL/PLL), prolymphocytic leukemia (PLL) and non-hodgkin's lymphoma with leukemic plase. The proliferation rate was determined for these patients at presentation and again two months after therapy (to detect any change with therapy). We found that the highest rate of proliferation in each group was parallel to the degree of malignancy i.e. PLL showed higher proliferation than CLL/PLL, and CLL/PLL showed higher proliferation than CLL. In the NHL group the highest proliferation rate was found in the high high-grade NHL, followed by intermediate grade NHL then the low grade NHL. Lymph node biopsies also showed the same relation between proliferation rates and degree of malignancy. Bone marrow cells did not show a particular pattern probably due to interference from the erythroid element and contamination by peripheral blood. Ki-67% was compared to other proliferation markers serum B2 microglobulin and lactate dehydrogenase. It was found to be an independent marker of proliferation it is unaffected by hepatic, renal and gastrointestinal elements and thus its specificity for the tumour proliferation

  16. Nuclear waste

    International Nuclear Information System (INIS)

    1991-01-01

    The Privacy Act of 1974 restricts both the type of information on private individuals that federal agencies may maintain in their records and the conditions under which such information may be disclosed. The Nuclear Regulatory Commission, which must approve DOE plans to build a nuclear waste repository at the Yucca Mountain site in Nevada, requires a quality assurance program to guarantee that studies of the site are done by qualified employees. Under such a program, the training and qualifications of DOE and contractor employees would be verified. This report reviews DOE's efforts to identify and resolve the implications of the Privacy Act for DOE's quality assurance program and how the delay in resolving Privacy Act issues may have affected preliminary work on the Yucca Mountain project

  17. Nuclear desalination

    International Nuclear Information System (INIS)

    Huyghe, J.

    1975-01-01

    The use of small or medium size nuclear reactors for the desalination of sea water has gained economic interest since the increase of oil prices. These reactors, with a wide range of power from 135 to 1,100Mwth, are parrticularly interesting because their production of fresh water or electricity is tailored to the present need. The replacement of conventional fuel boilers by nuclear reactor boilers does not change the traditional desalination technology and alters very little the coupling of the electricity and water producing parts of the plant. It is a reasonable assumption that the performance of desalination plants will increase with the optimization of the design technology of a mixed plant. The cost of the water produced in a mixed plant is mainly related to local conditions and to the method of splitting the cost between water and electricity. It is therefore impossible to give in this paper a cost for the fresh water production [fr

  18. Nuclear power

    Energy Technology Data Exchange (ETDEWEB)

    Hodgson, P.

    1985-01-01

    The question 'Do we really need nuclear power' is tackled within the context of Christian beliefs. First, an estimate is made of the energy requirements in the future and whether it can be got in conventional ways. The dangers of all the ways of supplying energy (eg coal mining, oil and gas production) are considered scientifically. Also the cost of each source and its environmental effects are debated. The consequences of developing a new energy source, as well as the consequences of not developing it, are considered. Decisions must also take into account a belief about the ultimate purpose of life, the relation of men to each other and to nature. Each issue is raised and questions for discussion are posed. On the whole the book comes down in favour of nuclear power.

  19. Nuclear reactors

    International Nuclear Information System (INIS)

    Barre, Bertrand

    2015-10-01

    After some remarks on the nuclear fuel, on the chain reaction control, on fuel loading and unloading, this article proposes descriptions of the design, principles and operations of different types of nuclear reactors as well as comments on their presence and use in different countries: pressurized water reactors (design of the primary and secondary circuits, volume and chemistry control, backup injection circuits), boiling water reactors, heavy water reactors, graphite and boiling water reactors, graphite-gas reactors, fast breeder reactors, and fourth generation reactors (definition, fast breeding). For these last ones, six concepts are presented: sodium-cooled fast reactor, lead-cooled fast reactor, gas-cooled fast reactor, high temperature gas-cooled reactor, supercritical water-cooled reactor, and molten salt reactor

  20. Nuclear energy and the nuclear industry

    International Nuclear Information System (INIS)

    1979-01-01

    These notes have been prepared by the Department of Energy to provide information and to answer questions often raised about nuclear energy and the nuclear industry and in the hope that they will contribute to the public debate about the future of nuclear energy in the UK. The subject is dealt with under the headings; contribution of nuclear power, energy forecasts, nuclear fuels and reactor types, cost, thermal reactor strategy, planning margin, safety, nuclear licensing, unlike an atomic bomb, radiation, waste disposal, transport of nuclear materials, emergency arrangements at nuclear sites, siting of nuclear stations, security of nuclear installations, world nuclear programmes, international regulation and non-proliferation, IAEA safeguards arrangements in the UK, INFCE, and uranium supplies. (U.K.)

  1. I wonder nuclear energy

    International Nuclear Information System (INIS)

    Lee, Eun Cheol

    2009-04-01

    This book consists seven chapters, which are powerful nuclear energy, principle of nuclear fission, nuclear energy in our daily life, is nuclear energy safe?, what is radiation?, radiation spread in pur daily life and radiation like a spy. It adds nuclear energy story through quiz. This book with pictures is for kids to explain nuclear energy easily.

  2. Nuclear medicine

    International Nuclear Information System (INIS)

    Casier, Ph.; Lepage, B.

    1998-01-01

    Except for dedicated devices for mobile nuclear cardiology for instance, the market is set on variable angulation dual heads cameras. These cameras are suited for all general applications and their cost effectiveness is optimized. Now, all major companies have such a camera in their of products. But, the big question in nuclear medicine is about the future of coincidence imaging for the monitoring of treatments in oncology. Many companies are focused on WIP assessments to find out the right crustal thickness to perform both high energy FDG procedures and low energy Tc procedures, with the same SPECT camera. The classic thickness is 3/8''. Assessments are made with 1/2'', 5/8'' or 3/4'' crystals. If FDG procedures proved to be of great interest in oncology, it may lead to the design of a dedicated SPECT camera with a 1'' crustal. Due to the short half of FDG, it may be the dawning of slip ring technology. (e.g. Varicam from Elscint). The three small heads camera market seems to be depressed. Will the new three large heads camera unveiled by Picker, reverse that trend? The last important topic in nuclear medicine is the emergence of new flat digital detectors to get rid of the old bulky ones. Digirad is the first company to manufacture a commercial product based on that technology. Bichron, Siemens and General Electric are working on that development, too. But that technology is very expensive and the market for digital detection in nuclear medicine is not as large as the market in digital detection in radiology. (author)

  3. Nuclear spintronics

    OpenAIRE

    Vagner, Israel D.

    2003-01-01

    The electron spin transport in condensed matter, Spintronics, is a subject of rapidly growing interest both scientifically and from the point of view of applications to modern and future electronics. In many cases the electron spin transport cannot be described adequately without accounting for the hyperfine interaction between electron and nuclear spins. Here, the progress in physics and applications of these phenomena will be reviewed.

  4. Nuclear facilities

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    During September and October 2001, 15 events were recorded on the first grade and 1 on the second grade of the INES scale. The second grade event is in fact a re-classification of an incident that occurred on the second april 2001 at Dampierre power plant. This event happened during core refueling, a shift in the operation sequence led to the wrong positioning of 113 assemblies. A preliminary study of this event shows that this wrong positioning could have led, in other circumstances, to the ignition of nuclear reactions. Even in that case, the analysis made by EDF shows that the consequences on the staff would have been limited. Nevertheless a further study has shown that the existing measuring instruments could not have detected the power increase announcing the beginning of the chain reaction. The investigation has shown that there were deficiencies in the control of the successive operations involved in refueling. EDF has proposed a series of corrective measures to be implemented in all nuclear power plants. The other 15 events are described in the article. During this period 121 inspections have been made in nuclear facilities. (A.C.)

  5. Nuclear medicine

    International Nuclear Information System (INIS)

    James, A.E. Jr.; Squire, L.F.

    1977-01-01

    The book presents a number of fundamental imaging principles in nuclear medicine. The fact that low radiation doses are sufficient for the study of normal and changed physiological functions of the body is an important advancement brought about by nuclear medicine. The possibility of quantitative investigations of organs and organ regions and of an assessment of their function as compared to normal values is a fascinating new diagnostic dimension. The possibility of comparing the findings with other pathological findings and of course control in the same patient lead to a dynamic continuity with many research possibilities not even recognized until now. The limits of nuclear scanning methods are presented by the imprecise structural information of the images. When scintiscans are compared with X-ray images or contrast angiography, the great difference in the imaging of anatomical details is clearly seen. But although the present pictures are not optimal, they are a great improvement on the pictures that were considered clinically valuable a few years ago. (orig./AJ) [de

  6. Nuclear energy

    International Nuclear Information System (INIS)

    Winkler, W.; Hintermann, K.

    1983-01-01

    Nuclear energy, naturally, is rated very high in discussions at the most different levels. Often it is noted that hasty opinions supported by little actual Knowledge are expressed and published. It is an active duty of scientists and technicians by speaking in plain language, to instil as many readers as possible with understanding of the bases and applications of the powers residing in an atomic core - which is all but an easy task. The two authors, experienced researchers and teachers, in the form of this book make an important contribution destined for the broad public. The natural scientist's supreme principle of keeping to facts and avoid personal tinges is satisfied in this book throughout. The first chapter describes the historical development of the atomic model. Its solid mooring in physics was the result of the research work and discovering in that field in the 19th and the beginning of the 20th century, of which we get a fine description in the second chapter. The third chapter describes the way to the discovery of nuclear fission by Otto Hahn, Fritz Strassmann and Lise Meitner. The fourth chapter is above all dedicated to the genial achievements of Enrico Fermi. Before the description of energy production from nuclear energy in the sixth chapter, the fifth chapter reflects on basic questions of energy conversion. In the last chapter problems of global character such as fuel reserves, the environment etc. are dealt with. This book fulfills an important obligation of the scientist to the public. (orig./GL) [de

  7. Nuclear energy

    International Nuclear Information System (INIS)

    1978-01-01

    2 1/2 years ago a consultation group was formed to help the Section for Social Questions of the Council of Churches in the Netherlands, to answer questions in the area of nuclear energy. During this time the character of the questions has changed considerably. In the beginning people spoke of fear and anxiety over the plans for the application of this new technical development but later this fear and anxiety turned to protest and opposition. This brochure has been produced to enlighten people and try and answer their alarm, by exploring the many facets of the problems. Some of these problems are already being deeply discussed by the public, others play no role in the forming of public opinion. The points of view of the churches over nuclear energy are not expressed, the brochure endeavours to express that nuclear energy problems are a concern for the churches. Technical and economic information and the most important social questions are discussed. (C.F.)

  8. Nuclear photonics

    Science.gov (United States)

    Habs, D.; Günther, M. M.; Jentschel, M.; Thirolf, P. G.

    2012-07-01

    With the planned new γ-beam facilities like MEGa-ray at LLNL (USA) or ELI-NP at Bucharest (Romania) with 1013 γ/s and a band width of ΔEγ/Eγ≈10-3, a new era of γ beams with energies up to 20MeV comes into operation, compared to the present world-leading HIγS facility at Duke University (USA) with 108 γ/s and ΔEγ/Eγ≈3ṡ10-2. In the long run even a seeded quantum FEL for γ beams may become possible, with much higher brilliance and spectral flux. At the same time new exciting possibilities open up for focused γ beams. Here we describe a new experiment at the γ beam of the ILL reactor (Grenoble, France), where we observed for the first time that the index of refraction for γ beams is determined by virtual pair creation. Using a combination of refractive and reflective optics, efficient monochromators for γ beams are being developed. Thus, we have to optimize the total system: the γ-beam facility, the γ-beam optics and γ detectors. We can trade γ intensity for band width, going down to ΔEγ/Eγ≈10-6 and address individual nuclear levels. The term "nuclear photonics" stresses the importance of nuclear applications. We can address with γ-beams individual nuclear isotopes and not just elements like with X-ray beams. Compared to X rays, γ beams can penetrate much deeper into big samples like radioactive waste barrels, motors or batteries. We can perform tomography and microscopy studies by focusing down to μm resolution using Nuclear Resonance Fluorescence (NRF) for detection with eV resolution and high spatial resolution at the same time. We discuss the dominating M1 and E1 excitations like the scissors mode, two-phonon quadrupole octupole excitations, pygmy dipole excitations or giant dipole excitations under the new facet of applications. We find many new applications in biomedicine, green energy, radioactive waste management or homeland security. Also more brilliant secondary beams of neutrons and positrons can be produced.

  9. Rapid quantification of glutaminase 2 (GLS2)-related metabolites by HILIC-MS/MS.

    Science.gov (United States)

    Chen, Guan-Yuan; Chao, Hsi-Chun; Liao, Hsiao-Wei; Tsai, I-Lin; Kuo, Ching-Hua

    2017-12-15

    Glutamine, glutamate and glutathione are key modulators of excessive oxidative stress in tumor cells. In this study, we developed a rapid and accurate HILIC-MS/MS method to simultaneously determine concentrations of cellular glutamine, glutamate and glutathione. A bared silica HILIC column was employed to analyze these polar metabolites. The LC-MS parameters were optimized to achieve high sensitivity and selectivity. The analysis can be completed within 4 min under optimal conditions. The method was validated in terms of accuracy, precision, and linearity. Intra-day (n = 9) precision was within 2.68-6.24% among QCs. Inter-day precision (n = 3) was below 12.4%. The method accuracy was evaluated by the recovery test, and the accuracy for three analytes were between 91.6 and 110%. The developed method was applied to study antioxidant function of GLS2 in non-small cell lung cancer cells. Changes in concentrations of glutamine, glutamate and glutathione revealed that the overexpression of GLS2 could effectively decrease oxidative stress. In summary, this study developed a rapid HILIC-MS/MS method for quantification of GLS2-related metabolites that could facilitate elucidation of the role of GLS2 in tumor development. Copyright © 2017. Published by Elsevier Inc.

  10. Nuclear power economic database

    International Nuclear Information System (INIS)

    Ding Xiaoming; Li Lin; Zhao Shiping

    1996-01-01

    Nuclear power economic database (NPEDB), based on ORACLE V6.0, consists of three parts, i.e., economic data base of nuclear power station, economic data base of nuclear fuel cycle and economic database of nuclear power planning and nuclear environment. Economic database of nuclear power station includes data of general economics, technique, capital cost and benefit, etc. Economic database of nuclear fuel cycle includes data of technique and nuclear fuel price. Economic database of nuclear power planning and nuclear environment includes data of energy history, forecast, energy balance, electric power and energy facilities

  11. Nuclear tele medicine; Telemedicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, L.; Hernandez, F.; Fernandez, R. [Departamento de Medicina Nuclear, Imagenologia Diagnostica, Xalapa, Veracruz (Mexico)

    2005-07-01

    The great majority of the digital images of nuclear medicine are susceptible of being sent through internet. This has allowed that the work in diagnosis cabinets by image it can benefit of this modern technology. We have presented in previous congresses works related with tele medicine, however, due to the speed in the evolution of the computer programs and the internet, becomes necessary to make a current position in this modality of work. (Author)

  12. Nuclear Law: A Key Against Nuclear Terrorism

    International Nuclear Information System (INIS)

    Cardozo, P.

    2004-01-01

    The role of the legal instruments in the war against nuclear terrorism. Control of radioactive sources. Elements of Nuclear Law: Definition: it is the body of special legislation that regulates the pacific uses of nuclear energy and the conduct of the persons engaged in activities related to fissionable materials and ionizing radiation . Objective: to provide a legal framework in order to protect individuals , property and the environment against the harmful effects of the use of nuclear energy and ionising radiation. Principles of nuclear energy legislation: safety principle, exclusively operator responsibility, authorization, independence of the regulatory body, inspections and enforcement, nuclear damage compensation, international cooperation. National regulatory infrastructure. Establishment of special law in Emergency Preparedness for nuclear or radiological disaster. IAEA Conventions. Transportation of nuclear material. IAEA regulations on radioactive material. Compensation for nuclear damage. Nuclear safety, security and terrorism. International and domestic instruments. Anti terrorism acts. International agreements on Safety Cooperation. (Author)

  13. Applications of nuclear physics

    Science.gov (United States)

    Hayes, A. C.

    2017-02-01

    Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

  14. Applications of nuclear physics

    International Nuclear Information System (INIS)

    Hayes-Sterbenz, Anna Catherine

    2017-01-01

    Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Lastly, each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

  15. Calcium homeostasis alterations in a mouse model of the Dynamin 2-related centronuclear myopathy

    Directory of Open Access Journals (Sweden)

    Bodvaël Fraysse

    2016-11-01

    Full Text Available Autosomal dominant centronuclear myopathy (CNM is a rare congenital myopathy characterized by centrally located nuclei in muscle fibers. CNM results from mutations in the gene encoding dynamin 2 (DNM2, a large GTPase involved in endocytosis, intracellular membrane trafficking, and cytoskeleton regulation. We developed a knock-in mouse model expressing the most frequent DNM2-CNM mutation; i.e. the KI-Dnm2R465W model. Heterozygous (HTZ KI-Dnm2 mice progressively develop muscle atrophy, impairment of contractile properties, histopathological abnormalities, and elevated cytosolic calcium concentration. Here, we aim at better characterizing the calcium homeostasis impairment in extensor digitorum longus (EDL and soleus muscles from adult HTZ KI-Dnm2 mice. We demonstrate abnormal contractile properties and cytosolic Ca2+ concentration in EDL but not soleus muscles showing that calcium impairment is correlated with muscle weakness and might be a determinant factor of the spatial muscle involvement. In addition, the elevated cytosolic Ca2+ concentration in EDL muscles is associated with an increased sarcolemmal permeability to Ca2+ and releasable Ca2+ content from the sarcoplasmic reticulum. However, amplitude and kinetics characteristics of the calcium transient appear unchanged. This suggests that calcium defect is probably not a primary cause of decreased force generation by compromised sarcomere shortening but may be involved in long-term deleterious consequences on muscle physiology. Our results highlight the first pathomechanism which may explain the spatial muscle involvement occurring in DNM2-related CNM and open the way toward development of a therapeutic approach to normalize calcium content.

  16. A cohort study of Han Chinese MFN2-related Charcot-Marie-Tooth 2A.

    Science.gov (United States)

    Lv, He; Wang, Lu; Zhang, Wei; Wang, Zhaoxia; Zuo, Yuehuan; Liu, Jing; Yuan, Yun

    2015-11-15

    Charcot-Marie-Tooth 2A (CMT2A) is caused by mutations in mitochondrial fusion protein mitofusin 2 (MFN2). CMT2A had a large variety of clinical symptoms and several cohort studies were published recently. This study is to summarized the clinical, electrophysiological, pathological and genetic features in Han Chinese CMT2A. 20 patients from 12 unrelated Chinese families with MFN2 related CMT2A were collected. Clinical symptom, nerve conduction velocity study, sural nerve pathology and MFN2 gene mutation were retrospectively analyzed. We confirmed MFN2 gene mutation in 12 indexes. Nineteen of 20 (95%) patients were classified as early onset phenotypes of CMT2A, including four cases (20%) with infantile onset. Motor nerve conduction velocity (MNCV) of median nerve was above 38m/s in 50% of patients and not recordable in remaining patients. MNCV was not affected by onset age, disease course and mutation site in different patients and MNCV had no correlation with severity of symptoms. Sural nerve biopsy revealed mixed axonal and demyelination change. Loss of myelinated fibers and atypical onions was found in all cases. Electron microscopic (EM) examination of sural nerve confirmed mitochondrial vacuation and aggregation both in myelinated and unmyelinated axons. Eight mutations were detected in 12 indexes, including two novel mutations. The amino acid residue at position 94 of MFN2 protein was a hot spot in Han Chinese patients, followed by R104W. Eraly onset, even infantile onset was more common in our Chinese population. MNCV of median nerve could be either above 38m/s or unrecordable in CMT2A. Pathologically, mixed axon and myelin change should be considered since onion change was frequently observed in most CMT2A. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Nuclear reactor

    International Nuclear Information System (INIS)

    Rau, P.

    1980-01-01

    The reactor core of nuclear reactors usually is composed of individual elongated fuel elements that may be vertically arranged and through which coolant flows in axial direction, preferably from bottom to top. With their lower end the fuel elements gear in an opening of a lower support grid forming part of the core structure. According to the invention a locking is provided there, part of which is a control element that is movable along the fuel element axis. The corresponding locking element is engaged behind a lateral projection in the opening of the support grid. The invention is particularly suitable for breeder or converter reactors. (orig.) [de

  18. Nuclear installations

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    The subject is covered in sections, entitled: competent authorities; control by land use, planning, including licensing; site licences and permits; controls over design, construction, maintenance and operation; monitoring [of ionising radiations from anything on the site, or from anything discharged on or from the site] to be done by the discharger; additional precautions (reporting dangerous occurrences; extended period of the licensee's responsibilities; flying near nuclear installations); enforcement; rights of the individual (to be informed; to appeal or make representations in respect of permission being granted; to initiate or intervene in the enforcement process; to compensation and injunction. (U.K.)

  19. Nuclear dualism.

    Science.gov (United States)

    Karrer, Kathleen M

    2012-01-01

    Nuclear dualism is a characteristic feature of the ciliated protozoa. Tetrahymena have two different nuclei in each cell. The larger, polyploid, somatic macronucleus (MAC) is the site of transcriptional activity in the vegetatively growing cell. The smaller, diploid micronucleus (MIC) is transcriptionally inactive in vegetative cells, but is transcriptionally active in mating cells and responsible for the genetic continuity during sexual reproduction. Although the MICs and MACs develop from mitotic products of a common progenitor and reside in a common cytoplasm, they are different from one another in almost every respect. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Nuclear emergencies

    International Nuclear Information System (INIS)

    1991-01-01

    This leaflet, which is in the form of a fold-up chart, has panels of text which summarize the emergencies that could arise and the countermeasures and emergency plans that have been prepared should nuclear accident occur or affect the United Kingdom. The levels of radiation doses at which various measures would be introduced are outlined. The detection and monitoring programmes that would operate is illustrated. The role of NRPB and the responsible government departments are set out together with an explanation of how the National Arrangements for Incidents involving Radioactivity would be coordinated. (UK)

  1. Nuclear reactor

    International Nuclear Information System (INIS)

    Anthony, A.J.; Gruber, E.A.

    1979-01-01

    A nuclear reactor with control rods in channels between fuel assemblies wherein the fuel assemblies incorporate guide rods which protrude outwardly into the control rod channels to prevent the control rods from engaging the fuel elements. The guide rods also extend back into the fuel assembly such that they are relatively rigid members. The guide rods are tied to the fuel assembly end or support plates and serve as structural members which are supported independently of the fuel element. Fuel element spacing and support means may be attached to the guide rods. 9 claims

  2. Nuclear decommissioning

    International Nuclear Information System (INIS)

    Lawton, H.

    1987-01-01

    Sufficient work has now been done, on a world-wide basis, to justify confidence that full decommissioning of nuclear installations, both plant and reactors, can be carried out safely and efficiently. Projects in several countries should confirm this in the next few years. In the United Kingdom, good progress has been made with the Windscale Advanced Gas-cooled Reactor and supporting development work is finding solutions to resolve uncertainties. Estimates from several sources suggest that decommissioning costs can be kept to an acceptable level. (author)

  3. Applications of Nuclear Physics

    OpenAIRE

    Hayes, Anna C.

    2017-01-01

    Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that und...

  4. Nuclear Installations Act 1965

    International Nuclear Information System (INIS)

    1965-01-01

    This Act governs all activities related to nuclear installations in the United Kingdom. It provides for the licensing procedure for nuclear installations, the duties of licensees, the competent authorities and carriers of nuclear material in respect of nuclear occurrences, as well as for the system of third party liability and compensation for nuclear damage. The Act repeals the Nuclear Installations (Licensing and Insurance) Act 1959 and the Nuclear Installations (Amendment Act) 1965 except for its Section 17(2). (NEA) [fr

  5. Nuclear energy - some aspects

    International Nuclear Information System (INIS)

    Bandeira, Fausto de Paula Menezes

    2005-05-01

    This work presents a brief history of research and development concerning to nuclear technology worldwide and in Brazil, also information about radiations and radioactive elements as well; the nuclear technology applications; nuclear reactor types and functioning of thermonuclear power plants; the number of existing nuclear power plants; the nuclear hazards occurred; the national fiscalization of nuclear sector; the Brazilian legislation in effect and the propositions under proceduring at House of Representatives related to the nuclear energy

  6. Nuclear cardiology

    International Nuclear Information System (INIS)

    Vos, P.H.

    1982-01-01

    This thesis deals with two topics in nuclear cardiology. In the first, left ventricular wall motion assessment using Fourier transform of local left ventricular time-activity curves in gated blood pool studies is evaluated. In the second, the interpretation of myocardial perfusion scintigrams is assessed which are obtained with thallium-201 or with another radiopharmaceutical with different physical, but identical biological properties. In all these investigations data acquisition and analysis by computer played an essential role. In chapter 1 the desirable properties of a nuclear medicine computer system are given and the computer system used for this work is described. Wall motion analysis of the left ventricle using Fourier transform of local time-activity curves in the left ventricular region in gated blood pool studies is described in chapter 2. In chapter 3 detection of non-perfused lesions in myocardial perfusion scintigraphy with thallium-201 is described. Detection of partly perfused lesions and the influence of scatter and photon energy on myocardial perfusion scintigraphy is described in chapter 4. (Auth.)

  7. Efficacy of nuclear forensics

    International Nuclear Information System (INIS)

    Kazi, Reshmi

    2011-01-01

    In a strange turn of history, the threat of global nuclear war has gone down, but the risk of a nuclear attack has gone up. The danger of nuclear terrorism and ways to thwart it, tackle it and manage it in the event of an attack is increasingly gaining the attention of nuclear analysts all over the world. There is rising awareness among nuclear experts to develop mechanisms to prevent, deter and deal with the threat of nuclear terrorism. Nuclear specialists are seeking to develop and improve the science of nuclear forensics so as to provide faster analysis during a crisis. Nuclear forensics can play an important role in detecting illicit nuclear materials to counter trafficking in nuclear and radiological materials. An effective nuclear forensic and attribution strategy can enable policy makers, decision makers and technical managers to respond to situations involving interception of special nuclear materials

  8. Inhibitors of Trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.

    Directory of Open Access Journals (Sweden)

    Luís Gaspar

    2018-01-01

    Full Text Available Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2 proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1 is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd (9, was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Å to

  9. Reconversion of nuclear weapons

    CERN Document Server

    Kapitza, Sergei P

    1992-01-01

    The nuclear predicament or nuclear option. Synopsis of three lectures : 1- The physical basis of nuclear technology. Physics of fission. Chain reaction in reactors and weapons. Fission fragments. Separration of isotopes. Radiochemistry.2- Nuclear reactors with slow and fast neutrons. Power, size, fuel and waste. Plutonium production. Dose rate, shielding and health hazard. The lessons of Chernobyl3- Nuclear weapons. Types, energy, blast and fallout. Fusion and hydrogen bombs. What to do with nuclear weapons when you cannot use them? Testing. Nonmilittary use. Can we get rid of the nuclear weapon? Nuclear proliferation. Is there a nuclear future?

  10. The nuclear dilemma

    International Nuclear Information System (INIS)

    Mason, Colin.

    1983-01-01

    This paper discusses nuclear war, disarmament and national defence policies. The author argues that in spite of the obvious advantages of nuclear power in many parts of the world, the world cannot afford the risk of continuing with it because of the demonstrated close and deadly association of nuclear power and nuclear reactors with nuclear weapons

  11. Nuclear energy data

    International Nuclear Information System (INIS)

    1990-01-01

    Nuclear Energy Data is the OECD Nuclear Energy Agency's annual compilation of basic statistics on electricity generation and nuclear power in OECD countries. The reader will find quick and easy reference to the present status of and projected trends in total electricity generating capacity, nuclear generating capacity, and actual electricity production as well as on supply and demand for nuclear fuel cycle services [fr

  12. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small amounts ... of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  13. Nuclear war nuclear proliferation and their consequences

    International Nuclear Information System (INIS)

    Aga Khan, Sadruddin

    1986-01-01

    The paper concerns the proceedings of a conference hosted by the Groupe de Bellerive to explore and discuss the implications for humanity of nuclear war, nuclear proliferation and their consequences, Geneva 1985. The conference was divided into five sessions, headed by the subject titles: the nuclear non-proliferation treaty (NPT) and its future, the spread of nuclear weapons among nations, global effects of a nuclear war, the nuclear arms race and arms control, the NPT and its future. Twenty eight papers were presented in the five sessions. (UK)

  14. Nuclear instrumentation for nuclear recycle facilities

    International Nuclear Information System (INIS)

    Deshpande, V.K.

    2013-01-01

    Back End Nuclear Fuel Cycle or Nuclear Recycle facilities comprise Reprocessing plants (RP), Nuclear Waste Management (WM) plants for high level, intermediate level and low level liquid waste, vitrified waste interim storage facilities such as interim storage and long term deep geological depositories, Near Surface Disposal Facilities (NSDF) and long term geological disposal for solid waste. At present, RPs processes the spent fuel (SF) from the PHWR - Nuclear Power Plants (NPP) to recover fissile and fertile nuclear material. The nuclear waste comprising of fission products is treated in different waste management facilities based on their radioactivity

  15. Nuclear reactor

    International Nuclear Information System (INIS)

    Gibbons, J.F.; McLaughlin, D.J.

    1978-01-01

    In the pressure vessel of the water-cooled nuclear reactor there is provided an internal flange on which the one- or two-part core barrel is hanging by means of an external flange. A cylinder is extending from the reactor vessel closure downwards to a seat on the core cupport structure and serves as compression element for the transmission of the clamping load from the closure head to the core barrel (upper guide structure). With the core barrel, subject to tensile stress, between the vessel internal flange and its seat on one hand and the compression of the cylinder resp. hold-down element between the closure head and the seat on the other a very strong, elastic sprung structure is obtained. (DG) [de

  16. Nuclear reactor

    International Nuclear Information System (INIS)

    Aleite, W.; Bock, H.W.; Struensee, S.

    1976-01-01

    The invention concerns the use of burnable poisons in a nuclear reactor, especially in PWRs, in order to improve the controllability of the reactor. An unsymmetrical arrangement in the lattice is provided, if necessary also by insertion of special rods for these additions. It is proposed to arrange the burnable poisons in fuel elements taken over from a previous burn-up cycle and to distribute them, going out from the side facing the control rods, over not more than 20% of the lenth of the fuel elements. It seems sufficient, for the burnable poisons to bind an initial reactivity of only 0.1% and to become ineffective after normal operation of 3 to 4 months. (ORU) [de

  17. Nuclear waste

    International Nuclear Information System (INIS)

    1989-01-01

    This paper reviews the Department of Energy's management of underground single-shell waste storage tanks at its Hanford, Washington, site. The tanks contain highly radioactive and nonradioactive hazardous liquid and solid wastes from nuclear materials production. Hundreds of thousands of gallons of these wastes have leaked, contaminating the soil, and a small amount of leaked waste has reached the groundwater. DOE does not collect sufficient data to adequately trace the migration of the leaks through the soil, and studies predicting the eventual environmental impact of tank leaks do not provide convincing support for DOE's conclusion that the impact will be low or nonexistent. DOE can do more to minimize the environmental risks associated with leaks. To reduce the environmental impact of past leaks, DOE may be able to install better ground covering over the tanks to reduce the volume of precipitation that drains through the soil and carries contaminants toward groundwater

  18. NUCLEAR REACTOR

    Science.gov (United States)

    Miller, H.I.; Smith, R.C.

    1958-01-21

    This patent relates to nuclear reactors of the type which use a liquid fuel, such as a solution of uranyl sulfate in ordinary water which acts as the moderator. The reactor is comprised of a spherical vessel having a diameter of about 12 inches substantially surrounded by a reflector of beryllium oxide. Conventionnl control rods and safety rods are operated in slots in the reflector outside the vessel to control the operation of the reactor. An additional means for increasing the safety factor of the reactor by raising the ratio of delayed neutrons to prompt neutrons, is provided and consists of a soluble sulfate salt of beryllium dissolved in the liquid fuel in the proper proportion to obtain the result desired.

  19. Nuclear dewatering

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    The Sizewell 'B' Nuclear Power Station, the first in a new family of PWR (Pressurised Water Reactor) stations in the UK, is currently under construction on the Suffolk coast. One of the first civil engineering tasks associated with the power station construction was the necessity to lower the water table by 17-18 m over an area of approximately 8 hectares to allow the excavation for the foundations to be carried out in the dry. The way chosen to do this was to construct a diaphragm wall around the site area. This had the least effect on surrounding sites -the Sizewell-A station and various nature reserves and wetlands. The reasons for the choice of method are discussed. Following the construction of the wall the water was pumped out from within the diaphragm wall in January 1988. (author)

  20. Nuclear insurance

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The German Nuclear Power Plant Insurance (DKVG) Association was able to increase its net capacity in property insurance to 637 million marks in 1993 (1992: 589 million). The reinsurance capacity of the other pools included, the total amount covered now amounts to 2 billion marks in property incurance and 200 million marks in liability incurance. As in the year before the pool can reckon with a stable gross premium yield around 175 million marks. The revival of the US dollar has played a decisive role in this development. In 1993 in the domestic market, the DKVG offered policies for 22 types of property risk and 43 types to third-party risk, operating with a gross target premium of 65 million marks and 16 million marks, respectively. The DKVG also participated in 540 foreign insurance contracts. (orig./HSCH) [de

  1. Nuclear waste

    International Nuclear Information System (INIS)

    1990-01-01

    Each year, nuclear power plants, businesses, hospitals, and universities generate more than 1 million cubic feet of hardware, rags, paper, liquid waste, and protective clothing that have been contaminated with radioactivity. While most of this waste has been disposed of in facilities in Nevada, South Carolina, and Washington state, recent legislation made the states responsible - either individually, or through groups of states called compacts - for developing new disposal facilities. This paper discusses the states' progress and problems in meeting facility development milestones in the law, federal and state efforts to resolve issues related to mixed waste (low-level waste that also contains hazardous chemicals) and waste with very low levels of radioactivity, and the Department of Energy's progress in discharging the federal government's responsibility under the law to manage the most hazardous low-level waste

  2. Nuclear reactors

    International Nuclear Information System (INIS)

    Prescott, R.F.; George, B.V.; Baglin, C.J.

    1978-01-01

    Reference is made to thermal insulation on the inner surfaces of containment vessels of fluid cooled nuclear reactors and particularly in situations where the thermal insulation must also serve a structural function and transmit substantial load forces to the surface which it covers. An arrangement is described that meets this requirement and also provides for core support means that favourably influences the flow of hot coolant from the lower end of the core into a plenum space in the hearth of the reactor. The arrangement comprises a course of thermally insulating bricks arranged as a mosaic covering a wall of the reactor and a course of thermally insulating tiles arranged as a mosaic covering the course of bricks. Full constructional details are given. (UK)

  3. Nuclear reactor

    International Nuclear Information System (INIS)

    Schweiger, F.; Glahe, E.

    1976-01-01

    In a nuclear reactor of the kind which is charged with spherical reaction elements and in which control rods are arranged to be thrust directly into the charge, each control rod has at least one screw thread on its external surface so that as the rod is thrust into the charge it is caused to rotate and thus make penetration easier. The length of each control rod may have two distinct portions, a latter portion which carries a screw thread and a lead-in portion which is shorter than the latter portion and which may carry a thread of greater pitch than that on the latter portion or may have a number of axially extending ribs instead of a thread

  4. Nuclear reactor

    International Nuclear Information System (INIS)

    Tilliette, Z.

    1975-01-01

    A description is given of a nuclear reactor and especially a high-temperature reactor in which provision is made within a pressure vessel for a main cavity containing the reactor core and a series of vertical cylindrical pods arranged in spaced relation around the main cavity and each adapted to communicate with the cavity through two collector ducts or headers for the primary fluid which flows downwards through the reactor core. Each pod contains two superposed steam-generator and circulator sets disposed in substantially symmetrical relation on each side of the hot primary-fluid header which conveys the primary fluid from the reactor cavity to the pod, the circulators of both sets being mounted respectively at the bottom and top ends of the pod

  5. Nuclear cardiology

    International Nuclear Information System (INIS)

    Cuaron, A.

    1992-01-01

    Today, nuclear medicine techniques are routinely used in cardiological practice. They include procedures for the atraumatic investigation of different physiological processes in the various structures included in the central circulation: pericardium, myocardium, myocardial adrenergic innervation, cardiac chambers and valves, coronary microcirculation, and great vessels. Beside these in-Vivo procedures, they also comprise of in-Vitro methods for the detection and measurement in blood of various biological molecules of significance in the management of cardiac diseases. A common feature in this collection of in-Vivo and in-Vitro techniques is their ability to provide helpful clinical information for the diagnosis, prognosis and management of cardiac diseases. Their simplicity and safety for the patient allow their repeated use in the follow up of the progress of disease and in the assessment of the efficacy of the therapeutic measures

  6. Nuclear waste

    International Nuclear Information System (INIS)

    1989-10-01

    The Department of Energy is awarding grants to the state of Nevada for the state's participation in DOE's program to investigate Yucca Mountain as a possible site for the disposal of civilian nuclear waste. This report has found that DOE's financial assistance budget request of $15 million for Nevada's fiscal year 1990 was not based on the amount the state requested but rather was derived by increasing Nevada's grant funds from the previous year in proportion to the increase that DOE requested for its own activities at the Nevada site. DOE's evaluations of Nevada's requests are performed too late to be used in DOE's budget formulation process because Nevada has been applying for financial assistance at about the same time that DOE submits its budget request to Congress

  7. Nuclear prophecy

    International Nuclear Information System (INIS)

    Michaelis, A.R.

    1981-01-01

    It is shown that there are at least four instances known of reasonably accurate forecasts of the benefits and dangers of nuclear energy. H.G. Wells' atomic bomb of 1914, A.W. Stewart's chain reaction of 1923, Olaf Stapeldon's mushroom cloud of 1930 and Hans Dominik's tactical atomic weapon of 1927 are briefly reviewed as well as a forecast of the Three Mile island accident. These examples show that although the trained imagination of writers can approach the truth none can claim accuracy in predicting the facts. Where they do approach the truth is in the prediction of the consequences of the discoveries, social as well as military, of unlimited energy and of unlimited disasters. (U.K.)

  8. Nuclear fuels

    International Nuclear Information System (INIS)

    Beauvy, M.; Berthoud, G.; Defranceschi, M.; Ducros, G.; Guerin, Y.; Limoge, Y.; Madic, Ch.; Santarini, G.; Seiler, J.M.; Sollogoub, P.; Vernaz, E.; Guillet, J.L.; Ballagny, A.; Bechade, J.L.; Bonin, B.; Brachet, J.Ch.; Delpech, M.; Dubois, S.; Ferry, C.; Freyss, M.; Gilbon, D.; Grouiller, J.P.; Iracane, D.; Lansiart, S.; Lemoine, P.; Lenain, R.; Marsault, Ph.; Michel, B.; Noirot, J.; Parrat, D.; Pelletier, M.; Perrais, Ch.; Phelip, M.; Pillon, S.; Poinssot, Ch.; Vallory, J.; Valot, C.; Pradel, Ph.; Bonin, B.; Bouquin, B.; Dozol, M.; Lecomte, M.; Vallee, A.; Bazile, F.; Parisot, J.F.; Finot, P.; Roberts, J.F.

    2009-01-01

    Fuel is one of the essential components in a reactor. It is within that fuel that nuclear reactions take place, i.e. fission of heavy atoms, uranium and plutonium. Fuel is at the core of the reactor, but equally at the core of the nuclear system as a whole. Fuel design and properties influence reactor behavior, performance, and safety. Even though it only accounts for a small part of the cost per kilowatt-hour of power provided by current nuclear power plants, good utilization of fuel is a major economic issue. Major advances have yet to be achieved, to ensure longer in-reactor dwell-time, thus enabling fuel to yield more energy; and improve ruggedness. Aside from economics, and safety, such strategic issues as use of plutonium, conservation of resources, and nuclear waste management have to be addressed, and true technological challenges arise. This Monograph surveys current knowledge regarding in-reactor behavior, operating limits, and avenues for R and D. It also provides illustrations of ongoing research work, setting out a few noteworthy results recently achieved. Content: 1 - Introduction; 2 - Water reactor fuel: What are the features of water reactor fuel? 9 (What is the purpose of a nuclear fuel?, Ceramic fuel, Fuel rods, PWR fuel assemblies, BWR fuel assemblies); Fabrication of water reactor fuels (Fabrication of UO 2 pellets, Fabrication of MOX (mixed uranium-plutonium oxide) pellets, Fabrication of claddings); In-reactor behavior of UO 2 and MOX fuels (Irradiation conditions during nominal operation, Heat generation, and removal, The processes involved at the start of irradiation, Fission gas behavior, Microstructural changes); Water reactor fuel behavior in loss of tightness conditions (Cladding, the first containment barrier, Causes of failure, Consequences of a failure); Microscopic morphology of fuel ceramic and its evolution under irradiation; Migration and localization of fission products in UOX and MOX matrices (The ceramic under irradiation

  9. Nuclear analytical chemistry

    International Nuclear Information System (INIS)

    Brune, D.; Forkman, B.; Persson, B.

    1984-01-01

    This book covers the general theories and techniques of nuclear chemical analysis, directed at applications in analytical chemistry, nuclear medicine, radiophysics, agriculture, environmental sciences, geological exploration, industrial process control, etc. The main principles of nuclear physics and nuclear detection on which the analysis is based are briefly outlined. An attempt is made to emphasise the fundamentals of activation analysis, detection and activation methods, as well as their applications. The book provides guidance in analytical chemistry, agriculture, environmental and biomedical sciences, etc. The contents include: the nuclear periodic system; nuclear decay; nuclear reactions; nuclear radiation sources; interaction of radiation with matter; principles of radiation detectors; nuclear electronics; statistical methods and spectral analysis; methods of radiation detection; neutron activation analysis; charged particle activation analysis; photon activation analysis; sample preparation and chemical separation; nuclear chemical analysis in biological and medical research; the use of nuclear chemical analysis in the field of criminology; nuclear chemical analysis in environmental sciences, geology and mineral exploration; and radiation protection

  10. Nuclear Stress Test

    Science.gov (United States)

    ... Nuclear Stress Test Menu Topics Topics FAQs Nuclear Stress Test A nuclear stress test lets doctors see ... with caffeine, such as coffee, tea, sodas, or chocolate. When you return, doctors will give you another ...

  11. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... What are the limitations of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is ... this time is PET/MRI. top of page What are some common uses of the procedure? Children's ( ...

  12. Themes in nuclear law

    International Nuclear Information System (INIS)

    2003-01-01

    The nuclear law was analyzed during a workshop. The main aspects were: the law of population to access to information on nuclear energy and the relationship between the Regulator Organism and the nuclear power plants managers

  13. Essay about nuclear right

    International Nuclear Information System (INIS)

    Puig, D.

    1994-01-01

    The present essay treat about all Uruguaian Nuclear Energy legislation. Nuclear energy history, international treaties, agreements, national programs, nuclear government politics, radiation protection regulations, wastes, radioactive materials transport, environment and safeguards has been given in this compilation

  14. Mean nuclear volume

    DEFF Research Database (Denmark)

    Mogensen, O.; Sørensen, Flemming Brandt; Bichel, P.

    1999-01-01

    We evaluated the following nine parameters with respect to their prognostic value in females with endometrial cancer: four stereologic parameters [mean nuclear volume (MNV), nuclear volume fraction, nuclear index and mitotic index], the immunohistochemical expression of cancer antigen (CA125...

  15. Nuclear thermal/nuclear electric hybrids

    Science.gov (United States)

    Reid, B. D.

    1991-01-01

    A description is given of the nuclear thermal and nuclear electric hybrid. The specifications are described along with its mission performance. Next, the technical status, development requirements, and some cost estimates are provided.

  16. France and nuclear proliferation

    International Nuclear Information System (INIS)

    Barrillot, B.

    2001-05-01

    The Observatory of French nuclear weapons looks forwards to the elimination of nuclear weapons in conformity with the aims of the nuclear non-proliferation Treaty. This file tackles the breakdown of disarmament, the missile-launching nuclear submarines ( new generation) program counter to non-proliferation, nuclear submarines, security and health, nuclear submarines and the environment, the program itself and the requirements of the non proliferation treaty. (N.C.)

  17. Nuclear energy data 2010

    CERN Document Server

    2010-01-01

    This 2010 edition of Nuclear Energy Data , the OECD Nuclear Energy Agency's annual compilation of official statistics and country reports on nuclear energy, provides key information on plans for new nuclear plant construction, nuclear fuel cycle developments as well as current and projected nuclear generating capacity to 2035 in OECD member countries. This comprehensive overview provides authoritative information for policy makers, experts and other interested stakeholders.

  18. Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.

    Science.gov (United States)

    Das, Ujjal; Manna, Krishnendu; Khan, Amitava; Sinha, Mahuya; Biswas, Sushobhan; Sengupta, Aaveri; Chakraborty, Anindita; Dey, Sanjit

    2017-01-01

    The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

  19. Nuclear energy data 2011

    CERN Document Server

    2011-01-01

     . Nuclear Energy Data, the OECD Nuclear Energy Agency's annual compilation of statistics and country reports on nuclear energy, contains official information provided by OECD member country governments on plans for new nuclear plant construction, nuclear fuel cycle developments as well as current and projected nuclear generating capacity to 2035. For the first time, it includes data for Chile, Estonia, Israel and Slovenia, which recently became OECD members. Key elements of this edition show a 2% increase in nuclear and total electricity production and a 0.5% increase in nuclear generating ca

  20. Transcriptional activation of nuclear-related factor 2 by FK506 in Jurkat T cells.

    Science.gov (United States)

    Chung, Y W; Jeong, Y M; Chung, M W; Choi, S K; Choi, S J N; Chung, S Y

    2015-04-01

    We investigated the effect of FK506 in transcriptional activation of nuclear factor (erythroid-derived 2)-like2 (Nrf2) in human Jurkat T cells. FK506 treatment increased the generation of reactive oxygen species and reactive nitrogen species in Jurkat cells in a dose-dependent manner. Generation of nitric oxide was also increased after treatment with FK506 in Jurkat cells. Peak levels of endothelial nitricoxide synthase expression occurred at 24 hours and then decreased after 48 hours. We found that a marked dissociation of Nrf 2 from Kelch-like ECH-associated protein-1 and subsequently Nrf 2 nuclear translocation occurred in Jurkat cells treated with FK506 during 48 hours. Immunohistochemistry and Western blot analysis data revealed that the FK506 treatment increased expression of heme oxygenase-1 (HO-1) in Jurkat cells in a dose-dependent manner. HO-1 expression was induced after 6 hours of treatment of FK506 to Jurkat cells, peaked at 24 hours, and then decreased after 48 hours. These results suggest that FK506 induces Nrf 2-driven transcriptional activation of the antioxidant response element by activating HO-1 and free radicals such as reactive oxygen species and nitric oxide. Copyright © 2015. Published by Elsevier Inc.

  1. Gene associations: true romance or chance meeting in a nuclear neighborhood?

    Science.gov (United States)

    Lawrence, Jeanne B; Clemson, Christine M

    2008-09-22

    Many recent studies have raised interest in the nuclear associations of coregulated genes from different chromosomes, often evoking interpretations of gene-gene interactions, communication, and even "romance." However, in some cases, the associations may be indirect and infrequent and may reflect the segregation of active and inactive genes into different nuclear compartments. The study by Brown et al. (see p. 1083 of this issue) reports that the apparent association of erythroid genes is not a direct interaction nor colocalization to one tiny transcription factory but arises as a result of the known clustering of many active genes with larger splicing factor-rich speckles (a.k.a., SC35-defined domains). This clustering appears largely stochastic but is impacted by the chromosomal neighborhood of the gene as well as its transcriptional status. The study adds a new twist by examining the same gene in a foreign chromosomal context, providing evidence that this impacts a gene's propensity to form gene-domain (or apparent gene-gene) associations within nuclei.

  2. Studies of erythroid inductive microenvironment in vitro

    International Nuclear Information System (INIS)

    van Zant, G.; Goldwasser, E.

    1977-01-01

    Spleen cells from radiated mice (XS), but not from normal mice (NS), when combined with mouse marrow cells in vitro, had two effects on hemoglobin synthesis: increased baseline and augmented erythropoietin-induced, hemoglobin formation. Spleen cells from normal and radiated rats caused increased hemoglobin synthesis by rat marrow cells in a dose-dependent manner. In addition, lung and thymus cells from radiated rats, but not from normal rats, caused increased hemoglobin synthesis by rat marrow cells. Rat NS augmented hemoglobin formation by mouse marrow, but neither mouse NS nor mouse XS had an effect on rat marrow. Medium from rat NS cultures stimulated hemoglobin synthesis when added to rat marrow cells. The increases in baseline, and in the response to erythropoietin, were dependent on the amount of ''conditioned medium.'' The substance in the medium responsible for these effects was not erythropoietin

  3. Sunken nuclear submarines

    International Nuclear Information System (INIS)

    Eriksen, V.O.

    1990-01-01

    The increasing number of accidents with nuclear submarines is a worriment to the general public. Five nuclear submarines are resting on the bottom of the North Atlantic. Design information on nuclear propulsion plants for submarines is classified. The author describes a potential generic nuclear submarine propulsion plant. Design information from the civilian nuclear industry, nuclear power plants, research reactors, nuclear cargo vessels and nuclear propelled icebreakers are used for illustration of relevant problems. A survey is given of nuclear submarines. Factors influencing the accident risks and safety characteristics of nuclear submarines are considered, and potential accident scenarios are described. The fission product content of the nuclear plant can be estimated, '' source terms'' can be guessed and potential release rates can be judged. The mechanisms of dispersion in the oceans is reviewed and compared with the dumping of radioactive waste in the Atlantic and other known releases. 46 refs., 49 figs., 14 tabs

  4. Nuclear policy of India

    International Nuclear Information System (INIS)

    Srinivasrao, Mouneshwara

    2012-01-01

    This paper analyses the Indian nuclear policy, doctrine, strategy and posture, clarifying the elastic concept of 'credible minimum deterrence' at the center of the country's approach to nuclear security. The Indian nuclear policy and thinking against the theories of nuclear war and strategic deterrence, nuclear escalation, and nuclear coercion, offers a strong theoretical grounding for the Indian approach to nuclear war and peace, nuclear deterrence and escalation, nonproliferation and disarmament, and to limited war in a nuclearized environment. On May 11 and 13, 1998, India tested a total of five nuclear devices in the desert stands at Pokhran. The tests caught the Indian public and the world by surprise. On other issues, while there were palpable differences of opinion in the country, the nature of the differences became progressively clearer, so that it is possible to delineate the major contending schools of thought on the future of Indian nuclear policy. (author)

  5. Nuclear knowledge management

    International Nuclear Information System (INIS)

    2007-01-01

    The management of nuclear knowledge has emerged as a growing challenge in recent years. The need to preserve and transfer nuclear knowledge is compounded by recent trends such as ageing of the nuclear workforce, declining student numbers in nuclear-related fields, and the threat of losing accumulated nuclear knowledge. Addressing these challenges, the IAEA promotes a 'knowledge management culture' through: - Providing guidance for policy formulation and implementation of nuclear knowledge management; - Strengthening the contribution of nuclear knowledge in solving development problems, based on needs and priorities of Member States; - Pooling, analysing and sharing nuclear information to facilitate knowledge creation and its utilization; - Implementing effective knowledge management systems; - Preserving and maintaining nuclear knowledge; - Securing sustainable human resources for the nuclear sector; and - Enhancing nuclear education and training

  6. Nuclear energy. Economical aspects

    International Nuclear Information System (INIS)

    Legee, F.

    2010-01-01

    This document present 43 slides of a power point presentation containing detailed data on economical and cost data for nuclear energy and nuclear power plants: evolution from 1971 to 2007 of world total primary energy supply, development of nuclear energy in the world, nuclear power plants in the world in 2009, service life of nuclear power plants and its extension; nuclear energy market and perspectives at 2030, the EPR concept (generation III) and its perspectives at 2030 in the world; cost assessment (power generation cost, nuclear power generation cost, costs due to nuclear safety, comparison of investment costs for gas, coal and nuclear power generation, costs for building a nuclear reactor and general cost; cost for the entire fuel cycle, the case of the closed cycle with recycling (MOX); costs for radioactive waste storage; financial costs and other costs such as environmental impacts, strategic stocks, comparative evaluation of the competitiveness of nuclear versus coal and gas

  7. Nuclear design

    International Nuclear Information System (INIS)

    Fujimoto, Nozomu; Nojiri, Naoki; Ando, Hiroei; Yamashita, Kiyonobu

    2004-01-01

    The high-temperature engineering test reactor (HTTR) has been designed for an outlet temperature of 950 deg. C. That is the highest temperature in the world for a block-type high-temperature gas-cooled reactor (HTGR). The functions of the reactivity control system are determined considering the operational conditions, and the reactivity balance is planned so that the design requirements are fully satisfied. Moreover, the reactivity coefficients are evaluated to confirm the safety characteristics of the reactor. The power distribution in the core was optimized by changing the uranium enrichment to maintain the fuel temperature at less than the limit (1600 deg. C). Deviation from the optimized distribution due to the burnup of fissile materials was avoided by flattening time-dependent changes in local reactivities. Flattening was achieved by optimizing the specifications of the burnable poisons. The original nuclear design model had to be modified based on the first critical experiments. The Monte Carlo code MVP was also used to predict criticality of the initial core. The predicted excess reactivities are now in good agreement with the experimental results

  8. Nuclear decisions

    International Nuclear Information System (INIS)

    Fischhoff, B.

    1991-01-01

    This attempts to identify the role of judgmental processes in various nuclear arms/war decisions. That task analysis is done with some confidence. The next two steps, diagnosing potential weaknesses in those judgments and suggesting ameliorative procedures, are done with increasing timidity. The empirical research base is not (ever) as large as one would like. It is particularly weak with regard to studies of experts forced to go beyond hard data and rely on intuitive judgments within their field of expertise. further evidence is needed to substantiate the claim that experts think like everyone else unless they have had the opportunity to master a particular kind of judgment as a learned skill. Although there is both theoretical and empirical reason to believe that various forms of decision aiding are possible, the high stakes involved mandate caution before proposing any intervention. Ineffective steps may make matters worse if they raise confidence without improving performance, or if they disrupt the cognitive ecology within which decision makers are accustomed to functioning, so that they lose touch with their own imperfect intuitions without acquiring viable alternatives

  9. Nuclear chemistry

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Topics covered include: mass asymmetry and total kinetic energy release in the spontaneous fission of 262 105; calculation of spontaneous fission properties of very heavy nuclei - 98 less than or equal to Z less than or equal to 106 and 150 less than or equal to N less than or equal to 164; energy losses for 84 Kr ions in nickel, aluminium and titanium; differences in compound nuclei formed with 40 Ar and 84 Kr projectiles; measurement of the energy division vs. mass in highly damped reactions; ambiguities in the inference of precompound emission from excitation function analysis; selective laser one-atom detection of neutral prompt fission fragments; laser induced nuclear polarization - application to the study of spontaneous fission isomers; quadrupole and hexadecapole deformations in the actinide nuclei; high-spin states in 164 Yb; contrasting behavior of h/sub 9/2/ and i/sub 13/2/ bands in 185 Au; multiple band crossings in 164 Er; recoil-distance measurement of lifetimes of rotational states in 164 Dy, lifetimes of ground-band states in 192 Pt and 194 Pt and application of the rotation-alignment model; coulomb excitation of vibrational nuclei with heavy ions; surface structure of deformed nuclei; valency contribution to neutron capture in 32 S; neutron capture cross section of manganese; search for superheavy elements in natural samples by neutron multiplicity counting; and gamma-ray studies on the geochemistry of achondritic meteorites

  10. Development of nuclear energy and nuclear policy in China

    International Nuclear Information System (INIS)

    You Deliang

    1993-11-01

    Status of nuclear power development in China, nuclear policy and nuclear power programme are described. Issues regarding nuclear fuel cycle system, radioactive waste management and international cooperation in the field of peaceful use of nuclear energy are discussed

  11. Nuclear energy and nuclear technology in Switzerland

    International Nuclear Information System (INIS)

    Graf, P.

    1975-01-01

    The energy crisis, high fuel costs and slow progress in the development of alternative energy sources, e.g. solar energy have given further impetus to nuclear power generation. The Swiss nuclear energy programme is discussed and details are given of nuclear station in operation, under construction, in the project stage and of Swiss participation in foreign nuclear stations. Reference is made to the difficulties, delays and resulting cost increases caused by local and regional opposition to nuclear power stations. The significant contributions made by Swiss industry and Swiss consulting engineers are discussed. (P.G.R.)

  12. Nuclear power and the nuclear fuel cycle

    International Nuclear Information System (INIS)

    Scurr, I.F.; Silver, J.M.

    1990-01-01

    Australian Nuclear Science and Technology Organization maintains an ongoing assessment of the world's nuclear technology developments, as a core activity of its Strategic Plan. This publication reviews the current status of the nuclear power and the nuclear fuel cycle in Australia and around the world. Main issues discussed include: performances and economics of various types of nuclear reactors, uranium resources and requirements, fuel fabrication and technology, radioactive waste management. A brief account of the large international effort to demonstrate the feasibility of fusion power is also given. 11 tabs., ills

  13. Nuclear structure

    International Nuclear Information System (INIS)

    Diamond, R.M.; Stephens, F.S.; Deleplanque, M.A.; Draper, J.E.; Dines, E.L.; Davis, U.C.; Macchiavelli, A.O.

    1984-01-01

    Essentially the whole range of spins possible for many nuclei in the periodic table is available with the use of the 88-Inch cyclotron and SuperHILAC accelerators. Nuclei carry angular momentum principally in two ways: by aligning individual high j nucleons, and by a collective rotation of the nucleus as a whole. Deformed nuclei use both modes and it is the interplay between the single-particle and collective modes that leads to the great diversity of nuclear properties at high spin. Information about these states and their properties is obtained only by detailed γ-ray spectroscopy of their de-exciting transitions. But for the higher spins the population is usually spread over so many states that only average values of continuum properties can be determined. So one of the goals of present-day research is to push discrete spectroscopic studies to higher spin states, reducing the continuum region. To do this requires that the number of cascade pathways observed be reduced to a small enough number so that individual transitions can show. One way is to use a combination of sum-energy and multiplicity selection, that is, to define a smaller entry region. This is what the NaI crystal balls can do. Another technique is to set gates on the highest-lying discrete transitions observed and look at what is in coincidence (ahead) of them. Either method requires a drastic decrease in the number of cascades selected, so very good statistics are needed and this means many detectors as close as possible to the target. The authors use both techniques simultaneously. Current and planned experiments are described

  14. Review of nuclear energy

    International Nuclear Information System (INIS)

    Mattila, L.; Anttila, M.; Pirilae, P.; Vuori, S.

    1997-05-01

    The report is an overview on the production of the nuclear energy all over the world. The amount of production at present and in future, availability of the nuclear fuel, development of nuclear technology, environmental and safety issues, radioactive waste management and commissioning of the plants and also the competitivity of nuclear energy compared with other energy forms are considered. (91 refs.)

  15. The French nuclear law

    International Nuclear Information System (INIS)

    Ito, Hiroshi

    2013-01-01

    The nuclear law had been out of the environmental law. The act on the transparency and the security of the nuclear matter was enacted in 2006 and set in the code of the environment in 2012. It means that the nuclear law is part of the environmental law and that it is advanced. I will report the French nuclear law. (author)

  16. Security with nuclear weapons

    International Nuclear Information System (INIS)

    Karp, R.C.

    1991-01-01

    Recent improvements in East-West relations and the process of dramatic political change in Europe may result in unprecedented opportunities to reduce the global arsenal of nuclear weapons. Despite these welcome developments, the prospects for effectively controlling the spread of nuclear capability in the Third World have remained much less encouraging. The possibility of large reductions in nuclear weapons poses fundamental questions about their purpose. Why have some states chosen to acquire nuclear weapons? How and why have these decisions been maintained over time? Why have some states elected to approach, but not cross, the nuclear threshold? This book examines the commonalities and differences in political approaches to nuclear weapons both within and between three groups of states: nuclear, non-nuclear and threshold. The chapters explore the evolution of thinking about nuclear weapons and the role these weapons play in national security planning, and question the official security rationales offered by the nuclear weapon states for the maintenance of nuclear capabilities. For the non-nuclear weapon states, the book presents an analysis of alternative ways of assuring security and foreign policy effectiveness. For the threshold states, it examines the regional contexts within which these states maintain their threshold status. This book transcends traditional East-West approaches to analysis of nuclear issues by giving equal prominence to the issues of nuclear proliferation and non-nuclearism. The book also provides a comprehensive analysis of how current approaches to nuclear weapons have evolved both within and among the groups of countries under study

  17. Nuclear power publications

    International Nuclear Information System (INIS)

    1982-01-01

    This booklet lists 69 publications on nuclear energy available free from some of the main organisations concerned with its development and operation in the UK. Headings are: general information; the need for nuclear energy; the nuclear industry; nuclear power stations; fuel cycle; safety; waste management. (U.K.)

  18. Nuclear Reaction Data Centers

    International Nuclear Information System (INIS)

    McLane, V.; Nordborg, C.; Lemmel, H.D.; Manokhin, V.N.

    1988-01-01

    The cooperating Nuclear Reaction Data Centers are involved in the compilation and exchange of nuclear reaction data for incident neutrons, charged particles and photons. Individual centers may also have services in other areas, e.g., evaluated data, nuclear structure and decay data, reactor physics, nuclear safety; some of this information may also be exchanged between interested centers. 20 refs., 1 tab

  19. China and nuclear power

    International Nuclear Information System (INIS)

    Fouquoire-Brillet, E.

    1999-01-01

    This book presents the history of nuclear power development in China from the first research works started in the 1950's for the manufacturing of nuclear weapons to the recent development of nuclear power plants. This study tries to answer the main questions raised by the attitude of China with respect to the civil and military nuclear programs. (J.S.)

  20. Applications of nuclear radiations

    International Nuclear Information System (INIS)

    Hanagodimath, S.M.

    2012-01-01

    Nuclear radiations are powerful and non destructive tools in industry, medicine, defence, agriculture and research. In the present lecture, the types of nuclear radiations, radiation sources, detection of radiation, uses of radiation, dangers of nuclear radiation and nuclear energy will be discussed. (author)

  1. Essay on nuclear law

    International Nuclear Information System (INIS)

    Puig, Diva

    1994-01-01

    This book is divided in seven parts, covering international organizations in nuclear energy. agreements, nuclear laws and environment, national legislation program and Uruguayan legislation. The texts of the nuclear laws in Uruguay are reproduced, and several aspects on nuclear energy are discussed

  2. Nuclear theory progress report

    International Nuclear Information System (INIS)

    1991-01-01

    This report discusses research performed at University of Washington in nuclear theory. Some of the topics discussed are: nuclear astrophysics; symmetry; time reversal invariance; quark matter; superallowed beta decay; exclusive reactions; nuclear probes; soliton model; relativistic heavy ion collisions; supernova explosions; neutrino processes in dense matter; field theories; weak interaction physics; and nuclear structure

  3. Nuclear energy and security

    International Nuclear Information System (INIS)

    Blejwas, Thomas E.; Sanders, Thomas L.; Eagan, Robert J.; Baker, Arnold B.

    2000-01-01

    Nuclear power is an important and, the authors believe, essential component of a secure nuclear future. Although nuclear fuel cycles create materials that have some potential for use in nuclear weapons, with appropriate fuel cycles, nuclear power could reduce rather than increase real proliferation risk worldwide. Future fuel cycles could be designed to avoid plutonium production, generate minimal amounts of plutonium in proliferation-resistant amounts or configurations, and/or transparently and efficiently consume plutonium already created. Furthermore, a strong and viable US nuclear infrastructure, of which nuclear power is a large element, is essential if the US is to maintain a leadership or even participatory role in defining the global nuclear infrastructure and controlling the proliferation of nuclear weapons. By focusing on new fuel cycles and new reactor technologies, it is possible to advantageously burn and reduce nuclear materials that could be used for nuclear weapons rather than increase and/or dispose of these materials. Thus, the authors suggest that planners for a secure nuclear future use technology to design an ideal future. In this future, nuclear power creates large amounts of virtually atmospherically clean energy while significantly lowering the threat of proliferation through the thoughtful use, physical security, and agreed-upon transparency of nuclear materials. The authors must develop options for policy makers that bring them as close as practical to this ideal. Just as Atoms for Peace became the ideal for the first nuclear century, they see a potential nuclear future that contributes significantly to power for peace and prosperity

  4. Nuclear power revisited

    International Nuclear Information System (INIS)

    Grear, B.

    2008-01-01

    Modern development of nuclear power technology and the established framework of international agreements and conventions are responding to the major political, economic and environmental issues - high capital costs, the risks posed by nuclear wastes and accidents, and the proliferation of nuclear weaponry - that until recently hindered the expansion of nuclear power.

  5. Nuclear literacy - Hungarian experiences

    International Nuclear Information System (INIS)

    Toth, E.; Marx, G.

    1996-01-01

    The operation of nuclear power plants and the related environmental sentiments make basic nuclear education to a precondition of modern democratic decision making. Nuclear chapters of the curriculum used to treat the topics in historical and descriptive, thus less convincing way. The question arises: how to offer nuclear literacy to the youth in general, to show its empirical aspects and relevance to citizens. (author)

  6. Fundamentals of nuclear chemistry

    International Nuclear Information System (INIS)

    Majer, K.

    1982-01-01

    The textbook is a Czech-to-German translation of the second revised edition and covers the subject under the headings: general nuclear chemistry, methods of nuclear chemistry, preparative nuclear chemistry, analytical nuclear chemistry, and applied chemistry. The book is especially directed to students

  7. Nuclear safety in France

    International Nuclear Information System (INIS)

    Servant, J.

    1979-12-01

    The main areas of nuclear safety are considered in this paper, recalling the laws and resolutions in force and also the appropriate authority in each case. The following topics are reviewed: radiological protection, protection of workers, measures to be taken in case of an accident, radioactive effluents, impact on the environment of non-nuclear pollution, nuclear plant safety, protection against malicious acts, control and safeguard of nuclear materials, radioisotopes, transport of radioactive substances, naval propulsion, waste management, nuclear plant decommissioning and export of nuclear equipment and materials. Finally, the author describes the role of the general Secretariat of the Interdepartmental Committee on Nuclear Safety

  8. Nuclear energy. 2. ed.

    International Nuclear Information System (INIS)

    Murray, R.L.

    1980-01-01

    The subject is covered in chapters, entitled:(Part 1 - basic concepts) energy and states of matter; atoms and nuclei; radioactivity; nuclear reactions; reaction rates; radiation and materials; fission; fusion; (Part 2- nuclear systems) particle accelerators; isotope separators; radiation detectors; neutron chain reactions; nuclear reactor concepts; energy conversion methods; breeder reactors; fusion reactors; (Part 3- nuclear energy and man) the history of nuclear energy; biological effects of radiation; radiation protection and control; reactor safety; radioactive waste processing and disposal; beneficial uses of isotopes; applications of radiation; nuclear explosives; alternative nuclear power systems; thermal effects and the environment; energy and resources. (U.K.)

  9. Collective nuclear dynamics. Abstracts

    International Nuclear Information System (INIS)

    Abrosimov, V.I.; Kolomietz, V.M.

    1994-01-01

    The fourth International school on nuclear physics was help on 29 Aug - 7 Sep, 1994 in Ukraine. The specialists discussed following subjects: liquid drop and the shell correction method; nuclear deformation energy and fission; nuclear structure at high spins, superdeformed states, structure of excited and exotic nuclei; nuclear fluid dynamics and large scale collective motion; order and chaos as they relate to the collective motion; quantum and interference phenomena in nuclear collisions; quasi-fission and multinucleon fragmentation effects; shell effects in non-nuclear systems; new nuclear facilities

  10. IAEA nuclear security program

    Energy Technology Data Exchange (ETDEWEB)

    Ek, D. [International Atomic Energy Agency, Vienna (Austria)

    2006-07-01

    Although nuclear security is a State responsibility, it is nevertheless an international concern, as the consequences of a nuclear security incident would have worldwide impact. These concerns have resulted in the development of numerous international instruments on nuclear security since the terrorist events in the USA on September 11, 2001. The IAEA Office of Nuclear Security has been charged to assist Member States to improvement their nuclear security and to meet the intent of these international obligations in order to ensure a cohesive thread of nuclear security protects the global community. The programs underway and planned by the Office of Nuclear Security will be discussed in this paper. (author)

  11. IAEA nuclear security program

    International Nuclear Information System (INIS)

    Ek, D.

    2006-01-01

    Although nuclear security is a State responsibility, it is nevertheless an international concern, as the consequences of a nuclear security incident would have worldwide impact. These concerns have resulted in the development of numerous international instruments on nuclear security since the terrorist events in the USA on September 11, 2001. The IAEA Office of Nuclear Security has been charged to assist Member States to improvement their nuclear security and to meet the intent of these international obligations in order to ensure a cohesive thread of nuclear security protects the global community. The programs underway and planned by the Office of Nuclear Security will be discussed in this paper. (author)

  12. Potential for nuclear terrorism

    International Nuclear Information System (INIS)

    Jenkins, B.M.

    1977-05-01

    The question of whether or not terrorists will ''go nuclear'' is discussed. It is possible, although there is no historical evidence that any criminal or terrorist group ever made any attempt to acquire nuclear material for use in an explosive or dispersal device. In terms of intentions, psychotics are potential nuclear terrorists, but in terms of capabilities, they are the farthest away from being able to acquire a nuclear weapon. The history of nuclear incidents in the U.S. and abroad is reviewed. As the nuclear industry expands, the number of low-level incidents (bomb threats, pilferage, etc.) will increase also, but not necessarily escalate to more serious incidents. Terrorists may ''go nuclear'' solely for the publicity value; nuclear hoaxes may be attenpted. Nuclear terrorism seems more attractive as a threat than as an action. But the nature of the threat may change in the future, and the danger of imitation of a successful nuclear terrorist act is pointed out

  13. Pakistans Nuclear Weapons

    Science.gov (United States)

    2016-02-12

    nuclear energy, or 400 MWe and electricity consumption in Pakistan is increasing. Islamabad plans to increase nuclear energy production to 8,800 MWe by...Pakistan’s Nuclear Weapons Paul K. Kerr Analyst in Nonproliferation Mary Beth Nikitin Specialist in Nonproliferation February 12, 2016...Congressional Research Service 7-5700 www.crs.gov RL34248 Pakistan’s Nuclear Weapons Congressional Research Service Summary Pakistan’s nuclear

  14. Dictionary of nuclear power

    International Nuclear Information System (INIS)

    Koelzer, W.

    2012-06-01

    The actualized version (June 2012) of the dictionary on nuclear power includes all actualizations and new inputs since the last version of 2001. The original publication dates from 1980. The dictionary includes definitions, terms, measuring units and helpful information on the actual knowledge concerning nuclear power, nuclear fuel cycle, nuclear facilities, radioactive waste management, nuclear physics, reactor physics, isotope production, biological radiation effects, and radiation protection.

  15. Ontario Hydro's nuclear program

    International Nuclear Information System (INIS)

    McCredie, J.

    1984-01-01

    This report briefly describes Ontario Hydro's nuclear program, examining the design and construction status, and the future from Ontario Hydro's perspective. Ontario Hydro relies heavily on nuclear power. Nuclear fuel was responsible for approximately 34% of Ontario Hydro's energy production in 1983. The nuclear proportion was supplied by twelve operating units located: NPD, Douglas Point, Pickering A and B. It is expected that by approximately 1992, 65% of the total energy needs will be generated through nuclear power

  16. Nuclear energy data

    International Nuclear Information System (INIS)

    2003-01-01

    This new edition of Nuclear Energy Data, the OECD Nuclear Energy Agency's annual compilation of essential statistics on nuclear energy in OECD countries, offers additional textual and graphical information as compared with previous editions. It provides the reader with a comprehensive but easy-to-access overview on the status of and trends in the nuclear power and fuel cycle sector. This publication is an authoritative information source of interest to policy makers, experts and academics involved in the nuclear energy field. (author)

  17. Nuclear energy data

    International Nuclear Information System (INIS)

    2002-01-01

    This new edition of Nuclear Energy Data, the OECD Nuclear Energy Agency's annual compilation of essential statistics on nuclear energy in OECD countries, offers additional textual and graphical information as compared with previous editions. It provides the reader with a comprehensive but easy-to-access overview on the status of and trends in the nuclear power and fuel cycle sector. This publication is an authoritative information source of interest to policy makers, experts and academics involved in the nuclear energy field. (authors)

  18. Nuclear energy data 2005

    CERN Document Server

    Publishing, OECD

    2005-01-01

    This 2005 edition of Nuclear Energy Data, the OECD Nuclear Energy Agency's annual compilation of essential statistics on nuclear energy in OECD countries, offers a projection horizon lengthened to 2025 for the first time.  It presents the reader with a comprehensive overview on the status and trends in nuclear electricity generation in OECD countries and in the various sectors of the nuclear fuel cycle.

  19. Porter with nuclear reservations

    International Nuclear Information System (INIS)

    Patterson, W.

    1978-01-01

    The Ontario Royal Commission on Electric Power Planning, chaired by Arthur Porter is reviewed. This interim report on nuclear power is relevant to nuclear power planning far beyond the confines of Ontario and discusses nuclear issues in the explicit context of electricity generation and use. Problems considered in the report include safety aspects of uranium mining, milling, and spent fuel disposal, the economic issues which affect nuclear planning and nuclear industry, and the proliferation issue. (U.K.)

  20. The nuclear era

    International Nuclear Information System (INIS)

    Leclercq, J.

    1986-01-01

    This book is a guide in the space and in the time, along the nuclear energy history and through all the industrial installations such as nuclear power plants and the associated plants. The main points developed in this book are the following ones: the nuclear energy in its historic perspective, the variety of reactors, safety and environment, architecture and large engineering, installation of the reactor components and associated machines, nuclear fuels, and the nuclear energy in the electricity service [fr

  1. Nuclear energy. Selective bibliography

    International Nuclear Information System (INIS)

    2011-07-01

    This bibliography gathers articles and books from the French National Library about civil nuclear energy, its related risks, and its perspectives of evolution: general overview (figures, legal framework, actors and markets, policies); what price for nuclear energy (environmental and health risks, financing, non-proliferation policy); future of nuclear energy in energy policies (nuclear energy versus other energies, nuclear phase-out); web sites selection

  2. Nuclear Education in France

    International Nuclear Information System (INIS)

    Guet, C.

    2013-01-01

    This series of slides draws a picture of nuclear engineering training in France. The nuclear sector is very active and developed in France and covers all the aspects of the fuel cycle which implies a strong demand for highly skilled and trained staff. There are both an active involvement of industry in the education process through the design of adequate curricula and a strong support of the State. There are 5 masters dedicated to Science Nuclear Energy (Paris), Nuclear Waste Management (Nantes), Separation Chemistry (Montpellier), Materials for Nuclear Engineering (Grenoble), and 1 engineer degree in nuclear engineering (Saclay). In 2010-2011 there were about 1000 students completing a nuclear energy curriculum (nuclear engineering or specialized nuclear domains) at the master-engineer level throughout France. The detailed curriculum of the Master of Science Nuclear Energy is given. The National Institute of Nuclear Sciences and Techniques (INSTN) plays an important role, it has trained a large fraction of the French leading nuclear practitioners through its 50 years old 'Genie Atomique' curriculum. INSTN proposes also high level courses in nuclear disciplines including training of nuclear physicians, radio-pharmacists and medical physicists and is a major player for continuing education in nuclear sciences. (A.C.)

  3. Nuclear Safety Regulations

    International Nuclear Information System (INIS)

    Novosel, N.; Prah, M.

    2008-01-01

    Beside new Ordinance on the control of nuclear material and special equipment ('Official Gazette' No. 15/08), from 2006 State Office for Nuclear Safety (SONS) adopted Ordinance on performing nuclear activities ('Official Gazette' No. 74/06) and Ordinance on special requirements which expert organizations must fulfil in order to perform certain activities in the field of nuclear safety ('Official Gazette' No. 74/06), based on Nuclear Safety Act ('Official Gazette' No. 173/03). The Ordinance on performing nuclear activities regulates the procedure of notification of the intent to perform nuclear activities, submitting the application for the issue of a licence to perform nuclear activities, and the procedure for issuing decisions on granting a licence to perform a nuclear activity. The Ordinance also regulates the content of the forms for notification of the intent to perform nuclear activities, as well as of the application for the issue of a licence to perform the nuclear activity and the method of keeping the register of nuclear activities. According to the Nuclear Safety Act, nuclear activities are the production, processing, use, storage, disposal, transport, import, export, possession or other handling of nuclear material or specified equipment. The Ordinance on special requirements which expert organizations must fulfil in order to perform certain activities in the field of nuclear safety regulates these mentioned conditions, whereas compliance is established by a decision passed by the SONS. Special requirements which expert organizations must fulfil in order to perform certain activities in the field of nuclear safety are organizational, technical, technological conditions and established system of quality assurance. In 2007, State Office for Nuclear Safety finalized the text of new Ordinance on conditions for nuclear safety and protection with regard to the siting, design, construction, use and decommissioning of a facility in which a nuclear activity is

  4. Nuclear energy and nuclear weapons proliferation

    International Nuclear Information System (INIS)

    1989-01-01

    A summary of the report dispatched in the middle of 1978 by the Atlantic Council of United States, organized by North American citizens, is presented. The report considers the relation between the production of nucleoelectric energy and the capacity of proliferation of nuclear weapons. The factors which affect the grade of proliferation risk represented by the use of nuclear energy in the world comparing this risk with the proliferation risks independently of nuclear energy, are examined. (M.C.K.) [pt

  5. Nuclear power and nuclear safety 2009

    International Nuclear Information System (INIS)

    Lauritzen, B.; Oelgaard, P.L.; Kampmann, D.; Nystrup, P.E.; Thorlaksen, B.

    2010-05-01

    The report is the seventh report in a series of annual reports on the international development of nuclear power production, with special emphasis on safety issues and nuclear emergency preparedness. The report is written in collaboration between Risoe DTU and the Danish Emergency Management Agency. The report for 2009 covers the following topics: status of nuclear power production, regional trends, reactor development, safety related events, international relations, conflicts and the European safety directive. (LN)

  6. Nuclear power and the nuclear fuel cycle

    International Nuclear Information System (INIS)

    1988-06-01

    The percentage of electricity generated by nuclear energy in each of the 26 countries that operated nuclear power plants in 1987 is given. The current policy and programs of some of these countries is described. News concerning uranium mining, enrichment, reprocessing and waste management is also included. Data in the form of a generalized status summary for all power reactors (> 30 MWEN) prepared from the nuclear power reactor data files of ANSTO is shown

  7. Nuclear power in perspective

    International Nuclear Information System (INIS)

    Addinall, E.; Ellington, H.

    1982-01-01

    The subject is covered in chapters: (the nature of nuclear power) the atomic nucleus - a potential source of energy; how nuclear reactors work; the nuclear fuel cycle; radioactivity - its nature and biological effects; (why we need nuclear power) use of energy in the non-communist world -the changing pattern since 1950; use of energy - possible future scenarios; how our future energy needs might be met; (a possible long term nuclear strategy) the history of nuclear power; a possible nuclear power strategy for the Western World; (social and environmental considerations) the hazards to workers in the nuclear power industry; the hazards to the general public (nuclear power industry; reactor operation; transport of radioactive materials; fuel reprocessing; radioactive waste disposal; genetic hazards); the threat to democratic freedom and world peace. (U.K.)

  8. Nuclear information access system

    International Nuclear Information System (INIS)

    Ham, C. H.; Yang, M. H.; Yoon, S. W.

    1998-01-01

    The energy supply in the countries, which have abundant energy resources, may not be affected by accepting the assertion of anti-nuclear and environment groups. Anti-nuclear movements in the countries which have little energy resources may cause serious problem in securing energy supply. Especially, it is distinct in Korea because she heavily depends on nuclear energy in electricity supply(nuclear share in total electricity supply is about 40%).The cause of social trouble surrounding nuclear energy is being involved with various circumstances. However, it is very important that we are not aware of the importance of information access and prepared for such a situation from the early stage of nuclear energy's development. In those matter, this paper analyzes the contents of nuclear information access system in France and Japan which have dynamic nuclear development program and presents the direction of the nuclear access regime through comparing Korean status and referring to progresses of the regime

  9. Nuclear technology in Peru

    International Nuclear Information System (INIS)

    Montoya, M.

    1993-01-01

    This book deals with the Nuclear Energy in Peru. It consists of ten chapters. In the first chapter is presented a rapid overview on nuclear science history. The second chapter describes the nuclear proliferation and the nuclear competition in South America. The nuclear organization in Peru, the Peruvian Institute of Nuclear Energy, and the main centers are described in the third chapter. The following chapters deals with peruvian advances in nuclear medicine, agriculture and food, nuclear application to industry, hydrology, earth sciences and environmental considerations. In the last chapter, the perspectives for nuclear science and technology in Peru are described from the inter institutional cooperation point of view. This book also includes appendix and bibliography. (author)

  10. The nuclear economic fraud

    International Nuclear Information System (INIS)

    Jeffery, J.W.

    1982-01-01

    Reference is made to a previous publication on the comparative economics of electricity from nuclear and coal-fired power plants. The present paper discusses further publications on this topic, and continues under the headings: propaganda money; the commitment of the CEGB to nuclear power; how to have nuclear electricity without paying for it; hiding the real nuclear costs; the effect of nuclear power on coal prices - the dilemma of nuclear power and dear coal or restricted nuclear power and cheap coal; the effects on electricity prices; the future of coal prices and subsidies; summary of the costs of building nuclear power stations; minimum total costs; the driving forces behind the nuclear programme. (U.K.)

  11. Technology Roadmaps: Nuclear Energy

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    This nuclear energy roadmap has been prepared jointly by the IEA and the OECD Nuclear Energy Agency (NEA). Unlike most other low-carbon energy sources, nuclear energy is a mature technology that has been in use for more than 50 years. The latest designs for nuclear power plants build on this experience to offer enhanced safety and performance, and are ready for wider deployment over the next few years. Several countries are reactivating dormant nuclear programmes, while others are considering nuclear for the first time. China in particular is already embarking on a rapid nuclear expansion. In the longer term, there is great potential for new developments in nuclear energy technology to enhance nuclear's role in a sustainable energy future.

  12. Nuclear energy in Spain

    International Nuclear Information System (INIS)

    Villota, C. de

    2007-01-01

    Carlos Villota. Director of Nuclear Energy of UNESA gave an overview of the Spanish nuclear industry, the utility companies and the relevant institutions. Companies of the nuclear industry include firms that produce heavy components or equipment (ENSA), manufacturers of nuclear fuel (ENUSA), engineering companies, the National Company for Radioactive Waste Management (ENRESA), and nuclear power plants (nine units at seven sites). Nuclear energy is a significant component of the energy mix in Spain: 11% of all energy produced in Spain is of nuclear origin, whilst the share of nuclear energy in the total electricity generation is approximately 23%. The five main players of the energy sector that provide for the vast majority of electricity production, distribution, and supply have formed the Spanish Electricity Industry Association (UNESA). The latter carries out co-ordination, representation, management and promotion tasks for its members, as well as the protection of their business and professional interests. In the nuclear field, UNESA through its Nuclear Energy Committee co-ordinates aspects related to nuclear safety and radiological protection, regulation, NPP operation and R and D. Regarding the institutional framework of the nuclear industry, ENSA, ENUSA and ENRESA are controlled by the national government through the Ministry of Economy and Finance and the Ministry of Science and Technology. All companies of the nuclear industry are licensed by the Ministry of Industry, Tourism and Trade (MITYC), while the regulatory body is the Nuclear Safety Council (CSN). It is noteworthy that CSN is independent of the government, as it reports directly to Parliament. (author)

  13. Clean energy : nuclear energy world

    International Nuclear Information System (INIS)

    2007-10-01

    This book explains the nuclear engineering to kids with easy way. There are explanations of birth of nuclear energy such as discover of nuclear and application of modern technology of nuclear energy, principles and structure of nuclear power plant, fuel, nuclear waste management, use of radiation for medical treatment, food supplies, industry, utilization of neutron. It indicates the future of nuclear energy as integral nuclear energy and nuclear fusion energy.

  14. Nuclear and radiochemistry

    CERN Document Server

    Konya, Jozsef

    2012-01-01

    The field of nuclear and radiochemistry is wide-reaching, with results having functions and use across a variety of disciplines. Drawing on 40 years of experience in teaching and research, this concise book explains the basic principles and applications of the primary areas of nuclear and radiochemistry. Separate chapters cover each main area of recent radiochemistry. This includes nuclear medicine and chemical aspects of nuclear power plants, namely the problems of nuclear wastes and nuclear analysis (both bulk and surface analysis), with the analytical methods based on the interactions of

  15. Frontiers in nuclear chemistry

    International Nuclear Information System (INIS)

    Sood, D.D.; Reddy, A.V.R.; Pujari, P.K.

    1996-01-01

    This book contains articles on the landmarks in nuclear and radiochemistry which takes through scientific history spanning over five decades from the times of Roentgen to the middle of this century. Articles on nuclear fission and back end of the nuclear fuel cycle give an insight into the current status of this subject. Reviews on frontier areas like lanthanides, actinides, muonium chemistry, accelerator based nuclear chemistry, fast radiochemical separations and nuclear medicine bring out the multidisciplinary nature of nuclear sciences. This book also includes an article on environmental radiochemistry and safety. Chapters relevant to INIS are indexed separately

  16. Nuclear cratering applications

    International Nuclear Information System (INIS)

    Williamson, M.M.

    1969-01-01

    The development of nuclear excavation technology is based on the promise that the relatively inexpensive energy available from thermonuclear explosives can be used to simultaneously break and move age quantities of rock and earth economically and safety. This paper discusses the economic and other advantages of using nuclear excavation for large engineering projects. A brief description of the phenomenology of nuclear excavation is given. Each of the several proposed general applications of nuclear excavation is discussed to include a few specific example of possible nuclear excavation projects. The discussion includes nuclear excavation for harbors, canals, terrain transits, aggregate production, mining and water resource development and conservation. (author)

  17. Introduction to nuclear physics

    International Nuclear Information System (INIS)

    Lee, Young Sun

    1987-03-01

    This book deals with nuclear physics with basic introduction, like atomic theory of material, movement theory of material, an atom, natural radioactivity, nuclear atom, electromagnetic waves, X rays, the quantum theory, special commercial theory, wavelength and particle, spectrum and hydrogen atom, meaning of wavelength driven, optics spectrum and electronic distribution, microstructure and Zeeman's effect, X rays spectrum and atom structure, an atomic nucleus, conversion rule of a radioactive element, properties of radiation and interaction with material, artificial nuclear decay and artificial radioactivity, acceleration of electric charge particle, neutron physics, nuclear fission, nuclear fission reactor and a thermonuclear reaction and nuclear fusion.

  18. Nuclear energy and society

    International Nuclear Information System (INIS)

    Bakacs, Istvan; Czeizel, Endre; Hajdu, Janos; Marx, Gyoergy.

    1984-01-01

    The text of a round-table discussion held on the occasion of the 50th anniversary of the discovery of neutron is given. The participants were the Chief Engineer of the Paks Nuclear Power Plant, the first nuclear power plant in Hungary started in November 1982, a geneticist treating the problems of genetic damages caused by nuclear and chemical effects, a nuclear physicist and a journalist interested in the social aspects of nuclear energy. They discussed the political, economical and social problems of nuclear energy in the context of its establishment in Hungary. (D.Gy.)

  19. Risks and nuclear insurance

    International Nuclear Information System (INIS)

    Debaets, M.; Springett, G.D.; Luotonen, K.; Virole, J.

    1988-01-01

    When analysing the nuclear insurance market, three elements must be taken into account: the nuclear operator's liability is regulated by national laws and/or international Conventions, such operators pay large premiums to insure their nuclear installations against property damage and finally, the nuclear insurance market is made up of pools and is mainly a monopoly. This report describes the different types of insurance coverage, the system governing nuclear third party liability under the Paris Convention and the Brussels Supplementary Convention and several national laws in that field. The last part of the report deals with liability and insurance aspects of international transport of nuclear materials [fr

  20. Nuclear energy data

    International Nuclear Information System (INIS)

    2004-01-01

    This new edition of Nuclear Energy Data, the OECD Nuclear Energy Agency's annual compilation of essential statistics on nuclear energy in OECD countries, offers additional graphical information as compared with previous editions allowing a rapid comparison between capacity and requirements in the various phases of the nuclear fuel cycle. It provides the reader with a comprehensive but easy-to-access overview on the status of and trends in the nuclear power and fuel cycle sector. This publication is an authoritative information source of interest to policy makers, experts and academics involved in the nuclear energy field. (author)

  1. Nuclear Security for Floating Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Skiba, James M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Scherer, Carolynn P. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-13

    Recently there has been a lot of interest in small modular reactors. A specific type of these small modular reactors (SMR,) are marine based power plants called floating nuclear power plants (FNPP). These FNPPs are typically built by countries with extensive knowledge of nuclear energy, such as Russia, France, China and the US. These FNPPs are built in one country and then sent to countries in need of power and/or seawater desalination. Fifteen countries have expressed interest in acquiring such power stations. Some designs for such power stations are briefly summarized. Several different avenues for cooperation in FNPP technology are proposed, including IAEA nuclear security (i.e. safeguards), multilateral or bilateral agreements, and working with Russian design that incorporates nuclear safeguards for IAEA inspections in non-nuclear weapons states

  2. US nuclear survey

    International Nuclear Information System (INIS)

    2002-08-01

    This document gives a broad overview of the organization of nuclear activities in the USA: nuclear park and availability (reactors, R and D), fuel cycle (uranium enrichment, wastes management (storage and disposal sites)). (J.S.)

  3. Nuclear non-proliferation

    International Nuclear Information System (INIS)

    Anon.

    1984-01-01

    DOE's nuclear non-proliferation responsibilities are defined by the provisions of the Atomic Energy Act of 1954, as amended, and of the Nuclear Non-Proliferation Act of 1978 (NNPA). The Department's major responsibilities in this area are to: (1) provide technical assistance to the Department of State in negotiating agreements for civil cooperation in the peaceful uses of nuclear energy with other countries and international organizations; (2) join with other agencies to reach executive branch judgments with respect to the issuance of export licenses by the Nuclear Regulatory Commission; (3) be responsible for processing subsequent arrangements with other agencies as required by the Nuclear Non-Proliferation Act; (4) control the distribution of special nuclear materials, components, equipment, and nuclear technology exports; (5) participate in bilateral and multilateral cooperation with foreign governments and organizations to promote the peaceful uses of nuclear energy; and (6) act as a primary technical resource with respect to US participation in the International Atomic Energy Agency

  4. Nuclear disarmament verification

    Energy Technology Data Exchange (ETDEWEB)

    DeVolpi, A.

    1993-12-31

    Arms control treaties, unilateral actions, and cooperative activities -- reflecting the defusing of East-West tensions -- are causing nuclear weapons to be disarmed and dismantled worldwide. In order to provide for future reductions and to build confidence in the permanency of this disarmament, verification procedures and technologies would play an important role. This paper outlines arms-control objectives, treaty organization, and actions that could be undertaken. For the purposes of this Workshop on Verification, nuclear disarmament has been divided into five topical subareas: Converting nuclear-weapons production complexes, Eliminating and monitoring nuclear-weapons delivery systems, Disabling and destroying nuclear warheads, Demilitarizing or non-military utilization of special nuclear materials, and Inhibiting nuclear arms in non-nuclear-weapons states. This paper concludes with an overview of potential methods for verification.

  5. Insurance of nuclear risk

    International Nuclear Information System (INIS)

    Lacroix, M.

    1976-01-01

    Insurance for large nuclear installations covers mainly four types of risk: third party liability which in accordance with the nuclear conventions, is borne by a nuclear operator following an incident occurring in his installation or during transport of nuclear substances; material damage to the installation itself, which precisely is not covered by third party liability insurance; machinery breakdown, i.e. accidental damage or interruption of operation. Only the first category must be insured. In view of the magnitude of the risk, nuclear insurance resorts to co-insurance and reinsurance techniques which results in a special organisation of the nuclear insurance market, based on national nuclear insurance pools and on the Standing Committee on Atomic Risk of the European Insurance Committee. Conferences of the chairmen of nuclear insurance pools are convened regularly at a worldwide level. (NEA) [fr

  6. Commercial nuclear ships

    International Nuclear Information System (INIS)

    Poirier d'Ange d'Orsay, P.; Andrieu, J.L.

    1975-01-01

    Following discussion of the arguments in favour of nuclear merchant ships and development of nuclear ship propulsion, the rentability of nuclear ships is dealt with in a comparative study with conventional ships regarding fuel costs, investments and environmental impact. The structure and components of a nuclear ship are described, with emphasis on its safety equipment. The problem of insurance is examined, particularly in connection with the difficulty in applying insurance for liability due to the present uncertainties of the legal position at international level. French legislation does not solve the problem of visiting foreign nuclear ships. The risk concept at operational, design and construction stages is also discussed. Unresolved difficulties, especially concerning the construction of nuclear ships, uncertainties in competitivity analyses between conventional and nuclear propulsion, and implementation of specific and complete legislation on nuclear ships are also mentioned, particularly in the context of their visits to ports [fr

  7. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Videos About Us News Physician Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) ... molecular information. In many centers, nuclear medicine images can be superimposed with computed tomography (CT) or magnetic ...

  8. Nuclear controls are stringent

    International Nuclear Information System (INIS)

    Sonnekus, D.

    1983-01-01

    The peace-time application of nuclear power in South Africa, the organisations concerned and certain provisions laid down by the Act on Nuclear Energy, aimed at safeguarding the general public, are discussed

  9. Nuclear Technology applications

    International Nuclear Information System (INIS)

    Cibils Machado, W. E- mail: wrcibils@adinet.com.uy

    2002-01-01

    The present work tries on the applications of the nuclear technology in the life daily, such as agriculture and feeding, human health, industry, non destructive essays, isotopic hydrology, and the nuclear power stations for electricity production and radioisotopes production

  10. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... nuclear medicine procedures are able to pinpoint molecular activity within the body, they offer the potential to ... otherwise, your child may resume his/her normal activities after the nuclear medicine scan. If the child ...

  11. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... liver and gallbladder. gastrointestinal tract. heart. lungs. brain. thyroid. Nuclear medicine scans are typically used to help ... children. epilepsy . location, anatomy and function of the thyroid gland. top of page How does the nuclear ...

  12. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... patient story here Images × Image Gallery Radiologist and patient consultation. View full size with caption Related Articles and Media General Nuclear Medicine Children's (Pediatric) CT (Computed Tomography) Epilepsy Images related to Children's (Pediatric) Nuclear Medicine ...

  13. ABACC's nuclear accounting area

    International Nuclear Information System (INIS)

    Nicolas, Ruben O.

    2001-01-01

    The functions and activities of the Brazilian-Argentine Agency for the Accounting and Control of Nuclear Materials (ABACC) accounting area is outlined together with a detailed description of the nuclear accounting system used by the bilateral organization

  14. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... MRI. top of page What are some common uses of the procedure? Children's (pediatric) nuclear medicine imaging ... at birth) or that develop during childhood. Physicians use nuclear medicine imaging to evaluate organ systems, including ...

  15. Nuclear radiation actuated valve

    Science.gov (United States)

    Christiansen, David W.; Schively, Dixon P.

    1985-01-01

    A nuclear radiation actuated valve for a nuclear reactor. The valve has a valve first part (such as a valve rod with piston) and a valve second part (such as a valve tube surrounding the valve rod, with the valve tube having side slots surrounding the piston). Both valve parts have known nuclear radiation swelling characteristics. The valve's first part is positioned to receive nuclear radiation from the nuclear reactor's fuel region. The valve's second part is positioned so that its nuclear radiation induced swelling is different from that of the valve's first part. The valve's second part also is positioned so that the valve's first and second parts create a valve orifice which changes in size due to the different nuclear radiation caused swelling of the valve's first part compared to the valve's second part. The valve may be used in a nuclear reactor's core coolant system.

  16. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... What are some common uses of the procedure? Children's (pediatric) nuclear medicine imaging is performed to help diagnose childhood disorders that are congenital (present at birth) or that develop during childhood. Physicians use nuclear medicine imaging to ...

  17. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Tell your doctor about your child’s recent illnesses, medical conditions, medications and allergies. Depending on the type ... Nuclear Medicine? Nuclear medicine is a branch of medical imaging that uses small amounts of radioactive material ...

  18. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... nuclear medicine imaging to evaluate organ systems, including the: kidneys and bladder. bones. liver and gallbladder. gastrointestinal tract. heart. lungs. brain. thyroid. Nuclear medicine scans are typically used to ...

  19. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... referring physician. top of page What are the benefits vs. risks? Benefits The information provided by nuclear medicine examinations is ... risk is very low compared with the potential benefits. Nuclear medicine diagnostic procedures have been used for ...

  20. Nuclear reactors; graphical symbols

    International Nuclear Information System (INIS)

    1987-11-01

    This standard contains graphical symbols that reveal the type of nuclear reactor and is used to design graphical and technical presentations. Distinguishing features for nuclear reactors are laid down in graphical symbols. (orig.) [de

  1. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Because nuclear medicine procedures are able to pinpoint molecular activity within the body, they offer the potential ... or imaging device that produces pictures and provides molecular information. In many centers, nuclear medicine images can ...

  2. Dictionary of nuclear engineering

    International Nuclear Information System (INIS)

    Sube, R.

    1985-01-01

    This dictionary covers nuclear engineering defined in its general sense as applied nuclear physics: industrial and other applications of nuclear power, isotopes and ionizing radiation, nuclear materials, nuclear facilities and nuclear weapons together with their scientific and technological fundamentals. During the compilation of terms, great attention was only given to generally valid basic expressions and to special terms where these occurred in all four languages. A great number of textbooks and monographs, as well as specialist journals covering many years, have been evaluated. Detailed attention has been paid to standards. Of importance in nuclear engineering are the international standards of the International Atomic Energy Organization (including the terminology employed by the International Nuclear Information System INIS), the International Organization of Standardization, the Council for Mutual Economic Assistance, the World Energy Conference, the International Electrical Engineering Commission, and also a great many national standards which, unfortunately, frequently deviate from one another as regards definition and, in particular, designation. (orig.)

  3. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... function of the thyroid gland. top of page How does the nuclear medicine procedure work? With ordinary ... area of your child's body. top of page How is the procedure performed? Nuclear medicine imaging is ...

  4. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... child is taking as well as vitamins and herbal supplements and if he or she has any ... What are the limitations of Children's (Pediatric) Nuclear Medicine? Nuclear medicine procedures can be time consuming. It ...

  5. Nuclear Research and Compliance

    International Nuclear Information System (INIS)

    Noramly Muslim

    2012-01-01

    In his speech, Professor Noramly stressed on any research conducted in Malaysian Nuclear Agency must be comply with the national and international regulations. This to avoid any problems in the future. Moreover, research conducted in Malaysian Nuclear Agency are based on nuclear matters that seems sensitive to the public communities. In order to attract the publics on the benefit of nuclear technologies in many applications, researcher also must aware about the regulations and must take care on their safety during their experiment and working. This to make the public feels that nuclear are not the bad things and erased the worseness of nuclear technology into public minds. This strategies can be used for Malaysia in embarking for their first nuclear power program and the public feels that nuclear power are not threatened to them and consequently, they will accept that program without any issues. (author)

  6. The ultimate nuclear accident

    International Nuclear Information System (INIS)

    Abdus Salam, A.

    1988-01-01

    The estimated energy equivalent of Chernobyl explosion was the 1/150 th of the explosive energy equivalent of atomic bomb dropped on Hiroshima; while the devastation that could be caused by the world's stock pile of nuclear weapons, could be equivalent to 160 millions of Chernobyl-like incidents. As known, the number of nuclear weapons is over 50,000 and 2000 nuclear weapons are sufficient to destroy the world. The Three Mile Island and Chernobyl accidents have been blamed on human factors but also the human element, particularly in the form of psychological stresses on those operating the nuclear weapons, could accidentally bring the world to a nuclear catastrophe. This opinion is encouraged by the London's Sunday Times magazine which gave a graphic description of life inside a nuclear submarine. So, to speak of nuclear reactor accidents and not of nuclear weapons is false security. (author)

  7. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Nuclear Medicine? Nuclear medicine is a branch of medical imaging that uses small amounts of radioactive material to ... a radiologist or other physician. To locate a medical imaging or radiation oncology provider in your community, you ...

  8. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... of page What are some common uses of the procedure? Children's (pediatric) nuclear medicine imaging is performed ... the thyroid gland. top of page How does the nuclear medicine procedure work? With ordinary x-ray ...

  9. Nuclear disarmament verification

    International Nuclear Information System (INIS)

    DeVolpi, A.

    1993-01-01

    Arms control treaties, unilateral actions, and cooperative activities -- reflecting the defusing of East-West tensions -- are causing nuclear weapons to be disarmed and dismantled worldwide. In order to provide for future reductions and to build confidence in the permanency of this disarmament, verification procedures and technologies would play an important role. This paper outlines arms-control objectives, treaty organization, and actions that could be undertaken. For the purposes of this Workshop on Verification, nuclear disarmament has been divided into five topical subareas: Converting nuclear-weapons production complexes, Eliminating and monitoring nuclear-weapons delivery systems, Disabling and destroying nuclear warheads, Demilitarizing or non-military utilization of special nuclear materials, and Inhibiting nuclear arms in non-nuclear-weapons states. This paper concludes with an overview of potential methods for verification

  10. Nuclear energy in question

    International Nuclear Information System (INIS)

    Simon, D.N.; Carvalho, J.F. de; Goldemberg, J.; Menezes, L.C.; Rosa, L.P.; Oliveira, R.G. de.

    1981-01-01

    The basic requirements demanded for the physical protection of nuclear operational units, is established. These units can be, production, utilization, processing, reprocessing, handling, transport or storage of materials of interesting to Brazilian Nuclear Program. (E.G.) [pt

  11. Nuclear energy in China

    International Nuclear Information System (INIS)

    Gourievidis, G.

    1984-01-01

    Having first outlined the main problems China must resolve in the field of energy supply, this paper presents the nuclear option trends established by the government, recalls the different stages in the nuclear Chinese development programme, achievements and projects. The organization of nuclear research and industry, as also the fuel cycle situation and uranium resources are then described. Finally, the international nuclear cooperation policy carried out by the chinese government and more particularly the agreement settled with France are presented [fr

  12. The nuclear arms race

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    During his visit to South Africa, dr. Edward Teller, one of the most outstanding nuclear physicists of the age, and intimately associated with American research during the most sensitive period in the development of nuclear energy, were interviewed. Dr. Teller was questioned on the following: his feelings about nuclear weapons; the American atomic bomb that was dropped on Japan; the Soviet Union's development of a hydrogen bomb and the nuclear balance between the Soviet Union and America

  13. Prevention of nuclear war

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Removing the threat of a nuclear war-as the General Assembly formally stated in the Final Document of its first special session devoted to disarmament, in 1978-is considered to be the task of the present day. In that Document, the General Assembly sought to establish principles, guidelines and procedures for preventing nuclear war. It declared that to that end, it was imperative to remove the threat of nuclear weapons, to halt and reverse the nuclear-arms race until the total elimination of nuclear weapons and their delivery systems had been achieved (see chapter iv), and to prevent the proliferation of nuclear weapons (see chapter VII). At the same time, it called for other measures designed to prevent the outbreak of nuclear war and to lessen the danger of the treat or use of nuclear weapons. The Assembly's clear call for action was dictated by the awareness that there was no insuperable barrier dividing peace from war and that, unless nations brought the spiralling nuclear-arms race to an end, the day might come when nuclear weapons would actually be used, with catastrophic consequences. In adopting the Final Document, the international community achieved, for the first time, a consensus on an international disarmament strategy having as its immediate goal the elimination of the danger of a nuclear war and the implementation of measures to halt and reverse the arms race. The General Assembly, at its second special session on disarmament, in 1982, reaffirmed the validity of the 1978 Final Document. This paper reports that nuclear issues and in particular the prevention of nuclear war remain, however, major concerns of all States. Undoubtedly, all nations have a vital interest in the negotiation of effective measures for her prevention of nuclear war, since nuclear weapons pose a unique threat to human survival. If nuclear war were to occur, its consequences would be global, not simple regional

  14. Nuclear energy dictionary

    International Nuclear Information System (INIS)

    1978-03-01

    This book is a dictionary for nuclear energy which lists the technical terms in alphabetical order. It adds four appendixes. The first appendix is about people involved with nuclear energy. The second one is a bibliography and the third one is a checklist of German, English and Korean. The last one has an index. This book gives explanations on technical terms of nuclear energy such as nuclear reaction and atomic disintegration.

  15. Planning for nuclear emergencies

    International Nuclear Information System (INIS)

    Lakey, J.R.A.

    1989-01-01

    This paper aims to stimulate discussions between nuclear engineers and the radiological protection professions in order to facilitate planning for nuclear emergencies. A brief review is given of the response to nuclear accidents. Studying accidents can lead to prevention, but some effort must be put into emergency response. Such issues as decontamination and decommissioning, socio-economic consequences, education and training for nuclear personnel and exercises and drills, are raised. (UK)

  16. JPRS Report, Nuclear Developments

    Science.gov (United States)

    1988-06-03

    Nuclear Power Station Projected for Jorf Lasfar [Casablanca LA VIE ECONOMIQUE , 18 Mar 88] 26 WEST EUROPE IRELAND Energy Minister Fights UK...factors mili- tate against further expansion. MOROCCO Nuclear Power Station Projected for Jorf Lasfar 51004603 Casablanca LA VIE ECONOMIQUE in...body to oversee nuclear activities at the national level and to hire and train personnel in nuclear sciences and techniques. A bill relating to the

  17. The IAEA Nuclear Security Programme Combating Nuclear Terrorism

    International Nuclear Information System (INIS)

    2010-01-01

    Discusses the four threats of nuclear terrorism,which are theft of a nuclear weapon, theft of material to make an improvised nuclear explosive device,theft of other radioactive material for an Radiological dispersal device and sabotage of a facility or transport. The IAEA Nuclear Security programme combating Nuclear Terrorism therefore adopts a comprehensive approach. The programme addresses the need to cover nuclear and other radioactive materials, nuclear facilities and transports, non-nuclear, medical and industrial applications of sources

  18. Nuclear and radioactivity

    International Nuclear Information System (INIS)

    2000-01-01

    Among the industrial risks of nuclear facilities, the nuclear risk is often associated to the Chernobyl accident. This paper presents the nuclear major risk in a french PWR type power plant, with consequences on the personnel, the surrounding population and the environment. (A.L.B.)

  19. Spain's nuclear components industry

    International Nuclear Information System (INIS)

    Kaibel, E.

    1985-01-01

    Spanish industrial participation in supply of components for nuclear power plants has grown steadily over the last fifteen years. The share of Spanish companies in work for the five second generation nuclear power plants increased to 50% of total capital investments. The necessity to maintain Spanish technology and production in the nuclear field is emphasized

  20. Introduction to nuclear energy

    International Nuclear Information System (INIS)

    2004-01-01

    After some descriptions about atoms, fission and fusion, explanations are given about the functioning of a nuclear power plant. The safety with the different plans of emergency and factors that lead to a better nuclear safety are exposed, then comes a part for the environmental protection; the fuel cycle is tackled. Some historical aspects of nuclear energy finish this file. (N.C.)

  1. Online nuclear data service

    International Nuclear Information System (INIS)

    Dunford, C.L.; Burrows, T.W.

    1998-01-01

    The US National Nuclear Data Center and the IAEA Nuclear Data Section offer online computer access through international networks to their nuclear-physics and photo-atomic numeric databases, related bibliographic systems and other related information of interest to basic and applied research and technology. A detailed description of the access procedures, the technical requirements, and the available databases is given. (author)

  2. The nuclear submarines dismantling

    International Nuclear Information System (INIS)

    Queau, Ph.

    2002-01-01

    The replacement of the first French nuclear submarines by these ones of new generation has led to put in place the dismantling and decommissioning of nuclear boilers on board. Technicatome is in charge of shutdown, decommissioning and dismantling studies of nuclear submarines. (N.C.)

  3. Submarine nuclear power plants

    International Nuclear Information System (INIS)

    Horton, C.C.

    1984-01-01

    The submarine nuclear power plant has revolutionised the strategy and tactics of under-sea warfare. Present day submarine nuclear power plants are discussed, as well as future developments. The endurance, speed, noise and diving depth of nuclear submarines are also outlined. (U.K.)

  4. Institute for Nuclear Theory

    International Nuclear Information System (INIS)

    Haxton, W.; Bertsch, G.; Henley, E.M.

    1993-01-01

    This report briefly discussion the following programs of the Institute for Nuclear Theory: fundamental interactions in nuclei; strangeness in hadrons and nuclei; microscopic nuclear structure theory; nuclear physics in atoms and molecules; phenomenology and lattice QCD; and large amplitude collective motion

  5. Dictionary of nuclear power

    International Nuclear Information System (INIS)

    Koelzer, W.

    2012-04-01

    The actualized version (April 2012) of the dictionary on nuclear power includes all actualizations and new inputs since the last version of 2001. The original publication dates from 1980. The dictionary includes definitions, terms, measuring units and helpful information on the actual knowledge concerning nuclear power, nuclear facilities, and radiation protection.

  6. Nuclear energy engineering

    International Nuclear Information System (INIS)

    Kim, Eul Gi

    2008-12-01

    It explains nuclear physics, nuclear fission, neutron physics, reactor physics, poison physics, neutron kinetics, neutron source and subcriticality, heat penetration curve and long-term reactivity effect and mass density, fuel cycle and reactivity control. In the last, it has questions, interpretation and answers of the test for nuclear engineers.

  7. Improved nuclear fuel element

    International Nuclear Information System (INIS)

    Gordon, G.M.; Cowan, R.L. II; Davies, J.H.

    1975-01-01

    A nuclear fuel element is described. It includes a central nuclear fuel core and a composite cladding composed of a substrate, the inner face of which is coated with copper, nickel, iron or one of their alloys. The nuclear fuel is selected from uranium compounds, plutonium compounds or mixtures thereof. The substrate is selected from zirconium and zirconium alloys [fr

  8. Nuclear Medicine Imaging

    Science.gov (United States)

    ... necesita saber acerca de... Estudios de Imagen de Medicina Nuclear Un procedimiento de medicina nuclear se describe algunas veces como unos rayos- ... través del cuerpo del paciente. Los procedimientos de medicina nuclear utilizan pequeñas cantidades de mate- riales radiactivos, ...

  9. Lasers in nuclear physics

    International Nuclear Information System (INIS)

    Inamura, T.T.

    1988-01-01

    The hyperfine interaction has been reviewed from a point of view of nuclear physics. Recent progress of nuclear spectroscopy with lasers is presented as one of laser studies of fundamental physics currently pursued in Japan. Especially, the hyperfine anomaly is discussed in connection with the origin of nuclear magnetism. (author)

  10. Nuclear criticality safety guide

    International Nuclear Information System (INIS)

    Ro, Seong Ki; Shin, Hee Seong; Park, Seong Won; Shin, Young Joon.

    1997-06-01

    Nuclear criticality safety guide was described for handling, transportation and storage of nuclear fissile materials in this report. The major part of the report was excerpted frp, TID-7016(revision 2) and nuclear criticality safety written by Knief. (author). 16 tabs., 44 figs., 5 refs

  11. World nuclear energy developments

    International Nuclear Information System (INIS)

    Hore-Lacy, Ian

    2013-01-01

    Presentation covers world nuclear power reactors in operation, fuels used for electricity generation, electricity markets in South Australia, UK, China, Germany, US, Vietnam, and the French nuclear reactor fleet. Also global perspective of world uranium supply and demand, resources, costs and production, types of new generation nuclear reactors, hydrogen economy and Generation IV reactors.

  12. Particle-nuclear intersections

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    With the traditional distinctions between particle and nuclear physics becoming increasing blurred, the Fifth Conference on the Intersections of Particle and Nuclear Physics, held from May 31 to June 6 in St. Petersburg, Florida, brought together particle and nuclear physicists to discuss common research efforts and to define and plan a united approach

  13. Nuclear energy technology

    Science.gov (United States)

    Buden, David

    1992-01-01

    An overview of space nuclear energy technologies is presented. The development and characteristics of radioisotope thermoelectric generators (RTG's) and space nuclear power reactors are discussed. In addition, the policy and issues related to public safety and the use of nuclear power sources in space are addressed.

  14. Nuclear physics looks ahead

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    A very wide-ranging report published by the Nuclear Physics European Collaboration Committee (NuPECC) looks at the future of nuclear physics in general, and in Europe in particular. However in view of the increasing interplay between nuclear and particle physics, many of the report's recommendations are of wider interest

  15. Future of nuclear science

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    A report is presented by the Ad Hoc Panel on the Future of Nuclear Science on its assessment of the scientific objectives and unexplored questions of nuclear science and recommendations of the manpower, funding, and facilities required to realize its full potential. Nuclear research and its facilities and budgetary, sociological, and application aspects of this research are considered

  16. Accelerator for nuclear transmutation

    International Nuclear Information System (INIS)

    Schapira, J.P.

    1984-01-01

    A review on nuclear transmutation of radioactive wastes using particle accelerators is given. Technical feasibility, nuclear data, costs of various projects are discussed. It appears that one high energy accelerator (1500 MeV, 300 mA proton) could probably handle the amount of actinides generated by the actual French nuclear program [fr

  17. Nuclear Energy in Perspective

    International Nuclear Information System (INIS)

    1989-01-01

    This report provides the interested non-specialist reader with insights on five major issues associated with nuclear power generation: nuclear development and economics, protection of man and the environment, power plant safety, radioactive waste management and compensation for damage from a nuclear accident

  18. Nuclear power in Canada

    International Nuclear Information System (INIS)

    1980-01-01

    The Canadian Nuclear Association believes that the CANDU nuclear power generation system can play a major role in achieving energy self-sufficiency in Canada. The benefits of nuclear power, factors affecting projections of electric power demand, risks and benefits relative to other conventional and non-conventional energy sources, power economics, and uranium supply are discussed from a Canadian perspective. (LL)

  19. Nuclear law in progress

    International Nuclear Information System (INIS)

    Manóvil, Rafael Mariano

    2014-01-01

    The 21. AIDN / INLA Congress was organized by the International Nuclear Law Association, in Buenos Aires, between the October 20 and 23, 2014. In this event, were presented almost 50 papers about these subjects: radioactive sources, safety and licensing, radioactive waste management, radiation protection, nuclear transport, security and non-proliferation, nuclear liability and insurance, etc.

  20. Spanish nuclear industry

    International Nuclear Information System (INIS)

    1994-01-01

    In this book published to commemorate the twentieth anniversary of the Spanish Nuclear Society, it is included a report on the Spanish Nuclear Industry. The Spanish Companies and Organizations in nuclear world are: CIEMAT, Empresarios Agrupados, ENRESA, ENUSA, ENDESA, Grupo Iberdrola, LAINSA, INITEC AND TECNATOM. Activities, history and research programs of each of them are included