Bibliographies thématiques / ERFE

Littérature scientifique sur le sujet « ERFE »

Auteur : Grafiati
Publié le 11 mars 2023

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Articles de revues sur le sujet "ERFE"

1

Kautz, Leon, Grace Jung, Elizabeta Nemeth et Tomas Ganz. « Role of Erythroferrone in the Pathophysiology of Common Anemias ». Blood 124, no 21 (6 décembre 2014) : 213. http://dx.doi.org/10.1182/blood.v124.21.213.213.

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Abstract Introduction: We recently described the erythroid hormone erythroferrone (ERFE) as a critical regulator of hepcidin production during increased erythropoietic activity. Both anemia of inflammation (AI) and beta-thalassemia are associated with elevated levels of erythropoietin, the signal directing ERFE expression, suggesting that ERFE may play a role in the pathogenesis of these disorders. Indeed, Erfe mRNA expression was highly increased in the bone marrow and the spleen of a mouse model of β-thalassemia Hbbth3/+ (Th3/+). We therefore investigated the role of erythroferrone in hepcidin regulation in anemia of inflammation and β-thalassemia. We report that ERFE contributes to the recovery from anemia of inflammation and may be a hepcidin-suppressive factor responsible for iron accumulation in thalassemia. Methods: We explored the role of ERFE in anemia of inflammation using the heat-killed Brucellaabortus (BA) mouse model of AI. Hepcidin regulation and recovery from anemia was compared between wild-type and Erfe-deficient mice. To determine whether ERFE is the hepcidin-suppressive factor in thalassemia, we generated Erfe-/-/Th3/+ double mutant mice and compared them to their littermate WT, Erfe-/- and Th3/+ mice. Mice were compared at 3, 6 and 12 weeks of age. Results: Compared to wild-type mice, Erfe-deficient mice did not appropriately decrease hepcidin production during recovery from AI and exhibited greater severity of anemia (figure). These data suggest that compensatory hepcidin suppression during the recovery phase of AI is mediated by ERFE. However, in mice this defect was partly compensated by prolonged stimulation of erythropoiesis and higher reticulocytosis resulting in Erfe-deficient mice reaching wild-type hemoglobin levels by day 28 (figure). Figure 1 Figure 1. At the other end of the spectrum, we showed that thalassemic mice exhibited greatly increased expression of Erfe mRNA in the bone marrow and the spleen. Ablation of Erfe in Th3/+ mice restored normal hepcidin levels and significantly reduced serum iron concentration and hepatic iron overload at 6 weeks of age. Comparison of Erfe-/- / Th3/+ and Th3/+ mice at 3, 6 and 12 weeks of age did not show any difference in the severity of the anemia in absence of ERFE suggesting that ERFE regulates hepcidin expression but its absence did not cause iron restriction and did not ameliorate ineffective erythropoiesis. Conclusion: ERFE is a critical regulator of hepcidin expression during recovery from AI and ERFE agonists may alleviate iron restriction in AI. ERFE may also be the factor responsible for hepcidin suppression and secondary iron overload in β-thalassemia. Disclosures Ganz: Intrinsic LifeSciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Keryx Pharma: Consultancy; Merganser Biotech: Consultancy, Equity Ownership.
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Kautz, Leon, Sharraya Aschemeyer, Victoria Gabayan, Tomas Ganz et Elizabeta Nemeth. « Erythroferrone Regulates Hepcidin Expression Independently of Matriptase 2 ». Blood 128, no 22 (2 décembre 2016) : 3616. http://dx.doi.org/10.1182/blood.v128.22.3616.3616.

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Abstract Introduction: The iron-regulatory hormone hepcidin regulates the body iron stores and its expression is repressed when erythropoietic activity intensifies to meet the iron requirements for erythropoiesis (e.g. during anemia). Under the influence of erythropoietin (EPO), the hormone erythroferrone (ERFE) is secreted by erythroid precursors in the bone marrow and the spleen, and suppresses hepcidin synthesis to facilitate the recovery from anemia. However, the mechanism by which ERFE suppresses hepcidin is unknown. In contrast with forms of anemia in which hepcidin is suppressed, patients with mutations in transmembrane serine protease 6 (TMPRSS6) have iron-refractory iron deficiency anemia (IRIDA) but increased hepcidin production despite a severe anemia and elevated EPO levels. Recently, it has been suggested that matriptase-2 activity facilitates ERFE-mediated suppression of hepcidin. We therefore investigated the potential crosstalk between ERFE and Matriptase 2. Methods: We first measured serum ERFE concentration in Tmprss6-/- mice. To assess the contribution of ERFE to the phenotype of Tmprss6-/-mice, we next generated Tmprss6-/-mice with disrupted Erfe (Erfe+/- Tmprss6-/-; Erfe-/- Tmprss6-/- and Erfe+/+ Tmprss6-/-). To determine whether ERFE requires TMPRSS6 to regulate hepcidin production, we treated freshly isolated hepatocytes from wild-type (WT) or Tmprss6-/- mice with conditioned medium from cells expressing recombinant ERFE or not. Results: While wild-type mice have undetectable plasma ERFE (below the 500 pg/ml limit of detection), plasma ERFE concentration was elevated in Tmprss6-/- to levels comparable to those of WT animals 24 hours after phlebotomy (~3 ng/ml) but was lower than ERFE levels in thalassemic mice (~10 ng/ml). Ablation of Erfe in Tmprss6-/- mice did not result in any change in hematological parameters, hepcidin expression and iron levels compared to Tmprss6-/- animals at 6 weeks of age. However, treatment of WT and Tmprss6-/-hepatocytes with ERFE resulted in a comparable suppression of hepcidin mRNA expression. Conclusion: Although matriptase-2 may dampen the BMP signaling under the influence of EPO, it is not part of the ERFE signaling pathway. Disclosures Ganz: Intrinsic Lifesciences: Other: shareholder and scientific advisor; Merganser Biotech: Other: shareholder and scientific advisor; Silarus therapeutics: Other: shareholder and scientific advisor; Keryx Biopharmaceuticals: Consultancy. Nemeth:Intrinsic Lifesciences: Other: shareholder and scientific advisor; Merganser Biotech: Other: shareholder and scientific advisor; Silarus therapeutics: Other: shareholder and scientific advisor.
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Arezes, João, Niall Foy, Kirsty McHugh, Doris Quinkert, Susan Benard, Anagha Sawant, Joe N. Frost et al. « Antibodies against the erythroferrone N-terminal domain prevent hepcidin suppression and ameliorate murine thalassemia ». Blood 135, no 8 (20 février 2020) : 547–57. http://dx.doi.org/10.1182/blood.2019003140.

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Abstract Erythroferrone (ERFE) is produced by erythroblasts in response to erythropoietin (EPO) and acts in the liver to prevent hepcidin stimulation by BMP6. Hepcidin suppression allows for the mobilization of iron to the bone marrow for the production of red blood cells. Aberrantly high circulating ERFE in conditions of stress erythropoiesis, such as in patients with β-thalassemia, promotes the tissue iron accumulation that substantially contributes to morbidity in these patients. Here we developed antibodies against ERFE to prevent hepcidin suppression and to correct the iron loading phenotype in a mouse model of β-thalassemia [Hbb(th3/+) mice] and used these antibodies as tools to further characterize ERFE’s mechanism of action. We show that ERFE binds to BMP6 with nanomolar affinity and binds BMP2 and BMP4 with somewhat weaker affinities. We found that BMP6 binds the N-terminal domain of ERFE, and a polypeptide derived from the N terminus of ERFE was sufficient to cause hepcidin suppression in Huh7 hepatoma cells and in wild-type mice. Anti-ERFE antibodies targeting the N-terminal domain prevented hepcidin suppression in ERFE-treated Huh7 cells and in EPO-treated mice. Finally, we observed a decrease in splenomegaly and serum and liver iron in anti–ERFE-treated Hbb(th3/+) mice, accompanied by an increase in red blood cells and hemoglobin and a decrease in reticulocyte counts. In summary, we show that ERFE binds BMP6 directly and with high affinity, and that antibodies targeting the N-terminal domain of ERFE that prevent ERFE–BMP6 interactions constitute a potential therapeutic tool for iron loading anemias.
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Han, Huiling, Keith Westerman, Vaughn Ostland, Patrick Gutschow, Gordana Olbina, Jacqueline da Silva Guimarães, Juçara Gastaldi Cominal et al. « A Novel Dual Monoclonal Sandwich ELISA for Human Erythroferrone ». Blood 128, no 22 (2 décembre 2016) : 1272. http://dx.doi.org/10.1182/blood.v128.22.1272.1272.

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Abstract Erythroferrone (ERFE) is a hormone produced by erythroblasts in the bone marrow in response to erythropoietin (EPO). Recent animal studies have shown that rather than being involved in regulation of baseline erythropoiesis, ERFE acts as a stress erythropoiesis-specific regulator of hepcidin expression. By suppressing hepcidin expression in the liver, EFRE contributes to increased dietary iron absorption and recycling of stored iron necessary for recovery of blood mass after hemorrhage. In addition, ERFE was found to be involved in hepcidin regulation in inherited iron loading anemias, such as b-Thalassemia. ERFE has potential as a clinical marker for assessing erythropoiesis in patients with blood disorders. To date, there have been no reports of a human ERFE assay development and validation. To study the biological function and potential clinical applications of ERFE in humans, we developed the first dual monoclonal sandwich ELISA for serum measurement. Purified recombinant ERFE was used as antigen to immunize mice and subsequently screen 3000 hybridomas for binding to human ERFE. The nine positive hybridomas were expanded and monoclonal antibody from each clone purified and isotyped. We biotinylated each antibody and queried all possible combinations of capture and detection antibodies for binding activity. We discovered at least two pairs of antibodies suitable for assay optimization. Two mAbs were selected, 4C1 and 2D2, as the capture and detection antibody, respectively. We used streptavidin-HRP to quantify binding and detection of ERFE. The ERFE ELISA standard curve ranges from 0-50 ng/mL. The assay's lower limit of detection (LLOD) is 0.15 ng/mL and lower limit of quantitation (LLOQ) is 0.17 ng/mL. We assessed the normal range of ERFE by analyzing serum from110 healthy first time blood donors with normal iron status determined by assessment of ferritin, plasma iron, and transferrin saturation. Serum ERFE in the first time blood donors ranged from 0.15 to 3.94 ng/mL with a mean of 0.83 ng/mL. To re-capitulate the animal data previously observed in mice (Kautz et al., Nat Genet. 2014; 46(7): 678-684), we examined the effect of blood donation on human serum ERFE concentrations (Figure 1). We analyzed sera from three donors which underwent platelet and plasma-apheresis at baseline and day 2, 3, 4, 5, 7, 9, 10, 14, and 120 (Li et al., J Clin Apher., 2016). It was estimated that 30ml of RBCs were lost in the procedure. Serum ERFE concentrations were elevated from baseline in each patient within 2 days and remained higher through 14 days. At 120 days serum ERFE returned to baseline levels. We went on to test the concept that serum ERFE concentrations would be elevated in blood disorders associated with ineffective erythropoiesis, we obtained serum samples from X-linked sideroblastic anemia probands and 15 of their family members. Nine of the probands had point mutation in the ALAS2 gene and two had a-globin duplications. We measured serum ERFE in the probands and family controls and discovered that ERFE was significantly increased in probands relative to familial controls (Figure 2). Family members had ERFE concentrations similar to healthy first time blood donors (<1 ng/ml). An additional study was conducted to examine ERFE in thalassemia patients whom are known to exhibit ineffective erythropoiesis due to mutations in the α- or β-globin genes that cause production of deformed red blood cells. We obtained sera from patients with both α- and β-thalassemia and discovered that both β+-thalassemia and β0-thalassemia patients had significantly higher serum ERFE concentrations than controls and a group of iron deficient (ID) controls (Figure 3). The β0-thalassemia patients had highly elevated serum ERFE which is likely due to the degree that erythropoiesis is affected. The data we present lends strong support to the quality of the dual monoclonal sandwich ELISA we have developed. The ERFE assay is very sensitive, has excellent reproducibility and spike recovery characteristics, and is easy to perform. The physiological and clinical data we present supports the assertion that the assay is specific for ERFE and will allow insight into a number of hematological diseases. Figure 1 Effect of plasma- or platelet-apheresis on ERFE. Figure 1. Effect of plasma- or platelet-apheresis on ERFE. Figure 2 ERFE in X-linked Sideroblastic Anemia. ****p<0.0001 Figure 2. ERFE in X-linked Sideroblastic Anemia. ****p<0.0001 Figure 3 ERFE in Iron Deficient and Thalassemic Patients. ****p<0.0001, **p<0.005 Figure 3. ERFE in Iron Deficient and Thalassemic Patients. ****p<0.0001, **p<0.005 Disclosures Han: Intrinsic Lifesciences.: Employment, Equity Ownership. Westerman:Intrinsic LifeSciences: Employment. Ostland:Intrinsic LifeScienc s: Employment, Equity Ownership. Gutschow:Intrinsic LifeSciences: Employment, Equity Ownership. Olbina:Intrinsic LifeSciences: Employment, Equity Ownership. Westerman:Intrinsic LifeSciences: Employment, Equity Ownership.
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Gutschow, Patrick, Huiling Han, Gordana Olbina, Keith Westerman, Eileen Westerman, Marc Ruiz Martinez, Yelena Ginzburg, Elizabeta Nemeth, Tomas Ganz et Vaughn Ostland. « A Novel Sandwich ELISA to Quantify Erythroferrone in Mouse Serum ». Blood 134, Supplement_1 (13 novembre 2019) : 2237. http://dx.doi.org/10.1182/blood-2019-130947.

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Erythroferrone (ERFE) is a hormone produced by erythroblasts in response to erythropoietin. ERFE acts as a regulator of hepcidin expression during stress erythropoiesis. By suppressing hepcidin expression, ERFE contributes to the mobilization of dietary and stored iron necessary for recovery from blood loss after hemorrhage. Furthermore, overproduction of ERFE plays a pathogenic role in β-thalassemia and other anemias with ineffective erythropoiesis, where it contributes to hepcidin suppression and consequent iron overload. Development of a method to quantify serum ERFE in mice would improve our ability to study the pathobiology of this erythroid regulator. A dual polyclonal sandwich ELISA was developed to quantify ERFE in mouse serum. Purified recombinant mouse ERFE was used to immunize rabbits and goats, and high titer antibodies were purified from serum via protein A. Western blotting of reduced ERFE protein demonstrated that both the capture and detection antibody specifically recognized mouse ERFE, weakly recognized recombinant human ERFE, but neither antibody recognized mouse, rabbit or human TNF-alpha. Antibody was biotinylated and screened to determine the optimal antibody pairs. ELISA optimization established the standard curve range from 0 to 4 ng/ml. With a 10% sample dilution the lower limit of quantitation (LLOQ) was 0.1 ng/ml. Average spike recovery of ERFE in 3 different mouse sera (0.75 - 24 ng/ml) ranged from 93-105% (mean 99%). Dilutional linearity of the same spiked samples ranged from 93-104% (mean 99%). Intra- and inter-assay precision was 4.9% and 3.9%, respectively, over a concentration range of 0.57 - 16.3ng/ml. The effect of phlebotomy on serum ERFE in 6- and 8-week-old male C57BL/6 mice (n=3 each) was examined 24 h after removal of 0.5 ml of blood (Figure 1). At time 0, all the mice had serum ERFE levels below the limit of detection, but serum ERFE had increased to a mean of 1.9 ng/ml at 24 hours (P=0.03). This increase in ERFE is associated with a decrease in hepcidin from 209 ng/ml to 104 ng/ml (p<0.0001). In a mouse model of β-Thalassemia (th3/+) there was significantly greater ERFE (1.2 ng/ml, n=5) compared to wild type (wt, <0.1 ng/ml, n=3, p < 0.04). Crossing the th3/+ mice with transferrin receptor 1 (TfR1) heterozygous mice (th3/+ TfR1+/-) produced a partial rescue of ERFE (0.6 ng/ml, n=5). Erfe knockout mice (th3/+ erfe-/- and th3/+ TfR1+/- erfe-/-) produced significantly less ERFE (p<0.02) than their respective single and double mutants (<0.1 ng/ml [n=7] and <0.1 ng/ml [n=4], respectively) (Figure 2). Collectively, this validated ELISA can quantify mouse serum ERFE in both healthy and diseased mouse models and can be used to study the pathobiology of this erythroid regulator in diseases associated with ineffective erythropoiesis. Disclosures Gutschow: Intrinsic LifeSciences: Employment, Equity Ownership. Han:Intrinsic LifeSciences: Employment, Equity Ownership. Olbina:Intrinsic LifeSciences: Employment, Equity Ownership. Westerman:Intrinsic LifeSciences: Employment, Equity Ownership. Westerman:Intrinsic LifeSciences: Employment, Equity Ownership. Ginzburg:La Jolla Pharma: Membership on an entity's Board of Directors or advisory committees. Nemeth:Silarus Therapeutics: Consultancy, Equity Ownership; Ionis Pharmaceuticals: Consultancy; Protagonist: Consultancy; La Jolla Pharma: Consultancy; Intrinsic LifeSciences: Consultancy, Equity Ownership; Keryx: Consultancy. Ganz:Intrinsic LifeSciences: Consultancy, Equity Ownership. Ostland:Intrinsic LifeSciences: Employment, Equity Ownership.
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Delaney, Katherine, Ronnie Guillet, Eva Pressman, Elizabeta Nemeth et Kimberly O'Brien. « Erythroferrone Is Associated with Maternal Erythropoietic Drive During Pregnancy ». Current Developments in Nutrition 4, Supplement_2 (29 mai 2020) : 968. http://dx.doi.org/10.1093/cdn/nzaa054_040.

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Abstract Objectives Iron (Fe) homeostasis must be tightly regulated during pregnancy to meet both maternal and fetal Fe demands. Several hormones are known to impact Fe homeostasis including hepcidin, erythropoietin and erythroferrone (ERFE). Few data are available on determinants of ERFE in pregnant women or in their newborns at birth. The objective of this study was to characterize concentrations of ERFE across gestation and evaluate this hormone in relation to other Fe status biomarkers and regulatory hormones in mothers across pregnancy. Methods ERFE was measured in serum from pregnant adolescents (n = 166, age 14–19) or women carrying multiple fetuses (n = 61, age 20–46). ERFE concentrations across gestation (wks 8 – 42.1) were compared to Fe status and nutritional indicators (hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), total body Fe (TBI), TR-F index (sTfR/log(SF)), folate and vitamin B-12), as well as regulatory hormones (erythropoietin (EPO), hepcidin) and inflammatory markers (IL-6, C-reactive protein (CRP)). Results ERFE concentrations increased significantly across pregnancy in women carrying multiple fetuses (P &lt; 0.01), but did not change across pregnancy in the adolescents (P = 0.3). In both populations, 16% (n = 30) of women were anemic at midgestation (MG) and 24% (n = 75) at delivery. ERFE concentrations were significantly increased in anemic women at both MG (P = 0.02) and at delivery (P = 0.02). At MG (median 26 wks), ERFE was significantly positively associated with TfR (P &lt; 0.001) and EPO (P = 0.002). Maternal TfR, IL-6 and serum Fe were the strongest determinants of maternal MG ERFE, and explained 29% of variance in ERFE. At delivery (median 38 wks), ERFE was significantly positively associated with TfR (P &lt; 0.001) and EPO (P &lt; 0.001), which together explained 18% of variance in ERFE at delivery. ERFE was not significantly associated with hepcidin at either MG (P = 0.87) or delivery (P = 0.52). Conclusions ERFE was significantly higher in anemic women across pregnancy and, as expected, was positively associated with indicators of erythropoietic drive. ERFE however, was not significantly associated with hepcidin, possibly because hepcidin is regulated by multiple competing signals. More research is needed to understand the relationship between maternal ERFE and neonatal Fe status at birth. Funding Sources Funded by the NIH (NIDDK/NICHD).
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Arezes, Joao, Niall Foy, Kirsty McHugh, Anagha Sawant, Susan Benard, Doris Quinkert, Virginie Terraube et al. « Erythroferrone Inhibits the Induction of Hepcidin By BMP6 ». Blood 132, Supplement 1 (29 novembre 2018) : 850. http://dx.doi.org/10.1182/blood-2018-99-111140.

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Abstract Decreased hepcidin mobilizes iron, which facilitates erythropoiesis, but excess iron is pathogenic in beta-thalassemia and other iron-loading anaemias. Erythropoietin (EPO) enhances erythroferrone (ERFE) synthesis by erythroblasts, and ERFE suppresses hepatic hepcidin production, through an unknown mechanism. The BMP/SMAD pathway in the liver is critical for control of hepcidin, and we show that EPO suppressed hepcidin and other BMP target genes in vivo in a partially ERFE-dependent manner. Furthermore, recombinant ERFE suppressed the hepatic BMP/SMAD pathway independently of changes in serum and liver iron, and in vitro, ERFE decreased SMAD 1/5/8 phosphorylation and inhibited expression of BMP target genes in hepatoma cells. ERFE specifically abrogated the induction of hepcidin by BMP5, BMP6 and BMP7, but had no or very little effect on hepcidin induction by BMP2, 4, 9 or Activin B. A neutralising anti-ERFE antibody prevented the ability of ERFE to inhibit hepcidin induction by BMP5, 6 and 7. Cell-free Homogeneous Time Resolved Fluorescence assays showed that BMP5, BMP6 and BMP7 competed with anti-ERFE for binding to ERFE. Biacore analysis showed that ERFE binds to BMP6 with a higher affinity compared to its binding to BMP2, BMP4 or Activin B, and does not bind to GDF15. We propose that ERFE suppresses hepcidin by inhibiting hepatic BMP/SMAD signaling via preferentially binding and impairing the function of an evolutionarily closely related BMP sub-group consisting of BMP5, BMP6 and BMP7. These findings indicate that ERFE can act as a natural ligand trap generated by stimulated erythropoiesis in order to regulate availability of iron. Disclosures Arezes: Pfizer: Research Funding. Foy:Pfizer: Employment. McHugh:Pfizer: Research Funding. Sawant:Pfizer: Employment. Benard:Pfizer: Employment. Quinkert:Pfizer: Research Funding. Terraube:Pfizer: Employment. Brinth:Pfizer: Employment. Tam:Pfizer: Employment. LaVallie:Pfizer: Employment. Cunningham:Pfizer: Employment. Lambert:Pfizer: Employment. Draper:Pfizer: Research Funding. Jasuja:Pfizer: Employment. Drakesmith:La Jolla Pharmaceutical Company: Research Funding; Pfizer: Research Funding; Alnylam: Consultancy; Kymab: Membership on an entity's Board of Directors or advisory committees.
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Than, Min Min, Pimpisid Koonyosying, Jetsada Ruangsuriya, Sunhawit Junrungsee, Chairat Uthaipibull et Somdet Srichairatanakool. « Effect of Recombinant Human Erythroferrone Protein on Hepcidin Gene (Hamp1) Expression in HepG2 and HuH7 Cells ». Materials 14, no 21 (28 octobre 2021) : 6480. http://dx.doi.org/10.3390/ma14216480.

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Iron is essential for all living organisms. It is strictly controlled by iron transporters, transferrin receptors, ferroportin and hepcidin. Erythroferrone (ERFE) is an iron-regulatory hormone which is highly expressed in erythroblasts by erythropoietin (EPO) stimulation and osteoblasts independently of EPO by sequestering bone morphogenetic proteins and inhibiting hepatic hepcidin expression. Although the hepcidin suppressive function of ERFE is known, its receptors still require investigation. Here, we aim to identify ERFE receptors on the HepG2 and Huh7 cells responsible for ERFE. Recombinant ERFE (rERFE) was first produced in HEK293 cells transfected with pcDNA3.1 + ERFE, then purified and detected by Western blot. The liver cells were treated with an rERFE-rich medium of transfected HEK293 cells and a purified rERFE-supplemented medium at various time points, and hepcidin gene (Hamp1) expression was determined using qRT-PCR. The results show that 37-kD rERFE was expressed in HEK293 cells. Hamp1 was suppressed at 3 h and 6 h in Huh7 cells after rERFE treatments (p < 0.05), then restored to the original levels. Hamp1 was activated after treatment with purified rERFE for 24 h and 48 h. Together, these results reveal that ERFE suppressed Hamp1 expression in liver cells, possibly acting on membrane ERFE receptor, which in Huh7 cells was more sensitive to the ERFE concentrate.
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Xu, Qingyu, Eva Altrock, Nanni Schmitt, Alexander Streuer, Felicitas Rapp, Verena Nowak, Julia Obländer et al. « In Silico Pan-Cancer Analysis Reveals Prognostic Role of the Erythroferrone (ERFE) Gene in Human Malignancies ». International Journal of Molecular Sciences 24, no 2 (15 janvier 2023) : 1725. http://dx.doi.org/10.3390/ijms24021725.

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The erythroferrone gene (ERFE), also termed CTRP15, belongs to the C1q tumor necrosis factor-related protein (CTRP) family. Despite multiple reports about the involvement of CTRPs in cancer, the role of ERFE in cancer progression is largely unknown. We previously found that ERFE was upregulated in erythroid progenitors in myelodysplastic syndromes and strongly predicted overall survival. To understand the potential molecular interactions and identify cues for further functional investigation and the prognostic impact of ERFE in other malignancies, we performed a pan-cancer in silico analysis utilizing the Cancer Genome Atlas datasets. Our analysis shows that the ERFE mRNA is significantly overexpressed in 22 tumors and affects the prognosis in 11 cancer types. In certain tumors such as breast cancer and adrenocortical carcinoma, ERFE overexpression has been associated with the presence of oncogenic mutations and a higher tumor mutational burden. The expression of ERFE is co-regulated with the factors and pathways involved in cancer progression and metastasis, including activated pathways of the cell cycle, extracellular matrix/tumor microenvironment, G protein-coupled receptor, NOTCH, WNT, and PI3 kinase-AKT. Moreover, ERFE expression influences intratumoral immune cell infiltration. Conclusively, ERFE is aberrantly expressed in pan-cancer and can potentially function as a prognostic biomarker based on its putative functions during tumorigenesis and tumor development.
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Miura, Shogo, Masayoshi Kobune, Soushi Ibata, Masahiro Yoshida, Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase et al. « CD34/EPO-R Double Positive MDS Cells Produce Erythroferrone in Response to Erythropoietin ». Blood 128, no 22 (2 décembre 2016) : 2455. http://dx.doi.org/10.1182/blood.v128.22.2455.2455.

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Abstract Background. It has been reported that iron absorption from gastrointestinal tract was enhanced in a subset of patients with myelodysplastic syndrome (MDS) exhibiting ineffective erythropoiesis. Iron absorption was achieved via an iron transporter ferroportin which was downregulated by hepcidin. Recently, three erythroid regulators such as growth differentiation factor 15 (GDF15), twisted gastrulation protein homolog 1 (TWSG1) and erythroferrone (ERFE) which down regulated hepatic hepcidin production has been identified. However, it has been not yet clarified which molecules could contribute to the increased iron absorption in patients with MDS. Materials and Methods. In the present study, we examined the expression level of GDF15, TWSG1 and ERFE mRNA during ex vivo erythroid differentiation from CD34+ bone marrow (BM) cells in the presence of 4 U/mL erythropoietin (EPO), 100 U/mL interleukin-3, 10 ng/mL stem cell factor, 20 ng/mL insulin-like growth factor (IGF)-1 and 500 micro g/mL iron-saturated transferrin. We further analyzed the expression level of GDF15 and ERFE in BM mononuclear cells (MNCs) derived from BM derived from MDS patients and lymphoma patients without BM involvement as a control by using quantitive RT-PCR. The expression of EPO-R was analyzed by flow cytometry. The CD34+ MDS cells were seeded on fibronectin substratum in 5 mL of a serum-free medium supplemented with 50 ng/mL human thrombopoietin (TPO), 10 ng/mL human SCF, 50 ng/mL human Fms-related tyrosin kinase 3 ligand (FLT3LG) and 100 ng/mL human delta like protein 4 (DLL4) with or without 4 U/mL EPO. For analysis of CD34+ cells, a GEO dataset (GSE58831) was downloaded as a matrix by GEOquery package (Bioconductor). The numerical data of the matrix were normalized by quantile normalization using limma package. Clinical and sequencing data were downloaded from supplementary materials. Those were combined with a GEO dataset (GSE58831) before analysis. Results. The level of ERFE mRNA was dramatically increased during erythroid differentiation from control CD34+ cells in response to EPO in vitro (Figure 1) although increase of the level of GDF15 and TWSG1 was marginal. Moreover, the level of ERFE mRNA in BM MNCs derived from MDS patients was significantly higher than that from control. Furthermore, the expression level of ERFE mRNA correlated with the percentage of CD34+ cells, but not percentage of erythroblasts derived from MDS patients. Using GEO data sets (GSE58831), the level of ERFE mRNA in CD34+ cells derived from MDS patients was significantly elevated as compared with that from healthy volunteers. Importantly, flow cytometric analysis indicated that CD34+ MDS cells highly expressed EPO receptors and the level of ERFE mRNA in CD34+ cells in a subset of MDS patients was enhanced after exposure of EPO ex vivo. In addition, the level of ERFE mRNA positively correlated with the level of EPO-R in CD34+ MDS cells (GSE58831). Conclusion. These results indicated that CD34+/EPO-R+ double positive MDS cells is one of the major sources of ERFN. The level of ERFE in CD34+ MDS cells may be associated with abnormal iron metabolism in MDS patients. These finding may be important for understanding the abnormal iron metabolism and predicting the efficacy of EPO administration. Disclosures No relevant conflicts of interest to declare.
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Preis, Anne [Verfasser], et Roland [Akademischer Betreuer] Beckmann. « Cryo-EM structures of eukaryotic translation termination and ribosome recycling complexes containing eRF1, eRF3 and ABCE1 / Anne Preis ; Betreuer : Roland Beckmann ». München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1213658837/34.

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Beißel, Christian [Verfasser]. « The RNA helicase Dbp5/DDX19 regulates the ribosomal entry of eRF1-eRF3 and Dom34-Hbs1 in translation termination and cytoplasmic mRNA quality control / Christian Beißel ». Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2020. http://d-nb.info/1233865706/34.

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Al-Jumaili, Diana. « Kulturelles Erbe in Gefahr ». Thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-206446.

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In den Diskussionen zu Globalisierung und Global Governance wird häufig darauf hingewiesen, dass Staaten und zwischenstaatliche Organisationen allein nicht in der Lage sind, die verstärkt auftretenden transnationalen Probleme zu lösen. Nichtregierungsorganisationen (NGOs) gelten als Hoffnungsträger, die Problemlösungskompetenzen beisteuern und die Legitimität internationaler Politik verbessern könnten. Obwohl die UNESCO bereits seit 1945 eine ausgeprägte und institutionalisierte Zusammenarbeit mit der Zivilgesellschaft pflegt, lassen viele politikwissenschaftliche Studien über die Einbeziehung von NGOs durch internationale Organisationen die UNESCO völlig unberücksichtigt. In Arbeiten zu globalen öffentlichen Gütern bleibt die UNESCO ebenso unter-belichtet. Der Fokus richtet sich vor allem auf Umwelt und Klima. Doch das Weltkulturerbe ist gleichfalls ein globales öffentliches Gut. Mit dem Welterbeprogramm ruft die UNESCO alle Menschen weltweit auf, auch die Kulturstätten anderer Völker als ihr eigenes kulturelles Erbe zu begreifen und sich für dessen Erhaltung einzusetzen. Seit der von der UNESCO initiierten Rettung der nubischen Kulturstätten in den 1960er Jahren etablierte sich ein spannendes transnationales Politikfeld – leider wenig beachtet von der Politikwissenschaft. Wird in Medien über das Welterbe berichtet, findet die UNESCO meist nur im Zusammenhang mit der Verleihung des Welterbetitels Erwähnung. Von der Öffentlichkeit kaum wahrgenommen, hat die UNESCO auch die Aufgabe, Welterbestätten zu überwachen und ggf. Hilfsprogramme zu initiieren. Diese Studienarbeit wird politikwissenschaftliches Licht auf die Interaktionen zwischen UNESCO und Zivilgesellschaft zum Schutze von gefährdetem Kulturerbe werfen. Dabei konzentriere ich mich auf die Notfallmaßnahmen für die Kulturgüter in Syrien, die seit Beginn der kriegerischen Auseinandersetzungen im Jahr 2011 massiv von Zerstörung und illegaler Entwendung bedroht sind. Eine umfassende Analyse aller Beziehungen zwischen NGOs und UNESCO im Rahmen der Arbeit ist unmöglich. Ich wählte deshalb die NGO ‚Heritage for Peace‘ aus, um an diesem Beispiel zu zeigen, aus welchen Gründen und in welchen Bereichen die UNESCO mit NGOs kooperiert bzw. welche Gründe dagegen sprechen. Theoretisch angeleitet wird die Arbeit von der Ressourcentausch-Theorie. Die Untersuchung beginne ich mit einer kurzen Darstellung des Kulturgutschutzes durch die UNESCO und der Situation, in der sich die syrischen Kulturgüter gegenwärtig befinden.
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Geitner, Daniel. « Der Erbe in der Insolvenz ». Hamburg Kovač, 2006. http://www.verlagdrkovac.de/978-3-8300-2636-5.htm.

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Geitner, Daniel. « Der Erbe in der Insolvenz / ». Hamburg : Kovač, 2007. http://www.verlagdrkovac.de/978-3-8300-2636-5.htm.

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Wziontek, Hartmut. « Zur Parametrisierung radialsymmetrischer Dichtemodelle für die Erde ». [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=970620179.

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Oehmichen, Grit. « Auf Satellitendaten basierende Ableitungen von Parametern zur Beschreibung terrestrischer Ökosysteme methodische Untersuchung zur Ableitung der Chlorophyll(a+b)- Konzentration und des Blattflächenindexes aus Fernerkundungsdaten / ». [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972662081.

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Sneeuw, Nicolaas. « A semi-analytical approach to gravity field analysis from satellite observations ». [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=960213988.

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Schröter, Michael W. « Mensch, Erde, Recht : Grundfragen ökologischer Rechtstheorie / ». Baden-Baden : Nomos-Verl.-Ges, 1999. http://www.gbv.de/dms/spk/sbb/recht/toc/267924720.pdf.

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Veit, Joachim. « Musikalisches Erbe im digitalen Zeitalter : Einführung ». Bärenreiter Verlag, 2012. https://slub.qucosa.de/id/qucosa%3A71878.

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Livres sur le sujet "ERFE"

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Drewermann, Eugen. Der tödliche Fortschritt : Von der Zerstörung der Erde und des Menschen im Erbe des Christentums. 4e éd. Regensburg : Pustet, 1986.

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Der tödliche Fortschritt : Von der Zerstörung der Erde und des Menschen im Erbe des Christentums. 6e éd. Regensburg : Pustet, 1990.

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Tibbetts, Jean. Erte ́. London : Bison Books, 1995.

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Stull, James B. Erie. Charleston, S.C : Arcadia Pub., 2011.

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Stull, James B. Erie. Charleston, S.C : Arcadia Pub., 2011.

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Bjøl, Erling. Fra magtens korridorer : Erindringer fra 60'erne, 70'erne & 80'erne. København : Politikens forlag, 1994.

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Leben mit der Erde : Der Jahreslauf der Erde ; Erde des Mesokosmos ; Erde, Wasser, Luft und Feuer. Stuttgart : Urachhaus, 1993.

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1953-, Mai Anne-Marie, dir. Prosa fra 80'erne til 90'erne. Copenhagen Valby : Borgen, 1994.

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1953-, Mai Anne-Marie, dir. Prosa fra 80'erne til 90'erne. Copenhagen Valby : Borgen, 1994.

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Grass, Günter. Gebrannte Erde. Göttingen : Steidl, 2002.

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Chapitres de livres sur le sujet "ERFE"

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Vedder, Ulrike. « Erbe ». Dans Stifter-Handbuch, 334–38. Stuttgart : J.B. Metzler, 2017. http://dx.doi.org/10.1007/978-3-476-05377-0_45.

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Hahn, Heidi, et Otto Hahn. « Erde ». Dans Notruf aus der Arche, 129–68. Basel : Birkhäuser Basel, 1990. http://dx.doi.org/10.1007/978-3-0348-5230-2_5.

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Posypaiko, V. I., et E. A. Alekseeva. « ErF3 ». Dans Phase Equilibria in Binary Halides, 169–70. Boston, MA : Springer US, 1987. http://dx.doi.org/10.1007/978-1-4684-9024-4_51.

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Römer, Thomas, et Vera Zingsem. « Erde ». Dans Wanderer am Himmel, 88–111. Berlin, Heidelberg : Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-642-55343-1_6.

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Oldham, Keith B., Jan C. Myland et Jerome Spanier. « The Error Function erf(x) and Its Complement erfc(x) ». Dans An Atlas of Functions, 405–15. New York, NY : Springer US, 2008. http://dx.doi.org/10.1007/978-0-387-48807-3_41.

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Bährle-Rapp, Marina. « Ägyptische Erde ». Dans Springer Lexikon Kosmetik und Körperpflege, 14. Berlin, Heidelberg : Springer Berlin Heidelberg, 2007. http://dx.doi.org/10.1007/978-3-540-71095-0_265.

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Matthes, Siegfried. « Die Erde ». Dans Mineralogie, 441–52. Berlin, Heidelberg : Springer Berlin Heidelberg, 2001. http://dx.doi.org/10.1007/978-3-662-08768-8_14.

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Matthes, Siegfried. « Die Erde ». Dans Mineralogie, 433–44. Berlin, Heidelberg : Springer Berlin Heidelberg, 1996. http://dx.doi.org/10.1007/978-3-662-08769-5_15.

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Matthes, Siegfried. « Die Erde ». Dans Mineralogie, 384–95. Berlin, Heidelberg : Springer Berlin Heidelberg, 1987. http://dx.doi.org/10.1007/978-3-662-08771-8_27.

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Schwanke, Karsten, Nadja Podbregar, Dieter Lohmann et Harald Frater. « Die Erde ». Dans Landschaftsformen, 34–59. Berlin, Heidelberg : Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-642-01313-3_2.

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Actes de conférences sur le sujet "ERFE"

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Tsukiji, Tetsuhiro, Shigeaki Saito, Yoshinobu Asako et Toshihiro Kawakami. « Shear Stress of ER Suspensions ». Dans ASME 1998 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1998. http://dx.doi.org/10.1115/imece1998-0459.

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Abstract The shear stresses of ER (Electro-rheological) suspensions are measured by changing a shear rate, amplitude and frequency of electric fields using rotational viscometer whose gap between electrodes can be changed. We use two ER suspensions which are called ERFC and ERFP. ERFC consist of cellulose suspended in silicone oil. The size of cellulose particles is typically about 10∼20 μm and a viscosity of silicone oil is 10mm2/s. Cellulose concentration is 20wt.% and the percentage of moisture content is 0.6%. ERFP contains highly sulfonated poly (styrene-co-divinylbenzene) particles. An average particle diameter of ERFP is 9 microns and the water content is 2.0 wt.%. Unipolar sine-wave electric fields which is AC with DC bias and bipolar sine-wave electric fields without DC bias are used. The shear rates of 400 s−1 are employed. Amplitudes of the electric fields are 0.4 and 0.8 kV/mm and DC component is 1.0 kV/mm for unipolar sine-wave electric fields. Amplitudes are between 1.0 and 2.5 kV/mm for bipolar sine-wave electric fields. The frequency of the electric fields is changed from 0.1 to 100 Hz. Dependence of the shear stress on electrical excitation frequency is investigared.
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Khanicheh, Azadeh, Andrew Muto, Christina Triantafyllou, Brian Weinberg, Loukas Astrakas, Aria Tzika et Constantinos Mavroidis. « MR Compatible ERF Driven Hand Device for Rehabilitation After Stroke ». Dans ASME 2005 International Mechanical Engineering Congress and Exposition. ASMEDC, 2005. http://dx.doi.org/10.1115/imece2005-82283.

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This paper presents the design, fabrication and testing of a novel, one degree of freedom, magnetic resonance (MR) compatible, computer controlled, variable resistance hand device that will be used in fMRI studies of the brain and motor performance during rehabilitation after stroke. The device consists of four major subsystems: a) the Electro-Rheological Fluid (ERF) resistive element; b) the gearbox; c) the handles and d) the sensors: one optical encoder and one force sensor was implemented into the device design to measure the patient induced motion and force, respectively. A key feature of the device is the use of electro rheological fluids (ERF) to achieve resistive force generation. ERFs are fluids that experience dramatic changes in rheological properties, such as viscosity or yield stress, in the presence of an electric field. Using the electrically controlled rheological properties of ERFs, compact resistive elements with an ability to supply high resistive torques in a controllable and tunable fashion, have been developed. The hand device is designed to resist up to 50% of maximum level of gripping force of a human hand and be controlled in real time. Our study demonstrates that there is neither an effect from MR environment on the ERF properties and performance of the sensors, nor significant degradation on MR images by the introduction of ERF driven hand device in the MR environment. The results are encouraging in combining functional Magnetic Resonance Imaging methods, with MR compatible robotic devices for improved effectiveness of rehabilitation therapy.
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Fisch, Avi, Jason Nikitczuk, Brian Weinberg, Juan Melli-Huber, Constantinos Mavroidis et Charles Wampler. « Development of an Electro-Rheological Fluidic Actuator and Haptic Systems for Vehicular Instrument Control ». Dans ASME 2003 International Mechanical Engineering Congress and Exposition. ASMEDC, 2003. http://dx.doi.org/10.1115/imece2003-43514.

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Force-feedback methanisms have been designed to simplify and enahance the human-vehicle interface. The increase in secondary controls within vehicle cockpits has created a desire for a simpler, more efficient human-vehicle interface. Haptic system, or systems that interact with the operator’s sense of touch, can be used to consolidate various controls into fever, haptic feedback control devices, so that information can be transmitted to the operator and the operator can change control settings without requiring the driver’s visual attention. In this paper an Electro-Rheological Fluid (ERF) based actuator and mechanisms are presented that provide haptic feedback. ERSs are fluids that change their viscosity in response to an electric field. Using the electrically controlled rheological properties of ERFs, haptic devices have been developed that can resist human operator forces in a controlled and tunable fashion. The design of an ERF-based actuator and its application to a haptic knob and haptic joystick is presented. The analytical model is given, analyses are performed, and experimental systems and data are presented for the actuator. Conceptual methods for the application to the haptic devices are presented.
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Prezza, Nicola, Cristian Del Fabbro, Francesco Vezzi, Emanuale De Paoli et Alberto Policriti. « ERNE-BS5 ». Dans the ACM Conference. New York, New York, USA : ACM Press, 2012. http://dx.doi.org/10.1145/2382936.2382938.

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Barkstrom, Bruce R. « Earth radiation budget measurements : pre-ERBE, ERBE, and CERES ». Dans Orlando '90, 16-20 April, sous la direction de Bruce R. Barkstrom. SPIE, 1990. http://dx.doi.org/10.1117/12.21364.

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« Erle Shobert Award ». Dans 2013 IEEE 59th Holm Conference on Electrical Contacts (Holm 2013). IEEE, 2013. http://dx.doi.org/10.1109/holm.2013.6651387.

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Schmoll, Friedemann. « Erbe, Altpapier, Archiv ? » Dans Forschungsdesign 4.0 Datengenerierung und Wissenstransfer in interdisziplinärer Perspektive. Jens Klingner ; Merve Lühr, 2020. http://dx.doi.org/10.25366/2019.06.

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« Erle Shobert Prize Paper ». Dans Electrical Contacts 2007. 53rd IEEE Holm Conference on Electrical Contacts. IEEE, 2007. http://dx.doi.org/10.1109/holm.2007.4318184.

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« ERLE SHOBERT PRIZE PAPER ». Dans 2008 Proceedings of the 54th IEEE Holm Conference on Electrical Contacts. IEEE, 2008. http://dx.doi.org/10.1109/holm.2008.ecp.11.

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« Erle Shobert Prize Paper ». Dans 2015 IEEE 61st Holm Conference on Electrical Contacts (Holm). IEEE, 2015. http://dx.doi.org/10.1109/holm.2015.7354946.

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Rapports d'organisations sur le sujet "ERFE"

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Manlutac, Janice Ian. Funding the Frontline : How an Oxfam Emergency Response Fund facilitated local humanitarian action. Oxfam, avril 2021. http://dx.doi.org/10.21201/2021.7451.

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From 2014 to 2020 Oxfam embedded an Emergency Response Fund (ERF) in its multiyear disaster risk reduction programs in Asia-Pacific and Central America. The Oxfam ERF was designed as a flexible funding mechanism to prioritize small-scale, under-the-radar, and forgotten emergencies and help local actors respond to and mitigate the impacts of disasters in their communities. ERF grants totaling US$1.9 million were disbursed and supported 24 small-scale responses led by 15 local organizations in nine countries. The ERF, through the support of a donor who values local leadership, helped local actors shape humanitarian responses, and the simplicity of fund administration unlocked creativity and delivered speed without compromising the quality and accountability of humanitarian aid.
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Ackerman, Aidan, Maria Bellalta et Jaryd McGonagle. Erie Street Plaza. Landscape Architecture Foundation, 2013. http://dx.doi.org/10.31353/cs0430.

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Powell, Bonnie, Colin Endsley, Stanley Young, Andrew Duvall, Josh Sperling et Rick Grahn. Fort Erie On-Demand Transit Case Study. Office of Scientific and Technical Information (OSTI), janvier 2023. http://dx.doi.org/10.2172/1908698.

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Cushman, D. Agriculture actions to reduce phosphorus to Lake Erie. Natural Resources Canada/ESS/Scientific and Technical Publishing Services, 2017. http://dx.doi.org/10.4095/299767.

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Söding, Emanuel. Die Dateninfrastruktur (DIS)-Erhebung im Forschungsbereich Erde und Umwelt der Helmholtz-Gemeinschaft : Erste Ergebnisse und Schlussfolgerungen. HMC Office, GEOMAR Helmholtz Centre for Ocean Research Kiel, 2022. http://dx.doi.org/10.3289/hmc_publ_06.

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Die Anschlussfähigkeit bestehender Helmholtz-Dateninfrastrukturen an nationale und internationale Initiativen (z.B. NFDI, EOSC und andere), ist ein wichtiges zentren-übergreifendes Ziel der Helmholtz- Gemeinschaft. Dafür ist es entscheidend, die bestehenden Zusammenhänge der Forschungsdaten- erhebenden und -nachnutzenden sowie die Dateninfrastrukturen (DIS) entlang der FAIR-Prinzipien1 zu ordnen. Ziel dieser Erhebung ist es, einen Überblick über bestehende Praktiken und Entwicklungs- stände der Dateninfrastrukturen (DIS) in der Helmholtz Gemeinschaft im Bereich Erde und Umwelt zu erhalten, um eine konsistente Strategie zur Umsetzung eines FAIRen Datenraumes entwickeln zu können.
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Beiswanger, Robert C. Daemen Alternative Energy/Geothermal Technologies Demonstration Program, Erie County. Office of Scientific and Technical Information (OSTI), février 2013. http://dx.doi.org/10.2172/1352059.

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Kaseman, Derrick. ERDE : THE EARTH-FIELD RESONANCE DETECTION AND EVALUATION DEVICES. Office of Scientific and Technical Information (OSTI), mars 2021. http://dx.doi.org/10.2172/1773303.

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Grace, Peter J. Investigation of Breakwater Stability at Presque Isle Peninsula Erie, Pennsylvania. Fort Belvoir, VA : Defense Technical Information Center, mai 1989. http://dx.doi.org/10.21236/ada208528.

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Rogers, D. R., et D. F. Dunning. Focused risk assessment : Mound Plant, Miami-Erie Canal Operable Unit 4. Office of Scientific and Technical Information (OSTI), septembre 1994. http://dx.doi.org/10.2172/10190107.

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Morang, Andrew, et Jeffrey Melton. Beach Erosion and Sediment Processes Study, North East Marina, Erie County, Pennsylvania. Fort Belvoir, VA : Defense Technical Information Center, juin 2001. http://dx.doi.org/10.21236/ada396033.

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