The DOI matches its Crossref record; 213 of the 213 references it cites were found in a registry or an index; 3 of the 179 sources its claims cite were checked for support.
Forging a field: the golden age of iron biology.
Open accessAbstract
Oh what a difference a decade makes! In a landmark paper published in 1996, Feder and colleagues identified the long-sought gene mutated in patients with classical hereditary hemochromatosis. In many ways, this seemed to ignite an explosion in iron biology which, over the next 10 years, led to a
Overview
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Written from the paper’s full text.
TL;DR
This review traces the “golden age” of iron biology from 1958 to 2008, emphasizing molecular discoveries in iron transport, regulation, and disease. It argues that understanding hepcidin/ferroportin regulation unified the pathophysiology of hemochromatosis, iron deficiency anemia, and anemia of chronic disease.
Key findings
- Ferritin is a 24-subunit cage that can hold up to 4500 iron atoms, while transferrin transports iron in plasma; both keep iron nonreactive and are used clinically in iron-status assays.
- The IRE/IRP posttranscriptional system regulates ferritin and TFR1: IRP binding blocks ferritin translation under low iron, whereas 3′ IRE binding protects TFR1 mRNA from degradation.
- Hepcidin, a 25-amino-acid liver peptide, binds ferroportin and triggers its internalization and lysosomal degradation, reducing serum iron; hemochromatosis is classified into 3 classes affecting the hepcidin/ferroportin axis.
- Iron deficiency anemia is estimated to affect 3 billion people worldwide; IRIDA patients fitting strict criteria carried inactivating TMPRSS6 mutations, and mutations in DMT1 or GLRX5 cause rare autosomal recessive microcytic anemia.
Methods
- Narrative review of iron biology from the birth of ASH in 1958 to 2008, focusing on physiology and inherited/acquired iron disorders.
- Synthesizes ferrokinetic studies, molecular biology, positional cloning, targeted mouse mutants, zebrafish mutants, and human genetic/clinical observations.
- No systematic search, meta-analysis, or new primary data are reported.
Limitations
- Stated by the author: important areas are neglected, including mitochondrial iron metabolism, heme metabolism, brain iron accumulation in neurodegenerative disorders, Fe-S cluster formation, therapeutic chelation, classical ferrokinetics, microbial iron metabolism, and structural characterizations.
- Stated by the author: topic choice reflects personal expertise and a focus on diseases that have only recently become understood, not a judgment of importance.
- Evident from the text: as a narrative review, it lacks systematic methods, quantitative synthesis, and formal assessment of evidence quality.
Model-written summary. Check it against the paper before relying on it.
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Verification
Claims the paper makes
115 Not checked yet · 19 Own interpretation · 2 No basis given · 1 Supported · 1 Supported so far · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The functional effects of altered hepcidin expression in vivo were apparent when Nicolas, Lesbordes-Brion, and colleagues showed that inactivation of the hepcidin gene in mice was associated with severe iron overload.101,102”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
- Not checked yetcites [101] Nicolas, 2001, Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice., Proc Natl Acad Sci U S A source
- Supportedcites [102] Lesbordes-Brion, 2006, Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis., Blood source
The Abstract reports that mice with targeted deletion of hepcidin 1 developed early, severe iron overload in multiple organs. The Results and discussion further document substantial iron accumulation in the liver, pancreas, and heart of Hepc1-knockout mice compared with controls. (LLM, conf=0.95)
plainstates an association- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“Accordingly, Roy and colleagues have developed a transgenic mouse model expressing hepcidin, which shows that most consistent features of the anemia of chronic disease can be attributed to increased hepcidin expression.104”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
What the sources say
- Supportedcites [104] Roy, 2007, Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation., Blood source
The Discussion says the TRE.Hepc1 transgenic mice show key features of anemia of inflammation common to multiple patient groups. It also concludes that Hepc1 overexpression alone can produce anemia indistinguishable from anemia of inflammation. This supports the citing sentence’s attribution of those features to increased hepcidin expression. (LLM, conf=0.94)
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Supported
None of the sources cited for this claim have been checked yet.
In the paper
“Every patient who fit our strict criteria for IRIDA carried inactivating mutations in TMPRSS6 that could explain the disease.190,192”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [190] Finberg, 2008, Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)., Nat Genet source
- Not checked yetcites [192] Beutler, 2007, The Mask mutation identifies TMPRSS6 as an essential suppressor of hepcidin gene expression, required for normal uptake of dietary iron., [abstract] Blood
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“We and others have observed that some patients have congenital, iron-refractory, iron-deficiency anemia (IRIDA) that cannot be explained by mutations in the genes encoding DMT1, GLRX5, TF, or ceruloplasmin.[185][186][187][188][189][190]”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [185][186][187][188][189][190]
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“We found that the hepatocytelike cells of the adenomas expressed very high levels of hepcidin 100 and speculated that our results could be generalized-that induction of hepcidin expression in response to inflammation might explain the anemia of chronic disease.”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
What the sources say
- Not checked yetcites [100] Weinstein, 2002, Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease., Blood source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Transferrin was identified as an abundant plasma iron transport protein a decade later.4”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [4] Schade, 1946, An iron-binding component in human blood plasma., Science source
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In 1987, investigators observed that conserved sequences in the 5Ј untranslated regions (UTRs) of both H-and L-ferritin mRNAs were needed to control a ready but quiescent pool of ferritin mRNA in the cell, which could quickly be mobilized to produce ferritin protein when iron was abundant.22,23”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [22] Aziz, 1987, Iron regulates ferritin mRNA translation through a segment of its 5′-untranslated region., PNAS source
- Not checked yetcites [23] Hentze, 1987, A cis-acting element is necessary and sufficient for translational regulation of human ferritin expression in response to iron., Proc Natl Acad Sci U S A source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In a landmark paper published in 1996, Feder and colleagues identified the long-sought gene mutated in patients with classical hereditary hemochromatosis.”
§ Forging a field: the golden age of iron biology > Introduction
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, mutations in mitoferrin result in a clinical disorder that is very similar to erythropoietic protoporphyria caused by ferrochelatase mutations.17”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [17] Shaw, 2006, Mitoferrin is essential for erythroid iron assimilation., Nature source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Targeted disruption of the mouse gene encoding FLVCR demonstrated the importance of this protein in vivo.21”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [21] Keel, 2008, A heme export protein is required for red blood cell differentiation and iron homeostasis., Science source
boostedstates a cause- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 50
- Probably not a substantial claim. 17
None of the sources cited for this claim have been checked yet.
In the paper
“Initially, murine hepcidin mRNA was shown to be elevated in response to iron overload 92 and decreased in response to iron deficiency.99,100”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
- Not checked yetcites [92] Pigeon, 2001, A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload., J Biol Chem source
- Could not verifycites [99] Nicolas, 2002, The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation., J Clin Invest sourceExperimental — accuracy not yet measured
The citation is attached to the claim that hepcidin mRNA decreases in response to iron deficiency. In the section “Hepcidin gene expression is decreased after experimentally induced anemia,” the paper reports decreased hepcidin in anemic mice but says their liver iron was unchanged or increased, not deficient. Our copy does not establish hepcidin’s response to iron deficiency itself. (LLM, conf=0.78)
- Not checked yetcites [100] Weinstein, 2002, Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease., Blood source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“With Weinstein, Roy, and colleagues, we observed that these patients also develop anemia resembling the anemia of chronic disease, the severity of which correlates directly with the extent of tumor burden.100”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
What the sources say
- Not checked yetcites [100] Weinstein, 2002, Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease., Blood source
plainstates an association- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“These individuals appear to have a defect in cellular iron export, 191 but the disorder has an autosomal recessive pattern of inheritance and no mutations have been detected in ferroportin or in the regulatory regions of the hepcidin gene.190”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [190] Finberg, 2008, Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)., Nat Genet source
- Not checked yetcites [191] Andrews, 1999, Commentary on: ferrokinetics in the syndrome of familial hypoferremic microcytic anemia with iron malabsorption., J Pediatr Hematol Oncol source
hedged- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Recently, however, Quigley and colleagues 20 have described a heme exporter, FLVCR, which appears to be necessary for normal erythroid development.”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [20] Quigley, 2004, Identification of a human heme exporter that is essential for erythropoiesis., Cell source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Ferritin is also the precursor to hemosiderin, a heterogeneous aggregate of iron, lysosomal components, and other products of intracellular digestion.8”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [8] Wixom, 1980, Hemosiderin: nature, formation and significance., Int Rev Exp Pathol
plainstates a cause- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In 1937, horse spleen ferritin was the second of all proteins to be crystallized.3”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [3] Laufberger, 1937, Sur la cristallisation de la ferritine., Soc Chim Biol
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Targeted disruption of the Tfr1 gene in mice demonstrated that most tissues develop normally without Tfr1, but erythroid precursors, early lymphoid cells, and neuroepithelial cells require Tfr1 for differentiation.18,19”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
boostedstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“FLVCR-null mice had a failure of definitive erythropoiesis, resulting in fetal demise.”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [21] Keel, 2008, A heme export protein is required for red blood cell differentiation and iron homeostasis., Science source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Both STEAP3 and DMT1 were discovered through positional cloning of genes altered in rodents carrying spontaneous mutations impairing iron transport.10,11”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [10] Ohgami, 2005, Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells., Nat Genet source
- Not checked yetcites [11] Fleming, 1998, Nramp2 is mutated in the anemic Belgrade 11. (b) rat: evidence of a role for Nramp2 in endosomal iron transport., Proc Natl Acad Sci U S A source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The mitochondrial iron importer was recently identified as mitoferrin (also known as SLC25A37), a transmembrane protein that plays a critical role in supplying iron to ferrochelatase for insertion into protoporphyrin IX.”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [16] Foury, 2002, Deletion of the mitochondrial carrier genes MRS3 and MRS4 suppresses mitochondrial iron accumulation in a yeast frataxin-deficient strain., J Biol Chem source
- Not checked yetcites [17] Shaw, 2006, Mitoferrin is essential for erythroid iron assimilation., Nature source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Liberated inorganic iron is then reduced by the ferrireductase STEAP3 to Fe 2ϩ , 10 which is the substrate for transmembrane transport by divalent metal transporter 1 (DMT1 or SLC11A2, formerly called NRAMP2, DCT1).”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [10] Ohgami, 2005, Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells., Nat Genet source
- Not checked yetcites [11] Fleming, 1998, Nramp2 is mutated in the anemic Belgrade 11. (b) rat: evidence of a role for Nramp2 in endosomal iron transport., Proc Natl Acad Sci U S A source
- Not checked yetcites [12] Fleming, 1997, Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene., Nat Genet source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Ferritin, which has homologs in all organisms except yeast, is a cagelike heteropolymer of 24 subunits of H-(heavy or heart) and L-(light or liver) types, which can hold up to 4500 iron atoms.5”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [5] Harrison, 1967, Ferric oxyhydroxide core of ferritin., Nature source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mitoferrin was originally discovered in yeast (called MRS3/MRS4 16 ) and in a mutant zebrafish.17”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [16] Foury, 2002, Deletion of the mitochondrial carrier genes MRS3 and MRS4 suppresses mitochondrial iron accumulation in a yeast frataxin-deficient strain., J Biol Chem source
- Not checked yetcites [17] Shaw, 2006, Mitoferrin is essential for erythroid iron assimilation., Nature source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“When the FLVCR gene was inactivated after birth the animals developed severe, macrocytic anemia, implying that heme export is important for normal erythropoiesis.”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [21] Keel, 2008, A heme export protein is required for red blood cell differentiation and iron homeostasis., Science source
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Ferritin, which has homologs in all organisms except yeast, is a cagelike heteropolymer of 24 subunits of H-(heavy or heart) and L-(light or liver) types, which can hold up to 4500 iron atoms.5”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [5] Harrison, 1967, Ferric oxyhydroxide core of ferritin., Nature source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Ferritin receptors are present on lymphocytes and some other cell types, but their physiologic function has not been fully defined.7”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [7] Chen, 2005, TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis., J Exp Med source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Gunshin 13 and Hediger 15 showed that DMT1 is electrogenic, requiring proton cotransport to move Fe 2ϩ across the membrane.”
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
What the sources say
- Not checked yetcites [13] Gunshin, 1997, Cloning and characterization of a mammalian proton-coupled metal-ion transporter., Nature source
- Not checked yetcites [15] Sacher, 2001, Properties of the mammalian and yeast metal-ion transporters DCT1 and Smf1p expressed in Xenopus laevis oocytes., J Exp Biol source
boostedstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“The IRE/IRP regulatory system is also used to control expression of other proteins.The best studied is TFR1, which has multiple IREs in the 3Ј UTR of its mRNA.39”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [39] Casey, 1989, Iron regulation of transferrin receptor mRNA levels requires iron-responsive elements and a rapid turnover determinant in the 3′ untranslated region of the mRNA., EMBO J source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“At the time of its discovery, IRP1 was recognized to bear strong similarity to aconitase, a mitochondrial enzyme of the tricarboxylic acid cycle.Remarkably, IRP1 also has aconitase activity, making it a prime candidate for a previously described cytoplasmic aconitase.29,30”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [29] Hentze, 1991, Homology between IRE-BP, a regulatory RNA-binding protein, aconitase, and isopropylmalate isomerase., Nucleic Acids Res source
- Not checked yetcites [30] Kaptain, 1991, A regulated RNA binding protein also possesses aconitase activity., Proc Natl Acad Sci U S A source
boostedstates an association- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because there is no regulated excretion of iron through the liver or kidneys, iron balance is primarily controlled at the level of intestinal absorption.”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
plainstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: In nontransfused individuals, iron enters the body exclusively through the diet.
- Rests on an assumption: There is no regulated excretion of iron through the liver or kidneys.
None of the sources cited for this claim have been checked yet.
In the paper
“CYBRD1 was one of 2 iron transport-related molecules discovered by McKie through a very productive RNA subtraction approach.53,54”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [53] McKie, 2001, An iron-regulated ferric reductase associated with the absorption of dietary iron., Science source
- Not checked yetcites [54] McKie, 2000, A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation., Mol Cell source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The sole mammalian homolog of DMT1, designated NRAMP1 for natural resistance associated macrophage protein 1, was identified by Vidal et al through positional cloning of a mouse locus involved in host defense against intracellular pathogens in mouse macrophages.60”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [60] Vidal, 1993, Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg., Cell source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“There is a siderophore-like iron uptake pathway mediated by lipocalin-2 (also called NGAL, 24p3) but its physiologic role is not fully worked out.”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [74] Goetz, 2002, The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition., Mol Cell source
- Not checked yetcites [75] Yang, 2002, An iron delivery pathway mediated by a lipocalin., Mol Cell source
- Not checked yetcites [76] Devireddy, 2005, A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake., Cell source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Haile and Rouault showed that the aconitase activity of IRP1 is present only when the iron-sulfur cluster is complete; when it is not, IRP1 acts as an RNA binding protein, recognizing IREs.31”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [31] Haile, 1992, Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: role of the iron-sulfur cluster., Proc Natl Acad Sci U S A source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Targeted disruption of the murine gene encoding DMT1 confirmed that DMT1 is the primary transmembrane iron transporter bringing dietary nonheme iron into intestinal epithelial cells and mediating iron uptake through the transferrin cycle in erythroid precursors.66”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [66] Gunshin, 2005, Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver., J Clin Invest source
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast, targeted disruption of IRP2 leads to a disorder of iron homeostasis characterized by microcytic, hypochromic anemia, 42,43 and, at least in one laboratory, a late onset neurodegenerative disorder.42,44,45”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [42] Cooperman, 2005, Microcytic anemia, erythropoietic protoporphyria and neurodegeneration in mice with targeted deletion of iron regulatory protein 2., Blood source
- Not checked yetcites [43] Galy, 2005, Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2)., Blood source
- Not checked yetcites [44] LaVaute, 2001, Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice., Nat Genet source
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“DMT1 may also serve as a physiologically significant portal of entry for other divalent metal cations including Mn 2ϩ , Co 2ϩ , Zn 2ϩ , Cu 2ϩ , and Pb 2ϩ , though its importance has only been definitively established for Fe 2ϩ in vivo.13”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [13] Gunshin, 1997, Cloning and characterization of a mammalian proton-coupled metal-ion transporter., Nature source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“At the time, 6 strains had been identified; all are now understood in molecular detail.14”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [14] Andrews, 2000, Iron homeostasis: insights from genetics and animal models., Nat Rev Genet source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“NRAMP1 is expressed in phagosomes of professional phagocytes.61”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [61] Gruenheid, 1997, Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome., J Exp Med source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Surprisingly, although Cybrd1 expression is markedly induced in iron-deficient animals, targeted disruption of the murine Cybrd1 gene was not associated with any apparent phenotype in mice fed standard chow.55”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [55] Gunshin, 2005, Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice., Blood
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Beaumont and colleagues 48 showed that disruption of the L-ferritin IRE results in hyperferritinemia-cataract disease, with prominent ocular findings and elevated serum ferritin but no evidence of disturbed iron homeostasis.”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [48] Beaumont, 1995, Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinemia and cataract., Nat Genet source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Under low iron conditions IRP2 accumulates, but when iron is abundant it triggers IRP2 degradation.”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [32] Guo, 1995, Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome., J Biol Chem source
- Not checked yetcites [33] Iwai, 1995, Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2., EMBO J source
- Not checked yetcites [34] Iwai, 1998, Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins., Proc Natl Acad Sci U S A source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“HFE is an atypical major histocompatibility class I-like molecule that forms a heterodimer with 2-microglobulin but is incapable of binding a small peptide.145”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [145] Lebron, 1998, Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor., Cell source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, penetrance of HFE hemochromatosis is incomplete, and only a fraction of affected patients have clinical disease, presumably due to both genetic and environmental modifiers. 122”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [122] Allen, 2008, Iron-overload-related disease in HFE hereditary hemochromatosis., N Engl J Med source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, more recent results suggest a different scenario: that TFR1 regulates HFE activity and inhibits HFE by sequestering it.149”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [149] Schmidt, 2008, The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression., Cell Metab source
hedgedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, the amount of hepcidin mRNA in liver cells is decreased in response to hypoxia and ineffective erythropoiesis (overlapping with the response to iron deficiency) 99,105 and induced in response to treatment with lipopolysaccharide or by inflammation of other etiologies.92,99”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
- Not checked yetcites [99] Nicolas, 2002, The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation., J Clin Invest source
- Not checked yetcites [105] Adamsky, 2004, Decreased hepcidin mRNA expression in thalassemic mice., Br J Haematol source
- Not checked yetcites [92] Pigeon, 2001, A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload., J Biol Chem source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several modifier gene candidates have been explored and, in some cases, verified.”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [123] Levy, 2000, Genes that modify the hemochromatosis phenotype in mice., J Clin Invest source
- Not checked yetcites [124] Sachot, 2001, Low penetrant hemochromatosis phenotype in eight families: no evidence of modifiers in the MHC region., Blood Cells Mol Dis source
- Not checked yetcites [125] Sproule, 2001, Naturally variant autosomal and sex-linked loci determine the severity of iron overload in beta 2-microglobulin-deficient mice., Proc Natl Acad Sci U S A source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As a consequence, intestinal iron absorption and macrophage iron release are not properly controlled, leading to iron overload, increased serum iron, and iron deposition in the liver, heart, and endocrine tissues.”
§ Forging a field: the golden age of iron biology > Hemochromatosis
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Three classes of hemochromatosis disorders all affect the hepcidin/ferroportin regulatory axis: Class I, defects in the hepcidin gene (HAMP) preventing production of functional hepcidin; Class II, defects in HFE, TFR2, or HFE2 genes preventing normal hepatic regulation of hepcidin expression; Class III, defects in ferroportin preventing normal regulation by hepcidin.”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accordingly, human iron disorders are invariably disorders of iron balance or iron distribution.”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Hepcidin binds to cell-surface ferroportin, triggering its tyrosine phosphorylation, internalization, and ubiquitin-mediated degradation in lysosomes.93,94”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both events have the same consequence-decreased serum iron.”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nonetheless, BMP treatment is a potent stimulus for hepcidin expression both in cultured cells 113,114,116,117 and in animals.”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
- Not checked yetcites [113] Wang, 2005, A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression., Cell Metab source
- Not checked yetcites [114] Babitt, 2006, Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression., Nat Genet source
- Not checked yetcites [116] Truksa, 2006, Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6., Proc Natl Acad Sci U S A source
boostedstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is particularly important in the intestine, where inactivation of basolateral ferroportin leads to retention of iron in the intestinal epithelium, and in iron-recycling macrophages of the reticuloendothelial system, where inactivation of ferroportin interrupts release of iron recovered from senescent red cells (Figure 2A).”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It has been detected and quantitated in urine samples, 91,96 and, with more difficulty, in serum.97”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
- Not checked yetcites [91] Park, 2001, Hepcidin, a urinary antimicrobial peptide synthesized in the liver., J Biol Chem source
- Not checked yetcites [96] Nemeth, 2003, Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein., Blood source
- Not checked yetcites [97] Kemna, 2007, Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications., Clin Chem source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The von Hippel-Lindau/hypoxia-inducible transcription factor (HIF) system also appears to control hepcidin expression, with HIF1␣ acting as a repressor when it binds to the hepcidin promoter.109”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
- Not checked yetcites [109] Peyssonnaux, 2007, Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)., J Clin Invest source
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Discovered independently by 3 laboratories and first reported in 2000 and 2001, hepcidin is a 25-amino-acid protein produced by processing of a larger precursor.”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
- Not checked yetcites [90] Krause, 2000, LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity., FEBS Lett source
- Not checked yetcites [91] Park, 2001, Hepcidin, a urinary antimicrobial peptide synthesized in the liver., J Biol Chem source
- Not checked yetcites [92] Pigeon, 2001, A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload., J Biol Chem source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The basolateral iron transporter, discovered simultaneously by 3 labs, is ferroportin (also called IREG1, MTP1, SLC39A1, and now SLC40A1).54,77,78”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [54] McKie, 2000, A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation., Mol Cell source
- Not checked yetcites [77] Abboud, 2000, A novel mammalian iron-regulated protein involved in intracellular iron metabolism., J Biol Chem source
- Not checked yetcites [78] Donovan, 2000, Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter., Nature source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The human patients have similar blood films and erythrocyte abnormalities, but also have hepatic iron overload that is not fully explained by their transfusion histories.[172][173][174][175][176]”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [172][173][174][175][176]
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mutations in the genes encoding DMT1 (SLC11A2) and glutaredoxin 5 (GLRX5) are associated with autosomal recessive hypochromic, microcytic anemia.171,172”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [171] Camaschella, 2007, The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload., Blood source
- Not checked yetcites [172] Mims, 2005, Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload., Blood source
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This disorder is typically seen in young women, is associated with gastric atrophy, and can be associated with other autoimmune phenomena.166,167”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [166] Carnicer, 1997, Helicobacter pylori gastritis and sideropenic refractory anemia., J Pediatr Gastroenterol Nutr source
- Not checked yetcites [167] Marignani, 1997, Reversal of long-standing iron deficiency anaemia after eradication of Helicobacter pylori infection., Scand J Gastroenterol source
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This disorder, hypotransferrinemia (also called atransferrinemia), has been observed in both human patients and in mice.[180][181][182][183]”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [180][181][182][183]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although both of these disorders are rare, each can be confused with hemochromatosis if the entire clinical picture is not taken into account.”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
plainstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because TF and HFE compete for binding to TFR1, displacement of HFE from TFR1 by TF may be a means to activate HFE to signal through an as-yet-unknown mechanism to increase hepcidin transcription.”
§ Forging a field: the golden age of iron biology > Hemochromatosis
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Through a different mechanism, deficiency of another major plasma protein, cerulopasmin, also causes mild iron deficiency anemia associated with iron accumulation in the liver and brain.184”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [184] Harris, 1995, Aceruloplasminemia: molecular characterization of this disorder of iron metabolism., Proc Natl Acad Sci U S A source
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, knockout mice heterozygous for a null ferroportin allele had no significant iron phenotype, and did not seem to model the human disease.79”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [79] Donovan, 2005, The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis., Cell Metab source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Elegantly described by Cartwright in a classic review, 194 this condition may be associated with infection, malignancy, organ failure, trauma, or other causes of inflammation.”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
What the sources say
- Not checked yetcites [194] Cartwright, 1966, The anemia of chronic disorders., Semin Hematol
hedgedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Although TFR2 is 43% homologous to TFR1 in its extracellular domain, it does not take up diferric-TF efficiently.152”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [152] Kawabata, 1999, Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family., J Biol Chem source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These proteins may be part of a larger BMP signaling complex along with hemojuvelin (P.J. Schmidt, F.W. Huang, and N.C.A., unpublished results).”
§ Forging a field: the golden age of iron biology > Hemochromatosis
hedgedstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“The anemia of chronic disease (also called anemia of inflammation) is an acquired disorder of iron homeostasis (reviewed in Roy and Andrews 193 ).”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
What the sources say
- Not checked yetcites Roy and Andrews 193
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Mutations in TFR2 are much less common than mutations in HFE, but the clinical disease can be indistinguishable.133”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [133] Camaschella, 2005, Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders., Blood source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mutations in the 5 genes currently associated with hemochromatosis probably do not account for all patients with the disease.”
§ Forging a field: the golden age of iron biology > Conclusions and future directions
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Mice expressing a hepcidin transgene are microcytic, similar to IRIDA.104”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
What the sources say
- Not checked yetcites [104] Roy, 2007, Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation., Blood source
plainstates an association- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
In nontransfused individuals, iron enters the body exclusively through the diet.
“In nontransfused individuals, iron enters the body exclusively through the diet.”
The paper relies on this without support.
There is no regulated excretion of iron through the liver or kidneys.
“Because there is no regulated excretion of iron through the liver or kidneys, iron balance is primarily controlled at the level of intestinal absorption.”
The paper relies on this without support.
Most dietary nonheme iron is in the ferric (Fe3+) form.
“Most dietary nonheme iron is in the ferric (Fe 3ϩ ) form.”
The paper relies on this without support.
Only iron exported across the basolateral membrane of the enterocyte is absorbed.
“Only iron exported across the basolateral membrane of the enterocyte is absorbed.”
The paper relies on this without support.
Hepcidin has primary responsibility for modulating iron availability to meet iron needs.
“In this context, we now know that hepcidin, a peptide hormone produced in the liver, has primary responsibility for modulating iron availability to meet iron needs.”
The paper relies on this without support.
All ferroportin mutations cause missense changes rather than truncations or frameshifts.
“Strikingly, all ferroportin mutations caused missense changes, rather than truncations or frameshifts.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Activation of signaling through the hemochromatosis protein HFE, TFR1, TFR2, or hemojuvelin (HJV), which acts as a co-receptor for bone morphogenetic protein 6 (BMP6), increases hepcidin transcription in a SMAD-dependent fashion.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [190]
Experimental — accuracy not yet measuredIn the citing paper
“Mammalian cellular immunity relies heavily on the action of macrophages, cells that also play a critical role in systemic Fe homeostasis [13].”
From Host Iron Withholding Demands Siderophore Utilization for Candida glabrata to Survive Macrophage Killing (2011) · cites this paper as [13]
In the citing paper
“The FPNC326Y disease-associated mutation results in a similar clinical outcome to that observed in patients carrying HFE mutations present in approximately 80% of HH patients and exhibiting an allelic frequency of over 10% in Caucasians of European descent [13].”
From Host Iron Withholding Demands Siderophore Utilization for Candida glabrata to Survive Macrophage Killing (2011) · cites this paper as [13]
In the citing paper
“In contrast, constitutively low hepcidin production in the liver, e.g. due to genetic defects in iron-signaling pathways, results in persistent hyperferremia and the development of hemochromatosis.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [190]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Forging a field: the golden age of iron biology > Cellular regulation of iron homeostasis
“Gunshin 13 and Hediger 15 showed that DMT1 is electrogenic, requiring proton cotransport to move Fe 2ϩ across the membrane.”
§ Forging a field: the golden age of iron biology > References
“15. Sacher A, Cohen A, Nelson N. Properties of the mammalian and yeast metal-ion transporters DCT1 and Smf1p expressed in Xenopus laevis oocytes.”
Citations
Cites
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R., Ellis, M. C., Fullan, A., et al. (1996) · Nature Genetics · doi:10.1038/ng0896-399 · Cited by 3,664
Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., & Hediger, M. A. (1997) · Nature · doi:10.1038/41343 · Cited by 3,166
Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion
Campuzano, V., Montermini, L., Moltò, M. D., Pianese, L., Cossée, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A., et al. (1996) · Science · doi:10.1126/science.271.5254.1423 · Cited by 2,786
Nemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., & Ganz, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420945 · Cited by 2,650
Hepcidin, a urinary antimicrobial peptide synthesized in the liver
Park, C. H., Valore, E. V., Waring, A. J., & Ganz, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008922200 · Cited by 2,168
Iron, brain ageing and neurodegenerative disorders
Zecca, L., Youdim, M. B. H., Riederer, P., Connor, J. R., & Crichton, R. R. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1537 · Cited by 1,801
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697
Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., et al. (2000) · Nature · doi:10.1038/35001596 · Cited by 1,667
Self-citationMcKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80425-6 · Cited by 1,422
Research works printed but not linked: 5
- Laufberger, 1937, Sur la cristallisation de la ferritine., Soc Chim Biol, 19, 1575
- Trousseau, 1865, Glycosurie; diabete sucre., Clinique medicale de l'Hotel-Dieu de Paris, 2, 663
- Blaud, 1832, Sur les maladies chlorotiques et sur un mode de traitement specifique dans ces affections., Rev Med Franc Etrang, 45, 357
- Faber, 1909, Achylia gastrica mit Anamie., Medizinishe Klinik, 5, 1310
- Heilmeyer, 1961, Congenital transferrin deficiency in a seven-year old girl., German Medical Monthly, 86, 1745
Cited by
Sorted by citations
The role of iron in brain ageing and neurodegenerative disorders
Ward, R. J., Zucca, F. A., Duyn, J. H., Crichton, R. R., & Zecca, L. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70117-6 · Cited by 1,819
Iron and cancer: more ore to be mined
Torti, S. V., & Torti, F. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3495 · Cited by 1,621
Metalloproteins and metal sensing
Waldron, K. J., Rutherford, J. C., Ford, D., & Robinson, N. J. (2009) · Nature · doi:10.1038/nature08300 · Cited by 1,269
Regulation of cellular iron metabolism
Wang, J., & Pantopoulos, K. (2011) · Biochemical Journal · doi:10.1042/bj20101825 · Cited by 986
Hepcidin and iron regulation, 10 years later
Ganz, T. (2011) · Blood · doi:10.1182/blood-2011-01-258467 · Cited by 962
Metadata
- Authors
- Andrews, N. C.
- Affiliations
- Duke University (US)
- Corresponding author
- Andrews, Nancy C.
- ORCID
- Andrews, Nancy C.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-07-15
- Volume
- 112
- Issue
- 2
- Pages
- 219-230
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2442739
- OpenAlex
- W2074040887
- Cited by
- 623
- References
- 213
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 19 · 2023: 9 · 2022: 31 · 2021: 29 · 2020: 31 · 2019: 25 · 2018: 27 · 2017: 28 · 2016: 36 · 2015: 27 · 2014: 31 · 2013: 52 · 2012: 49
- FWCI
- 8.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL051057)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK066373, R01DK053813, DK06637, DK053813)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- hereditary hemochromatosis, HFE gene, iron metabolism, iron overload
- MeSH terms
- Iron Deficiencies, Homeostasis, Humans, Iron, Iron Metabolism Disorders, Antimicrobial Cationic Peptides, Hepcidins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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