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
AI snapshot
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.
Integrity signals
Registry
Cites
Statistics
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.
- 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.
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.
- 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.
- 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.
- 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.
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.
- 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.
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.
- 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.
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.
- 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.
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.
- 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.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
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.
- 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.
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.
- 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.
In the paper
“Thermodynamic predictions indicated that the UTR sequences could form stable RNA hairpins with a characteristic secondary structure, termed iron responsive (or regulatory) elements (IREs).24”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [24] Casey, 1988, Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation., Science 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.
In the paper
“Perhaps surprisingly, targeted disruption of the IRP1 gene in mice produces no apparent phenotypic abnormalities.41”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [41] Meyron-Holtz, 2004, Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis., EMBO J 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.
In the paper
“After DMT1 was shown to serve as a transmembrane metal transporter, functional studies indicated that NRAMP1 had similar activity.62”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [62] Forbes, 2003, Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane., Blood source
hedgedstates 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies of non-transferrin bound iron uptake by cultured cells support this conclusion.”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [67] Barisani, 1995, Evidence for a low Km transporter for non-transferrin-bound iron in isolated rat hepatocytes., Am J Physiol
- Not checked yetcites [68] Inman, 1994, Extracellular ferrireductase activity of K562 cells is coupled to transferrin-independent iron transport., Biochemistry source
- Not checked yetcites [69] Kaplan, 1991, Regulation of the transferrin-independent iron transport system in cultured cells., J Biol Chem 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.
In the paper
“Surprisingly, however, most other cell types do not appear to require DMT1 for iron uptake.”
§ 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
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: passes — The paper gives a reason why it holds.
In the paper
“Interestingly, a mutation that prevents formation of the mouse ferroportin IRE causes an unusual and complex disorder of iron homeostasis, underscoring the significance of this IRE in vivo.50”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [50] Mok, 2004, Disruption of ferroportin 1 regulation causes dynamic alterations in iron homeostasis and erythropoiesis in polycythaemia mice., Development 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.
In the paper
“Disruption of the H-ferritin IRE in one Japanese family was associated with a familial iron overload disorder.49”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [49] Kato, 2001, A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload., Am J Hum Genet source
plainstates an associationSingle case- 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.
In the paper
“It must be reduced to ferrous (Fe 2ϩ ) iron, either chemically or through the action of a brush border ferrireductase such as duodenal cytochrome B (CYBRD1, also known as DCYTB), a cytochrome B561 homolog that may use ascorbic acid as a cofactor.53”
§ 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
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.
- Rests on an assumption: Most dietary nonheme iron is in the ferric (Fe3+) form.
In the paper
“However, aside from L-type calcium channels, which have some iron carrying capability, 73 no compelling candidates have been identified that transport iron atoms directly into cells.”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [73] Oudit, 2003, L-type Ca(2+) channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy., Nat Med 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.
In the paper
“One in particular, microcytic anemia (mk), had been carefully studied and shown to have a defect in intestinal iron absorption.52”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [52] Russell, 1970, Characterization and genetic studies of microcytic anemia in house mouse., Blood 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Soon afterward it was shown that cytoplasmic proteins, now known as iron regulatory proteins (IRPs, formerly IREBPs), recognize and bind to the IREs.”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [25] Caughman, 1988, The iron-responsive element is the single element responsible for iron-dependent translational regulation of ferritin biosynthesis: evidence for function as the binding site for a translational repressor., J Biol Chem source
- Not checked yetcites [26] Hentze, 1987, Identification of the iron-responsive element for the translational regulation of human ferritin mRNA., Science source
- Not checked yetcites [27] Leibold, 1988, Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5′ untranslated region of ferritin heavy- and light-subunit mRNAs., 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.
None of the sources cited for this claim have been checked yet.
In the paper
“The intestinal form of DMT1 is produced from a different mRNA splice isoform, resulting in an alternate C-terminus of the protein.57,58”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [57] Hubert, 2002, Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function., Proc Natl Acad Sci U S A source
- Not checked yetcites [58] Lam-Yuk-Tseung, 2005, Carboxyl-terminus determinants of the iron transporter DMT1/SLC11A2 isoform II (-IRE/1B) mediate internalization from the plasma membrane into recycling endosomes., Biochemistry 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.
None of the sources cited for this claim have been checked yet.
In the paper
“In spite of these obstacles and entirely by chance, the first mammalian transmembrane iron transporter was discovered simultaneously in 2 laboratories, located within a city block of each other in Boston, using singularly modern techniques.12,13”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
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.
In the paper
“Muckenthaler and colleagues showed that IRP binding sterically blocks recruitment of the small ribosomal subunit to the initiation complex, thus preventing translation.38”
§ Forging a field: the golden age of iron biology > Regulation of intracellular iron homeostasis
What the sources say
- Not checked yetcites [38] Muckenthaler, 1998, IRP-1 binding to ferritin mRNA prevents the recruitment of the small ribosomal subunit by the cap-binding complex eIF4F., Mol Cell 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.
In the paper
“Intestinal DMT1 is primarily localized to the apical membrane and to subapical endosomes.59”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [59] Canonne-Hergaux, 1999, Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron., 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Homologous proteins in yeast, 63 flies, 64 and zebrafish 65 also transport iron and similar divalent cations.”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [63] Supek, 1996, A yeast manganese transporter related to the macrophage protein involved in conferring resistance to mycobacteria., Proc Natl Acad Sci U S A source
- Not checked yetcites [64] Rodrigues, 1995, Malvolio, the Drosophila homologue of mouse NRAMP-1 (Bcg), is expressed in macrophages and in the nervous system and is required for normal taste behaviour., EMBO J source
- Not checked yetcites [65] Donovan, 2002, The zebrafish mutant gene chardonnay (cdy) encodes divalent metal transporter 1 (DMT1)., Blood 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.
In the paper
“Members of the STEAP ferrireductase family are also expressed in the intestine.56”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [56] Ohgami, 2006, The Steap proteins are metalloreductases., 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.
In the paper
“DMT1 expression is dramatically induced in iron deficiency, 13 and possibly regulated at a posttranscriptional level by a 3Ј IRE present in the splice isoform expressed in intestine.57”
§ 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
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.
In the paper
“It was one of the first genetic diseases to be linked to a discrete chromosomal position, through the groundbreaking work of Simon, an astute French physician-scientist who found that hemochromatosis patients were disproportionately likely to have particular HLA haplotypes.120”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [120] Simon, 1976, Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis., Gut 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.
In the paper
“Two decades later that insight led to the identification of HFE (originally called HLA-H), the gene mutated in the large majority of patients with hemochromatosis.121”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [121] Feder, 1996, A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis., 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.
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
“By removing ferroportin from the plasma membrane, hepcidin shuts off cellular iron export.”
§ 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.
In the paper
“Similarly, mouse models of hemochromatosis developed through targeted disruption of any of these 3 genes have diminished hepcidin mRNA in their livers.[140][141][142][143][144]”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [140][141][142][143][144]
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.
In the paper
“Targeted disruption of the murine ferroportin gene demonstrated its importance in both sites.79”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [79] Donovan, 2005, The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis., Cell Metab 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Like hemojuvelin, both HFE and transferrin receptor-2 (TFR2, another hemochromatosis-associated protein) are inferred to be involved in regulation of hepcidin expression.”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [136][137][138][139]
- Not checked yetcites [140][141][142][143][144]
hedgedstates 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.
In the paper
“In the course of their general studies of cellular signaling, Wang and colleagues inactivated the gene encoding an essential SMAD protein, SMAD4, exclusively in hepatocytes.113 To their surprise, the dominant phenotype that resulted was severe hemochromatosis, similar to that seen in mice lacking hepcidin.”
§ 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
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Conversely, transgenic overexpression of hepcidin resulted in iron deficiency.103,104”
§ 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.
In the paper
“Proteolytic processing of the prohormone is carried out by furin in a relatively unregulated manner.98”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
- Not checked yetcites [98] Valore, 2008, Posttranslational processing of hepcidin in human hepatocytes is mediated by the prohormone convertase furin., Blood Cells Mol Dis 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.
None of the sources cited for this claim have been checked yet.
In the paper
“A consensus STAT3 binding site has been shown to mediate the induction of hepcidin in inflammation, through a signaling pathway triggered by interleukin-6.107,108”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
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.
In the paper
“Human patients with mutations in the genes encoding hemojuvelin, HFE, or TFR2 have inappropriately low urinary hepcidin levels for their overall body iron status.[136][137][138][139]”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [136][137][138][139]
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Transport is facilitated by multicopper ferroxidases including the abundant serum protein ceruloplasmin and its membrane-bound intestinal homolog hephaestin.”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [80] Osaki, 1969, Mobilization of liver iron by ferroxidase (ceruloplasmin)., J Biol Chem source
- Not checked yetcites [81] Osaki, 1966, The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum., J Biol Chem source
- Not checked yetcites [82] Roeser, 1970, The role of ceruloplasmin in iron metabolism., J Clin Invest 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.
In the paper
“However, De Domenico and colleagues have recently shown that ceruloplasmin is required to maintain cell-surface localization of ferroportin.84”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
- Not checked yetcites [84] De Domenico, 2007, Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasmin., EMBO J 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.
In the paper
“Soon after its discovery, HFE was shown to interact with TFR1 to form a protein-protein complex.[145][146][147]”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [145][146][147]
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.
None of the sources cited for this claim have been checked yet.
In the paper
“A description of a putative heme importer in 2005 87 later proved to be incorrect.88”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
What the sources say
hedged- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“This situation is somewhat analogous to iron transport in yeast, where the ferrous iron permease FTR1 (functionally analogous but structurally unrelated to DMT1) requires the multicopper ferroxidase FET3 for correct localization on the cell surface.85,86”
§ Forging a field: the golden age of iron biology > Intestinal iron absorption
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: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“They showed that hemojuvelin acts as a BMP coreceptor to stimulate hepcidin transcription.”
§ Forging a field: the golden age of iron biology > Regulation of iron homeostasis by hepcidin
What the sources say
- Not checked yetcites [114] Babitt, 2006, Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression., 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.
None of the sources cited for this claim have been checked yet.
In the paper
“However, as shown by Chen and Enns, HFE does not bind to homologous portions of TFR1 and TFR2.151”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites Chen and Enns
- Not checked yetcites [151] Chen, 2007, The cytoplasmic domain of transferrin receptor 2 dictates its stability and response to holo-transferrin in Hep3B cells., J Biol Chem source
boosted- 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.
In the paper
“Eradication of H pylori infection can lead to correction of the anemia.167”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [167] Marignani, 1997, Reversal of long-standing iron deficiency anaemia after eradication of Helicobacter pylori infection., Scand J Gastroenterol 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.
In the paper
“Perhaps less surprising, the clinical phenotype of a unique patient carrying a GLRX5 mutation also differs somewhat from an earlier animal model with a deletion of that gene, the shiraz zebrafish.177”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [177] Wingert, 2005, Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis., Nature source
plainSingle case- 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.
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
“Second, mutations in the genes encoding HFE (HFE), TFR2 (TFR2), and hemojuvelin (HFE2) inactivate signaling pathways that normally up-regulate hepcidin expression.”
§ 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.
In the paper
“In addition to a bizarre hair pattern that led to the strain name, Mask mice have severe iron deficiency anemia attributable to elevated hepcidin expression.”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- 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.
- 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.
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
“In a sense, anemia of chronic disease is the phenotypic opposite of hemochromatosis.”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
hedged- 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.
In the paper
“As reported by Harris and colleagues, 184 iron deficiency results from lack of ferroxidase activity needed to mobilize iron from storage.”
§ 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Finally, mutations in the gene encoding ferroportin (SLC40A1) can cause hemochromatosis by rendering the transporter insensitive to hepcidin regulation.158,162”
§ Forging a field: the golden age of iron biology > Hemochromatosis
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: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Thus, based on our current understanding, the molecular pathogenesis of hemochromatosis can be divided into 3 classes (Figure 2B).”
§ Forging a field: the golden age of iron biology > Hemochromatosis
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The first mutations in ferroportin were discovered simultaneously by Montosi et al 156 and Njajou et al 157 in families with iron overload segregating in an autosomal dominant pattern.”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites Montosi et al 156
- Not checked yetcites Njajou et al 157
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.
In the paper
“An important clue to the etiology of IRIDA came recently when Ernest Beutler and his son Bruce identified Tmprss6, encoding matriptase-2, as the gene mutated in a novel mouse mutant, Mask.192”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- 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 causeSingle case- 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.
None of the sources cited for this claim have been checked yet.
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 [96] Nemeth, 2003, Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein., Blood source
- Not checked yetcites [197] Nemeth, 2004, IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin., 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: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“First, mutations in the hepcidin gene itself (called HAMP) cause hemochromatosis by preventing the production of functional hepcidin protein.161”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [161] Roetto, 2003, Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis., 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.
In the paper
“Like TFR1, TFR2 interacts with HFE to form a stable protein complex.150”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [150] Goswami, 2006, Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing., J Biol Chem 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Recently it was rediscovered that infection with H pylori, even in the absence of significant bleeding, can lead to profound iron deficiency anemia that is poorly responsive to oral iron therapy.”
§ 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 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.
In the paper
“Interestingly, the clinical phenotype of patients with DMT1 mutations differs slightly from the corresponding mouse model, mk. 12”
§ Forging a field: the golden age of iron biology > Iron deficiency anemia
What the sources say
- Not checked yetcites [12] Fleming, 1997, Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene., Nat 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.
None of the sources cited for this claim have been checked yet.
In the paper
“These issues were resolved by the discovery that there are 2 broad categories of ferroportin mutations.158,159”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
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.
- Rests on an assumption: All ferroportin mutations cause missense changes rather than truncations or frameshifts.
None of the sources cited for this claim have been checked yet.
In the paper
“Hemochromatosis can also result from mutations in the gene encoding ferroportin, the target of hepcidin activity.”
§ Forging a field: the golden age of iron biology > Hemochromatosis
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: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast, missense mutations that rendered ferroportin insensitive to regulation by hepcidin (”
§ Forging a field: the golden age of iron biology > Hemochromatosis
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.
- Rests on an assumption: All ferroportin mutations cause missense changes rather than truncations or frameshifts.
In the paper
“Recently, a mouse model of the disease associated with loss-of-function ferroportin mutations, flatiron, was identified through a positional cloning effort.160”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [160] Zohn, 2007, The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease., 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Taking this into account, we have proposed a model in which TFR2 escorts HFE away from TFR1 when the serum iron level (reflected in the transferrin saturation) is elevated.149,150”
§ 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
- Not checked yetcites [150] Goswami, 2006, Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing., 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: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Missense mutations that affected the subcellular localization or transporter function of ferroportin (”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
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.
- Rests on an assumption: All ferroportin mutations cause missense changes rather than truncations or frameshifts.
None of the sources cited for this claim have been checked yet.
In the paper
“Amounts of TFR2 protein increase in response to iron-saturated transferrin.151,[153][154][155]”
§ Forging a field: the golden age of iron biology > Hemochromatosis
What the sources say
- Not checked yetcites [151] Chen, 2007, The cytoplasmic domain of transferrin receptor 2 dictates its stability and response to holo-transferrin in Hep3B cells., J Biol Chem source
- Not checked yetcites [153][154][155]
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.
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
“Rather, its primary function seems to be to interpret body iron status.”
§ Forging a field: the golden age of iron biology > Hemochromatosis
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: passes — The paper gives a reason why it holds.
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
“The implication of this model is that HFE and TFR2 collaborate in a signaling complex that acts to augment hepcidin expression.”
§ 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.
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
“There is likely to be at least one additional gene yet to be identified.”
§ 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: passes — The paper gives a reason why it holds.
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
“Our recent discovery that IRIDA is also caused by inappropriately high hepcidin expression suggests that IRIDA and the anemia of chronic disease should have common clinical features.”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
hedgedstates 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.
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
“Consequently, decreased serum iron is available for erythropoiesis.”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
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.
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
“Expression of hepcidin that is inappropriately high for body iron status results in interruption of intestinal iron absorption and iron recycling.”
§ Forging a field: the golden age of iron biology > Anemia of chronic disease
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.
In the paper
“Finally, although we have made great strides in understanding hemochromatosis in individuals of European descent, we remain largely ignorant of the causes and manifestations of iron overload in individuals of African descent, in spite of the apparent prevalence of the condition in that population.[201][202][203][204][205][206][207][208][209][210]”
§ Forging a field: the golden age of iron biology > Conclusions and future directions
What the sources say
- Not checked yetcites [201][202][203][204][205][206][207][208][209][210]
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. 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.
- 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
“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.
- 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
“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.
- 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.
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.
- 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
“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.
- 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
“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.
- 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.
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.
- 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
“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.
- 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
“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.
- 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
“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.
- 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
“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.
- 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
“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.
- 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
“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.
- 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.
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.
- 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.
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.
- 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
“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.
- 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
“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.
- 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 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.
- 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
“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.
- 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 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.
- 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.
- 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.
- 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
“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.
- 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.
None of the sources cited for this claim have been checked yet.
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 ›
Are you an author, or do you see a problem with this page? Request a review
