Relocation Of Iron Research Articles

Relocating Industrial Plants Delivers Win-Win Emission Reduction Benefits to Origin and Destination Regions.

Relocating pollution-intensive factories is one of the most effective measures to meet mandatory environmental regulations in developed cities while simultaneously imposing environmental pressure on the receiving cities. Existing studies often assume that relocated plants produce the same or higher emissions when relocated. However, the current pollution mitigation policies enforce even higher emission standards in the destination after plant relocation. We employ a bottom-up pollution accounting approach to assess the impact of intraregional or interregional relocation of iron and steel plants in China's Beijing-Tianjin-Hebei (BTH) area on various air pollutants; specifically, seven policy scenarios are modeled, based on stringency, implementation scope, and production technologies. We find that relocation combined with emission standards enforcement and shifts from BOF (basic oxygen furnace) to EAF (electric arc furnace) production technology may significantly reduce emissions within and outside BTH areas by as much as 28.8% compared to business as usual. The observed reduction is mainly due to the requirement of meeting ultralow emission standards directly or indirectly after relocation. Both origin and destination cities benefit from the relocation, with limited emission spillovers (+9.1%) for destinations outside BTH and even a net reduction (9.4%) in Tangshan. We conclude that combining factory relocation with stricter emission standards and production technological innovation could circumvent the Pollution Haven Hypothesis and deliver win-win air pollution reduction benefits for both origins and destinations.

The iron transporter Transferrin 1 mediates homeostasis of the endosymbiotic relationship between Drosophila melanogaster and Spiroplasma poulsonii.

Iron is involved in numerous biological processes in both prokaryotes and eukaryotes and is therefore subject to a tug-of-war between host and microbes upon pathogenic infections. In the fruit fly Drosophila melanogaster, the iron transporter Transferrin 1 (Tsf1) mediates iron relocation from the hemolymph to the fat body upon infection as part of the nutritional immune response. The sequestration of iron in the fat body renders it less available for pathogens, hence limiting their proliferation and enhancing the host ability to fight the infection. Here we investigate the interaction between host iron homeostasis and Spiroplasma poulsonii, a facultative, vertically transmitted, endosymbiont of Drosophila. This low-pathogenicity bacterium is devoid of cell wall and is able to thrive in the host hemolymph without triggering pathogen-responsive canonical immune pathways. However, hemolymph proteomics revealed an enrichment of Tsf1 in infected flies. We find that S. poulsonii induces tsf1 expression and triggers an iron sequestration response similarly to pathogenic bacteria. We next demonstrate that free iron cannot be used by Spiroplasma while Tsf1-bound iron promotes bacterial growth, underlining the adaptation of Spiroplasma to the intra-host lifestyle where iron is mostly protein-bound. Our results show that Tsf1 is used both by the fly to sequester iron and by Spiroplasma to forage host iron, making it a central protein in endosymbiotic homeostasis.

Iron sequestration by transferrin 1 mediates nutritional immunity in Drosophila melanogaster.

Iron sequestration is a recognized innate immune mechanism against invading pathogens mediated by iron-binding proteins called transferrins. Despite many studies on antimicrobial activity of transferrins in vitro, their specific in vivo functions are poorly understood. Here we use Drosophila melanogaster as an in vivo model to investigate the role of transferrins in host defense. We find that systemic infections with a variety of pathogens trigger a hypoferremic response in flies, namely, iron withdrawal from the hemolymph and accumulation in the fat body. Notably, this hypoferremia to infection requires Drosophila nuclear factor κB (NF-κB) immune pathways, Toll and Imd, revealing that these pathways also mediate nutritional immunity in flies. Next, we show that the iron transporter Tsf1 is induced by infections downstream of the Toll and Imd pathways and is necessary for iron relocation from the hemolymph to the fat body. Consistent with elevated iron levels in the hemolymph, Tsf1 mutants exhibited increased susceptibility to Pseudomonas bacteria and Mucorales fungi, which could be rescued by chemical chelation of iron. Furthermore, using siderophore-deficient Pseudomonas aeruginosa, we discover that the siderophore pyoverdine is necessary for pathogenesis in wild-type flies, but it becomes dispensable in Tsf1 mutants due to excessive iron present in the hemolymph of these flies. As such, our study reveals that, similar to mammals, Drosophila uses iron limitation as an immune defense mechanism mediated by conserved iron-transporting proteins transferrins. Our in vivo work, together with accumulating in vitro studies, supports the immune role of insect transferrins against infections via an iron withholding strategy.

Renewables‐based decarbonization and relocation of iron and steel making: A case study

AbstractThe article assesses the future role of hydrogen‐based iron and steel making and its potential impact on global material flows, based on a combination of technology assessment, material flow analysis, and microeconomic analysis. Renewable hydrogen‐based iron production can become the least‐cost supply option at a carbon dioxide (CO2) price of around United States dollars (USD) 67 per tonne. Availability of low‐cost renewable electricity is a precondition. Australia is the world's largest producer of iron ore and at the same time a country with significant low‐cost renewable electricity potential. A shift to direct reduced iron (DRI) exports could reduce global CO2 emissions substantially and at the same time increase value added in Australia, while maintaining steel production in countries that are currently processing ore into iron and steel, such as China, South Korea, and Japan. The approach could be expanded to other parts of the world and other energy‐intensive industry sectors. Such relocation analysis in a climate context can become a new industrial ecology research area. Iron and steel industry CO2 emissions can be reduced by nearly a third, around 0.7 gigatonnes (Gt) CO2 per year. To achieve these emission reductions, investment of USD 0.9 trillion, or 0.7% of the total energy sector investment needs, would be required, global DRI production would have to increase seven‐fold from today's level, and the hydrogen energy used would equal 1% of global primary energy supply. Such a shift could develop from 2025 onward at scale, if the right policies are put in place.

Increased ferroportin-1 expression and rapid splenic iron loss occur with anemia caused by Salmonella enterica Serovar Typhimurium infection in mice.

The Gram-negative intracellular bacterium Salmonella enterica serovar Typhimurium causes persistent systemic inflammatory disease in immunocompetent mice. Following oral inoculation with S. Typhimurium, mice develop a hematopathological syndrome akin to typhoid fever with splenomegaly, microcytic anemia, extramedullary erythropoiesis, and increased hemophagocytic macrophages in the bone marrow, liver, and spleen. Additionally, there is marked loss of iron from the spleen, an unanticipated result, given the iron sequestration reported in anemia of inflammatory disease. To establish why tissue iron does not accumulate, we evaluated multiple measures of pathology for 4 weeks following oral infection in mice. We demonstrate a quantitative decrease in splenic iron following infection despite increased numbers of splenic phagocytes. Infected mice have increased duodenal expression of the iron exporter ferroportin-1, consistent with increased uptake of dietary iron. Liver and splenic macrophages also express high levels of ferroportin-1. These observations indicate that splenic and hepatic macrophages export iron during S. Typhimurium infection, in contrast to macrophage iron sequestration observed in anemia of inflammatory disease. Tissue macrophage export of iron occurs concurrent with high serum concentrations of interferon gamma (IFN-γ) and interleukin 12 (IL-12). In individual mice, high concentrations of both proinflammatory (tumor necrosis factor alpha [TNF-α]) and anti-inflammatory (IL-10) cytokines in serum correlate with increased tissue bacterial loads throughout 4 weeks of infection. These in vivo observations are consistent with previous cell culture studies and suggest that the relocation of iron from tissue macrophages during infection may contribute to anemia and also to host survival of acute S. Typhimurium infection.

Differences in activation of mouse hepcidin by dietary iron and parenterally administered iron dextran: compartmentalization is critical for iron sensing

The iron regulatory hormone hepcidin responds to both oral and parenteral iron. Here, we hypothesized that the diverse iron trafficking routes may affect the dynamics and kinetics of the hepcidin activation pathway. To address this, C57BL/6 mice were administered an iron-enriched diet or injected i.p. with iron dextran and analyzed over time. After 1 week of dietary loading with carbonyl iron, mice exhibited significant increases in serum iron and transferrin saturation, as well as in hepatic iron, Smad1/5/8 phosphorylation and bone morphogenetic protein 6 (BMP6), and hepcidin mRNAs. Nevertheless, hepcidin expression reached a plateau afterward, possibly due to upregulation of inhibitory Smad7, Id1, and matriptase-2 mRNAs, while hepatic and splenic iron continued to accumulate over 9 weeks. One day following parenteral administration of iron dextran, mice manifested elevated serum and hepatic iron levels and Smad1/5/8 phosphorylation, but no increases in transferrin saturation or BMP6 mRNA. Surprisingly, hepcidin failed to appropriately respond to acute overload with iron dextran, and a delayed (after 5-7 days) hepcidin upregulation correlated with increased transferrin saturation, partial relocation of iron from macrophages to hepatocytes, and induction of BMP6 mRNA. Our data suggest that the physiological hepcidin response is saturable and are consistent with the idea that hepcidin senses exclusively iron compartmentalized within circulating transferrin and/or hepatocytes.

Rescuing iron‐overloaded macrophages by conservative relocation of the accumulated metal

Systemic iron deficiency concomitant with macrophage iron retention is characteristic of iron-refractory anaemias associated with chronic disease. The systemic misdistribution of iron, which is further exacerbated by parenteral iron supplementation, is mainly attributable to iron retention exerted on resident macrophages by hepcidin-mediated down-regulation of the iron exporter ferroportin. We aimed at developing an experimental macrophage-based cell model that recapitulates pathophysiological features of iron misdistribution found in chronic disorders and use it as a screening platform for identifying agents with the potential for relocating the accumulated metal and restoring affected functions. A raw macrophage subline was selected as cell model of iron retention based on their capacity to take up polymeric iron or aged erythrocytes excessively, resulting in a demonstrable increase of cell labile iron pools and oxidative damage that are aggravated by hepcidin. This model provided a three-stage high throughput screening platform for identifying agents with the combined ability to: (i) scavenge cell iron and thereby rescue macrophage cells damaged by iron-overload; (ii) bypass the ferroportin blockade by conveying the scavenged iron to other iron-starved cells in co-culture via transferrin but (iii) without promoting utilization of the scavenged iron by intracellular pathogens. As test agents we used chelators in clinical practice and found the oral chelator deferiprone fulfilled essentially all of the three criteria. We provide a proof of principle for conservative iron relocation as complementary therapeutic approach for correcting the misdistribution of iron associated with chronic disease and exacerbated by parenteral iron supplementation.

Iron redistribution as a therapeutic strategy for treating diseases of localized iron accumulationThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

Defective iron utilization leading to either systemic or regional misdistribution of the metal has been identified as a critical feature of several different disorders. Iron concentrations can rise to toxic levels in mitochondria of excitable cells, often leaving the cytosol iron-depleted, in some forms of neurodegeneration with brain accumulation (NBIA) or following mutations in genes associated with mitochondrial functions, such as ABCB7 in X-linked sideroblastic anemia with ataxia (XLSA/A) or the genes encoding frataxin in Friedreich's ataxia (FRDA). In anemia of chronic disease (ACD), iron is withheld by macrophages, while iron levels in extracellular fluids (e.g., plasma) are drastically reduced. One possible therapeutic approach to these diseases is iron chelation, which is known to effectively reduce multiorgan iron deposition in iron-overloaded patients. However, iron chelation is probably inappropriate for disorders associated with misdistribution of iron within selected tissues or cells. One chelator in clinical use for treating iron overload, deferiprone (DFP), has been identified as a reversed siderophore, that is, an agent with iron-relocating abilities in settings of regional iron accumulation. DFP was applied to a cell model of FRDA, a paradigm of a disorder etiologically associated with cellular iron misdistribution. The treatment reduced the mitochondrial levels of labile iron pools (LIP) that were increased by frataxin deficiency. DFP also conferred upon cells protection against oxidative damage and concomitantly mediated the restoration of various metabolic parameters, including aconitase activity. Administration of DFP to FRDA patients for 6 months resulted in selective and significant reduction in foci of brain iron accumulation (assessed by T2* MRI) and initial functional improvements, with only minor changes in net body iron stores. The prospects of drug-mediated iron relocation versus those of chelation are discussed in relation to other disorders involving iron misdistribution, such as ACD and XLSA/A.

Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation

AbstractVarious human disorders are associated with misdistribution of iron within or across cells. Friedreich ataxia (FRDA), a deficiency in the mitochondrial iron-chaperone frataxin, results in defective use of iron and its misdistribution between mitochondria and cytosol. We assessed the possibility of functionally correcting the cellular properties affected by frataxin deficiency with a siderophore capable of relocating iron and facilitating its metabolic use. Adding the chelator deferiprone at clinical concentrations to inducibly frataxin-deficient HEK-293 cells resulted in chelation of mitochondrial labile iron involved in oxidative stress and in reactivation of iron-depleted aconitase. These led to (1) restoration of impaired mitochondrial membrane and redox potentials, (2) increased adenosine triphosphate production and oxygen consumption, and (3) attenuation of mitochondrial DNA damage and reversal of hypersensitivity to staurosporine-induced apoptosis. Permeant chelators of higher affinity than deferiprone were not as efficient in restoring affected functions. Thus, although iron chelation might protect cells from iron toxicity, rendering the chelated iron bioavailable might underlie the capacity of deferiprone to restore cell functions affected by frataxin deficiency, as also observed in FRDA patients. The siderophore-like properties of deferiprone provide a rational basis for treating diseases of iron misdistribution, such as FRDA, anemia of chronic disease, and X-linked sideroblastic anemia with ataxia.

Trace-element mobility during early diagenesis in distal turbidites: late Quaternary of the Madeira Abyssal Plain, N Atlantic

Summary Sediments deposited on the Madeira Abyssal Plain (MAP) during the late Quaternary consist of an alternating succession of distal turbidites and pelagites. Individual turbidites may be correlated over most of the northern MAP. The sediment geochemistry of the succession has been investigated in detail using material from a representative 10 m piston core. The turbidites have been divided into organic-rich (at least 0.5% C org ) and organic-poor groups. At the time of emplacement all turbidites were characterized by homogeneous major- and trace-element distributions, although thicker beds have thin silty bases of different compositions. Organic-rich turbidites, however, have undergone considerable early post-depositional modification as a result of oxidation of labile organic matter by sea-water oxygen diffusing downwards from the sediment-water interface. The progressive advance of oxidation fronts through the turbidites has produced distinctive two-tone colourations with light-brown tops and olive-green bottoms, and has caused significant early diagenetic relocation of iron, manganese, phosphorus, cobalt, copper, nickel, uranium, vanadium and zinc. Iron is marginally enriched in formerly oxic sediments. Manganese oxyhydroxides occur as dark-brown diagenetic laminations in recently oxidized turbidite tops, but have been dissolved by anoxic conditions in older examples. Mn 2+ pore-water profiles have been preserved by the adsorption of manganese by calcite. Phosphorus, cobalt, nickel and some copper were initially complexed by the precipitation of manganese oxyhydroxides and other processes occurring at active redox boundaries. Copper was also concentrated in the reduced sediments at this time. Later migration of these elements as reduced phases has produced thin purple diagenetic laminations in both turbidities and pelagites. Uranium, vanadium and zinc were relocated into reduced sediments during early diagenesis, but were not remobilized later. The diagenetic sequence in MAP sediments contrasts strongly with established ‘steady-state’ models based on hemipelagic and pelagic environments, but may be typical of a significant proportion of recent and ancient sequences.

Effects of Iron Deficiency on Respiration of Sunflower Plants

1. Sunflower plants were grown in sand culture with nutrient solution. One group had iron salt as ferric citrate added to the nutrient solution; the other had no iron salt added. 2. The plants of the minus-iron treatment developed the typical chlorosis symptoms of iron deficiency; the controls were of normal color. 3. Respiration rate was depressed in the young chlorotic leaves of the iron deficient plants. 4- The chlorotic leaves of the iron-deficient plants contained only half as much iron as comparable leaves of control plants. No relocation of iron from older to younger leaves occurred in the iron deficient plants. In both the gradients were of decreasing iron content in going from the bottom to the top of the plants. 5. The iron contents of the leaves of a given plant of either treatment were found to be related to the ages of the leaves. The older contained more iron than the younger leaves.