Research progress in role of iron overload in non-alcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

LI Guangming

2013-12-01

Full Text Available Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD. The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iron overload and lipid metabolism, and relationship between type of iron deposition and liver damage; the significance of iron overload in the diagnosis and treatment of NAFLD is discussed from iron overload as a new marker of risk stratification and potential therapeutic target in NAFLD. It is currently considered that iron overload, whether the cause or result of NAFLD progression, will promote the progression of NAFLD once it occurs; as a new marker of risk stratification and potential therapeutic target in NAFLD, iron load is worthy of further study.

Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein

Energy Technology Data Exchange (ETDEWEB)

Sekine, Shuichi; Ito, Konomi; Watanabe, Haruna; Nakano, Takafumi [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan); Moriya, Kyoji; Shintani, Yoshizumi; Fujie, Hajime; Tsutsumi, Takeya; Miyoshi, Hideyuki; Fujinaga, Hidetake; Shinzawa, Seiko; Koike, Kazuhiko [Department of Internal Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Horie, Toshiharu, E-mail: t.horie@thu.ac.jp [Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675 (Japan)

2015-02-01

Patients with long-lasting hepatitis C virus (HCV) infection are at major risk of hepatocellular carcinoma (HCC). Iron accumulation in the livers of these patients is thought to exacerbate conditions of oxidative stress. Transgenic mice that express the HCV core protein develop HCC after the steatosis stage and produce an excess of hepatic reactive oxygen species (ROS). The overproduction of ROS in the liver is the net result of HCV core protein-induced dysfunction of the mitochondrial respiratory chain. This study examined the impact of ferric nitrilacetic acid (Fe-NTA)-mediated iron overload on mitochondrial damage and ROS production in HCV core protein-expressing HepG2 (human HCC) cells (Hep39b cells). A decrease in mitochondrial membrane potential and ROS production were observed following Fe-NTA treatment. After continuous exposure to Fe-NTA for six days, cell toxicity was observed in Hep39b cells, but not in mock (vector-transfected) HepG2 cells. Moreover, mitochondrial iron ({sup 59}Fe) uptake was increased in the livers of HCV core protein-expressing transgenic mice. This increase in mitochondrial iron uptake was inhibited by Ru360, a mitochondrial Ca{sup 2+} uniporter inhibitor. Furthermore, the Fe-NTA-induced augmentation of mitochondrial dysfunction, ROS production, and cell toxicity were also inhibited by Ru360 in Hep39b cells. Taken together, these results indicate that Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates hepatocyte toxicity caused by the HCV core protein. - Highlights: • Iron accumulation in the livers of patients with hepatitis C virus (HCV) infection is thought to exacerbate oxidative stress. • The impact of iron overload on mitochondrial damage and ROS production in HCV core protein-expressing cells were examined. • Mitochondrial iron uptake was increased in the livers of HCV core protein-expressing transgenic mice. • Ca{sup 2+} uniporter-mediated mitochondrial accumulation of iron exacerbates

Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

Science.gov (United States)

Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

2013-01-01

Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

INFLUENCE OF THERMOHALINE CONVECTION ON DIFFUSION-INDUCED IRON ACCUMULATION IN A STARS

International Nuclear Information System (INIS)

Theado, S.; Vauclair, S.; Alecian, G.; LeBlanc, F.

2009-01-01

Atomic diffusion may lead to heavy-element accumulation inside stars in certain specific layers. Iron accumulation in the Z-bump opacity region has been invoked by several authors to quantitatively account for abundance anomalies observed in some stars, or to account for stellar oscillations through the induced κ-mechanism. These authors, however, never took into account the fact that such an accumulation creates an inverse μ-gradient, unstable for thermohaline convection. Here, we present results for A-F stars, where abundance variations are computed with and without this process. We show that iron accumulation is still present when thermohaline convection is taken into account, but much reduced compared to when this physical process is neglected. The consequences of thermohaline convection for A-type stars as well as for other types of stars are presented.

Influence of iron and zinc status on cadmium accumulation in Bangladeshi women

International Nuclear Information System (INIS)

Kippler, Maria; Ekstroem, Eva-Charlotte; Loennerdal, Bo; Goessler, Walter; Akesson, Agneta; El Arifeen, Shams; Persson, Lars-Ake; Vahter, Marie

2007-01-01

Cadmium is a widespread environmental contaminant present in food. The absorption in the intestine increases in individuals with low iron stores, but the effect of zinc deficiency is not clear. The aim of the present study was to assess the influence of iron and zinc status on cadmium accumulation in pregnant Bangladeshi women. We measured cadmium in urine from 890 women using inductively coupled plasma mass spectrometry (ICPMS). Further, we also measured ferritin and zinc in plasma. The median cadmium concentration in urine was 0.59 μg/L (adjusted to mean specific gravity of 1.012 g/mL). Analysis of covariance (ANCOVA) showed that urinary cadmium was associated with plasma ferritin and plasma zinc via a significant interaction between dichotomized plasma ferritin and plasma zinc. The analysis was adjusted for age and socioeconomic status. Women with low iron stores and adequate zinc status had significantly higher urinary cadmium compared to women with both adequate iron stores and zinc status. There was no difference in urinary cadmium between women with both low iron stores and zinc status compared to those with both adequate iron stores and zinc status. In conclusion, low iron stores were associated with increased cadmium accumulation, but only at adequate zinc status

Cell wall targeted in planta iron accumulation enhances biomass conversion and seed iron concentration in Arabidopsis and rice

Energy Technology Data Exchange (ETDEWEB)

Yang, Haibing [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Department of Biological Sciences, Purdue University, West Lafayette IN USA; Wei, Hui [Biosciences Center, National Renewable Energy Laboratory, Golden CO USA; Ma, Guojie [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Antunes, Mauricio S. [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Biological Sciences, Purdue University, West Lafayette IN USA; Vogt, Stefan [X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne IL USA; Cox, Joseph [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Zhang, Xiao [Department of Horticulture, Purdue University, West Lafayette IN USA; Liu, Xiping [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Bu, Lintao [National Bioenergy Center, National Renewable Energy Laboratory, Golden CO USA; Gleber, S. Charlotte [X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne IL USA; Carpita, Nicholas C. [Department of Biological Sciences, Purdue University, West Lafayette IN USA; Department of Botany and Plant Pathology, Purdue University, West Lafayette IN USA; Makowski, Lee [Department of Bioengineering, Northeastern University, Boston MA USA; Department of Chemistry and Chemical Biology, Northeastern University, Boston MA USA; Himmel, Michael E. [Biosciences Center, National Renewable Energy Laboratory, Golden CO USA; Tucker, Melvin P. [X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne IL USA; McCann, Maureen C. [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Biological Sciences, Purdue University, West Lafayette IN USA; Murphy, Angus S. [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Department of Plant Science and Landscape Architecture, University of Maryland, College Park MD USA; Peer, Wendy A. [Center for Direct Catalytic Conversion Of Biomass to Biofuels (C3Bio), Purdue University, West Lafayette IN USA; Department of Horticulture, Purdue University, West Lafayette IN USA; Department of Plant Science and Landscape Architecture, University of Maryland, College Park MD USA; Department of Environmental Science and Technology, University of Maryland, College Park MD USA

2016-04-07

Conversion of nongrain biomass into liquid fuel is a sustainable approach to energy demands as global population increases. Previously, we showed that iron can act as a catalyst to enhance the degradation of lignocellulosic biomass for biofuel production. However, direct addition of iron catalysts to biomass pretreatment is diffusion-limited, would increase the cost and complexity of biorefinery unit operations and may have deleterious environmental impacts. Here, we show a new strategy for in planta accumulation of iron throughout the volume of the cell wall where iron acts as a catalyst in the deconstruction of lignocellulosic biomass. We engineered CBM-IBP fusion polypeptides composed of a carbohydrate-binding module family 11 (CBM11) and an iron-binding peptide (IBP) for secretion into Arabidopsis and rice cell walls. CBM-IBP transformed Arabidopsis and rice plants show significant increases in iron accumulation and biomass conversion compared to respective controls. Further, CBM-IBP rice shows a 35% increase in seed iron concentration and a 40% increase in seed yield in greenhouse experiments. CBM-IBP rice potentially could be used to address iron deficiency, the most common and widespread nutritional disorder according to the World Health Organization.

Neurodegeneration with inflammation is accompanied by accumulation of iron and ferritin in microglia and neurons.

Science.gov (United States)

Thomsen, Maj Schneider; Andersen, Michelle Vandborg; Christoffersen, Pia Rægaard; Jensen, Malene Duedal; Lichota, Jacek; Moos, Torben

2015-09-01

Chronic inflammation in the substantia nigra (SN) accompanies conditions with progressive neurodegeneration. This inflammatory process contributes to gradual iron deposition that may catalyze formation of free-radical mediated damage, hence exacerbating the neurodegeneration. This study examined proteins related to iron-storage (ferritin) and iron-export (ferroportin) (aka metal transporter protein 1, MTP1) in a model of neurodegeneration. Ibotenic acid injected stereotactically into the striatum leads to loss of GABAergic neurons projecting to SN pars reticulata (SNpr), which subsequently leads to excitotoxicity in the SNpr as neurons here become vulnerable to their additional glutamatergic projections from the subthalamic nucleus. This imbalance between glutamate and GABA eventually led to progressive shrinkage of the SNpr and neuronal loss. Neuronal cell death was accompanied by chronic inflammation as revealed by the presence of cells expressing ED1 and CD11b in the SNpr and the adjacent white matter mainly denoted by the crus cerebri. The SNpr also exhibited changes in iron metabolism seen as a marked accumulation of inflammatory cells containing ferric iron and ferritin with morphology corresponding to macrophages and microglia. Ferritin was detected in neurons of the lesioned SNpr in contrast to the non-injected side. Compared to non-injected rats, surviving neurons of the SNpr expressed ferroportin at unchanged level. Analyses of dissected SNpr using RT-qPCR showed a rise in ferritin-H and -L transcripts with increasing age but no change was observed in the lesioned side compared to the non-lesioned side, indicating that the increased expression of ferritin in the lesioned side occurred at the post-transcriptional level. Hepcidin transcripts were higher in the lesioned side in contrast to ferroportin mRNA that remained unaltered. The continuous entry of iron-containing inflammatory cells into the degenerating SNpr and their subsequent demise is probably

The interplay between iron accumulation, mitochondrial dysfunction and inflammation during the execution step of neurodegenerative disorders

Directory of Open Access Journals (Sweden)

Pamela J. Urrutia

2014-03-01

Full Text Available A growing set of observations points to mitochondrial dysfunction, iron accumulation, oxidative damage and chronic inflammation as common pathognomonic signs of a number of neurodegenerative diseases that includes Alzheimer's disease, Huntington disease, amyotrophic lateral sclerosis, Friedrich’s ataxia and Parkinson’s disease. Particularly relevant for neurodegenerative processes is the relationship between mitochondria and iron. The mitochondrion upholds the synthesis of iron-sulfur clusters and heme, the most abundant iron-containing prosthetic groups in a large variety of proteins, so a fraction of incoming iron must go through this organelle before reaching its final destination. In turn, the mitochondrial respiratory chain is the source of reactive oxygen species (ROS derived from leaks in the electron transport chain. The co-existence of both iron and ROS in the secluded space of the mitochondrion makes this organelle particularly prone to hydroxyl radical-mediated damage. In addition, a connection between the loss of iron homeostasis and inflammation is starting to emerge; thus, inflammatory cytokines like TNF-alpha and IL-6 induce the synthesis of the divalent metal transporter 1 and promote iron accumulation in neurons and microglia. Here, we review the recent literature on mitochondrial iron homeostasis and the role of inflammation on mitochondria dysfunction and iron accumulation on the neurodegenerative process that lead to cell death in Parkinson’s disease. We also put forward the hypothesis that mitochondrial dysfunction, iron accumulation and inflammation are part of a synergistic self-feeding cycle that ends in apoptotic cell death, once the antioxidant cellular defense systems are finally overwhelmed.

Iron-dependent formation of reactive oxygen species and glutathione depletion after accumulation of magnetic iron oxide nanoparticles by oligodendroglial cells

International Nuclear Information System (INIS)

Hohnholt, Michaela C.; Dringen, Ralf

2011-01-01

Magnetic iron oxide nanoparticles (IONP) are currently used for various neurobiological applications. To investigate the consequences of a treatment of brain cells with such particles, we have applied dimercaptosuccinate (DMSA)-coated IONP that had an average hydrodynamic diameter of 60 nm to oligodendroglial OLN-93 cells. After exposure to 4 mM iron applied as DMSA–IONP, these cells increased their total specific iron content within 8 h 600-fold from 7 to 4,200 nmol/mg cellular protein. The strong iron accumulation was accompanied by a change in cell morphology, although the cell viability was not compromized. DMSA–IONP treatment caused a concentration-dependent increase in the iron-dependent formation of reactive oxygen species and a decrease in the specific content of the cellular antioxidative tripeptide glutathione. During a 16 h recovery phase in IONP-free culture medium following exposure to DMSA–IONP, OLN-93 cells maintained their high iron content and replenished their cellular glutathione content. These data demonstrate that viable OLN-93 cells have a remarkable potential to deal successfully with the consequences of an accumulation of large amounts of iron after exposure to DMSA–IONP.

Research progress in role of iron overload in non-alcoholic fatty liver disease

OpenAIRE

LI Guangming

2013-01-01

Iron overload is an important research focus in non-alcoholic fatty liver disease (NAFLD). The relationship between iron overload and NAFLD is summarized from the assessment method for iron overload, relationship between iron load and hemochromatosis gene mutations, incidence of iron load in NAFLD, and relationship between iron load and progression of NAFLD; the action mechanism of iron overload in the progression of NAFLD is reviewed from the causes of iron overload, relationship between iro...

Augmenting Iron Accumulation in Cassava by the Beneficial Soil Bacterium Bacillus subtilis (GBO3

Directory of Open Access Journals (Sweden)

Monica A Freitas

2015-08-01

Full Text Available Cassava (Manihot esculenta, a major staple food in the developing world, provides a basic carbohydrate diet for over half a billion people living in the tropics. Despite the iron abundance in most soils, cassava provides insufficient iron for humans as the edible roots contain 3-12 times less iron than other traditional food crops such as wheat, maize, and rice. With the recent identification that the beneficial soil bacterium Bacillus subtilis (strain GB03 activates iron acquisition machinery to increase metal ion assimilation in Arabidopsis, the question arises as to whether this plant-growth promoting rhizobacterium (PGPR also augments iron assimilation to increase endogenous iron levels in cassava. Biochemical analyses reveal that shoot-propagated cassava with GB03-inoculation exhibit elevated iron accumulation after 140 days of plant growth as determined by X-ray microanalysis and total foliar iron analysis. Growth promotion and increased photosynthetic efficiency were also observed for greenhouse-grown plants with GB03-exposure. These results demonstrate the potential of microbes to increase iron accumulation in an important agricultural crop and is consistent with idea that microbial signaling can regulate plant photosynthesis.

Analysis method of intracellular iron accumulated in phytoplankton

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Jorge Falcão Paredes

1977-01-01

Full Text Available A colorimetric method for the assessment of iron accumulated in the cells of phytoplankton utilizing potassium ferrocyanide was developed. Two experiences with Phaeodactylum tricornutum and Chlorella sp. were carried out: the first one, on uptake of the iron relatively to the age of the culture: the second one, on the iron uptake by the cells, relatively to different concentrations of the chelator EDTA.Foi desenvolvido um método para análise do ferro acumulado em células de fitoplâncton, usando ferrocianeto de potássio como agente complexante. Com esse objetivo montaram-se duas experiências: uma em que se mostra o acúmulo de ferro em relação à idade das células e uma segunda experiência onde a assimilação é plotada em função da concentração de EDTA no meio de cultura.

Gene co-expression networks shed light into diseases of brain iron accumulation.

Science.gov (United States)

Bettencourt, Conceição; Forabosco, Paola; Wiethoff, Sarah; Heidari, Moones; Johnstone, Daniel M; Botía, Juan A; Collingwood, Joanna F; Hardy, John; Milward, Elizabeth A; Ryten, Mina; Houlden, Henry

2016-03-01

Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whether other NBIA-related genes also regulate iron homeostasis in the human brain, and whether aberrant iron deposition contributes to neurodegenerative processes remains largely unknown. This study aims to expand our understanding of these iron overload diseases and identify relationships between known NBIA genes and their main interacting partners by using a systems biology approach. We used whole-transcriptome gene expression data from human brain samples originating from 101 neuropathologically normal individuals (10 brain regions) to generate weighted gene co-expression networks and cluster the 10 known NBIA genes in an unsupervised manner. We investigated NBIA-enriched networks for relevant cell types and pathways, and whether they are disrupted by iron loading in NBIA diseased tissue and in an in vivo mouse model. We identified two basal ganglia gene co-expression modules significantly enriched for NBIA genes, which resemble neuronal and oligodendrocytic signatures. These NBIA gene networks are enriched for iron-related genes, and implicate synapse and lipid metabolism related pathways. Our data also indicates that these networks are disrupted by excessive brain iron loading. We identified multiple cell types in the origin of NBIA disorders. We also found unforeseen links between NBIA networks and iron-related processes, and demonstrate convergent pathways connecting NBIAs and phenotypically overlapping diseases. Our results are of further relevance for these diseases by providing candidates for new causative genes and possible points for therapeutic intervention. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.

Science.gov (United States)

Zhang, De-Liang; Wu, Jian; Shah, Binal N; Greutélaers, Katja C; Ghosh, Manik C; Ollivierre, Hayden; Su, Xin-Zhuan; Thuma, Philip E; Bedu-Addo, George; Mockenhaupt, Frank P; Gordeuk, Victor R; Rouault, Tracey A

2018-03-30

Malaria parasites invade red blood cells (RBCs), consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. Here we found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the Fpn gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent FPN mutation, Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease. FPN Q248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Specific expression of the vacuolar iron transporter, TgVit, causes iron accumulation in blue-colored inner bottom segments of various tulip petals.

Science.gov (United States)

Momonoi, Kazumi; Tsuji, Toshiaki; Kazuma, Kohei; Yoshida, Kumi

2012-01-01

Several flowers of Tulipa gesneriana exhibit a blue color in the bottom segments of the inner perianth. We have previously reported the inner-bottom tissue-specific iron accumulation and expression of the vacuolar iron transporter, TgVit1, in tulip cv. Murasakizuisho. To clarify whether the TgVit1-dependent iron accumulation and blue-color development in tulip petals are universal, we analyzed anthocyanin, its co-pigment components, iron contents and the expression of TgVit1 mRNA in 13 cultivars which show a blue color in the bottom segments of the inner perianth accompanying yellow- and white-colored inner-bottom petals. All of the blue bottom segments contained the same anthocyanin component, delphinidin 3-rutinoside. The flavonol composition varied with cultivar and tissue part. The major flavonol in the bottom segments of the inner perianth was rutin. The iron content in the upper part was less than that in the bottom segments of the inner perianth. The iron content in the yellow and white petals was higher in the bottom segment of the inner perianth than in the upper tissues. TgVit1 mRNA expression was apparent in all of the bottom tissues of the inner perianth. The result of a reproduction experiment by mixing the constituents suggests that the blue coloration in tulip petals is generally caused by iron complexation to delphinidin 3-rutinoside and that the iron complex is solubilized and stabilized by flavonol glycosides. TgVit1-dependent iron accumulation in the bottom segments of the inner perianth might be controlled by an unknown system that differentiated the upper parts and bottom segments of the inner perianth.

Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress.

Science.gov (United States)

Camacho, A; Simão, M; Ea, H-K; Cohen-Solal, M; Richette, P; Branco, J; Cancela, M L

2016-03-01

Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Mini-review: The Morphology, Mineralogy and Microbiology of Accumulated Iron Corrosion Products

Science.gov (United States)

2014-03-11

including the morphology, mineralogy , microbiology and the mecha- nisms for formation. Use of descriptive terms to denote specific iron corrosion product...RESPONSIBLE PERSON 19b. TELEPHONE NUMBER (Include area code) 11-03-2014 Journal Article Mini-review: the morphology, mineralogy and microbiology of...oxides/ hydroxides with a preponderance of α-FeOOH (goethite) and accumulation of metals. Bacteria, particularly iron-oxidizing and sulfatereducing

Accumulation of radioactive iron in marine organisms

International Nuclear Information System (INIS)

Tateda, Yuzuru

1985-01-01

The accumulation and excretion of radioactive iron in some marine organisms was investigated by radio-tracer experiments. The concentration factor, biological half-life, distribution in body, and combining form in some organs, are compared and discussed between mollusks and fishes. The results obtained are: 1) The concentration factor of seaweed was higher than those of worm and fish in uptake from seawater. Abalone showed a higher concentration factor than fish. 2) The first component of excretion curve was small in case of a longer period of uptake from seawater. 3) Abalone and octopus showed a higher radioactivity retention than flounder and black-fish. 4) The fish fed labelled seaweed showed a lower radioactivity retention than fish fed labelled worm. 5) The fish fed radioisotopes with prey showed a higher radioactivity retention than fish fed labelled prey. 6) Biological half-lives were longer in abalone and octopus than in fishes. The biological half-lives of radioactive iron in fishes varied according to the uptake modes. 7) The distribution ratio of radioactive iron in organisms were large in the liver and degestive tract. 8) The GFC profile of 59 Fe in some organs of organisms showed combining form of same molecular weight of proteinous matter. (author)

Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity

Energy Technology Data Exchange (ETDEWEB)

Fader, Kelly A.; Nault, Rance [Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Kirby, Mathew P.; Markous, Gena [Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Matthews, Jason [Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo 0316 (Norway); Zacharewski, Timothy R., E-mail: tzachare@msu.edu [Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States)

2017-04-15

Persistent aryl hydrocarbon receptor (AhR) agonists elicit dose-dependent hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis in mice. Iron (Fe) promotes AhR-mediated oxidative stress by catalyzing reactive oxygen species (ROS) production. To further characterize the role of Fe in AhR-mediated hepatotoxicity, male C57BL/6 mice were orally gavaged with sesame oil vehicle or 0.01–30 μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4 days for 28 days. Duodenal epithelial and hepatic RNA-Seq data were integrated with hepatic AhR ChIP-Seq, capillary electrophoresis protein measurements, and clinical chemistry analyses. TCDD dose-dependently repressed hepatic expression of hepcidin (Hamp and Hamp2), the master regulator of systemic Fe homeostasis, resulting in a 2.6-fold increase in serum Fe with accumulating Fe spilling into urine. Total hepatic Fe levels were negligibly increased while transferrin saturation remained unchanged. Furthermore, TCDD elicited dose-dependent gene expression changes in heme biosynthesis including the induction of aminolevulinic acid synthase 1 (Alas1) and repression of uroporphyrinogen decarboxylase (Urod), leading to a 50% increase in hepatic hemin and a 13.2-fold increase in total urinary porphyrins. Consistent with this heme accumulation, differential gene expression suggests that heme activated BACH1 and REV-ERBα/β, causing induction of heme oxygenase 1 (Hmox1) and repression of fatty acid biosynthesis, respectively. Collectively, these results suggest that Hamp repression, Fe accumulation, and increased heme levels converge to promote oxidative stress and the progression of TCDD-elicited hepatotoxicity. - Highlights: • TCDD represses hepatic hepcidin expression, leading to systemic iron overloading. • Dysregulation of heme biosynthesis is consistent with heme and porphyrin accumulation. • Heme-activated REV-ERBα/β repress circadian-regulated hepatic lipid metabolism. • Disruption of iron

Capital accumulation and embodied technological progress

NARCIS (Netherlands)

Grass, D.; Hartl, R.F.; Kort, P.M.

This paper combines technology adoption with capital accumulation taking into account technological progress. We model this as a multi-stage optimal control problem and solve it using the corresponding maximum principle. The model with linear revenue can be solved analytically, while the model with

Interaction between sulfur and lead in toxicity, iron plaque formation and lead accumulation in rice plant.

Science.gov (United States)

Yang, Junxing; Liu, Zhiyan; Wan, Xiaoming; Zheng, Guodi; Yang, Jun; Zhang, Hanzhi; Guo, Lin; Wang, Xuedong; Zhou, Xiaoyong; Guo, Qingjun; Xu, Ruixiang; Zhou, Guangdong; Peters, Marc; Zhu, Guangxu; Wei, Rongfei; Tian, Liyan; Han, Xiaokun

2016-06-01

Human activities have resulted in lead and sulfur accumulation in paddy soils in parts of southern China. A combined soil-sand pot experiment was conducted to investigate the influence of S supply on iron plaque formation and Pb accumulation in rice (Oryza sativa L.) under two Pb levels (0 and 600 mg kg(-1)), combined with four S concentrations (0, 30, 60, and 120 mg kg(-1)). Results showed that S supply significantly decreased Pb accumulation in straw and grains of rice. This result may be attributed to the enhancement of Fe plaque formation, decrease of Pb availability in soil, and increase of reduced glutathione (GSH) in rice leaves. Moderate S supply (30 mg kg(-1)) significantly increased Fe plaque formation on the root surface and in the rhizosphere, whereas excessive S supply (60 and 120 mg kg(-1)) significantly decreased the amounts of iron plaque on the root surface. Sulfur supply significantly enhanced the GSH contents in leaves of rice plants under Pb treatment. With excessive S application, the rice root acted as a more effective barrier to Pb accumulation compared with iron plaque. Excessive S supply may result in a higher monosulfide toxicity and decreased iron plaque formation on the root surface during flooded conditions. However, excessive S supply could effectively decrease Pb availability in soils and reduce Pb accumulation in rice plants. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Iron Containing Supplements on Rats' Dental Caries Progression

Directory of Open Access Journals (Sweden)

AR. Eshghi

2012-01-01

Full Text Available Objective: Iron deficiency is the most common form of malnutrition in developing countries. Iron containing supplements have been used effectively to solve this problem. In children, because of teeth staining after taking iron drops, parents have the idea that iron drops are the cause of tooth decay; therefore, they limit thisvital supplement in their children’s diet. Hereby, we evaluate the histologic effect of iron containing supplements on tooth caries in rice rats with cariogenic or noncariogenic diet.Materials and Methods: Twelve rats were selected and divided into four groups for this interventional experimental study. Four different types of dietary regimens were used for four months; group A, cariogenic diet with iron containing supplements; group B, cariogenic diet without iron containing supplements; groupC, non-cariogenic diet with iron containing supplements; group D, non-cariogenic diet without iron containing supplements. After sacrificing the rats, 20-micron histological sections of their posterior teeth were prepared using the Ground Sectionmethod, then they were studied under polarized light microscopy. In order to compare the progression of caries in different samples, the depth of the lesions in the enamel was measured as three grades I, II and III.Results: The mean grade value of A, B, C and D groups were 1.61, 2.61, 1.37 and 1.80, respectively. Statistical analysis revealed that significantly fewer caries were seen in the group which had received iron containing supplements and cariogenicdiet compared with cariogenic diet without iron supplements (p<0.05.Conclusion: Ferrous sulfate reduces the progression of dental caries in the cariogenic dietary regimen.

Experimental oral iron administration: Histological investigations and expressions of iron handling proteins in rat retina with aging.

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Kumar, Pankaj; Nag, Tapas Chandra; Jha, Kumar Abhiram; Dey, Sanjay Kumar; Kathpalia, Poorti; Maurya, Meenakshi; Gupta, Chandan Lal; Bhatia, Jagriti; Roy, Tara Sankar; Wadhwa, Shashi

2017-12-01

Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.5 month-old. At 8, 14 and 20 months of age, they were sacrificed and serum and retinal iron levels were detected by HPLC. Oxidative stress was analyzed by TBARS method. The retinas were examined for cell death (TUNEL), histology (electron microscopy) and the expressions of transferrin, transferrin receptor-1 [TFR-1], H- and L-ferritin. In control animals, at any age, there was no difference in the serum and retinal iron levels, but the latter increased significantly in 14- and 20 month-old iron-fed rats, indicating that retinal iron accumulation proceeds with progression of aging (>14 months). The serum and retinal TBARS levels increased significantly with progression of aging in experimental but not in control rats. There was significant damage to choriocapillaris, accumulation of phagosomes in retinal pigment epithelium and increased incidence of TUNEL+ cells in outer nuclear layer and vacuolation in inner nuclear layer (INL) of 20 month-aged experimental rats, compared to those in age-matched controls. Vacuolations in INL could indicate a long-term effect of iron accumulation in the inner retina. These events paralleled the increased expression of ferritins and transferrin and a decrease in the expression of TFR-1 in iron-fed rats with aging, thereby maintaining iron homeostasis in the retina. As some of these changes mimic with those happening in eyes with AMD, this model can be utilized to understand iron-induced pathophysiological changes in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

Desferrioxamine, an iron chelator, enhances HIF-1α accumulation via cyclooxygenase-2 signaling pathway

International Nuclear Information System (INIS)

Woo, Kyung Jin; Lee, Tae-Jin; Park, Jong-Wook; Kwon, Taeg Kyu

2006-01-01

Cyclooxygenase-2 (COX-2) is an important inducible enzyme in inflammation and is overexpressed in a variety of cancers. Evidence is rapidly accumulating that chronic inflammation may contribute to carcinogenesis through increase of cell proliferation, angiogenesis, and metastasis in a number of neoplasms, including colorectal carcinoma. In the present study, we investigated some mechanistic aspects of DFX-induced hypoxia-driven COX-2 expression. Desferrioxamine (DFX), an iron chelator, is known to upregulate inflammatory mediators. DFX induced the expression of COX-2 and accumulation of HIF-1α protein in dose-dependent manners, but hypoxia mimetic agent cobalt chloride (CoCl 2 ) induced accumulation of HIF-1α protein but not increase of COX-2 expression. DFX-induced increase of COX-2 expression and HIF-1α protein level was attenuated by addition of ferric citrate. This result suggested that the iron chelating function of DFX was important to induce the increase of COX-2 and HIF-1α protein. PD98059 significantly inhibited the induction of COX-2 protein and accumulation of HIF-1α, suggesting that DFX-induced increase of HIF-1α and COX-2 protein was mediated, at least in part, through the ERK signaling pathway. In addition, pretreatment with NS-398 to inhibit COX-2 activity also effectively suppressed DFX-induced HIF-1α accumulation in human colon cancer cells, providing the evidence that COX-2 plays as a regulator of HIF-1α accumulation in DFX-treated colon cancer cells. Together, our findings suggest that iron metabolism may regulate stabilization of HIF-1α protein by modulating cyclooxygenase-2 signaling pathway

The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation.

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Martins, Telma S; Pereira, Clara; Canadell, David; Vilaça, Rita; Teixeira, Vítor; Moradas-Ferreira, Pedro; de Nadal, Eulàlia; Posas, Francesc; Costa, Vítor

2018-01-01

Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression.

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Chaudhary, Kapil; Promsote, Wanwisa; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Tawfik, Amany; Arjunan, Pachiappan; Martin, Pamela; Smith, Sylvia B; Thangaraju, Muthusamy; Kisselev, Oleg; Ganapathy, Vadivel; Gnana-Prakasam, Jaya P

2018-02-14

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.

C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis.

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Deschauer, M; Gaul, C; Behrmann, C; Prokisch, H; Zierz, S; Haack, T B

2012-11-01

Mutations in C19orf12 have been recently identified as the molecular genetic cause of a subtype of neurodegeneration with brain iron accumulation (NBIA). Given the mitochondrial localization of the gene product the new NBIA subtype was designated mitochondrial membrane protein-associated neurodegeneration. Frequent features in the patients described so far included extrapyramidal signs and pyramidal tract involvement. Here, we report three C19orf12-mutant patients from two families presenting with predominant upper and lower motor neuron dysfunction mimicking amyotrophic lateral sclerosis with juvenile onset. While extrapyramidal signs were absent, all patients showed neuropsychological abnormalities with disinhibited or impulsive behavior. Optic atrophy was present in the simplex case. T2-weighted cranial MRI showed hypointensities suggestive of iron accumulation in the globi pallidi and the midbrain in all patients. Sequence analysis of C19orf12 revealed a novel mutation, p.Gly66del, compound heterozygous with known mutations in all patients. These patients highlight that C19orf12 defects should be considered as a differential diagnosis in patients with juvenile onset motor neuron diseases. Patients have to be examined carefully for neuropsychological abnormalities, optic neuropathy, and signs of brain iron accumulation in MRI.

Enhanced iron and zinc accumulation in genetically engineered pineapple plants using soybean ferritin gene.

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Mhatre, Minal; Srinivas, Lingam; Ganapathi, Thumballi R

2011-12-01

Pineapple (Ananas comosus L. Merr., cv. "Queen") leaf bases were transformed with Agrobacterium tumefaciens strain EHA 105 harboring the pSF and pEFESF plasmids with soybean ferritin cDNA. Four to eight percent of the co-cultivated leaf bases produced multiple shoots 6 weeks after transfer to Murashige and Skoog's medium supplemented with α-naphthalene acetic acid 1.8 mg/l, indole-3-butyric acid 2.0 mg/l, kinetin 2.0 mg/l, cefotaxime 400 mg/l, and kanamycin 50 mg/l. Putatively transformed shoots (1-2 cm) were selected and multiplied on medium of the same composition and elongated shoots (5 cm) were rooted on liquid rooting medium supplemented with cefotaxime 400 mg/l and kanamycin 100 mg/l. The rooted plants were analyzed through PCR, genomic Southern analysis, and reverse transcription PCR. The results clearly confirmed the integration and expression of soybean ferritin gene in the transformed plants. Atomic absorption spectroscopic analysis carried out with six independently transformed lines of pSF and pEFE-SF revealed a maximum of 5.03-fold increase in iron and 2.44-fold increase in zinc accumulation in the leaves of pSF-transformed plants. In pEFE-SF-transformed plants, a 3.65-fold increase in iron and 2.05-fold increase in zinc levels was observed. Few of the transgenic plants were hardened in the greenhouse and are being grown to maturity to determine the enhanced iron and zinc accumulation in the fruits. To the best of our knowledge this is the first report on the transformation of pineapple with soybean ferritin for enhanced accumulation of iron and zinc content in the transgenic plants.

Intestinal Iron Homeostasis and Colon Tumorigenesis

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Yatrik M. Shah

2013-06-01

Full Text Available Colorectal cancer (CRC is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.

Overload of iron in the skin of patients with varicose ulcers. Possible contributing role of iron accumulation in progression of the disease

International Nuclear Information System (INIS)

Ackerman, Z.; Seidenbaum, M.; Loewenthal, E.; Rubinow, A.

1988-01-01

The brown pigmentation of the skin associated with venous ulceration is caused by increased local iron deposition. Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for the noninvasive determination of iron levels in the skin of patients with venous ulceration. The mean (+/- SEM) iron concentration in the skin around the venous ulcer was elevated, compared with control values of nonulcerated skin (250 +/- 54 vs 128 +/- 39 micrograms) and compared with normal skin from the forearm (250 +/- 54 vs 14 +/- 2.5 micrograms). These data suggest that dermal iron deposition may not be an incidental by-product of increased venous pressure, but may actively perpetuate tissue damage in venous ulcerations

Effect of iron containing supplements on rats' dental caries progression.

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Eshghi, Ar; Kowsari-Isfahan, R; Rezaiefar, M; Razavi, M; Zeighami, S

2012-01-01

Iron deficiency is the most common form of malnutrition in developing countries. Iron containing supplements have been used effectively to solve this problem. In children, because of teeth staining after taking iron drops, parents have the idea that iron drops are the cause of tooth decay; therefore, they limit this vital supplement in their children's diet. Hereby, we evaluate the histologic effect of iron containing supplements on tooth caries in rice rats with cariogenic or non-cariogenic diet. Twelve rats were selected and divided into four groups for this interventional experimental study. Four different types of dietary regimens were used for four months; group A, cariogenic diet with iron containing supplements; group B, cariogenic diet without iron containing supplements; group C, non-cariogenic diet with iron containing supplements; group D, non-cariogenic diet without iron containing supplements. After sacrificing the rats, 20-micron histological sections of their posterior teeth were prepared using the Ground Section method, then they were studied under polarized light microscopy. In order to compare the progression of caries in different samples, the depth of the lesions in the enamel was measured as three grades I, II and III. The mean grade value of A, B, C and D groups were 1.61, 2.61, 1.37 and 1.80, respectively. Statistical analysis revealed that significantly fewer caries were seen in the group which had received iron containing supplements and cariogenic diet compared with cariogenic diet without iron supplements (pcariogenic dietary regimen.

Size-Dependent Accumulation of PEGylated Silane-Coated Magnetic Iron Oxide Nanoparticles in Murine Tumors

DEFF Research Database (Denmark)

Larsen, Esben Kjær Unmack; Nielsen, T.; Wittenborn, T.

2009-01-01

following intravenous injection. Biocompatible iron oxide MNPs coated with PEG were prepared by replacing oleic acid with a biocompatible and commercially available silane-PEG to provide an easy and effective method for chemical coating. The colloidal stable PEGylated MNPs were magnetically separated...... into two distinct size subpopulations of 20 and 40 nm mean diameters with increased phagocytic uptake observed for the 40 nm size range in vitro. MRI detection revealed greater iron accumulation in murine tumors for 40 nm nanoparticles after intravenous injection. The enhanced MRI contrast of the larger...

Accumulation of iron and arsenic in the Chandina alluvium of the lower delta plain, Southeastern Bangladesh

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Zahid, A.; Hassan, M.Q.; Breit, G.N.; Balke, K.-D.; Flegr, M.

2009-01-01

Accumulations of iron, manganese, and arsenic occur in the Chandina alluvium of southeastern Bangladesh within 2.5 m of the ground surface. These distinctive orange-brown horizons are subhorizontal and consistently occur within 1 m of the contact of the aerated (yellow-brown) and water-saturated (gray) sediment. Ferric oxyhydroxide precipitates that define the horizons form by oxidation of reduced iron in pore waters near the top of the saturated zone when exposed to air in the unsaturated sediment. Hydrous Fe-oxide has a high specific surface area and thus a high adsorption capacity that absorbs the bulk of arsenic also present in the reduced pore water, resulting in accumulations containing as much as 280 ppm arsenic. The steep redox gradient that characterizes the transition of saturated and unsaturated sediment also favors accumulation of manganese oxides in the oxidized sediment. Anomalous concentrations of phosphate and molybdenum also detected in the ferric oxyhydroxide-enriched sediment are attributed to sorption processes. ?? Springer Science+Business Media B.V. 2008.

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis.

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Fujiwara, E; Kmech, J A; Cobzas, D; Sun, H; Seres, P; Blevins, G; Wilman, A H

2017-05-01

Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging-based iron-susceptibility measures. Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions. Compared with controls, patients showed reduced memory ( P processing speed ( P = .02) and smaller putamen ( P deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis. © 2017 by American Journal of Neuroradiology.

Field experiment for determining lead accumulation in rice grains of different genotypes and correlation with iron oxides deposited on rhizosphere soil.

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Lai, Yu-Cheng; Syu, Chien-Hui; Wang, Pin-Jie; Lee, Dar-Yuan; Fan, Chihhao; Juang, Kai-Wei

2018-01-01

Paddy rice (Oryza sativa L.) is a major staple crop in Asia. However, heavy metal accumulation in paddy soil poses a health risk for rice consumption. Although plant uptake of Pb is usually low, Pb concentrations in rice plants have been increasing with Pb contamination in paddy fields. It is known that iron oxide deposits in the rhizosphere influence the absorption of soil Pb by rice plants. In this study, 14 rice cultivars bred in Taiwan, including ten japonica cultivars (HL21, KH145, TC192, TK9, TK14, TK16, TN11, TNG71, TNG84, and TY3) and four indica cultivars (TCS10, TCS17, TCSW2, and TNGS22), were used in a field experiment. We investigated the genotypic variation in rice plant Pb in relation to iron oxides deposited in the rhizosphere, as seen in a suspiciously contaminated site in central Taiwan. The results showed that the cultivars TCSW2, TN11, TNG71, and TNG84 accumulated brown rice Pb exceeding the tolerable level of 0.2mgkg -1 . In contrast, the cultivars TNGS22, TK9, TK14, and TY3 accumulated much lower brown rice Pb (iron oxides deposited on the rhizosphere soil show stronger affinity to soil-available Pb than those on the root surface to form iron plaque. The relative tendency of Pb sequestration toward rhizosphere soil was negatively correlated with the Pb concentrations in brown rice. The iron oxides deposited on the rhizosphere soil but not on the root surface to form iron plaque dominate Pb sequestration in the rhizosphere. Therefore, the enhancement of iron oxide deposits on the rhizosphere soil could serve as a barrier preventing soil Pb on the root surface and result in reduced Pb accumulation in brown rice. Copyright © 2017 Elsevier B.V. All rights reserved.

Interaction between cadmium and iron. Accumulation and distribution of metals and changes in growth parameters of Phaseolus vulgaris L. seedlings

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Anna Siedlecka

2014-01-01

Full Text Available The interaction between cadmium, one of the most toxic heavy metals, and iron, an essential plant nutritional element, was investigated in Phaseolus vulgaris L. (cv. Słowianka seedlings. The interaction was externally induced by changing the content of both metals in the nutrient medium. Under iron deficiency conditions (0 and 0.5 of normal dose of this element, the toxic effects of cadmium on plant growth parameters, like fresh and dry weight accumulation, primary leaves area, etc., were generally much more pronounced than under normal iron supply. At normal and excess iron supply (1, 2 and 4 doses cadmium diminished iron accumulation in roots and primary leaves, but on the other hand excess iron decreased cadmium level, preventing plants from extreme toxicity of very high cadmium concentrations in the growth environment. It is to be noted that iron is classified also as a heavy metal, and its excess may become toxic, e.g. decreasing root dry weight or diminishing leaf area, especially at the highest dose. The detoxication role of iron against cadmium, and possibly other toxic metals is, however, limited to concentrations of this element in the nutrient solution which themselves are not toxic for the organism.

The problem of iron partition between Earth and Moon during simultaneous formation as a double planet system

Science.gov (United States)

Cassidy, W. A.

1984-01-01

A planetary model is described which requires fractional vapor/liquid condensation, planet accumulation during condensation, a late start for accumulation of the Moon, and volatile accretion to the surfaces of each planet only near the end of the accumulation process. In the model, initial accumulation of small objects is helped if the agglomerating particles are somewhat sticky. Assuming that growth proceeds through this range, agglomeration continues. If the reservoir of vapor is being preferentially depleted in iron by fractional condensation, an iron-rich planetary core forms. As the temperature decreases, condensing material becomes progressively richer in silicates and poorer in iron, forming the silicate-rich mantle of an already differentiated Earth. A second center of agglomeration successfully forms near the growing Earth after most of the iron in the reservoir has been used up. The bulk composition of the Moon then is similar to the outer mantle of the accumulating Earth.

A Dextral Primary Progressive Aphasia Patient with Right Dominant Hypometabolism and Tau Accumulation and Left Dominant Amyloid Accumulation

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Young Kyoung Jang

2016-04-01

Full Text Available Background: Primary progressive aphasia (PPA is a degenerative disease that presents as progressive decline of language ability with preservation of other cognitive functions in the early stages. Three subtypes of PPA are known: progressive nonfluent aphasia, semantic dementia, and logopenic aphasia (LPA. Patients and Methods: We report the case of a 77-year-old patient with PPA whose clinical findings did not correspond to the three subtypes but mainly fit LPA. Unlike other LPA patients, however, this patient showed a right hemisphere predominant glucose hypometabolism and tau accumulation and a left hemisphere predominant amyloid deposition. The right-handed patient presented with comprehension difficulty followed by problems naming familiar objects. This isolated language problem had deteriorated rapidly for 2 years, followed by memory difficulties and impairment of daily activities. Using a Korean version of the Western Aphasia Battery, aphasia was consistent with a severe form of Wernicke's aphasia. According to the brain magnetic resonance imaging and 18F-fludeoxyglucose positron emission tomography results, right hemisphere atrophy and hypometabolism, more predominant on the right hemisphere than the left, were apparent despite the fact that Edinburgh Handedness Questionnaire scores indicated strong right-handedness. On Pittsburgh compound B-PET, amyloid accumulation was asymmetrical with the left hemisphere being more predominant than the right, whereas 18F-T807-PET showed a right dominant tau accumulation. Conclusions: This is the first report of atypical PPA, in which the patient exhibited crossed aphasia and asymmetrical amyloid accumulation.

Arabidopsis Glutaredoxin S17 Contributes to Vegetative Growth, Mineral Accumulation, and Redox Balance during Iron Deficiency

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Han Yu

2017-06-01

Full Text Available Iron (Fe is an essential mineral nutrient and a metal cofactor required for many proteins and enzymes involved in the processes of DNA synthesis, respiration, and photosynthesis. Iron limitation can have detrimental effects on plant growth and development. Such effects are mediated, at least in part, through the generation of reactive oxygen species (ROS. Thus, plants have evolved a complex regulatory network to respond to conditions of iron limitations. However, the mechanisms that couple iron deficiency and oxidative stress responses are not fully understood. Here, we report the discovery that an Arabidopsis thaliana monothiol glutaredoxin S17 (AtGRXS17 plays a critical role in the plants ability to respond to iron deficiency stress and maintain redox homeostasis. In a yeast expression assay, AtGRXS17 was able to suppress the iron accumulation in yeast ScGrx3/ScGrx4 mutant cells. Genetic analysis indicated that plants with reduced AtGRXS17 expression were hypersensitive to iron deficiency and showed increased iron concentrations in mature seeds. Disruption of AtGRXS17 caused plant sensitivity to exogenous oxidants and increased ROS production under iron deficiency. Addition of reduced glutathione rescued the growth and alleviates the sensitivity of atgrxs17 mutants to iron deficiency. These findings suggest AtGRXS17 helps integrate redox homeostasis and iron deficiency responses.

Flavonoids-induced accumulation of hypoxia-inducible factor (HIF)-1alpha/2alpha is mediated through chelation of iron.

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Park, Sung-Soo; Bae, Insoo; Lee, Yong J

2008-04-15

Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the regulatory subunit of the heterodimeric transcription factor HIF-1 that is the key regulator of cellular response to low oxygen tension. Under normoxic conditions, HIF-1alpha is continuously degraded by the ubiquitin-proteasome pathway through pVHL (von Hippel-Lindau tumor suppressor protein). Under hypoxic conditions, HIF-1alpha is stabilized and induces the transcription of HIF-1 target genes. Quercetin, a flavonoid with anti-oxidant, anti-inflammatory, and kinase modulating properties, has been found to induce HIF-1alpha accumulation and VEGF secretion in normoxia. In this study, the molecular mechanisms of quercetin-mediated HIF-1alpha accumulation were investigated. Previous studies have shown that, in addition to being induced by hypoxia, HIF-1alpha can be induced through the phosphatidylinositol 3-kinase (PI3K)/Akt and p53 signaling pathways. But our study revealed, through p53 mutant-type as well as p53 null cell lines, that neither the PI3K/Akt nor the p53 signaling pathway is required for quercetin-induced HIF-1alpha accumulation. And we observed that HIF-1alpha accumulated by quercetin is not ubiquitinated and the interaction of HIF-1alpha with pVHL is reduced, compared with HIF-1alpha accumulated by the proteasome inhibitor MG132. The use of quercetin's analogues showed that only quercetin and galangin induce HIF-1/2alpha accumulation and this effect is completely reversed by additional iron ions. This is because quercetin and galangin are able to chelate cellular iron ions that are cofactors of HIF-1/2alpha proline hydroxylase (PHD). These data suggest that quercetin inhibits the ubiquitination of HIF-1/2alpha in normoxia by hindering PHD through chelating iron ions.

Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein-expressing mice

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Korenaga, Masaaki; Nishina, Sohji; Korenaga, Keiko; Tomiyama, Yasuyuki; Yoshioka, Naoko; Hara, Yuichi; Sasaki, Yusuke; Shimonaka, Yasushi; Hino, Keisuke

2015-01-01

Background & Aims Branched-chain amino acids (BCAA) reduce the incidence of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the mechanisms that underlie these effects remain unknown. Previously, we reported that oxidative stress in male transgenic mice that expressed hepatitis C virus polyprotein (HCVTgM) caused hepatic iron accumulation by reducing hepcidin transcription, thereby leading to HCC development. This study investigated whether long-term treatment with BCAA reduced hepatic iron accumulation and oxidative stress in iron-overloaded HCVTgM and in patients with HCV-related advanced fibrosis. Methods Male HCVTgM were fed an excess-iron diet that comprised either casein or 3.0% BCAA, or a control diet, for 6 months. Results For HCVTgM, BCAA supplementation increased the serum hepcidin-25 levels and antioxidant status [ratio of biological antioxidant potential (BAP) relative to derivatives of reactive oxygen metabolites (dROM)], decreased the hepatic iron contents, attenuated reactive oxygen species generation, and restored mitochondrial superoxide dismutase expression and mitochondrial complex I activity in the liver compared with mice fed the control diet. After 48 weeks of BCAA supplementation in patients with HCV-related advanced fibrosis, BAP/dROM and serum hepcidin-25 increased and serum ferritin decreased compared with the pretreatment levels. Conclusions BCAA supplementation reduced oxidative stress by restoring mitochondrial function and improved iron metabolism by increasing hepcidin-25 in both iron-overloaded HCVTgM and patients with HCV-related advanced fibrosis. These activities of BCAA may partially account for their inhibitory effects on HCC development in cirrhosis patients. PMID:25156780

Variation and inheritance of iron reductase activity in the roots of common bean (Phaseolus vulgaris L.) and association with seed iron accumulation QTL.

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Blair, Matthew W; Knewtson, Sharon Jb; Astudillo, Carolina; Li, Chee-Ming; Fernandez, Andrea C; Grusak, Michael A

2010-10-05

Iron deficiency anemia is a global problem which often affects women and children of developing countries. Strategy I plants, such as common bean (Phaseolus vulgaris L.) take up iron through a process that involves an iron reduction mechanism in their roots; this reduction is required to convert ferric iron to ferrous iron. Root absorbed iron is critical for the iron nutrition of the plant, and for the delivery of iron to the shoot and ultimately the seeds. The objectives of this study were to determine the variability and inheritance for iron reductase activity in a range of genotypes and in a low × high seed iron cross (DOR364 x G19833), to identify quantitative trait loci (QTL) for this trait, and to assess possible associations with seed iron levels. The experiments were carried out with hydroponically grown plants provided different amounts of iron varying between 0 and 20 μM Fe(III)-EDDHA. The parents, DOR364 and G19833, plus 13 other cultivated or wild beans, were found to differ in iron reductase activity. Based on these initial experiments, two growth conditions (iron limited and iron sufficient) were selected as treatments for evaluating the DOR364 × G19833 recombinant inbred lines. A single major QTL was found for iron reductase activity under iron-limited conditions (1 μM Fe) on linkage group b02 and another major QTL was found under iron sufficient conditions (15 μM Fe) on linkage group b11. Associations between the b11 QTL were found with several QTL for seed iron. Genes conditioning iron reductase activity in iron sufficient bean plants appear to be associated with genes contributing to seed iron accumulation. Markers for bean iron reductase (FRO) homologues were found with in silico mapping based on common bean synteny with soybean and Medicago truncatula on b06 and b07; however, neither locus aligned with the QTL for iron reductase activity. In summary, the QTL for iron reductase activity under iron limited conditions may be useful in

Variation and inheritance of iron reductase activity in the roots of common bean (Phaseolus vulgaris L. and association with seed iron accumulation QTL

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Fernandez Andrea C

2010-10-01

Full Text Available Abstract Background Iron deficiency anemia is a global problem which often affects women and children of developing countries. Strategy I plants, such as common bean (Phaseolus vulgaris L. take up iron through a process that involves an iron reduction mechanism in their roots; this reduction is required to convert ferric iron to ferrous iron. Root absorbed iron is critical for the iron nutrition of the plant, and for the delivery of iron to the shoot and ultimately the seeds. The objectives of this study were to determine the variability and inheritance for iron reductase activity in a range of genotypes and in a low × high seed iron cross (DOR364 × G19833, to identify quantitative trait loci (QTL for this trait, and to assess possible associations with seed iron levels. Results The experiments were carried out with hydroponically grown plants provided different amounts of iron varying between 0 and 20 μM Fe(III-EDDHA. The parents, DOR364 and G19833, plus 13 other cultivated or wild beans, were found to differ in iron reductase activity. Based on these initial experiments, two growth conditions (iron limited and iron sufficient were selected as treatments for evaluating the DOR364 × G19833 recombinant inbred lines. A single major QTL was found for iron reductase activity under iron-limited conditions (1 μM Fe on linkage group b02 and another major QTL was found under iron sufficient conditions (15 μM Fe on linkage group b11. Associations between the b11 QTL were found with several QTL for seed iron. Conclusions Genes conditioning iron reductase activity in iron sufficient bean plants appear to be associated with genes contributing to seed iron accumulation. Markers for bean iron reductase (FRO homologues were found with in silico mapping based on common bean synteny with soybean and Medicago truncatula on b06 and b07; however, neither locus aligned with the QTL for iron reductase activity. In summary, the QTL for iron reductase activity

Evaluation of constitutive iron reductase (AtFRO2 expression on mineral accumulation and distribution in soybean (Glycine max. L

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Marta Wilton Vasconcelos

2014-04-01

Full Text Available Iron is an important micronutrient in human and plant nutrition. Adequate iron nutrition during crop production is central for assuring appropriate iron concentrations in the harvestable organs, for human food or animal feed. The whole-plant movement of iron involves several processes, including the reduction of ferric to ferrous iron at several locations throughout the plant, prior to transmembrane trafficking of ferrous iron. In this study, soybean plants that constitutively expressed the AtFRO2 iron reductase gene were analyzed for leaf iron reductase activity, as well as the effect of this transgene's expression on root, leaf, pod wall, and seed mineral concentrations. High Fe supply, in combination with the constitutive expression of AtFRO2, resulted in significantly higher concentrations of different minerals in roots (K, P, Zn, Ca, Ni, Mg and Mo, pod walls (Fe, K, P, Cu and Ni, leaves (Fe, P, Cu, Ca, Ni and Mg and seeds (Fe, Zn, Cu and Ni. Leaf and pod wall iron concentrations increased as much as 500% in transgenic plants, while seed iron concentrations only increased by 10%, suggesting that factors other than leaf and pod wall reductase activity were limiting the translocation of iron to seeds. Protoplasts isolated from transgenic leaves had three-fold higher reductase activity than controls. Expression levels of the iron storage protein, ferritin, were higher in the transgenic leaves than in wild-type, suggesting that the excess iron may be stored as ferritin in the leaves and therefore unavailable for phloem loading and delivery to the seeds. Also, citrate and malate levels in the roots and leaves of transgenic plants were significantly higher than in wild-type, suggesting that organic acid production could be related to the increased accumulation of minerals in roots, leaves and pod walls, but not in the seeds. All together, these results suggest a more ubiquitous role for the iron reductase in whole-plant mineral accumulation and

Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features.

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Heidari, M; Johnstone, D M; Bassett, B; Graham, R M; Chua, A C G; House, M J; Collingwood, J F; Bettencourt, C; Houlden, H; Ryten, M; Olynyk, J K; Trinder, D; Milward, E A

2016-11-01

The 'neurodegeneration with brain iron accumulation' (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe -/- × Tfr2 mut brain (P=0.002, n ≥5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (Pgross myelin structure and integrity appear unaffected (P>0.05). Overlap (P0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis.

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Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

2016-12-01

While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression. We suggest one reason that a greater percentage of patients with MS didn't respond to biotin therapy is the inaccessibility or lack of other nutrients, such as iron. In addition to biotin, iron (or heme) is necessary for energy production, biosynthesis of cholesterol and lipids, and for some protective mechanisms. Both biotin and iron are required for myelination during development, and by inference, remyelination. However, iron can also play a role in the pathology of MS. Increased deposition of iron can occur in some CNS structures possibly promoting oxidative damage while low iron levels can occur in other areas. Thus, the potential, detrimental effects of iron need to be considered together with the need for iron to support metabolic demands associated with repair and/or protective processes. We propose the optimal utilization of iron may be necessary to maximize the beneficial effects of biotin. This review will examine the interactions between biotin and iron in pathways that may have therapeutic or pathogenic implications for MS.

IRON, ZINC, AND FERRITIN ACCUMULATION IN COMMON BEANS

DEFF Research Database (Denmark)

Urbanski, Dorian Fabian; Sørensen, Kirsten; Jurkiewicz, Anna Malgorzata

Iron and zinc malnutrition are major threats to human health and development around the world. The World Health Organization states that over two billion people are affected by iron deficiency. In particular children and pregnant women in developing countries are affected by iron deficiency...... in mature seeds, but the ferritin protein was suggested to be the major iron storing protein in legumes [1]. Both iron and zinc localization, as well as speciation, can have an impact on their nutritional availability. We will present detailed information about iron, zinc, and ferritin distribution...

Red mud (RM)-Induced enhancement of iron plaque formation reduces arsenic and metal accumulation in two wetland plant species.

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Yang, J X; Guo, Q J; Yang, J; Zhou, X Y; Ren, H Y; Zhang, H Z; Xu, R X; Wang, X D; Peters, M; Zhu, G X; Wei, R F; Tian, L Y; Han, X K

2016-01-01

Human activities have resulted in arsenic (As) and heavy metals accumulation in paddy soils in China. Phytoremediation has been suggested as an effective and low-cost method to clean up contaminated soils. A combined soil-sand pot experiment was conducted to investigate the influence of red mud (RM) supply on iron plaque formation and As and heavy metal accumulation in two wetland plant species (Cyperus alternifolius Rottb., Echinodorus amazonicus Rataj), using As and heavy metals polluted paddy soil combined with three rates of RM application (0, 2%, 5%). The results showed that RM supply significantly decreased As and heavy metals accumulation in shoots of the two plants due to the decrease of As and heavy metal availability and the enhancement of the formation of iron plaque on the root surface and in the rhizosphere. Both wetland plants supplied with RM tended to have more Fe plaque, higher As and heavy metals on roots and in their rhizospheres, and were more tolerant of As and heavy metal toxicity. The results suggest that RM-induced enhancement of the formation of iron plaque on the root surface and in the rhizosphere of wetland plants may be significant for remediation of soils contaminated with As and heavy metals.

Oxidative stress and damage in liver, but not in brain, of Fischer 344 rats subjected to dietary iron supplementation with lipid-soluble[(3,5,5-Trimethylhexanoyl)ferrocene

DEFF Research Database (Denmark)

Lykkesfeldt, Jens; Morgan, Evan; Christen, Stephan

2007-01-01

Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month old rats following supplementationwith the lipophilic iron derivative [(3,5,5-trimethylhexanoyl)ferrocene] (......, they also demonstrated that the brain is well protected against dietary iron overload by using iron in a lipid-soluble formulation.......Accumulation of iron probably predisposes the aging brain to progressive neuronal loss. We examined various markers of oxidative stress and damage in the brain and liver of 3- and 24-month old rats following supplementationwith the lipophilic iron derivative [(3,5,5-trimethylhexanoyl......)ferrocene] (TMHF), which is capable of crossing the blood-brain barrier. At both ages, iron concentration increased markedly in the liver but failed to increase in the brain. In the liver of TMHF-treated young rats, levels of a- and ¿-tocopherols and glutathione (GSH) were also higher. In contrast, the brain...

Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology.

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Justin Y Kwan

Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI studies have previously shown hypointense signal in the motor cortex on T(2-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or definite ALS by El Escorial criteria and 19 healthy controls underwent 3T MRI. A 7T MRI scan was carried out on five ALS patients who had motor cortex hypointensity on the 3T FLAIR sequence and on three healthy controls. Postmortem 7T MRI of the brain was performed in one ALS patient and histological studies of the brains and spinal cords were obtained post-mortem in two patients. The motor cortex hypointensity on 3T FLAIR images was present in greater frequency in ALS patients. Increased hypointensity correlated with greater severity of upper motor neuron impairment. Analysis of 7T T(2(*-weighted gradient echo imaging localized the signal alteration to the deeper layers of the motor cortex in both ALS patients. Pathological studies showed increased iron accumulation in microglial cells in areas corresponding to the location of the signal changes on the 3T and 7T MRI of the motor cortex. These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia.

GLP-1-RA Corrects Mitochondrial Labile Iron Accumulation and Improves β-Cell Function in Type 2 Wolfram Syndrome.

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Danielpur, Liron; Sohn, Yang-Sung; Karmi, Ola; Fogel, Chen; Zinger, Adar; Abu-Libdeh, Abdulsalam; Israeli, Tal; Riahi, Yael; Pappo, Orit; Birk, Ruth; Zangen, David H; Mittler, Ron; Cabantchik, Zvi-Ioav; Cerasi, Erol; Nechushtai, Rachel; Leibowitz, Gil

2016-10-01

Type 2 Wolfram syndrome (T2-WFS) is a neuronal and β-cell degenerative disorder caused by mutations in the CISD2 gene. The mechanisms underlying β-cell dysfunction in T2-WFS are not known, and treatments that effectively improve diabetes in this context are lacking. Unraveling the mechanisms of β-cell dysfunction in T2-WFS and the effects of treatment with GLP-1 receptor agonist (GLP-1-RA). A case report and in vitro mechanistic studies. We treated an insulin-dependent T2-WFS patient with the GLP-1-RA exenatide for 9 weeks. An iv glucose/glucagon/arginine stimulation test was performed off-drug before and after intervention. We generated a cellular model of T2-WFS by shRNA knockdown of CISD2 (nutrient-deprivation autophagy factor-1 [NAF-1]) in rat insulinoma cells and studied the mechanisms of β-cell dysfunction and the effects of GLP-1-RA. Treatment with exenatide resulted in a 70% reduction in daily insulin dose with improved glycemic control, as well as an off-drug 7-fold increase in maximal insulin secretion. NAF-1 repression in INS-1 cells decreased insulin content and glucose-stimulated insulin secretion, while maintaining the response to cAMP, and enhanced the accumulation of labile iron and reactive oxygen species in mitochondria. Remarkably, treatment with GLP-1-RA and/or the iron chelator deferiprone reversed these defects. NAF-1 deficiency leads to mitochondrial labile iron accumulation and oxidative stress, which may contribute to β-cell dysfunction in T2-WFS. Treatment with GLP-1-RA and/or iron chelation improves mitochondrial function and restores β-cell function. Treatment with GLP-1-RA, probably aided by iron chelation, should be considered in WFS and other forms of diabetes associated with iron dysregulation.

The effect of silicon on iron plaque formation and arsenic accumulation in rice genotypes with different radial oxygen loss (ROL).

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Wu, Chuan; Zou, Qi; Xue, Sheng-Guo; Pan, Wei-Song; Huang, Liu; Hartley, William; Mo, Jing-Yu; Wong, Ming-Hung

2016-05-01

Rice is one of the major pathways of arsenic (As) exposure in human food chain, threatening over half of the global population. Greenhouse pot experiments were conducted to examine the effects of Si application on iron (Fe) plaque formation, As uptake and rice grain As speciation in indica and hybrid rice genotypes with different radial oxygen loss (ROL) ability. The results demonstrated that Si significantly increased root and grain biomass. Indica genotypes with higher ROL induced greater Fe plaque formation, compared to hybrid genotypes and sequestered more As in Fe plaque. Silicon applications significantly increased Fe concentrations in iron plaque of different genotypes, but it decreased As concentrations in the roots, straws and husks by 28-35%, 15-35% and 32-57% respectively. In addition, it significantly reduced DMA accumulation in rice grains but not inorganic As accumulation. Rice of indica genotypes with higher ROL accumulated lower concentrations of inorganic As in grains than hybrid genotypes with lower ROL. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antifibrotic effect of xanthohumol in combination with praziquantel is associated with altered redox status and reduced iron accumulation during liver fluke-associated cholangiocarcinogenesis

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Wassana Jamnongkan

2018-01-01

Full Text Available Cholangiocarcinoma (CCA caused by infection of the liver fluke Opisthorchis viverrini, (Ov is the major public health problem in northeast Thailand. Following Ov infection the subsequent molecular changes can be associated by reactive oxygen species (ROS induced chronic inflammation, advanced periductal fibrosis, and cholangiocarcinogenesis. Notably, resistance to an activation of cell death in prolonged oxidative stress conditions can occur but some damaged/mutated cells could survive and enable clonal expansion. Our study used a natural product, xanthohumol (XN, which is an anti-oxidant and anti-inflammatory compound, to examine whether it could prevent Ov-associated CCA carcinogenesis. We measured the effect of XN with or without praziquantel (PZ, an anti-helminthic treatment, on DNA damage, redox status change including iron accumulation and periductal fibrosis during CCA genesis induced by administration of Ov and N-dinitrosomethylamine (NDMA in hamsters. Animals were randomly divided into four groups: group I, Ov infection and NDMA administration (ON; group II, Ov infection and NDMA administration and PZ treatment (ONP; the latter 2 groups were similar to group I and II, but group III received additional XN (XON and group IV received XN plus PZ (XONP. The results showed that high 8-oxodG (a marker of DNA damage was observed throughout cholangiocarcinogenesis. Moreover, increased expression of CD44v8-10 (a cell surface in regulation of the ROS defense system, whereas decreased expression of phospho-p38MAPK (a major ROS target, was found during the progression of the bile duct cell transformation. In addition, high accumulation of iron and expression of transferrin receptor-1 (TfR-1 in both malignant bile ducts and inflammatory cells were detected. Furthermore, fibrosis also increased with the highest level being on day 180. On the other hand, the groups of XN with or without PZ supplementations showed an effective reduction in all the

Non-Motor Symptom Burdens Are Not Associated with Iron Accumulation in Early Parkinson's Disease: a Quantitative Susceptibility Mapping Study.

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Shin, Chaewon; Lee, Seon; Lee, Jee Young; Rhim, Jung Hyo; Park, Sun Won

2018-03-26

Quantitative susceptibility mapping (QSM) has been used to measure iron accumulation in the deep nuclei of patients with Parkinson's disease (PD). This study examined the relationship between non-motor symptoms (NMSs) and iron accumulation in the deep nuclei of patients with PD. The QSM data were acquired from 3-Tesla magnetic resonance imaging (MRI) in 29 patients with early PD and 19 normal controls. The Korean version of the NMS scale (K-NMSS) was used for evaluation of NMSs in patients. The patients were divided into high NMS and low NMS groups. The region-of-interest analyses were performed in the following deep nuclei: red nucleus, substantia nigra pars compacta, substantia nigra pars reticulata, dentate nucleus, globus pallidus, putamen, and head of the caudate nucleus. Thirteen patients had high NMS scores (total K-NMSS score, mean = 32.1), and 16 had low NMS scores (10.6). The QSM values in the deep were not different among the patients with high NMS scores, low NMS scores, and controls. The QSM values were not correlated linearly with K-NMSS total score after adjusting the age at acquisition of brain MRI. The study demonstrated that the NMS burdens are not associated with iron accumulation in the deep nuclei of patients with PD. These results suggest that future neuroimaging studies on the pathology of NMSs in PD should use more specific and detailed clinical tools and recruit PD patients with severe NMSs. © 2018 The Korean Academy of Medical Sciences.

Measurement of helium production cross sections of iron for d-T neutrons by helium accumulation method

Energy Technology Data Exchange (ETDEWEB)

Takao, Yoshiyuki; Kanda, Yukinori; Nagae, Koji; Fujimoto, Toshihiro [Kyushu Univ., Fukuoka (Japan); Ikeda, Yujiro

1997-03-01

Helium production cross sections of Iron were measured by helium accumulation method for neutron energies from 13.5 to 14.9 MeV. Iron samples were irradiated with FNS, an intense d-T neutron source of JAERI. As the neutron energy varies according to the emission angle at the neutron source, the samples were set around the neutron source and were irradiated by neutrons of different energy depending on each sample position. The amount of helium produced in a sample was measured by Helium Atoms Measurement System at Kyushu University. The results of this work are in good agreement with other experimental data in the literature and also compared with the evaluated values in JENDL-3. (author)

Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms

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Elena Gammella

2015-01-01

Full Text Available The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies.

Iron metabolism and toxicity

International Nuclear Information System (INIS)

Papanikolaou, G.; Pantopoulos, K.

2005-01-01

Iron is an essential nutrient with limited bioavailability. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis has to be tightly controlled. Iron's toxicity is largely based on its ability to catalyze the generation of radicals, which attack and damage cellular macromolecules and promote cell death and tissue injury. This is lucidly illustrated in diseases of iron overload, such as hereditary hemochromatosis or transfusional siderosis, where excessive iron accumulation results in tissue damage and organ failure. Pathological iron accumulation in the liver has also been linked to the development of hepatocellular cancer. Here we provide a background on the biology and toxicity of iron and the basic concepts of iron homeostasis at the cellular and systemic level. In addition, we provide an overview of the various disorders of iron overload, which are directly linked to iron's toxicity. Finally, we discuss the potential role of iron in malignant transformation and cancer

Enhanced lipid accumulation and biodiesel production by oleaginous Chlorella protothecoides under a structured heterotrophic-iron (II) induction strategy.

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Li, Yuqin; Mu, Jinxiu; Chen, Di; Xu, Hua; Han, Fangxin

2015-05-01

A structured heterotrophic-iron (II) induction (HII) strategy was proposed to enhance lipid accumulation in oleaginous Chlorella protothecoides. C. protothecoides subjected to heterotrophic-iron (II) induction achieved a favorable lipid accumulation up to 62 % and a maximum lipid productivity of 820.17 mg/day, representing 2.78-fold and 3.64-fold increase respectively over heterotrophic cultivation alone. HII-induced cells produced significantly elevated levels of 16:0, 18:1(Δ9), and 18:2(Δ9,12) fatty acids (over 90 %). The lipid contents and plant lipid-like fatty acid compositions exhibit the potential of HII-induced C. protothecoides as biodiesel feedstock. Furthermore, 31 altered proteins in HII-induced algal cells were successfully identified. These differentially expressed proteins were assigned into nine molecular function categories, including carbohydrate metabolism, lipid biosynthesis, Calvin cycle, cellular respiration, photosynthesis, energy and transport, protein biosynthesis, regulate and defense, and unclassified. Analysis using the Kyoto encyclopedia of genes and genomes and gene ontology annotation showed that malic enzyme, acyltransferase, and ACP were key metabolic checkpoints found to modulate lipid accumulation in C. protothecoides. The results provided possible applications of HII cultivation strategy in other microalgal species and new possibilities in developing genetic and metabolic engineering microalgae for desirable lipid productivity.

Sulfur and iron accumulation in three marine-archaeological shipwrecks in the Baltic Sea: The Ghost, the Crown and the Sword

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Fors, Yvonne; Grudd, Håkan; Rindby, Anders; Jalilehvand, Farideh; Sandström, Magnus; Cato, Ingemar; Bornmalm, Lennart

2014-02-01

Sulfur and iron concentrations in wood from three 17th century shipwrecks in the Baltic Sea, the Ghost wreck, the Crown and the Sword, were obtained by X-ray fluorescence (XRF) scanning. In near anaerobic environments symbiotic microorganisms degrade waterlogged wood, reduce sulfate and promote accumulation of low-valent sulfur compounds, as previously found for the famous wrecks of the Vasa and Mary Rose. Sulfur K-edge X-ray absorption near-edge structure (XANES) analyses of Ghost wreck wood show that organic thiols and disulfides dominate, together with elemental sulfur probably generated by sulfur-oxidizing Beggiatoa bacteria. Iron sulfides were not detected, consistent with the relatively low iron concentration in the wood. In a museum climate with high atmospheric humidity oxidation processes, especially of iron sulfides formed in the presence of corroding iron, may induce post-conservation wood degradation. Subject to more general confirmation by further analyses no severe conservation concerns are expected for the Ghost wreck wood.

Hemochromatosis enhances tumor progression via upregulation of intracellular iron in head and neck cancer.

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Michelle Lenarduzzi

Full Text Available Despite improvements in treatment strategies for head and neck squamous cell carcinoma (HNSCC, outcomes have not significantly improved; highlighting the importance of identifying novel therapeutic approaches to target this disease. To address this challenge, we proceeded to evaluate the role of iron in HNSCC.Expression levels of iron-related genes were evaluated in HNSCC cell lines using quantitative RT-PCR. Cellular phenotypic effects were assessed using viability (MTS, clonogenic survival, BrdU, and tumor formation assays. The prognostic significance of iron-related proteins was determined using immunohistochemistry.In a panel of HNSCC cell lines, hemochromatosis (HFE was one of the most overexpressed genes involved in iron regulation. In vitro knockdown of HFE in HNSCC cell lines significantly decreased hepcidin (HAMP expression and intracellular iron level. This in turn, resulted in a significant decrease in HNSCC cell viability, clonogenicity, DNA synthesis, and Wnt signalling. These cellular changes were reversed by re-introducing iron back into HNSCC cells after HFE knockdown, indicating that iron was mediating this phenotype. Concordantly, treating HNSCC cells with an iron chelator, ciclopirox olamine (CPX, significantly reduced viability and clonogenic survival. Finally, patients with high HFE expression experienced a reduced survival compared to patients with low HFE expression.Our data identify HFE as potentially novel prognostic marker in HNSCC that promotes tumour progression via HAMP and elevated intracellular iron levels, leading to increased cellular proliferation and tumour formation. Hence, these findings suggest that iron chelators might have a therapeutic role in HNSCC management.

Hemochromatosis Enhances Tumor Progression via Upregulation of Intracellular Iron in Head and Neck Cancer

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Lenarduzzi, Michelle; Hui, Angela B. Y.; Yue, Shijun; Ito, Emma; Shi, Wei; Williams, Justin; Bruce, Jeff; Sakemura-Nakatsugawa, Noriko; Xu, Wei; Schimmer, Aaron; Liu, Fei-Fei

2013-01-01

Introduction Despite improvements in treatment strategies for head and neck squamous cell carcinoma (HNSCC), outcomes have not significantly improved; highlighting the importance of identifying novel therapeutic approaches to target this disease. To address this challenge, we proceeded to evaluate the role of iron in HNSCC. Experimental Design Expression levels of iron-related genes were evaluated in HNSCC cell lines using quantitative RT-PCR. Cellular phenotypic effects were assessed using viability (MTS), clonogenic survival, BrdU, and tumor formation assays. The prognostic significance of iron-related proteins was determined using immunohistochemistry. Results In a panel of HNSCC cell lines, hemochromatosis (HFE) was one of the most overexpressed genes involved in iron regulation. In vitro knockdown of HFE in HNSCC cell lines significantly decreased hepcidin (HAMP) expression and intracellular iron level. This in turn, resulted in a significant decrease in HNSCC cell viability, clonogenicity, DNA synthesis, and Wnt signalling. These cellular changes were reversed by re-introducing iron back into HNSCC cells after HFE knockdown, indicating that iron was mediating this phenotype. Concordantly, treating HNSCC cells with an iron chelator, ciclopirox olamine (CPX), significantly reduced viability and clonogenic survival. Finally, patients with high HFE expression experienced a reduced survival compared to patients with low HFE expression. Conclusions Our data identify HFE as potentially novel prognostic marker in HNSCC that promotes tumour progression via HAMP and elevated intracellular iron levels, leading to increased cellular proliferation and tumour formation. Hence, these findings suggest that iron chelators might have a therapeutic role in HNSCC management. PMID:23991213

Iron-reducing bacteria accumulate ferric oxyhydroxide nanoparticle aggregates that may support planktonic growth.

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Luef, Birgit; Fakra, Sirine C; Csencsits, Roseann; Wrighton, Kelly C; Williams, Kenneth H; Wilkins, Michael J; Downing, Kenneth H; Long, Philip E; Comolli, Luis R; Banfield, Jillian F

2013-02-01

Iron-reducing bacteria (FeRB) play key roles in anaerobic metal and carbon cycling and carry out biogeochemical transformations that can be harnessed for environmental bioremediation. A subset of FeRB require direct contact with Fe(III)-bearing minerals for dissimilatory growth, yet these bacteria must move between mineral particles. Furthermore, they proliferate in planktonic consortia during biostimulation experiments. Thus, a key question is how such organisms can sustain growth under these conditions. Here we characterized planktonic microbial communities sampled from an aquifer in Rifle, Colorado, USA, close to the peak of iron reduction following in situ acetate amendment. Samples were cryo-plunged on site and subsequently examined using correlated two- and three-dimensional cryogenic transmission electron microscopy (cryo-TEM) and scanning transmission X-ray microscopy (STXM). The outer membranes of most cells were decorated with aggregates up to 150 nm in diameter composed of ∼3 nm wide amorphous, Fe-rich nanoparticles. Fluorescent in situ hybridization of lineage-specific probes applied to rRNA of cells subsequently imaged via cryo-TEM identified Geobacter spp., a well-studied group of FeRB. STXM results at the Fe L(2,3) absorption edges indicate that nanoparticle aggregates contain a variable mixture of Fe(II)-Fe(III), and are generally enriched in Fe(III). Geobacter bemidjiensis cultivated anaerobically in the laboratory on acetate and hydrous ferric oxyhydroxides also accumulated mixed-valence nanoparticle aggregates. In field-collected samples, FeRB with a wide variety of morphologies were associated with nano-aggregates, indicating that cell surface Fe(III) accumulation may be a general mechanism by which FeRB can grow while in planktonic suspension.

Clinical and Imaging Presentation of a Patient with Beta-Propeller Protein-Associated Neurodegeneration, a Rare and Sporadic form of Neurodegeneration with Brain Iron Accumulation (NBIA).

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Hattingen, Elke; Handke, Nikolaus; Cremer, Kirsten; Hoffjan, Sabine; Kukuk, Guido Matthias

2017-12-01

Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of inherited neurologic disorders with iron accumulation in the basal ganglia, which share magnetic resonance (MR) imaging characteristics, histopathologic and clinical features. According to the affected basal nuclei, clinical features include extrapyramidal movement disorders and varying degrees of intellectual disability status. The most common NBIA subtype is caused by pathogenic variants in PANK2. The hallmark of MR imaging in patients with PANK2 mutations is an eye-of-the-tiger sign in the globus pallidus. We report a 33-year-old female with a rare subtype of NBIA, called beta-propeller protein-associated neurodegeneration (BPAN) with a hitherto unknown missense variant in WDR45. She presented with BPAN's particular biphasic course of neurological symptoms and with a dominant iron accumulation in the midbrain that enclosed a spotty T2-hyperintensity.

Cp/Heph mutant mice have iron-induced neurodegeneration diminished by deferiprone

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Zhao, Liangliang; Hadziahmetovic, Majda; Wang, Chenguang; Xu, Xueying; Song, Ying; Jinnah, H.A.; Wodzinska, Jolanta; Iacovelli, Jared; Wolkow, Natalie; Krajacic, Predrag; Weissberger, Alyssa Cwanger; Connelly, John; Spino, Michael; Lee, Michael K.; Connor, James; Giasson, Benoit; Harris, Z. Leah; Dunaief, Joshua L.

2016-01-01

Brain iron accumulates in several neurodegenerative diseases and can cause oxidative damage, but mechanisms of brain iron homeostasis are incompletely understood. Patients with mutations in the cellular iron-exporting ferroxidase ceruloplasmin (Cp) have brain iron accumulation causing neurodegeneration. Here, we assessed the brains of mice with combined mutation of Cp and its homolog hephaestin. Compared to single mutants, brain iron accumulation was accelerated in double mutants in the cerebellum, substantia nigra, and hippocampus. Iron accumulated within glia, while neurons were iron deficient. There was loss of both neurons and glia. Mice developed ataxia and tremor, and most died by 9 months. Treatment with the oral iron chelator deferiprone diminished brain iron levels, protected against neuron loss, and extended lifespan. Ferroxidases play important, partially overlapping roles in brain iron homeostasis by facilitating iron export from glia, making iron available to neurons. PMID:26303407

In-situ Characterization and Mapping of Iron Compounds in Alzheimer's Tissue

International Nuclear Information System (INIS)

Collingwood, J.F.; Mikhaylova, A.; Davidson, M.; Batich, C.; Streit, W.J.; Terry, J.; Dobson, J.

2005-01-01

There is a well-established link between iron overload in the brain and pathology associated with neurodegeneration in a variety of disorders such as Alzheimer's (AD), Parkinson's (PD) and Huntington's (HD) diseases. This association was first discovered in AD by Goodman in 1953, where, in addition to abnormally high concentrations of iron in autopsy brain tissue, iron has also been shown to accumulate at sites of brain pathology such as senile plaques. However, since this discovery, progress in understanding the origin, role and nature of iron compounds associated with neurodegeneration has been slow. Here we report, for the first time, the location and characterization of iron compounds in human AD brain tissue sections. Iron fluorescence was mapped over a frontal-lobe tissue section from an Alzheimer's patient, and anomalous iron concentrations were identified using synchrotron X-ray absorption techniques at 5 (micro)m spatial resolution. Concentrations of ferritin and magnetite, a magnetic iron oxide potentially indicating disrupted brain-iron metabolism, were evident. These results demonstrate a practical means of correlating iron compounds and disease pathology in-situ and have clear implications for disease pathogenesis and potential therapies.

Combined Therapy of Iron Chelator and Antioxidant Completely Restores Brain Dysfunction Induced by Iron Toxicity

Science.gov (United States)

Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

2014-01-01

Background Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. Methodology Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. Conclusion In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload. PMID:24400127

Fungal Iron Availability during Deep Seated Candidiasis Is Defined by a Complex Interplay Involving Systemic and Local Events

Science.gov (United States)

Potrykus, Joanna; Stead, David; MacCallum, Donna M.; Urgast, Dagmar S.; Raab, Andrea; van Rooijen, Nico; Feldmann, Jörg; Brown, Alistair J. P.

2013-01-01

Nutritional immunity – the withholding of nutrients by the host – has long been recognised as an important factor that shapes bacterial-host interactions. However, the dynamics of nutrient availability within local host niches during fungal infection are poorly defined. We have combined laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS), MALDI imaging and immunohistochemistry with microtranscriptomics to examine iron homeostasis in the host and pathogen in the murine model of systemic candidiasis. Dramatic changes in the renal iron landscape occur during disease progression. The infection perturbs global iron homeostasis in the host leading to iron accumulation in the renal medulla. Paradoxically, this is accompanied by nutritional immunity in the renal cortex as iron exclusion zones emerge locally around fungal lesions. These exclusion zones correlate with immune infiltrates and haem oxygenase 1-expressing host cells. This local nutritional immunity decreases iron availability, leading to a switch in iron acquisition mechanisms within mature fungal lesions, as revealed by laser capture microdissection and qRT-PCR analyses. Therefore, a complex interplay of systemic and local events influences iron homeostasis and pathogen-host dynamics during disease progression. PMID:24146619

Antioxidant responses of cortex neurons to iron loading

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PABLA AGUIRRE

2006-01-01

Full Text Available Brain cells have a highly active oxidative metabolism, yet they contain only low to moderate superoxide dismutase and catalase activities. Thus, their antioxidant defenses rely mainly on cellular reduced glutathione levels. In this work, in cortical neurons we characterized viability and changes in reduced and oxidized glutathione levels in response to a protocol of iron accumulation. We found that massive death occurred after 2 days in culture with 10 mM Fe. Surviving cells developed an adaptative response that included increased synthesis of GSH and the maintenance of a glutathione-based reduction potential. These results highlight the fundamental role of glutathione homeostasis in the antioxidant response and provide novel insights into the adaptative mechanisms of neurons subjected to progressive iron loads.

NCOA4 Deficiency Impairs Systemic Iron Homeostasis

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Roberto Bellelli

2016-01-01

Full Text Available The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and spleen, increased levels of transferrin saturation, serum ferritin, and liver hepcidin, and decreased levels of duodenal ferroportin. Despite signs of iron overload, NCOA4-null mice had mild microcytic hypochromic anemia. Under an iron-deprived diet (2–3 mg/kg, mice failed to release iron from ferritin storage and developed severe microcytic hypochromic anemia and ineffective erythropoiesis associated with increased erythropoietin levels. When fed an iron-enriched diet (2 g/kg, mice died prematurely and showed signs of liver damage. Ferritin accumulated in primary embryonic fibroblasts from NCOA4-null mice consequent to impaired autophagic targeting. Adoptive expression of the NCOA4 COOH terminus (aa 239–614 restored this function. In conclusion, NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels in vivo.

Impact of two iron(III) chelators on the iron, cadmium, lead and nickel accumulation in poplar grown under heavy metal stress in hydroponics.

Science.gov (United States)

Mihucz, Victor G; Csog, Árpád; Fodor, Ferenc; Tatár, Enikő; Szoboszlai, Norbert; Silaghi-Dumitrescu, Luminiţa; Záray, Gyula

2012-04-15

Poplar (Populus jacquemontiana var. glauca cv. Kopeczkii) was grown in hydroponics containing 10 μM Cd(II), Ni(II) or Pb(II), and Fe as Fe(III) EDTA or Fe(III) citrate in identical concentrations. The present study was designed to compare the accumulation and distribution of Fe, Cd, Ni and Pb within the different plant compartments. Generally, Fe and heavy-metal accumulation were higher by factor 2-7 and 1.6-3.3, respectively, when Fe(III) citrate was used. Iron transport towards the shoot depended on the Fe(III) chelate and, generally, on the heavy metal used. Lead was accumulated only in the root. The amounts of Fe and heavy metals accumulated by poplar were very similar to those of cucumber grown in an identical way, indicating strong Fe uptake regulation of these two Strategy I plants: a cultivar and a woody plant. The Strategy I Fe uptake mechanism (i.e. reducing Fe(III) followed by Fe(II) uptake), together with the Fe(III) chelate form in the nutrient solution had significant effects on Fe and heavy metal uptake. Poplar appears to show phytoremediation potential for Cd and Ni, as their transport towards the shoot was characterized by 51-54% and 26-48% depending on the Fe(III) supply in the nutrient solution. Copyright © 2012 Elsevier GmbH. All rights reserved.

A cascade of iron-containing proteins governs the genetic iron starvation response to promote iron uptake and inhibit iron storage in fission yeast.

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Javier Encinar del Dedo

2015-03-01

Full Text Available Iron is an essential cofactor, but it is also toxic at high levels. In Schizosaccharomyces pombe, the sensor glutaredoxin Grx4 guides the activity of the repressors Php4 and Fep1 to mediate a complex transcriptional response to iron deprivation: activation of Php4 and inactivation of Fep1 leads to inhibition of iron usage/storage, and to promotion of iron import, respectively. However, the molecular events ruling the activity of this double-branched pathway remained elusive. We show here that Grx4 incorporates a glutathione-containing iron-sulfur cluster, alone or forming a heterodimer with the BolA-like protein Fra2. Our genetic study demonstrates that Grx4-Fra2, but not Fep1 nor Php4, participates not only in iron starvation signaling but also in iron-related aerobic metabolism. Iron-containing Grx4 binds and inactivates the Php4 repressor; upon iron deprivation, the cluster in Grx4 is probably disassembled, the proteins dissociate, and Php4 accumulates at the nucleus and represses iron consumption genes. Fep1 is also an iron-containing protein, and the tightly bound iron is required for transcriptional repression. Our data suggest that the cluster-containing Grx4-Fra2 heterodimer constitutively binds to Fep1, and upon iron deprivation the disassembly of the iron cluster between Grx4 and Fra2 promotes reverse metal transfer from Fep1 to Grx4-Fra2, and de-repression of iron-import genes. Our genetic and biochemical study demonstrates that the glutaredoxin Grx4 independently governs the Php4 and Fep1 repressors through metal transfer. Whereas iron loss from Grx4 seems to be sufficient to release Php4 and allow its nuclear accumulation, total or partial disassembly of the Grx4-Fra2 cluster actively participates in iron-containing Fep1 activation by sequestering its iron and decreasing its interaction with promoters.

Acute Toxicity and Accumulation of Iron, Manganese and, Aluminum in Caspian Kutum Fish (Rutilus kutum

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Saeed Zahedi

2014-03-01

Full Text Available Background: Iron, manganese, and aluminum are three abundant metals on earth and their concentrations have increased in aquatic environments as a result of natural and industrial activities. This study was undertaken to report the median acute toxicity (LC50 and accumulation of the sub-lethal concentration (10% 96-h LC50 of iron (Fe, manganese (Mn and aluminum (Al in kutum (Rutilus kutum fingerlings. Methods: For the 96-h LC50, the fish were exposed to concentrations of 105, 111, 117, 123, 129 and 135 mg/l of Fe and 40, 45, 50, 55, 60, and 65 mg/l of Mn and 18, 22, 26, 30, 34 and 38 mg/l of aluminum for 4 days. For sublethal exposure, they were exposed to mediums with concentrations of 12.3, 5.4 and 2.9 for Fe, Mn, and aluminum, respectively. Metal concentrations were determined by atomic absorption spectrophotometry in the gill tissues. Results: Probit analysis showed the 96-h LC50 values of 122.98, 54.39, and 28.89 mg/l for Fe, Mn, and aluminum, respectively. Sub-lethal tests were conducted with nominal concentrations of 12.3, 5.4, and 2.9 mg/l of Fe, Mn, and aluminum for four days, respectively. Significant accumulations were observed in gills for all tested metals as compared to the control groups in short-term exposure (P<0.05. Conclusion: Obtained results clearly show that aluminum is the most toxic metal among tested ones for kutum fingerlings and it has the highest branchial AF value during sub-lethal exposure.

Bio-accumulation of copper, zinc, iron and manganese in oyster Saccostrea cucullata, Snail Cerithium rubus and Clam Tellina angulata from the Bombay coast

Digital Repository Service at National Institute of Oceanography (India)

Krishnakumari, L.; Nair, V.R; Moraes, C.

accumulation was high in S. cucullata, manganese in C. rubus and iron in T. angulata. Similarly, copper and zinc in S. cucullata and copper in C. rubus were found occasionally higher than accepted health standards...

Seasonal arsenic accumulation in stream sediments at a groundwater discharge zone.

Science.gov (United States)

MacKay, Allison A; Gan, Ping; Yu, Ran; Smets, Barth F

2014-01-21

Seasonal changes in arsenic and iron accumulation rates were examined in the sediments of a brook that receives groundwater discharges of arsenic and reduced iron. Clean glass bead columns were deployed in sediments for known periods over the annual hydrologic cycle to monitor changes in arsenic and iron concentrations in bead coatings. The highest accumulation rates occurred during the dry summer period (July-October) when groundwater discharges were likely greatest at the sample locations. The intermediate flow period (October-March), with higher surface water levels, was associated with losses of arsenic and iron from bead column coatings at depths below 2-6 cm. Batch incubations indicated iron releases from solids to be induced by biological reduction of iron (oxy)hydroxide solids. Congruent arsenic releases during incubation were limited by the high arsenic sorption capacity (0.536 mg(As)/mg(Fe)) of unreacted iron oxide solids. The flooded spring (March-June) with high surface water flows showed the lowest arsenic and iron accumulation rates in the sediments. Comparisons of accumulation rates across a shoreline transect were consistent with greater rates at regions exposed above surface water levels for longer times and greater losses at locations submerged below surface water. Iron (oxy)hydroxide solids in the shallowest sediments likely serve as a passive barrier to sorb arsenic released to pore water at depth by biological iron reduction.

The natural history of early versus late disability accumulation in primary progressive MS.

Science.gov (United States)

Koch, Marcus W; Greenfield, Jamie; Javizian, Omid; Deighton, Stephanie; Wall, Winona; Metz, Luanne M

2015-06-01

Primary progressive multiple sclerosis (PPMS) is the least common MS disease course and carries the worst prognosis. In relapsing-remitting multiple sclerosis (RRMS) disability accumulation occurs in two distinct phases, but it is unclear whether this is also true for PPMS. Here we investigate factors associated with early and late disability accumulation in PPMS. We used Kaplan-Meier survival analyses and Cox regression to investigate the influence of sex, age at disease onset and onset symptoms on time to, and age at, Expanded Disability Status Scale (EDSS) 4 and 6, as well as the time from EDSS 4 to 6 in patients with PPMS. We identified 500 patients with PPMS. The analyses on time to EDSS 4 included 358 patients, and those on time to EDSS 6 included 392 patients. The median times to EDSS 4 and EDSS 6 were 5 and 9 years. The analyses on age at EDSS 4 included 360 patients, and those on age at EDSS 6 included 402 patients. The median ages at EDSS 4 and EDSS 6 were 51 and 55 years. Older age at onset and bilateral motor onset symptoms were independently associated with a shorter time to both EDSS 4 and EDSS 6. Sex and other onset symptoms were not associated with time to, or age at, landmark disability. Only age at onset was significantly associated with the time from EDSS 4 to EDSS 6. Age at disease onset is the most important predictor of disability accumulation in PPMS. Bilateral motor onset symptoms were associated with quicker disease progression. In contrast to RRMS, we found no evidence for distinct phases of disability accumulation in PPMS. Disability accumulation in PPMS appears to be affected by the same factors throughout its course. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Role of glutaredoxin 3 in iron homeostasis

Science.gov (United States)

Iron is an essential mineral nutrient that is tightly regulated through mechanisms involving iron regulatory genes, intracellular storage, and iron recycling. Dysregulation of these mechanisms often results in either excess tissue iron accumulation (overload) or iron deficiency (anemia). Many bioche...

Effects of chloride, sulfate and natural organic matter (NOM) on the accumulation and release of trace-level inorganic contaminants from corroding iron.

Science.gov (United States)

Peng, Ching-Yu; Ferguson, John F; Korshin, Gregory V

2013-09-15

This study examined effects of varying levels of anions (chloride and sulfate) and natural organic matter (NOM) on iron release from and accumulation of inorganic contaminants in corrosion scales formed on iron coupons exposed to drinking water. Changes of concentrations of sulfate and chloride were observed to affect iron release and, in lesser extent, the retention of representative inorganic contaminants (vanadium, chromium, nickel, copper, zinc, arsenic, cadmium, lead and uranium); but, effects of NOM were more pronounced. DOC concentration of 1 mg/L caused iron release to increase, with average soluble and total iron concentrations being four and two times, respectively, higher than those in the absence of NOM. In the presence of NOM, the retention of inorganic contaminants by corrosion scales was reduced. This was especially prominent for lead, vanadium, chromium and copper whose retention by the scales decreased from >80% in the absence of NOM to chloride levels. Modeling indicated that the observed effects were associated with the formation of metal-NOM complexes and effects of NOM on the sorption of the inorganic contaminants on solid phases that are typical for iron corrosion in drinking water. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influence of iron plaque on uptake and accumulation of Cd by rice (Oryza sativa L.) seedlings grown in soil.

Science.gov (United States)

Liu, Houjun; Zhang, Junling; Christie, Peter; Zhang, Fusuo

2008-05-15

Iron plaque is ubiquitously formed on the root surfaces of rice. However, little is known about the role of iron plaque in Cd movement from soil to the plant aboveground parts. A pot experiment was conducted to investigate the influence of iron plaque in Cd uptake and accumulation by rice seedlings in soil. Rice seedlings were pre-cultivated in solution culture for 16 days. Two seedlings were transplanted in a nylon bag containing no substrate but surrounded by soil amended with Fe and Cd combined at rates of 0, 1, or 2 g Fe kg(-1) and 0, 2.0, or 10 mg Cd kg(-1) soil. Fe was added to induce different amounts of iron plaque, and Cd to simulate Cd-polluted soils. Plants were grown for a further 43 days and then harvested. The length of the longest leaf and SPAD values of the newly mature leaves were measured during plant growth. Fe and Cd concentrations were determined in dithionite-citrate-bicarbonate (DCB) soil extracts and in plant roots and shoots. Shoot and root dry weights were significantly affected by Fe supply level but not by added Cd. Root dry weight declined with increasing Fe supply but shoot dry weight decreased at 2 g Fe kg(-1) and increased at 1 g Fe kg(-1) (except at 2 mg Cd kg(-1)). The length of the longest leaf and SPAD values of the newly mature leaves were significantly affected by plant growth stage and added Fe and Cd. Fe tended to diminish the negative effect of Cd on these two parameters. Cd concentrations in DCB extracts increased with increasing Cd and Fe supply. In contrast, external Fe supply markedly reduced shoot and root Cd concentrations and there was generally no significant difference between the two Fe supply levels. Shoot and root Cd concentrations increased with increasing Cd addition. Root Cd concentrations were negatively correlated with root Fe concentrations. The proportion of Cd in DCB extracts was significantly lower than in roots or shoots. The results indicate that enhanced Fe uptake by plants can diminish the negative

Heavy metal accumulation in Pseudevernia furfuracea (L.) Zopf from the Karabük iron-steel factory in Karabük, Turkey.

Science.gov (United States)

Cansaran-Duman, Demet; Atakol, Orhan; Atasoy, Ilknur; Kahya, Didem; Aras, Sümer; Beyaztaş, Taylan

2009-01-01

Pseudevernia furfuracea (L.) Zopf lichen specimens were collected every 5 km starting from around an iron-steel factory located in the central area of Karabük province, up to Yenice Forest. Zn, Cu, Mn, Fe, Pb, Ni, Cd, Cr contents were analyzed in the samples collected from polluted and unpolluted areas. A Pseudevernia furfuracea (L.) Zopf sample from Yenice Forest was used as a control. The reason for this choise was the abundance of species diversity, and therefore sample collection might cause a very low impact on natural population density. The forest is among the 100 forested areas that must be urgently taken under protection according to WWF (World Wildlife Fund) researches. Results of the current study manifested significant variations among the contents of these elements between stations. As expected, the pollution sources, such as iron-steel factory, roads and railroads, industry, heavy traffic, and waste treatment plants, have major impact on the heavy metal accumulation in P. furfuracea (L.) Zopf, and, in accordance to their location, samples 8 and 10 displayed high element accumulation. Surprisingly, although Yenice Forest is under protection, results of our study showed that the region is becoming polluted by the influence of many pollution sources in the area. The present study also confirms the efficient metal accumulation capacity of lichens.

Evidence for the Influence of the Iron Regulatory MHC Class I Molecule HFE on Tumor Progression in Experimental Models and Clinical Populations

Science.gov (United States)

Weston, Cody; Connor, James

2014-01-01

Proteins involved in iron regulation are modifiers of cancer risk and progression. Of these, the HFE protein (high iron gene and its protein product) is of particular interest because of its interaction with both iron handling and immune function and the high rate of genetic polymorphisms resulting in a mutant protein. Clinical studies suggest that HFE polymorphisms increase the risk of certain cancers, but the inconsistent outcomes suggest a more nuanced effect, possibly interacting with other genetic or environmental factors. Some basic science research has been conducted to begin to understand the implications of variant HFE genotype on cancer, but the story is far from complete. In particular, putative mechanisms exist for HFE to affect tumor progression through its role in iron handling and its major histocompatibility complex class I structural features. In this review, the current understanding of the role of HFE in cancer is described and models for future directions are identified. PMID:25520556

A Room Temperature Ultrasensitive Magnetoelectric Susceptometer for Quantitative Tissue Iron Detection

Science.gov (United States)

Xi, Hao; Qian, Xiaoshi; Lu, Meng-Chien; Mei, Lei; Rupprecht, Sebastian; Yang, Qing X.; Zhang, Q. M.

2016-07-01

Iron is a trace mineral that plays a vital role in the human body. However, absorbing and accumulating excessive iron in body organs (iron overload) can damage or even destroy an organ. Even after many decades of research, progress on the development of noninvasive and low-cost tissue iron detection methods is very limited. Here we report a recent advance in a room-temperature ultrasensitive biomagnetic susceptometer for quantitative tissue iron detection. The biomagnetic susceptometer exploits recent advances in the magnetoelectric (ME) composite sensors that exhibit an ultrahigh AC magnetic sensitivity under the presence of a strong DC magnetic field. The first order gradiometer based on piezoelectric and magnetostrictive laminate (ME composite) structure shows an equivalent magnetic noise of 0.99 nT/rt Hz at 1 Hz in the presence of a DC magnetic field of 0.1 Tesla and a great common mode noise rejection ability. A prototype magnetoelectric liver susceptometry has been demonstrated with liver phantoms. The results indicate its output signals to be linearly responsive to iron concentrations from normal iron dose (0.05 mg Fe/g liver phantom) to 5 mg Fe/g liver phantom iron overload (100X overdose). The results here open up many innovative possibilities for compact-size, portable, cost-affordable, and room-temperature operated medical systems for quantitative determinations of tissue iron.

Misregulation of iron homeostasis in amyotrophic lateral sclerosis

Directory of Open Access Journals (Sweden)

Anna Gajowiak

2016-06-01

Full Text Available Iron is essential for all mammalian cells, but it is toxic in excess. Our understanding of molecular mechanisms ensuring iron homeostasis at both cellular and systemic levels has dramatically increased over the past 15 years. However, despite major advances in this field, homeostatic regulation of iron in the central nervous system (CNS requires elucidation. It is unclear how iron moves in the CNS and how its transfer to the CNS across the blood-brain and the blood-cerebrospinal fluid barriers, which separate the CNS from the systemic circulation, is regulated. Increasing evidence indicates the role of iron dysregulation in neuronal cell death observed in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS. ALS is a progressive neurodegenerative disorder characterized by selective cortical czynand spinal motor neuron dysfunction that results from a complex interplay among various pathogenic factors including oxidative stress. The latter is known to strongly affect cellular iron balance, creating a vicious circle to exacerbate oxidative injury. The role of iron in the pathogenesis of ALS is confirmed by therapeutic effects of iron chelation in ALS mouse models. These models are of great importance for deciphering molecular mechanisms of iron accumulation in neurons. Most of them consist of transgenic rodents overexpressing the mutated human superoxide dismutase 1 (SOD1 gene. Mutations in the SOD1 gene constituteone of the most common genetic causes of the inherited form of ALS. However, it should beconsidered that overexpression of the SOD1 gene usually leads to increased SOD1 enzymaticactivity, a condition which does not occur in human pathology and which may itself changethe expression of iron metabolism genes.

Accumulation and Toxicity of Superparamagnetic Iron Oxide Nanoparticles in Cells and Experimental Animals.

Science.gov (United States)

Jarockyte, Greta; Daugelaite, Egle; Stasys, Marius; Statkute, Urte; Poderys, Vilius; Tseng, Ting-Chen; Hsu, Shan-Hui; Karabanovas, Vitalijus; Rotomskis, Ricardas

2016-08-19

The uptake and distribution of negatively charged superparamagnetic iron oxide (Fe₃O₄) nanoparticles (SPIONs) in mouse embryonic fibroblasts NIH3T3, and magnetic resonance imaging (MRI) signal influenced by SPIONs injected into experimental animals, were visualized and investigated. Cellular uptake and distribution of the SPIONs in NIH3T3 after staining with Prussian Blue were investigated by a bright-field microscope equipped with digital color camera. SPIONs were localized in vesicles, mostly placed near the nucleus. Toxicity of SPION nanoparticles tested with cell viability assay (XTT) was estimated. The viability of NIH3T3 cells remains approximately 95% within 3-24 h of incubation, and only a slight decrease of viability was observed after 48 h of incubation. MRI studies on Wistar rats using a clinical 1.5 T MRI scanner were showing that SPIONs give a negative contrast in the MRI. The dynamic MRI measurements of the SPION clearance from the injection site shows that SPIONs slowly disappear from injection sites and only a low concentration of nanoparticles was completely eliminated within three weeks. No functionalized SPIONs accumulate in cells by endocytic mechanism, none accumulate in the nucleus, and none are toxic at a desirable concentration. Therefore, they could be used as a dual imaging agent: as contrast agents for MRI and for traditional optical biopsy by using Prussian Blue staining.

Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation.

Science.gov (United States)

Hilty, Florentine M; Arnold, Myrtha; Hilbe, Monika; Teleki, Alexandra; Knijnenburg, Jesper T N; Ehrensperger, Felix; Hurrell, Richard F; Pratsinis, Sotiris E; Langhans, Wolfgang; Zimmermann, Michael B

2010-05-01

Effective iron fortification of foods is difficult, because water-soluble compounds that are well absorbed, such as ferrous sulphate (FeSO(4)), often cause unacceptable changes in the colour or taste of foods. Poorly water-soluble compounds, on the other hand, cause fewer sensory changes, but are not well absorbed. Here, we show that poorly water-soluble nanosized Fe and Fe/Zn compounds (specific surface area approximately 190 m(2) g(-1)) made by scalable flame aerosol technology have in vivo iron bioavailability in rats comparable to FeSO(4) and cause less colour change in reactive food matrices than conventional iron fortificants. The addition of Zn to FePO(4) and Mg to Fe/Zn oxide increases Fe absorption from the compounds, and doping with Mg also improves their colour. After feeding rats with nanostructured iron-containing compounds, no stainable Fe was detected in their gut wall, gut-associated lymphatics or other tissues, suggesting no adverse effects. Nanosizing of poorly water-soluble Fe compounds sharply increases their absorption and nutritional value.

Iron metabolism in BeWo chorion carcinoma cells. Transferrin-mediated uptake and release of iron

NARCIS (Netherlands)

van der Ende, A.; du Maine, A.; Simmons, C. F.; Schwartz, A. L.; Strous, G. J.

1987-01-01

Growing human choriocarcinoma BeWo b24 cells contain 1.5 X 10(6) functional cell surface transferrin binding sites and 2.0 X 10(6) intracellular binding sites. These cells rapidly accumulate iron at a rate of 360,000 iron atoms/min/cell. During iron uptake the transferrin and its receptor recycle at

Use of Acoustic Emission to Monitor Progressive Damage Accumulation in KEVLAR® 49 Composites

Science.gov (United States)

Waller, J. M.; Andrade, E.; Saulsberry, R. L.

2010-02-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar® 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio <1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

Progress in development of iron base alloys

International Nuclear Information System (INIS)

Zackay, V.V.; Parker, E.R.

1980-01-01

The ways of development of new iron base high-strength alloys are considered. Perspectiveness of ferritic steel strengthening with intermetallides (TaFe 2 , for instance) is shown. Favourable combination of plasticity, strength and fracture toughness in nickel-free iron-manganese alloys (16-20%) is also pointed out. A strength level of alloyed maraging steels can be achieved by changes in chemical composition and by proper heat treatments of low- and medium-alloyed steels

Mammalian iron metabolism and its control by iron regulatory proteins☆

Science.gov (United States)

Anderson, Cole P.; Shen, Lacy; Eisenstein, Richard S.; Leibold, Elizabeth A.

2013-01-01

Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1 and IRP2). IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs encoding protein involved in iron uptake, storage, utilization and export. Over the past decade, significant progress has been made in understanding how IRPs are regulated by iron-dependent and iron-independent mechanisms and the pathological consequences of IRP2 deficiency in mice. The identification of novel IREs involved in diverse cellular pathways has revealed that the IRP–IRE network extends to processes other than iron homeostasis. A mechanistic understanding of IRP regulation will likely yield important insights into the basis of disorders of iron metabolism. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID:22610083

Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

Directory of Open Access Journals (Sweden)

Kimberly B Zumbrennen-Bullough

Full Text Available Iron Regulatory Protein 2 (Irp2, Ireb2 is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc, expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

Effect of Iron Containing Supplements on Rats' Dental Caries Progression

OpenAIRE

AR. Eshghi; R. Kowsari-Isfahan; M. Rezaiefar; M. Razavi; S. Zeighami

2012-01-01

Objective: Iron deficiency is the most common form of malnutrition in developing countries. Iron containing supplements have been used effectively to solve this problem. In children, because of teeth staining after taking iron drops, parents have the idea that iron drops are the cause of tooth decay; therefore, they limit this vital supplement in their children’s diet. Hereby, we evaluate the histologic effect of iron containing supplements on tooth caries in rice rats with cariogenic or non-...

Seasonal Arsenic Accumulation in Stream Sediments at a Groundwater Discharge Zone

DEFF Research Database (Denmark)

MacKay, Allison A.; Gan, Ping; Yu, Ran

2014-01-01

Seasonal changes in arsenic and iron accumulation rates were examined in the sediments of a brook that receives groundwater discharges of arsenic and reduced iron. Clean glass bead columns were deployed in sediments for known periods over the annual hydrologic cycle to monitor changes in arsenic...... and iron concentrations in bead coatings. The highest accumulation rates occurred during the dry summer period (July-October) when groundwater discharges were likely greatest at the sample locations. The intermediate flow period (October-March), With higher surface water: levels, was associated with losses...... of arsenic and iron from bead column coatings at. depths below 2-6 cm. Batch incubations indicated iron releases from solids to be induced by biological reduction of iron (oxy)hydroxide solids. Congruent arsenic releases during incubation were limited by the high arsenic sorption capacity (0.536 mg...

Treating iron overload in patients with non-transfusion-dependent thalassemia

Science.gov (United States)

Taher, Ali T; Viprakasit, Vip; Musallam, Khaled M; Cappellini, M Domenica

2013-01-01

Despite receiving no or only occasional blood transfusions, patients with non-transfusion-dependent thalassemia (NTDT) have increased intestinal iron absorption and can accumulate iron to levels comparable with transfusion-dependent patients. This iron accumulation occurs more slowly in NTDT patients compared to transfusion-dependent thalassemia patients, and complications do not arise until later in life. It remains crucial for these patients' health to monitor and appropriately treat their iron burden. Based on recent data, including a randomized clinical trial on iron chelation in NTDT, a simple iron chelation treatment algorithm is presented to assist physicians with monitoring iron burden and initiating chelation therapy in this group of patients. Am. J. Hematol. 88:409–415, 2013. © 2013 Wiley Periodicals, Inc. PMID:23475638

Use of Acoustic Emission to Monitor Progressive Damage Accumulation in Kevlar (R) 49 Composites

Science.gov (United States)

Waller, Jess M.; Saulsberry, Regor L.; Andrade, Eduardo

2009-01-01

Acoustic emission (AE) data acquired during intermittent load hold tensile testing of epoxy impregnated Kevlar(Registeres TradeMark) 49 (K/Ep) composite strands were analyzed to monitor progressive damage during the approach to tensile failure. Insight into the progressive damage of K/Ep strands was gained by monitoring AE event rate and energy. Source location based on energy attenuation and arrival time data was used to discern between significant AE attributable to microstructural damage and spurious AE attributable to noise. One of the significant findings was the observation of increasing violation of the Kaiser effect (Felicity ratio < 1.0) with damage accumulation. The efficacy of three different intermittent load hold stress schedules that allowed the Felicity ratio to be determined analytically is discussed.

Liver steatosis correlates with iron overload but not with HFE gene mutations in chronic hepatitis C.

Science.gov (United States)

Sikorska, Katarzyna; Stalke, Piotr; Romanowski, Tomasz; Rzepko, Robert; Bielawski, Krzysztof Piotr

2013-08-01

Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serum markers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.

In Vivo MRI Mapping of Brain Iron Deposition across the Adult Lifespan.

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Acosta-Cabronero, Julio; Betts, Matthew J; Cardenas-Blanco, Arturo; Yang, Shan; Nestor, Peter J

2016-01-13

Disruption of iron homeostasis as a consequence of aging is thought to cause iron levels to increase, potentially promoting oxidative cellular damage. Therefore, understanding how this process evolves through the lifespan could offer insights into both the aging process and the development of aging-related neurodegenerative brain diseases. This work aimed to map, in vivo for the first time with an unbiased whole-brain approach, age-related iron changes using quantitative susceptibility mapping (QSM)--a new postprocessed MRI contrast mechanism. To this end, a full QSM standardization routine was devised and a cohort of N = 116 healthy adults (20-79 years of age) was studied. The whole-brain and ROI analyses confirmed that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their exact anatomical location. Whereas only patchy signs of iron scavenging were observed in white matter, strong, bilateral, and confluent QSM-age associations were identified in several deep-brain nuclei--chiefly the striatum and midbrain-and across motor, premotor, posterior insular, superior prefrontal, and cerebellar cortices. The validity of QSM as a suitable in vivo imaging technique with which to monitor iron dysregulation in the human brain was demonstrated by confirming age-related increases in several subcortical nuclei that are known to accumulate iron with age. The study indicated that, in addition to these structures, there is a predilection for iron accumulation in the frontal lobes, which when combined with the subcortical findings, suggests that iron accumulation with age predominantly affects brain regions concerned with motor/output functions. This study used a whole--brain imaging approach known as quantitative susceptibility mapping (QSM) to provide a novel insight into iron accumulation in the brain across the adult lifespan. Validity of the method was demonstrated by showing concordance with ROI analysis and prior knowledge

Studies on the mechanism of pyrophosphate-mediated uptake of iron from transferrin by isolated rat-liver mitochondria

International Nuclear Information System (INIS)

Konopka, K.; Romslo, I.; Bergen Univ.

1981-01-01

1. Respiring rat liver mitochondria accumulate iron released from transferrin by pyrophosphate. The amount of iron accumulated is 1-1.5 nmol mg protein -1 h -1 , or approximately 60% of the amount of iron mobilized from transferrin. 2. The uptake declines if respiration is inhibited, substrate is depleted, or the experiments are run under anaerobic conditions. Substrate, depletion and respiratory inhibitors are less inhibitory under anaerobic conditions. 3. More than 80% of the amount of iron accumulated by aerobic, actively respiring mitochondria can be chelated by bathophenanthroline sulphonate, and with deuteroporphyrin included, up to 30% of the amount of iron accumulated is recovered as deuteroheme. Iron accumulated by respiration-inhibited mitochondria under aerobic conditions is not available for heme synthesis. 4. With time the uptake of iron increases eightfold relative to the uptake of pyrophosphate. 5. The results are compatible with a model in which ferric iron is mobilized from transferrin by pyrophosphate, ferric iron pyrophosphate is bound to the mitochondria, iron is reduced, dissociates from pyrophosphate and is taken up by the mitochondria. Ferrous irons thus formed is available for heme synthesis. (orig.) [de

Characterization of accumulated precipitates during subsurface iron removal

KAUST Repository

Van Halem, Doris; De Vet, W. W. J. M.; Verberk, Jasper Q J C; Amy, Gary L.; Van Dijk, Hans C.

2011-01-01

The principle of subsurface iron removal for drinking water supply is that aerated water is periodically injected into the aquifer through a tube well. On its way into the aquifer, the injected O2-rich water oxidizes adsorbed Fe 2+, creating a

Iron biomineralization by anaerobic neutrophilic iron-oxidizing bacteria

DEFF Research Database (Denmark)

Miot, Jennyfer; Benzerara, Karim; Morin, Guillaume

2009-01-01

Minerals formed by bio-oxidation of ferrous iron (Fe(II)) at neutral pH, their association with bacterial ultrastructures as well as their impact on the metabolism of iron-oxidizing bacteria remain poorly understood. Here, we investigated iron biomineralization by the anaerobic nitrate-dependent ......Minerals formed by bio-oxidation of ferrous iron (Fe(II)) at neutral pH, their association with bacterial ultrastructures as well as their impact on the metabolism of iron-oxidizing bacteria remain poorly understood. Here, we investigated iron biomineralization by the anaerobic nitrate...... precipitation in the periplasm (in a few tens of minutes), followed by the formation of surface-bound globules. Moreover, we frequently observed an asymmetric mineral thickening at the cell poles. In parallel, the evolution of iron oxidation was quantified by STXM: iron both contained in the bacteria...... and in the extracellular precipitates reached complete oxidation within 6 days. While a progressive oxidation of Fe in the bacteria and in the medium could be observed, spatial redox (oxido-reduction state) heterogeneities were detected at the cell poles and in the extracellular precipitates after 1 day. All...

Obesity Promotes Alterations in Iron Recycling

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Marta Citelli

2015-01-01

Full Text Available Hepcidin is a key hormone that induces the degradation of ferroportin (FPN, a protein that exports iron from reticuloendothelial macrophages and enterocytes. The aim of the present study was to experimentally evaluate if the obesity induced by a high-fat diet (HFD modifies the expression of FPN in macrophages and enterocytes, thus altering the iron bioavailability. In order to directly examine changes associated with iron metabolism in vivo, C57BL/6J mice were fed either a control or a HFD. Serum leptin levels were evaluated. The hepcidin, divalent metal transporter-1 (DMT1, FPN and ferritin genes were analyzed by real-time polymerase chain reaction. The amount of iron present in both the liver and spleen was determined by flame atomic absorption spectrometry. Ferroportin localization within reticuloendothelial macrophages was observed by immunofluorescence microscopy. Obese animals were found to exhibit increased hepcidin gene expression, while iron accumulated in the spleen and liver. They also exhibited changes in the sublocation of splenic cellular FPN and a reduction in the FPN expression in the liver and the spleen, while no changes were observed in enterocytes. Possible explanations for the increased hepcidin expression observed in HFD animals may include: increased leptin levels, the liver iron accumulation or endoplasmic reticulum (ER stress. Together, the results indicated that obesity promotes changes in iron bioavailability, since it altered the iron recycling function.

Mapping and characterization of iron compounds in Alzheimer's tissue

International Nuclear Information System (INIS)

Collingwood, Joanna; Dobson, Jon

2006-01-01

Understanding the management of iron in the brain is of great importance in the study of neurodegeneration, where regional iron overload is frequently evident. A variety of approaches have been employed, from quantifying iron in various anatomical structures, to identifying genetic risk factors related to iron metabolism, and exploring chelation approaches to tackle iron overload in neurodegenerative disease. However, the ease with which iron can change valence state ensures that it is present in vivo in a wide variety of forms, both soluble and insoluble. Here, we review recent developments in approaches to locate and identify iron compounds in neurodegenerative tissue. In addition to complementary techniques that allow us to quantify and identify iron compounds using magnetometry, extraction, and electron microscopy, we are utilizing a powerful combined mapping/characterization approach with synchrotron X-rays. This has enabled the location and characterization of iron accumulations containing magnetite and ferritin in human Alzheimer's disease (AD) brain tissue sections in situ at micron-resolution. It is hoped that such approaches will contribute to our understanding of the role of unusual iron accumulations in disease pathogenesis, and optimise the potential to use brain iron as a clinical biomarker for early detection and diagnosis.

Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).

Science.gov (United States)

Ingrassia, Rosaria; Memo, Maurizio; Garavaglia, Barbara

2017-01-01

Mutations in WDR45 gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been clarified. We found the up-regulation of the ferrous iron transporter (-)IRE/Divalent Metal Transporter1 and down-regulation of Transferrin receptor in the fibroblasts of two BPAN affected patients with splicing mutations 235+1G>A (BPAN1) and 517_519ΔVal 173 (BPAN2). The BPAN patients showed a concomitant increase of intracellular ferrous iron after starvation. An altered pattern of iron transporters with iron overload is highlighted in BPAN human fibroblasts, supporting for a role of DMT1 in NBIA. We here present a novel element, about iron accumulation, to the existing knowledge in field of NBIA. Attention is focused to a starvation-dependent iron overload, possibly accounting for iron accumulation in the basal ganglia. Further investigation could clarify iron regulation in BPAN.

Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high-fat diet-fed mice.

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Katsumura, Masanori; Takagi, Shoko; Oya, Hana; Tamura, Shohei; Saneyasu, Takaoki; Honda, Kazuhisa; Kamisoyama, Hiroshi

2017-08-01

Animal by-products can be recycled and used as sources of essential nutrients. Water-soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high-fat diet. Exercise-trained mice had significantly less perirenal adipose tissue, whereas WSHI-fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone-sensitive lipase. WSHI-fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation-related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism-related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high-fat diet. © 2016 Japanese Society of Animal Science.

Overexpression of Arabidopsis VIT1 increases accumulation of iron in cassava roots and stems.

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Narayanan, Narayanan; Beyene, Getu; Chauhan, Raj Deepika; Gaitán-Solis, Eliana; Grusak, Michael A; Taylor, Nigel; Anderson, Paul

2015-11-01

Iron is extremely abundant in the soil, but its uptake in plants is limited due to low solubility in neutral or alkaline soils. Plants can rely on rhizosphere acidification to increase iron solubility. AtVIT1 was previously found to be involved in mediating vacuolar sequestration of iron, which indicates a potential application for iron biofortification in crop plants. Here, we have overexpressed AtVIT1 in the starchy root crop cassava using a patatin promoter. Under greenhouse conditions, iron levels in mature cassava storage roots showed 3-4 times higher values when compared with wild-type plants. Significantly, the expression of AtVIT1 showed a positive correlation with the increase in iron concentration of storage roots. Conversely, young leaves of AtVIT1 transgenic plants exhibit characteristics of iron deficiency such as interveinal chlorosis of leaves (yellowing) and lower iron concentration when compared with the wild type plants. Interestingly, the AtVIT1 transgenic plants showed 4 and 16 times higher values of iron concentration in the young stem and stem base tissues, respectively. AtVIT1 transgenic plants also showed 2-4 times higher values of iron content when compared with wild-type plants, with altered partitioning of iron between source and sink tissues. These results demonstrate vacuolar iron sequestration as a viable transgenic strategy to biofortify crops and to help eliminate micronutrient malnutrition in at-risk human populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Characterization and uranium bioleaching performance of mixed iron- and sulfur-oxidizers versus iron-oxidizers

International Nuclear Information System (INIS)

Qian Li; Jing Sun; Dexin Ding; Qingliang Wang; Wenge Shi; Eming Hu; Xiaoyu Jiang; University of South China, Hengyang; Xingxing Wang

2017-01-01

In order to develop and apply mixed iron- and sulfur-oxidizers in uranium bioleaching, the characteristics of a mixed iron- and sulfur-oxidizing consortium (Consortium ISO) were comparatively investigated versus an iron-oxidizing consortium (Consortium IO). The results showed, the Consortium ISO exerted stronger oxidative ability and acid-producing ability than Consortium IO did. The synergy of sulfur-oxidizers and iron-oxidizers could change the structure and properties of the passivation substance, and work positively for eliminating the accumulation of passivation substance. In the bioleaching process, the uranium bioleaching experiments showed the recovery percentage of uranium reached 99.5% with Consortium ISO, 6.3% more than that of Consortium IO. (author)

Siderophore-mediated iron trafficking in humans is regulated by iron

Science.gov (United States)

Liu, Zhuoming; Lanford, Robert; Mueller, Sebastian; Gerhard, Glenn S.; Luscieti, Sara; Sanchez, Mayka; Devireddy, L.

2013-01-01

Siderophores are best known as small iron binding molecules that facilitate microbial iron transport. In our previous study we identified a siderophore-like molecule in mammalian cells and found that its biogenesis is evolutionarily conserved. A member of the short chain dehydrogenase family of reductases, 3-OH butyrate dehydrogenase (BDH2) catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore. We have shown that depletion of the mammalian siderophore by inhibiting expression of bdh2 results in abnormal accumulation of cellular iron and mitochondrial iron deficiency. These observations suggest that the mammalian siderophore is a critical regulator of cellular iron homeostasis and facilitates mitochondrial iron import. By utilizing bioinformatics, we identified an iron-responsive element (IRE; a stem-loop structure that regulates genes expression post-transcriptionally upon binding to iron regulatory proteins or IRPs) in the 3′-untranslated region (3′-UTR) of the human BDH2 (hBDH2) gene. In cultured cells as well as in patient samples we now demonstrate that the IRE confers iron-dependent regulation on hBDH2 and binds IRPs in RNA electrophoretic mobility shift assays. In addition, we show that the hBDH2 IRE associates with IRPs in cells and that abrogation of IRPs by RNAi eliminates the iron-dependent regulation of hBDH2 mRNA. The key physiologic implication is that iron-mediated post-transcriptional regulation of hBDH2 controls mitochondrial iron homeostasis in human cells. These observations provide a new and an unanticipated mechanism by which iron regulates its intracellular trafficking. PMID:22527885

Progress in electrochemical synthesis of magnetic iron oxide nanoparticles

International Nuclear Information System (INIS)

Ramimoghadam, Donya; Bagheri, Samira; Hamid, Sharifah Bee Abd

2014-01-01

Recently, magnetic iron oxide particles have been emerged as significant nanomaterials due to its extensive range of application in various fields. In this regard, synthesis of iron oxide nanoparticles with desirable properties and high potential applications are greatly demanded. Therefore, investigation on different iron oxide phases and their magnetic properties along with various commonly used synthetic techniques are remarked and thoroughly described in this review. Electrochemical synthesis as a newfound method with unique advantages is elaborated, followed by design approaches and key parameters to control the properties of the iron oxide nanoparticles. Additionally, since the dispersion of iron oxide nanoparticles is as important as its preparation, surface modification issue has been a serious challenge which is comprehensively discussed using different surfactants. Despite the advantages of the electrochemical synthesis method, this technique has been poorly studied and requires deep investigations on effectual parameters such as current density, pH, electrolyte concentration etc. - Highlights: • IONPs are applied in chemical industries, medicine, magnetic storage etc. • Electrochemical synthesis (EC) is convenient, eco-friendly, selective and low-cost. • EC key factors are current density, pH, electrolyte concentration, electrode type. • Organic, inorganic and biological materials can be used to modify IONPs’ surface. • The physicochemical properties of IONPs can be controlled by adding surfactants

The presence of serum alters the properties of iron oxide nanoparticles and lowers their accumulation by cultured brain astrocytes

International Nuclear Information System (INIS)

Geppert, Mark; Petters, Charlotte; Thiel, Karsten; Dringen, Ralf

2013-01-01

Iron oxide nanoparticles (IONPs) are considered for various diagnostic and therapeutic applications. Such particles are able to cross the blood–brain barrier and are taken up into brain cells. To test whether serum components affect the properties of IONPs and/or their uptake into brain cells, we have incubated dimercaptosuccinate-coated magnetic IONPs without and with fetal calf serum (FCS) and have exposed cultured brain astrocytes with IONPs in the absence or presence of FCS. Incubation with FCS caused a concentration-dependent increase in the average hydrodynamic diameter of the particles and of their zeta-potential. In the presence of 10 % FCS, the diameter of the IONPs increased from 57 ± 2 to 107 ± 6 nm and the zeta-potential of the particles from −22 ± 5 to −9 ± 1 mV. FCS affected also strongly the uptake of IONPs by cultured astrocytes. The efficient time- and temperature-dependent cellular accumulation of IONPs was lowered with increasing concentration of FCS by up to 90 %. In addition, in the absence of serum, endocytosis inhibitors did not alter the IONP accumulation by astrocytes, while chlorpromazine or wortmannin lowered significantly the accumulation of IONPs in the presence of FCS, suggesting that clathrin-mediated endocytosis and macropinocytosis are involved in astrocytic IONP uptake from serum-containing medium. These data demonstrate that the presence of FCS strongly affects the properties of IONPs as well as their accumulation by cultured brain cells.

Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease.

Science.gov (United States)

Zucca, Fabio A; Segura-Aguilar, Juan; Ferrari, Emanuele; Muñoz, Patricia; Paris, Irmgard; Sulzer, David; Sarna, Tadeusz; Casella, Luigi; Zecca, Luigi

2017-08-01

There are several interrelated mechanisms involving iron, dopamine, and neuromelanin in neurons. Neuromelanin accumulates during aging and is the catecholamine-derived pigment of the dopamine neurons of the substantia nigra and norepinephrine neurons of the locus coeruleus, the two neuronal populations most targeted in Parkinson's disease. Many cellular redox reactions rely on iron, however an altered distribution of reactive iron is cytotoxic. In fact, increased levels of iron in the brain of Parkinson's disease patients are present. Dopamine accumulation can induce neuronal death; however, excess dopamine can be removed by converting it into a stable compound like neuromelanin, and this process rescues the cell. Interestingly, the main iron compound in dopamine and norepinephrine neurons is the neuromelanin-iron complex, since neuromelanin is an effective metal chelator. Neuromelanin serves to trap iron and provide neuronal protection from oxidative stress. This equilibrium between iron, dopamine, and neuromelanin is crucial for cell homeostasis and in some cellular circumstances can be disrupted. Indeed, when neuromelanin-containing organelles accumulate high load of toxins and iron during aging a neurodegenerative process can be triggered. In addition, neuromelanin released by degenerating neurons activates microglia and the latter cause neurons death with further release of neuromelanin, then starting a self-propelling mechanism of neuroinflammation and neurodegeneration. Considering the above issues, age-related accumulation of neuromelanin in dopamine neurons shows an interesting link between aging and neurodegeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis, Characterization, and Toxicity Evaluation of Dextran-Coated Iron Oxide Nanoparticles

Directory of Open Access Journals (Sweden)

Mihaela Balas

2017-02-01

Full Text Available We report the synthesis of dextran-coated iron oxide magnetic nanoparticles (DIO-NPs with spherical shape and uniform size distribution as well as their accumulation and toxic effects on Jurkat cells up to 72 h. The characterization of dextran-coated maghemite nanoparticles was done by X-ray diffraction and dynamic light scattering analyses, transmission electron microscopy imaging, attenuated total reflectance Fourier transform infrared (ATR-FTIR spectroscopy, magnetic hysteresis, and relaxometry measurements. The quantification of DIO-NPs intracellular uptake showed a progressive accumulation of iron as a function of time and dose accompanied by additional lysosome formation and an increasing darkening exhibited by a magnetic resonance imaging (MRI scanner. The cytotoxicity assays revealed a decrease of cell viability and a loss of membrane integrity in a time- and dose-dependent manner. Exposure to DIO-NPs determined an increase in reactive oxygen species level up to 72 h. In the first two days of exposure, the level of reduced glutathione decreased and the amount of malondyaldehyde increased, but at the end of the experiment, their concentrations returned to control values. These nanoparticles could be used as contrast agents for MRI but several parameters concerning their interaction with the cells should be taken into consideration for a safe utilization.

Iron induction of ferritin synthesis in soybean cell suspensions.

Science.gov (United States)

Proudhon, D; Briat, J F; Lescure, A M

1989-06-01

In animal cells specialized for iron storage, iron-induced accumulation of ferritin is known to result from a shift of stored mRNA from the ribonucleoprotein fraction to polysomes. Previous reports with bean leaves suggested that in plants iron induction of ferritin synthesis would result from a regulation at the transcriptional level (F van der Mark, F Bienfait, H van der Ende [1983] Biochem Biophys Res Commun 115:463-469). Soybean (Glycine max, cv Mandarin) cell suspension cultures have been used here to support these findings. Ferritin induction is obtained by addition of Fe-citrate to the culture medium. A good correlation is found between cellular iron content and the amount of ferritin accumulation. This protein accumulation corresponds to an increase of in vitro translatable ferritin mRNA. Addition of 4 micrograms actinomycin D per milliliter to the cultures inhibits completely in vivo RNA synthesis, whereas protein synthesis was poorly affected, at least for 24 hours. During the same time, this concentration of actinomycin D strongly inhibits the iron-induced synthesis of ferritin. These results show that in soybean cell cultures, the mechanism of regulation of ferritin synthesis in response to iron does not result from recruitment of preexisting mRNA. They confirm that in plant systems, ferritin synthesis results from increased transcription of the corresponding genes.

Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis.

Directory of Open Access Journals (Sweden)

Dong Lin

Full Text Available PURPOSE: Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level. METHODS: Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters. RESULTS: Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients. CONCLUSIONS: Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional

Different Phosphorus Supplies Altered the Accumulations and Quantitative Distributions of Phytic Acid, Zinc, and Iron in Rice (Oryza sativa L.) Grains.

Science.gov (United States)

Su, Da; Zhou, Lujian; Zhao, Qian; Pan, Gang; Cheng, Fangmin

2018-02-21

Development of rice cultivars with low phytic acid (lpa) is considered as a primary strategy for biofortification of zinc (Zn) and iron (Fe). Here, two rice genotypes (XS110 and its lpa mutant) were used to investigate the effect of P supplies on accumulations and distributions of PA, Zn, and Fe in rice grains by using hydroponics and detached panicle culture system. Results showed that higher P level increased grain PA concentration on dry matter basis (g/kg), but it markedly decreased PA accumulation on per grain basis (mg/grain). Meanwhile, more P supply reduced the amounts and bioavailabilities of Zn and Fe both in milled grains and in brown grains. Comparatively, lpa mutant was more susceptive to exogenous P supply than its wild type. Hence, the appropriate P fertilizer application should be highlighted in order to increase grain microelement (Zn and Fe) contents and improve nutritional quality in rice grains.

Magnetic resonance imaging of reconstructed ferritin as an iron-induced pathological model system

Energy Technology Data Exchange (ETDEWEB)

Balejcikova, Lucia [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Strbak, Oliver [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Baciak, Ladislav [Faculty of Chemical and Food Technology STU, Radlinskeho 9, 812 37 Bratislava (Slovakia); Kovac, Jozef [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia); Masarova, Marta; Krafcik, Andrej; Frollo, Ivan [Institute of Measurement Science SAS, Dubravska cesta 9, 841 04 Bratislava 4 (Slovakia); Dobrota, Dusan [Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin (Slovakia); Kopcansky, Peter [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Kosice (Slovakia)

2017-04-01

Iron, an essential element of the human body, is a significant risk factor, particularly in the case of its concentration increasing above the specific limit. Therefore, iron is stored in the non-toxic form of the globular protein, ferritin, consisting of an apoferritin shell and iron core. Numerous studies confirmed the disruption of homeostasis and accumulation of iron in patients with various diseases (e.g. cancer, cardiovascular or neurological conditions), which is closely related to ferritin metabolism. Such iron imbalance enables the use of magnetic resonance imaging (MRI) as a sensitive technique for the detection of iron-based aggregates through changes in the relaxation times, followed by the change in the inherent image contrast. For our in vitrostudy, modified ferritins with different iron loadings were prepared by chemical reconstruction of the iron core in an apoferritin shell as pathological model systems. The magnetic properties of samples were studied using SQUID magnetometry, while the size distribution was detected via dynamic light scattering. We have shown that MRI could represent the most advantageous method for distinguishing native ferritin from reconstructed ferritin which, after future standardisation, could then be suitable for the diagnostics of diseases associated with iron accumulation. - Highlights: • MRI is the sensitive technique for detecting iron-based aggregates. • Reconstructed Ferritin is suitable model system of iron-related disorders. • MRI allow distinguish of native ferritin from reconstructed ferritin. • MRI could be useful for diagnostics of diseases associated with iron accumulation.

Obesity alters adipose tissue macrophage iron content and tissue iron distribution.

Science.gov (United States)

Orr, Jeb S; Kennedy, Arion; Anderson-Baucum, Emily K; Webb, Corey D; Fordahl, Steve C; Erikson, Keith M; Zhang, Yaofang; Etzerodt, Anders; Moestrup, Søren K; Hasty, Alyssa H

2014-02-01

Adipose tissue (AT) expansion is accompanied by the infiltration and accumulation of AT macrophages (ATMs), as well as a shift in ATM polarization. Several studies have implicated recruited M1 ATMs in the metabolic consequences of obesity; however, little is known regarding the role of alternatively activated resident M2 ATMs in AT homeostasis or how their function is altered in obesity. Herein, we report the discovery of a population of alternatively activated ATMs with elevated cellular iron content and an iron-recycling gene expression profile. These iron-rich ATMs are referred to as MFe(hi), and the remaining ATMs are referred to as MFe(lo). In lean mice, ~25% of the ATMs are MFe(hi); this percentage decreases in obesity owing to the recruitment of MFe(lo) macrophages. Similar to MFe(lo) cells, MFe(hi) ATMs undergo an inflammatory shift in obesity. In vivo, obesity reduces the iron content of MFe(hi) ATMs and the gene expression of iron importers as well as the iron exporter, ferroportin, suggesting an impaired ability to handle iron. In vitro, exposure of primary peritoneal macrophages to saturated fatty acids also alters iron metabolism gene expression. Finally, the impaired MFe(hi) iron handling coincides with adipocyte iron overload in obese mice. In conclusion, in obesity, iron distribution is altered both at the cellular and tissue levels, with AT playing a predominant role in this change. An increased availability of fatty acids during obesity may contribute to the observed changes in MFe(hi) ATM phenotype and their reduced capacity to handle iron.

Iron-induced neuronal damage in a rat model of post-traumatic stress disorder.

Science.gov (United States)

Zhao, Ming; Yu, Zhibo; Zhang, Yang; Huang, Xueling; Hou, Jingming; Zhao, YanGang; Luo, Wei; Chen, Lin; Ou, Lan; Li, Haitao; Zhang, Jiqiang

2016-08-25

Previous studies have shown that iron redistribution and deposition in the brain occurs in some neurodegenerative diseases, and oxidative damage due to abnormal iron level is a primary cause of neuronal death. In the present study, we used the single prolonged stress (SPS) model to mimic post-traumatic stress disorder (PTSD), and examined whether iron was involved in the progression of PTSD. The anxiety-like behaviors of the SPS group were assessed by the elevated plus maze (EPM) and open field tests, and iron levels were measured by inductively coupled plasma optical emission spectrometer (ICP-OES). Expression of glucocorticoid receptors and transferrin receptor 1 (TfR1) and ferritin (Fn) was detected by Western blot and immunohistochemistry in selected brain areas; TfR1 and Fn mRNA expression were detected by quantitative-polymerase chain reaction (Q-PCR). Ultrastructures of the hippocampus were observed under a transmission electron microscope. Our results showed that SPS exposure induced anxiety-like symptoms and increased the level of serum cortisol and the concentration of iron in key brain areas such as the hippocampus, prefrontal cortex, and striatum. The stress induced region-specific changes in both protein and mRNA levels of TfR1 and Fn. Moreover, swelling mitochondria and cell apoptosis were observed in neurons in brain regions with iron accumulation. We concluded that SPS stress increased iron in some cognition-related brain regions and subsequently cause neuronal injury, indicating that the iron may function in the pathology of PTSD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

The effect of psychological stress on iron absorption in rats

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Zhao Min

2009-11-01

Full Text Available Abstract Background Psychological stress (PS is recognized as an important pathogenic factor which leads to metabolism disorder in many diseases. Previous studies have shown that systemic iron homeostasis in mammalians was changed under specific stress conditions. Methods In present study, we used communication box to create psychological stress model and investigated the iron apparent absorption, iron accumulation in the apical poles of villous enterocytes and protein expressions of ferroportin 1 (FPN1, ferritin, divalent metal transporter 1 (DMT1. Results Our study showed that iron apparent absorption decreased and iron significantly accumulated in the apical poles of villous enterocytes in 3 d and 7 d PS groups. The expression of intestinal FPN1 in 3 d and 7 d PS groups was lower than that of control, while the change of intestinal ferritin was opposite. However, the expression of DMT1 did not change. Conclusion These results demonstrate that PS can decrease iron absorption in rats, which might be related to regulation expression of iron transporters.

Excessive sulfur supply reduces cadmium accumulation in brown rice (Oryza sativa L.)

International Nuclear Information System (INIS)

Fan Jianling; Hu Zhengyi; Ziadi, Noura; Xia Xu; Wu Congyanghui

2010-01-01

Human activities have resulted in cadmium (Cd) and sulfur (S) accumulation in paddy soils in parts of southern China. A combined soil-sand pot experiment was conducted to investigate the influence of excessive S supply on iron plaque formation and Cd accumulation in rice plants, using two Cd levels (0, 1.5 mg kg -1 ) combined with three S concentrations (0, 60, 120 mg kg -1 ). The results showed that excessive S supply significantly decreased Cd accumulation in brown rice due to the decrease of Cd availability and the increase of glutathione in rice leaves. But excessive S supply obviously increased Cd accumulation in roots due to the decrease of iron plaque formation on the root surface of rice. Therefore, excessive S supply may result in loss of rice yield, but it could effectively reduce Cd accumulation in brown rice exposed to Cd contaminated soils. - Excessive sulfur reduces cadmium accumulation in brown rice.

Overexpression of Arabidopsis VIT1 increases accumulation of iron in cassava roots and stems

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Iron is extremely abundant in the soil, but its uptake in plants is limited due to low solubility in neutral or alkaline soils. Plants can rely on rhizosphere acidification to increase iron solubility. AtVIT1 was previously found to be involved in mediating vacuolar sequestration of iron, which indi...

Hydrogen sulphide improves adaptation of Zea mays seedlings to iron deficiency.

Science.gov (United States)

Chen, Juan; Wu, Fei-Hua; Shang, Yu-Ting; Wang, Wen-Hua; Hu, Wen-Jun; Simon, Martin; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

2015-11-01

Hydrogen sulphide (H2S) is emerging as a potential molecule involved in physiological regulation in plants. However, whether H2S regulates iron-shortage responses in plants is largely unknown. Here, the role of H2S in modulating iron availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient culture solution is reported. The main results are as follows: Firstly, NaHS, a donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings grown in iron-deficient culture solution. Secondly, electron micrographs of mesophyll cells from iron-deficient maize seedlings revealed plastids with few photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll chloroplasts appeared completely developed in H2S-treated maize seedlings. Thirdly, H2S treatment increased iron accumulation in maize seedlings by changing the expression levels of iron homeostasis- and sulphur metabolism-related genes. Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S treatment in seedlings grown in iron-deficient solution. Indeed, the gene expression of ferric-phytosiderophore transporter (ZmYS1) was specifically induced by iron deficiency in maize leaves and roots, whereas their abundance was decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS), D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution. These results indicate that H2S is closely related to iron uptake, transport, and accumulation, and consequently increases chlorophyll biosynthesis, chloroplast development, and photosynthesis in plants. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Two-Component Signaling System VgrRS Directly Senses Extracytoplasmic and Intracellular Iron to Control Bacterial Adaptation under Iron Depleted Stress.

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Li Wang

2016-12-01

Full Text Available Both iron starvation and excess are detrimental to cellular life, especially for animal and plant pathogens since they always live in iron-limited environments produced by host immune responses. However, how organisms sense and respond to iron is incompletely understood. Herein, we reveal that in the phytopathogenic bacterium Xanthomonas campestris pv. campestris, VgrS (also named ColS is a membrane-bound receptor histidine kinase that senses extracytoplasmic iron limitation in the periplasm, while its cognate response regulator, VgrR (ColR, detects intracellular iron excess. Under iron-depleted conditions, dissociation of Fe3+ from the periplasmic sensor region of VgrS activates the VgrS autophosphorylation and subsequent phosphotransfer to VgrR, an OmpR-family transcription factor that regulates bacterial responses to take up iron. VgrR-VgrS regulon and the consensus DNA binding motif of the transcription factor VgrR were dissected by comparative proteomic and ChIP-seq analyses, which revealed that in reacting to iron-depleted environments, VgrR directly or indirectly controls the expressions of hundreds of genes that are involved in various physiological cascades, especially those associated with iron-uptake. Among them, we demonstrated that the phosphorylated VgrR tightly represses the transcription of a special TonB-dependent receptor gene, tdvA. This regulation is a critical prerequisite for efficient iron uptake and bacterial virulence since activation of tdvA transcription is detrimental to these processes. When the intracellular iron accumulates, the VgrR-Fe2+ interaction dissociates not only the binding between VgrR and the tdvA promoter, but also the interaction between VgrR and VgrS. This relieves the repression in tdvA transcription to impede continuous iron uptake and avoids possible toxic effects of excessive iron accumulation. Our results revealed a signaling system that directly senses both extracytoplasmic and intracellular

Excessive sulfur supply reduces cadmium accumulation in brown rice (Oryza sativa L.).

Science.gov (United States)

Fan, Jian-Ling; Hu, Zheng-Yi; Ziadi, Noura; Xia, Xu; Wu, Cong-Yang-Hui

2010-02-01

Human activities have resulted in cadmium (Cd) and sulfur (S) accumulation in paddy soils in parts of southern China. A combined soil-sand pot experiment was conducted to investigate the influence of excessive S supply on iron plaque formation and Cd accumulation in rice plants, using two Cd levels (0, 1.5 mg kg(-1)) combined with three S concentrations (0, 60, 120 mg kg(-1)). The results showed that excessive S supply significantly decreased Cd accumulation in brown rice due to the decrease of Cd availability and the increase of glutathione in rice leaves. But excessive S supply obviously increased Cd accumulation in roots due to the decrease of iron plaque formation on the root surface of rice. Therefore, excessive S supply may result in loss of rice yield, but it could effectively reduce Cd accumulation in brown rice exposed to Cd contaminated soils. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Accumulation and transport of minerals by marine protozoa. Progress report, September 1, 1976--November 30, 1977

International Nuclear Information System (INIS)

Gold, K.

1977-08-01

Tintinnida are abundant microzooplankton found in all of the world's oceans, and important components of the marine food web as predators, prey, and as regenerators of nutrients. The agglutinated forms take on added importance in coastal waters. Representatives of this group have the unique ability among ciliates to pick up particles from the environment and incorporate them into the lorica. The ecological significance of the phenomenon lies in: it is a pathway whereby radionuclides, metals and other toxic substance can be biologically concentrated and transferred from sediments and the water column to the biota; from the viewpoint of microzooplankton as indicators of environmental perturbations, pollution, or water mass movements, it is important to determine whether minerals accumulated on the lorica can serve as a guide to the site where they originate. Results are reported from studies in progress on the types of mineral matter accumulated by tintinnids

Superparamagnetic iron oxides for MRI

International Nuclear Information System (INIS)

Weissleder, R.; Reimer, P.

1993-01-01

Pharmaceutical iron oxide preparations have been used as MRI contrast agents for a variety of purposes. These agents predominantly decrease T2 relaxation times and therefore cause a decrease in signal intensity of tissues that contain the agent. After intravenous administration, dextran-coated iron oxides typically accumulate in phagocytic cells in liver and spleen. Clinical trials have shown that iron oxide increases lesion/liver and lesion/spleen contrast, that more lesions can be depicted than on plain MRI or CT, and that the size threshold for lesion detection decreases. Decreased uptake of iron oxides in liver has been observed in hepatitis and cirrhosis, potentially allowing the assessment of organ function. More recently a variety of novel, target-specific monocrystalline iron oxides compounds have been used for receptor and immunospecific images. Future development of targeted MRI contrast agents is critical for organ- or tissue-specific quantitative and functional MRI. (orig.)

Superparamagnetic iron oxides for MRI

Energy Technology Data Exchange (ETDEWEB)

Weissleder, R [MGH-NMR Center, Dept. of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Reimer, P [MGH-NMR Center, Dept. of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); [Inst. fuer Klinische Radiologie, Zentrale Roentgendiagnostik, Westfaelische-Wilhelms-Univ., Muenster (Germany)

1993-06-01

Pharmaceutical iron oxide preparations have been used as MRI contrast agents for a variety of purposes. These agents predominantly decrease T2 relaxation times and therefore cause a decrease in signal intensity of tissues that contain the agent. After intravenous administration, dextran-coated iron oxides typically accumulate in phagocytic cells in liver and spleen. Clinical trials have shown that iron oxide increases lesion/liver and lesion/spleen contrast, that more lesions can be depicted than on plain MRI or CT, and that the size threshold for lesion detection decreases. Decreased uptake of iron oxides in liver has been observed in hepatitis and cirrhosis, potentially allowing the assessment of organ function. More recently a variety of novel, target-specific monocrystalline iron oxides compounds have been used for receptor and immunospecific images. Future development of targeted MRI contrast agents is critical for organ- or tissue-specific quantitative and functional MRI. (orig.)

Dissipation and accumulation of energy during plastic deformation of Armco -iron and 12Cr18Ni10Ti stainless steel irradiated by neutrons

International Nuclear Information System (INIS)

Toktogulova, D.; Maksimkin, O.; Gusev, M.; Garner, F.

2007-01-01

Full text of publication follows: Much attention is currently being paid in the fusion materials community to modeling of radiation damage and its consequences in structural alloys on mechanical properties. Such activities are best guided with experimental data on the fundamental microstructural and thermodynamic processes involved. This report addresses such fundamental concerns. During plastic deformation of metals some fraction of the externally-applied mechanical energy is converted into heat and is partially accumulated in the form of crystal lattice defects. The thermal release arises from gliding dislocations, their various interactions, their annihilation etc. With respect to irradiated material, one might expect additional heat release caused by interactions of dislocation and radiation-induced defects. To explore this possibility flat mini-tensile specimens of Armco-iron and 12Cr18Ni10Ti stainless steel, both in the annealed condition, were irradiated in the range 2x10 18 to 1.3x10 20 n/cm 2 (E>0.1 MeV) in the WWR-K reactor at T≤350 K. Mechanical tests of both irradiated and non-irradiated specimens were conducted at room temperature in a facility that was a combination of a Calvet calorimeter and a micro-tensile device. This allows simultaneous measurement of mechanical properties and thermodynamic parameters such as deformation work, dissipated heat and latent energy during deformation. The authors derived the kinetics of changes in thermodynamic characteristics versus the deformation level. As the neutron fluence rises, the material's capability to accumulate energy appears to be declining. For example, 12Cr18Ni10Ti irradiated to 1.3x10 20 n/cm 2 did not show any energy accumulation under deformation. In Armco-iron at 1.4x10 19 n/cm 2 the heat release considerably exceeded the deformation work value. The authors assume that such effects might be related with annihilation of point defects and their complexes introduced during irradiation. To test this

Virtual iron concentration imaging based on dual-energy CT for noninvasive quantification and grading of liver iron content: An iron overload rabbit model study

Energy Technology Data Exchange (ETDEWEB)

Luo, Xian Fu; Yang, Yi; Xie, Xue Qian; Zhang, Huan; Chai, Wei Min; Yan, Fu Hua [Shanghai Jiao Tong University School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); Yan, Jing [Siemens Shanghai Medical Equipment Ltd., Shanghai (China); Wang, Li [Fudan University, Center of Analysis and Measurement, Shanghai (China); Schmidt, Bernhard [Siemens AG, Healthcare Sector, Forchheim (Germany)

2015-09-15

To assess the accuracy of liver iron content (LIC) quantification and grading ability associated with clinical LIC stratification using virtual iron concentration (VIC) imaging on dual-energy CT (DECT) in an iron overload rabbit model. Fifty-one rabbits were prepared as iron-loaded models by intravenous injection of iron dextran. DECT was performed at 80 and 140 kVp. VIC images were derived from an iron-specific algorithm. Postmortem LIC assessments were conducted on an inductively coupled plasma (ICP) spectrometer. Correlation between VIC and LIC was analyzed. VIC were stratified according to the corresponding clinical LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g. Diagnostic performance of stratification was evaluated by receiver operating characteristic analysis. VIC linearly correlated with LIC (r = 0.977, P < 0.01). No significant difference was observed between VIC-derived LICs and ICP (P > 0.05). For the four clinical LIC thresholds, the corresponding cutoff values of VIC were 19.6, 25.3, 36.9, and 61.5 HU, respectively. The highest sensitivity (100 %) and specificity (100 %) were achieved at the threshold of 15.0 mg Fe/g. Virtual iron concentration imaging on DECT showed potential ability to accurately quantify and stratify hepatic iron accumulation in the iron overload rabbit model. (orig.)

Iron-responsive olfactory uptake of manganese improves motor function deficits associated with iron deficiency.

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Jonghan Kim

Full Text Available Iron-responsive manganese uptake is increased in iron-deficient rats, suggesting that toxicity related to manganese exposure could be modified by iron status. To explore possible interactions, the distribution of intranasally-instilled manganese in control and iron-deficient rat brain was characterized by quantitative image analysis using T1-weighted magnetic resonance imaging (MRI. Manganese accumulation in the brain of iron-deficient rats was doubled after intranasal administration of MnCl(2 for 1- or 3-week. Enhanced manganese level was observed in specific brain regions of iron-deficient rats, including the striatum, hippocampus, and prefrontal cortex. Iron-deficient rats spent reduced time on a standard accelerating rotarod bar before falling and with lower peak speed compared to controls; unexpectedly, these measures of motor function significantly improved in iron-deficient rats intranasally-instilled with MnCl(2. Although tissue dopamine concentrations were similar in the striatum, dopamine transporter (DAT and dopamine receptor D(1 (D1R levels were reduced and dopamine receptor D(2 (D2R levels were increased in manganese-instilled rats, suggesting that manganese-induced changes in post-synaptic dopaminergic signaling contribute to the compensatory effect. Enhanced olfactory manganese uptake during iron deficiency appears to be a programmed "rescue response" with beneficial influence on motor impairment due to low iron status.

In vivo assessment of iron content of the cerebral cortex in healthy aging using 7-Tesla T2*-weighted phase imaging.

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Buijs, Mathijs; Doan, Nhat Trung; van Rooden, Sanneke; Versluis, Maarten J; van Lew, Baldur; Milles, Julien; van der Grond, Jeroen; van Buchem, Mark A

2017-05-01

Accumulation of brain iron has been suggested as a biomarker of neurodegeneration. Increased iron has been seen in the cerebral cortex in postmortem studies of neurodegenerative diseases and healthy aging. Until recently, the diminutive thickness of the cortex and its relatively low iron content have hampered in vivo study of cortical iron accumulation. Using phase images of a T2*-weighted sequence at ultrahigh field strength (7 Tesla), we examined the iron content of 22 cortical regions in 70 healthy subjects aged 22-80 years. The cortex was automatically segmented and parcellated, and phase shift was analyzed using an in-house developed method. We found a significant increase in phase shift with age in 20 of 22 cortical regions, concurrent with current understanding of cortical iron accumulation. Our findings suggest that increased cortical iron content can be assessed in healthy aging in vivo. The high spatial resolution and sensitivity to iron of our method make it a potentially useful tool for studying cortical iron accumulation in healthy aging and neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Subcellular Iron Localization Mechanisms in Plants

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Emre Aksoy

2017-12-01

Full Text Available The basic micro-nutrient element iron (Fe is present as a cofactor in the active sites of many metalloproteins with important roles in the plant. On the other hand, since it is excessively reactive, excess accumulation in the cell triggers the production of reactive oxygen species, leading to cell death. Therefore, iron homeostasis in the cell is very important for plant growth. Once uptake into the roots, iron is distributed to the subcellular compartments. Subcellular iron transport and hence cellular iron homeostasis is carried out through synchronous control of different membrane protein families. It has been discovered that expression levels of these membrane proteins increase under iron deficiency. Examination of the tasks and regulations of these carriers is very important in terms of understanding the iron intake and distribution mechanisms in plants. Therefore, in this review, the transporters responsible for the uptake of iron into the cell and its subcellular distribution between organelles will be discussed with an emphasis on the current developments about these transporters.

Exploring the iron metabolism in multidrug resistant tuberculosis ...

African Journals Online (AJOL)

The iron metabolism plays a key role in the progression of active Tuberculosis. Several studies have shown a link between iron metabolism disorders an active tuberculosis. The aim of this study was to explore the iron metabolism of 100 patients with multidrug-resistant tuberculosis (MDR-TB) treated with second generation ...

Exploring the iron metabolism in multidrug resistant tuberculosis ...

African Journals Online (AJOL)

The iron metabolism plays a key role in the progression of active Tuberculosis. Several studies have shown a link between iron metabolism disorders an active tuberculosis. The aim of this study was to explore the iron metabolism of 100 patients with multidrug-resistant tuberculosis. (MDR-TB) treated with second ...

Secondary Hemochromatosis due to Chronic Oral Iron Supplementation

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Ronald Lands

2017-01-01

Full Text Available Iron may accumulate in excess due to a mutation in the HFE gene that upregulates absorption or when it is ingested or infused at levels that exceed the body’s ability to clear it. Excess iron deposition in parenchymal tissue causes injury and ultimately organ dysfunction. Diabetes mellitus and hepatic cirrhosis due to pancreas and liver damage are just two examples of diseases that result from iron overload. Despite the rapid growth of information regarding iron metabolism and iron overload states, the most effective treatment is still serial phlebotomies. We present a patient who developed iron overload due to chronic ingestion of oral ferrous sulfate. This case illustrates the importance of querying geriatric patients regarding their use of nonprescription iron products without a medical indication.

Characterization of a tricationic trigonal bipyramidal iron(IV) cyanide complex, with a very high reduction potential, and its iron(II) and iron(III) congeners.

Science.gov (United States)

England, Jason; Farquhar, Erik R; Guo, Yisong; Cranswick, Matthew A; Ray, Kallol; Münck, Eckard; Que, Lawrence

2011-04-04

Currently, there are only a handful of synthetic S = 2 oxoiron(IV) complexes. These serve as models for the high-spin (S = 2) oxoiron(IV) species that have been postulated, and confirmed in several cases, as key intermediates in the catalytic cycles of a variety of nonheme oxygen activating enzymes. The trigonal bipyramidal complex [Fe(IV)(O)(TMG(3)tren)](2+) (1) was both the first S = 2 oxoiron(IV) model complex to be generated in high yield and the first to be crystallographically characterized. In this study, we demonstrate that the TMG(3)tren ligand is also capable of supporting a tricationic cyanoiron(IV) unit, [Fe(IV)(CN)(TMG(3)tren)](3+) (4). This complex was generated by electrolytic oxidation of the high-spin (S = 2) iron(II) complex [Fe(II)(CN)(TMG(3)tren)](+) (2), via the S = 5/2 complex [Fe(III)(CN)(TMG(3)tren)](2+) (3), the progress of which was conveniently monitored by using UV-vis spectroscopy to follow the growth of bathochromically shifting ligand-to-metal charge transfer (LMCT) bands. A combination of X-ray absorption spectroscopy (XAS), Mössbauer and NMR spectroscopies was used to establish that 4 has a S = 0 iron(IV) center. Consistent with its diamagnetic iron(IV) ground state, extended X-ray absorption fine structure (EXAFS) analysis of 4 indicated a significant contraction of the iron-donor atom bond lengths, relative to those of the crystallographically characterized complexes 2 and 3. Notably, 4 has an Fe(IV/III) reduction potential of ∼1.4 V vs Fc(+/o), the highest value yet observed for a monoiron complex. The relatively high stability of 4 (t(1/2) in CD(3)CN solution containing 0.1 M KPF(6) at 25 °C ≈ 15 min), as reflected by its high-yield accumulation via slow bulk electrolysis and amenability to (13)C NMR at -40 °C, highlights the ability of the sterically protecting, highly basic peralkylguanidyl donors of the TMG(3)tren ligand to support highly charged high-valent complexes.

Non-coding keratin variants associate with liver fibrosis progression in patients with hemochromatosis.

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Pavel Strnad

Full Text Available BACKGROUND: Keratins 8 and 18 (K8/K18 are intermediate filament proteins that protect the liver from various forms of injury. Exonic K8/K18 variants associate with adverse outcome in acute liver failure and with liver fibrosis progression in patients with chronic hepatitis C infection or primary biliary cirrhosis. Given the association of K8/K18 variants with end-stage liver disease and progression in several chronic liver disorders, we studied the importance of keratin variants in patients with hemochromatosis. METHODS: The entire K8/K18 exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous C282Y HFE (hemochromatosis gene mutations. 234 liver-healthy subjects were used as controls. Exonic regions were PCR-amplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Previously-generated transgenic mice overexpressing K8 G62C were studied for their susceptibility to iron overload. Susceptibility to iron toxicity of primary hepatocytes that express K8 wild-type and G62C was also assessed. RESULTS: We identified amino-acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients (6.2% and non-coding heterozygous variants in 6 additional patients (3.7%. Two novel K8 variants (Q169E/R275W were found. K8 R341H was the most common amino-acid altering variant (4 patients, and exclusively associated with an intronic KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants associated with the development of liver fibrosis. In mice, or ex vivo, the K8 G62C variant did not affect iron-accumulation in response to iron-rich diet or the extent of iron-induced hepatocellular injury. CONCLUSION: In patients with hemochromatosis, intronic but not exonic K8/K18 variants associate with liver fibrosis development.

The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism.

Science.gov (United States)

Lill, Roland; Hoffmann, Bastian; Molik, Sabine; Pierik, Antonio J; Rietzschel, Nicole; Stehling, Oliver; Uzarska, Marta A; Webert, Holger; Wilbrecht, Claudia; Mühlenhoff, Ulrich

2012-09-01

Mitochondria play a key role in iron metabolism in that they synthesize heme, assemble iron-sulfur (Fe/S) proteins, and participate in cellular iron regulation. Here, we review the latter two topics and their intimate connection. The mitochondrial Fe/S cluster (ISC) assembly machinery consists of 17 proteins that operate in three major steps of the maturation process. First, the cysteine desulfurase complex Nfs1-Isd11 as the sulfur donor cooperates with ferredoxin-ferredoxin reductase acting as an electron transfer chain, and frataxin to synthesize an [2Fe-2S] cluster on the scaffold protein Isu1. Second, the cluster is released from Isu1 and transferred toward apoproteins with the help of a dedicated Hsp70 chaperone system and the glutaredoxin Grx5. Finally, various specialized ISC components assist in the generation of [4Fe-4S] clusters and cluster insertion into specific target apoproteins. Functional defects of the core ISC assembly machinery are signaled to cytosolic or nuclear iron regulatory systems resulting in increased cellular iron acquisition and mitochondrial iron accumulation. In fungi, regulation is achieved by iron-responsive transcription factors controlling the expression of genes involved in iron uptake and intracellular distribution. They are assisted by cytosolic multidomain glutaredoxins which use a bound Fe/S cluster as iron sensor and additionally perform an essential role in intracellular iron delivery to target metalloproteins. In mammalian cells, the iron regulatory proteins IRP1, an Fe/S protein, and IRP2 act in a post-transcriptional fashion to adjust the cellular needs for iron. Thus, Fe/S protein biogenesis and cellular iron metabolism are tightly linked to coordinate iron supply and utilization. This article is part of a Special Issue entitled: Cell Biology of Metals. Copyright © 2012 Elsevier B.V. All rights reserved.

Fungal accumulation of metals from building materials during brown rot wood decay.

Science.gov (United States)

Hastrup, Anne Christine Steenkjær; Jensen, Bo; Jellison, Jody

2014-08-01

This study analyzes the accumulation and translocation of metal ions in wood during the degradation performed by one strain of each of the three brown rot fungi; Serpula lacrymans, Meruliporia incrassata and Coniophora puteana. These fungi species are inhabitants of the built environment where the prevention and understanding of fungal decay is of high priority. This study focuses on the influence of various building materials in relation to fungal growth and metal uptake. Changes in the concentration of iron, manganese, calcium and copper ions in the decayed wood were analyzed by induced coupled plasma spectroscopy and related to wood weight loss and oxalic acid accumulation. Metal transport into the fungal inoculated wood was found to be dependent on the individual strain/species. The S. lacrymans strain caused a significant increase in total iron whereas the concentration of copper ions in the wood appeared decreased after 10 weeks of decay. Wood inoculated with the M. incrassata isolate showed the contrary tendency with high copper accumulation and low iron increase despite similar weight losses for the two strains. However, significantly lower oxalic acid accumulation was recorded in M. incrassata degraded wood. The addition of a building material resulted in increased weight loss in wood degraded by C. puteana in the soil-block test; however, this could not be directly linked specifically to the accumulation of any of the four metals recorded. The accumulation of oxalic acid seemed to influence the iron uptake. The study assessing the influence of the presence of soil and glass in the soil-block test revealed that soil contributed the majority of the metals for uptake by the fungi and contributed to increased weight loss. The varying uptake observed among the three brown rot fungi strains toward the four metals analyzed may be related to the specific non-enzymatic and enzymatic properties including bio-chelators employed by each of the species during wood

Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).

OpenAIRE

Ingrassia, Rosaria; Memo, Maurizio; Garavaglia, Barbara

2017-01-01

Mutations in WDR45 gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been cla...

Composition, speciation and distribution of iron minerals in Imperata cylindrica.

Science.gov (United States)

Amils, Ricardo; de la Fuente, Vicenta; Rodríguez, Nuria; Zuluaga, Javier; Menéndez, Nieves; Tornero, Jesús

2007-05-01

A comparative study of the roots, rhizomes and leaves of an iron hyperaccumulator plant, Imperata cylindrica, isolated from the banks of an extreme acidic environment, using complementary techniques: Mösbauer spectroscopy (MS), X-ray diffraction (XRD), scanning electron microscopy (SEM) coupled to energy-dispersive X-ray microanalysis (EDAX) and transmission electron microscopy (TEM), has shown that two main biominerals, jarosite and ferrihydrate-ferritin, accumulate in the different tissues. Jarosite accumulates mainly in roots and rhizomes, while ferritin has been detected in all the structures. A model of iron management in I. cylindrica is presented.

Mice lacking liver-specific β-catenin develop steatohepatitis and fibrosis after iron overload.

Science.gov (United States)

Preziosi, Morgan E; Singh, Sucha; Valore, Erika V; Jung, Grace; Popovic, Branimir; Poddar, Minakshi; Nagarajan, Shanmugam; Ganz, Tomas; Monga, Satdarshan P

2017-08-01

Iron overload disorders such as hereditary hemochromatosis and iron loading anemias are a common cause of morbidity from liver diseases and increase risk of hepatic fibrosis and hepatocellular carcinoma (HCC). Treatment options for iron-induced damage are limited, partly because there is lack of animal models of human disease. Therefore, we investigated the effect of iron overload in liver-specific β-catenin knockout mice (KO), which are susceptible to injury, fibrosis and tumorigenesis following chemical carcinogen exposure. Iron overload diet was administered to KO and littermate control (CON) mice for various times. To ameliorate an oxidant-mediated component of tissue injury, N-Acetyl-L-(+)-cysteine (NAC) was added to drinking water of mice on iron overload diet. KO on iron diet (KO +Fe) exhibited remarkable inflammation, followed by steatosis, oxidative stress, fibrosis, regenerating nodules and occurrence of occasional HCC. Increased injury in KO +Fe was associated with activated protein kinase B (AKT), ERK, and NF-κB, along with reappearance of β-catenin and target gene Cyp2e1, which promoted lipid peroxidation and hepatic damage. Addition of NAC to drinking water protected KO +Fe from hepatic steatosis, injury and fibrosis, and prevented activation of AKT, ERK, NF-κB and reappearance of β-catenin. The absence of hepatic β-catenin predisposes mice to hepatic injury and fibrosis following iron overload, which was reminiscent of hemochromatosis and associated with enhanced steatohepatitis and fibrosis. Disease progression was notably alleviated by antioxidant therapy, which supports its chemopreventive role in the management of chronic iron overload disorders. Lack of animal models for iron overload disorders makes it hard to study the disease process for improving therapies. Feeding high iron diet to mice that lack the β-catenin gene in liver cells led to increased inflammation followed by fat accumulation, cell death and wound healing that mimicked

[The efficacy of phlebotomy with a low iron diet in the management of pulmonary iron overload].

Science.gov (United States)

Fukuda, Tomoko; Kimura, Fumiaki; Watanabe, Yoichi; Yoshino, Tadasi; Kimura, Ikuro

2003-05-01

Numerous studies have shown that workers in ferriferous industries have an elevated risk of respiratory tract neoplasia and other airway diseases. Evidence is presented that iron is a carcinogenic and tissue toxic hazard as regarding the inhalation of ferriferous substances. Elimination of the inhaled iron and prevention from accumulation of iron in the lung seems to be very important. A 26-year-old man was admitted to our hospital complaining of right chest pain. He had worked as an arc welder for two years without a mask. A chest CT showed diffuse ground glass opacity in the bilateral lung fields. A transbronchial lung biopsy specimen showed numerous alveolar and interstitial iron-laden macrophages. A 200 ml phlebotomy was carried out biweekly in combination with a low iron diet (8 mg/day). When serum ferritin reached 20 ng/ml, phlebotomy was stopped. After that, serum ferritin level was kept at around 20 ng/ml with the low iron diet alone. A transbronchial lung biopsy was carried out again 7 months later and the specimen showed remarkable reduction in the number of iron-laden alveolar and interstitial macrophages. Phlebotomy in combination with a low iron diet might become a useful strategy in the management of pulmonary conditions associated with iron loading.

The evaluation of the bone marrow accumulation of Ga-67 citrate

Energy Technology Data Exchange (ETDEWEB)

Ohnishi, Takashi; Jinnouchi, Seishi; Hoshi, Hiroaki; Yoshimura, Hiroshi; Nagamachi, Shigeki; Watanabe, Katsushi (Miyazaki Medical Coll., Kiyotake (Japan))

1989-11-01

The bone marrow distribution of Ga-67 citrate may be influenced by various elements in serum. In order to make these points clear, 1,955 whole body images were reviewed on the relationship between the accumulation of bone marrow and laboratory examination data of each patients. Increasing accumulation in the bone marrow was determined as positive when the bones of lower extremities were deposited on the images, because these bones was not visualized in normal gallium image. Laboratory data of 20 patients without having bone marrow accumulation was used as control. The positive findings of bone marrow accumulation was observed in 38 patients (2%) including 23 malignancies and 15 benign disease. The malignant tumor infiltration to the bone marrow was demonstrated by bone marrow aspiration biopsy in 2 out of 7 patients with bone marrow accumulation of Ga-67. Seven out of 15 patients with benign disease were collagen disease such as aortitis syndrome or SLE. The values of hemoglobin, hematocrit, serum iron and creatinine clearance were significantly lower in the patients with positive findings in comparison with control. These results suggest that the lower level of serum iron and anemia may cause increasing bone marrow accumulation of Ga-67 citrate. (author).

The evaluation of the bone marrow accumulation of Ga-67 citrate

International Nuclear Information System (INIS)

Ohnishi, Takashi; Jinnouchi, Seishi; Hoshi, Hiroaki; Yoshimura, Hiroshi; Nagamachi, Shigeki; Watanabe, Katsushi

1989-01-01

The bone marrow distribution of Ga-67 citrate may be influenced by various elements in serum. In order to make these points clear, 1,955 whole body images were reviewed on the relationship between the accumulation of bone marrow and laboratory examination data of each patients. Increasing accumulation in the bone marrow was determined as positive when the bones of lower extremities were deposited on the images, because these bones was not visualized in normal gallium image. Laboratory data of 20 patients without having bone marrow accumulation was used as control. The positive findings of bone marrow accumulation was observed in 38 patients (2%) including 23 malignancies and 15 benign disease. The malignant tumor infiltration to the bone marrow was demonstrated by bone marrow aspiration biopsy in 2 out of 7 patients with bone marrow accumulation of Ga-67. Seven out of 15 patients with benign disease were collagen disease such as aortitis syndrome or SLE. The values of hemoglobin, hematocrit, serum iron and creatinine clearance were significantly lower in the patients with positive findings in comparison with control. These results suggest that the lower level of serum iron and anemia may cause increasing bone marrow accumulation of Ga-67 citrate. (author)

Effects of dietary cadmium exposure on tissue-specific cadmium accumulation, iron status and expression of iron-handling and stress-inducible genes in rainbow trout: Influence of elevated dietary iron

Energy Technology Data Exchange (ETDEWEB)

Kwong, Raymond W.M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Andres, Jose A. [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada); Niyogi, Som, E-mail: som.niyogi@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada)

2011-03-15

Recent evidences suggest that dietary cadmium (Cd) uptake likely occurs via the dietary iron (Fe) uptake pathway in freshwater fish, at least in part. The present study investigated the interactive effects of dietary Cd and Fe in juvenile rainbow trout (Oncorhynchus mykiss). Fish were treated for four weeks with four different diets: normal Fe, high Fe, normal Fe plus Cd, and high Fe plus Cd. Physiological parameters, tissue-specific Fe and Cd level, plasma Fe status, and tissue-specific mRNA expression of transferrin, metallothioneins (MT-A and MT-B) and heat shock proteins 70 (HSP70a and HSP70b) were analyzed. Exposure to dietary Cd increased Cd burden in the following order: intestine > kidney > stomach > liver > gill > carcass. Interestingly, high dietary Fe reduced Cd accumulation in the stomach and intestine as well as in the wholebody of fish. Dietary Cd increased hepatic transferrin mRNA expression and total Fe binding capacity in the plasma, indicating the effect of Cd on Fe handling in fish. The mRNA expression of MTs and HSP70s was also increased in various tissues following dietary Cd exposure, however the response profile of different MT and HSP70 genes was not consistent among different tissues. In general, MT-A was more responsive to Cd exposure in the intestine and liver, whereas MT-B was more responsive in the kidney. Similarly, HSP70a expression was more sensitive to Cd exposure than HSP70b, particularly in the intestine. Interestingly, high Fe diet suppressed Cd-induced induction of transferrin, MT and HSP70 genes in various tissues. Overall, our study suggests that elevated dietary Fe can reduce Cd accumulation and ameliorate Cd-induced stress responses in freshwater fish.

Effects of dietary cadmium exposure on tissue-specific cadmium accumulation, iron status and expression of iron-handling and stress-inducible genes in rainbow trout: Influence of elevated dietary iron

International Nuclear Information System (INIS)

Kwong, Raymond W.M.; Andres, Jose A.; Niyogi, Som

2011-01-01

Recent evidences suggest that dietary cadmium (Cd) uptake likely occurs via the dietary iron (Fe) uptake pathway in freshwater fish, at least in part. The present study investigated the interactive effects of dietary Cd and Fe in juvenile rainbow trout (Oncorhynchus mykiss). Fish were treated for four weeks with four different diets: normal Fe, high Fe, normal Fe plus Cd, and high Fe plus Cd. Physiological parameters, tissue-specific Fe and Cd level, plasma Fe status, and tissue-specific mRNA expression of transferrin, metallothioneins (MT-A and MT-B) and heat shock proteins 70 (HSP70a and HSP70b) were analyzed. Exposure to dietary Cd increased Cd burden in the following order: intestine > kidney > stomach > liver > gill > carcass. Interestingly, high dietary Fe reduced Cd accumulation in the stomach and intestine as well as in the wholebody of fish. Dietary Cd increased hepatic transferrin mRNA expression and total Fe binding capacity in the plasma, indicating the effect of Cd on Fe handling in fish. The mRNA expression of MTs and HSP70s was also increased in various tissues following dietary Cd exposure, however the response profile of different MT and HSP70 genes was not consistent among different tissues. In general, MT-A was more responsive to Cd exposure in the intestine and liver, whereas MT-B was more responsive in the kidney. Similarly, HSP70a expression was more sensitive to Cd exposure than HSP70b, particularly in the intestine. Interestingly, high Fe diet suppressed Cd-induced induction of transferrin, MT and HSP70 genes in various tissues. Overall, our study suggests that elevated dietary Fe can reduce Cd accumulation and ameliorate Cd-induced stress responses in freshwater fish.

Arsenic rich iron plaque on macrophyte roots - an ecotoxicological risk?

International Nuclear Information System (INIS)

Taggart, M.A.; Mateo, R.; Charnock, J.M.; Bahrami, F.; Green, A.J.; Meharg, A.A.

2009-01-01

Arsenic is known to accumulate with iron plaque on macrophyte roots. Three to four years after the Aznalcollar mine spill (Spain), residual arsenic contamination left in seasonal wetland habitats has been identified in this form by scanning electron microscopy. Total digestion has determined arsenic concentrations in thoroughly washed 'root + plaque' material in excess of 1000 mg kg -1 , and further analysis using X-ray absorption spectroscopy suggests arsenic exists as both arsenate and arsenite. Certain herbivorous species feed on rhizomes and bulbs of macrophytes in a wide range of global environments, and the ecotoxicological impact of consuming arsenic rich iron plaque associated with such food items remains to be quantified. Here, greylag geese which feed on Scirpus maritimus rhizome and bulb material in areas affected by the Aznalcollar spill are shown to have elevated levels of arsenic in their feces, which may originate from arsenic rich iron plaque. - Accumulation of metals with iron plaque on macrophyte roots in wetlands poses an ecotoxicological risk to certain herbivores

Role of sulfate reduction in long term accumulation of organic and inorganic sulfur in lake sediments

International Nuclear Information System (INIS)

Rudd, J.W.M.; Kelly, C.A.; Furutani, A.

1986-01-01

Sulfate reduction and the accumulation of reduced sulfur in epilimnetic sediments were studied in lakes in southern Norway, the Adirondack Mountains, and at the Experimental Lakes Area (ELA) of northwestern Ontario. In all of the lakes, sulfate reduction produced substantial quantities of pyrite and organic sulfur compounds. In 9-month in situ experiments at ELA using 35 S, there was a large loss (55%) with time of the S initially reduced and deposited in the sediments and a preferential loss of inorganic S compounds which led to a predominance of organic 35 S accumulation in the sediments. An intensive study of long term accumulation of sulfur in the epilimnetic sediments of four Adirondack lakes also showed that the most important long term end product of sulfate reduction was organic S and that sulfate reduction was the major source of S to the sediments. Because of high concentrations of iron in all of the sediments samples and because of the long term storage of sulfur in sediments, mostly as organic S, iron did not limit iron sulfide accumulation in these sediments. Iron limitation is unlikely to occur except in unusual circumstances. This study indicates that formation of organic S in epilimnetic sediments is primarily responsible for H + consumption via sulfate reduction in acidified lakes

Mixed graphite cast iron for automotive exhaust component applications

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De-lin Li

2017-11-01

Full Text Available Both spheroidal graphite iron and compacted graphite iron are used in the automotive industry. A recently proposed mixed graphite iron exhibits a microstructure between the conventional spheroidal graphite iron and compacted graphite iron. Evaluation results clearly indicate the suitability and benefits of mixed graphite iron for exhaust component applications with respect to casting, machining, mechanical, thermophysical, oxidation, and thermal fatigue properties. A new ASTM standard specification (A1095 has been created for compacted, mixed, and spheroidal graphite silicon-molybdenum iron castings. This paper attempts to outline the latest progress in mixed graphite iron published.

Moessbauer and EXAFS spectroscopy investigation of iron and arsenic adsorption to lettuce leaves

International Nuclear Information System (INIS)

Vasconcelos, Igor F.; Silva, Gabriela C.; Carvalho, Regina P.; Dantas, Maria Sylvia S.; Ciminelli, Virginia S. T.

2010-01-01

The accumulation of iron and arsenic from aqueous solution by lettuce leaves biomass was investigated using Moessbauer and EXAFS spectroscopic techniques. Moessbauer spectroscopy results show that iron is oxidized during sorption while EXAFS results indicate that iron is coordinated by approximately 6 oxygen and 2 carbon atoms while arsenic is coordinated by approximately 4 oxygen atoms with iron as a second neighbor.

Moessbauer and EXAFS spectroscopy investigation of iron and arsenic adsorption to lettuce leaves

Energy Technology Data Exchange (ETDEWEB)

Vasconcelos, Igor F., E-mail: ifvasco@ufc.br [Universidade Federal do Ceara, Dep. Eng. Metalurgica e de Materiais (Brazil); Silva, Gabriela C.; Carvalho, Regina P.; Dantas, Maria Sylvia S.; Ciminelli, Virginia S. T. [Universidade Federal de Minas Gerais, Dep. Eng. Metalurgica e de Materiais (Brazil)

2010-01-15

The accumulation of iron and arsenic from aqueous solution by lettuce leaves biomass was investigated using Moessbauer and EXAFS spectroscopic techniques. Moessbauer spectroscopy results show that iron is oxidized during sorption while EXAFS results indicate that iron is coordinated by approximately 6 oxygen and 2 carbon atoms while arsenic is coordinated by approximately 4 oxygen atoms with iron as a second neighbor.

HFE gene variants affect iron in the brain.

Science.gov (United States)

Nandar, Wint; Connor, James R

2011-04-01

Iron accumulation in the brain and increased oxidative stress are consistent observations in many neurodegenerative diseases. Thus, we have begun examination into gene mutations or allelic variants that could be associated with loss of iron homeostasis. One of the mechanisms leading to iron overload is a mutation in the HFE gene, which is involved in iron metabolism. The 2 most common HFE gene variants are C282Y (1.9%) and H63D (8.9%). The C282Y HFE variant is more commonly associated with hereditary hemochromatosis, which is an autosomal recessive disorder, characterized by iron overload in a number of systemic organs. The H63D HFE variant appears less frequently associated with hemochromatosis, but its role in the neurodegenerative diseases has received more attention. At the cellular level, the HFE mutant protein resulting from the H63D HFE gene variant is associated with iron dyshomeostasis, increased oxidative stress, glutamate release, tau phosphorylation, and alteration in inflammatory response, each of which is under investigation as a contributing factor to neurodegenerative diseases. Therefore, the HFE gene variants are proposed to be genetic modifiers or a risk factor for neurodegenerative diseases by establishing an enabling milieu for pathogenic agents. This review will discuss the current knowledge of the association of the HFE gene variants with neurodegenerative diseases: amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and ischemic stroke. Importantly, the data herein also begin to dispel the long-held view that the brain is protected from iron accumulation associated with the HFE mutations.

Iron plaque formation and heavy metal uptake in Spartina alterniflora at different tidal levels and waterlogging conditions.

Science.gov (United States)

Xu, Yan; Sun, Xiangli; Zhang, Qiqiong; Li, Xiuzhen; Yan, Zhongzheng

2018-05-30

Tidal flat elevation in the estuarine wetland determines the tidal flooding time and flooding frequency, which will inevitably affect the formation of iron plaque and accumulations of heavy metals (HMs) in wetland plants. The present study investigated the formation of iron plaque and HM's (copper, zinc, lead, and chromium) accumulation in S. alterniflora, a typical estuarine wetland species, at different tidal flat elevations (low, middle and high) in filed and at different time (3, 6, 9, 12 h per day) of waterlogging treatment in greenhouse conditions. Results showed that the accumulation of copper, zinc, lead, and chromium in S. alterniflora was proportional to the exchangeable fraction of these metals in the sediments, which generally increased with the increase of waterlogging time, whereas the formations of iron plaque in roots decreased with the increase of waterlogging time. Under field conditions, the uptake of copper and zinc in the different parts of the plants generally increased with the tidal levels despite the decrease in the metals' exchangeable fraction with increasing tidal levels. The formation of iron plaque was found to be highest in the middle tidal positions and significantly lower in low and high tidal positions. Longer waterlogging time increased the metals' accumulation but decreased the formation of iron plaque in S. alterniflora. The binding of metal ions on iron plaque helped impede the uptake and accumulation of copper and chromium in S. alterniflora. Copyright © 2018 Elsevier Inc. All rights reserved.

TIMP3 deficiency exacerbates iron overload-mediated cardiomyopathy and liver disease.

Science.gov (United States)

Zhabyeyev, Pavel; Das, Subhash K; Basu, Ratnadeep; Shen, Mengcheng; Patel, Vaibhav B; Kassiri, Zamaneh; Oudit, Gavin Y

2018-05-01

Chronic iron overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron overload. We investigated the role of tissue inhibitor of metalloproteinase 3 (TIMP3) in iron overload-mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3 -/- ) and wild-type (WT) mice to 12 wk of chronic iron overload. Whereas WT mice with iron overload developed diastolic dysfunction, iron-overloaded Timp3 -/- mice showed worsened cardiac dysfunction coupled with systolic dysfunction. In the heart, loss of Timp3 was associated with increased myocardial fibrosis, greater Timp1, matrix metalloproteinase ( Mmp) 2, and Mmp9 expression, increased active MMP-2 levels, and gelatinase activity. Iron overload in Timp3 -/- mice showed twofold higher iron accumulation in the liver compared with WT mice because of constituently lower levels of ferroportin. Loss of Timp3 enhanced the hepatic inflammatory response to iron overload, leading to greater neutrophil and macrophage infiltration and increased hepatic fibrosis. Expression of inflammation-related MMPs (MMP-12 and MMP-13) and inflammatory cytokines (IL-1β and monocyte chemoattractant protein-1) was elevated to a greater extent in iron-overloaded Timp3 -/- livers. Gelatin zymography demonstrated equivalent increases in MMP-2 and MMP-9 levels in WT and Timp3 -/- iron-overloaded livers. Loss of Timp3 enhanced the susceptibility to iron overload-mediated heart and liver injury, suggesting that Timp3 is a key protective molecule against iron-mediated pathology. NEW & NOTEWORTHY In mice, loss of tissue inhibitor of metalloproteinase 3 ( Timp3) was associated with systolic and diastolic dysfunctions, twofold higher hepatic iron accumulation (attributable to constituently lower levels of ferroportin), and increased hepatic inflammation. Loss of Timp3 enhanced the susceptibility to iron overload-mediated injury, suggesting that Timp3 plays a key

Nitric oxide–mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection

Science.gov (United States)

Nairz, Manfred; Schleicher, Ulrike; Schroll, Andrea; Sonnweber, Thomas; Theurl, Igor; Ludwiczek, Susanne; Talasz, Heribert; Brandacher, Gerald; Moser, Patrizia L.; Muckenthaler, Martina U.; Fang, Ferric C.; Bogdan, Christian

2013-01-01

Nitric oxide (NO) generated by inducible NO synthase 2 (NOS2) affects cellular iron homeostasis, but the underlying molecular mechanisms and implications for NOS2-dependent pathogen control are incompletely understood. In this study, we found that NO up-regulated the expression of ferroportin-1 (Fpn1), the major cellular iron exporter, in mouse and human cells. Nos2−/− macrophages displayed increased iron content due to reduced Fpn1 expression and allowed for an enhanced iron acquisition by the intracellular bacterium Salmonella typhimurium. Nos2 gene disruption or inhibition of NOS2 activity led to an accumulation of iron in the spleen and splenic macrophages. Lack of NO formation resulted in impaired nuclear factor erythroid 2-related factor-2 (Nrf2) expression, resulting in reduced Fpn1 transcription and diminished cellular iron egress. After infection of Nos2−/− macrophages or mice with S. typhimurium, the increased iron accumulation was paralleled by a reduced cytokine (TNF, IL-12, and IFN-γ) expression and impaired pathogen control, all of which were restored upon administration of the iron chelator deferasirox or hyperexpression of Fpn1 or Nrf2. Thus, the accumulation of iron in Nos2−/− macrophages counteracts a proinflammatory host immune response, and the protective effect of NO appears to partially result from its ability to prevent iron overload in macrophages PMID:23630227

Ironing Out the Unconventional Mechanisms of Iron Acquisition and Gene Regulation in Chlamydia

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Nick D. Pokorzynski

2017-09-01

Full Text Available The obligate intracellular pathogen Chlamydia trachomatis, along with its close species relatives, is known to be strictly dependent upon the availability of iron. Deprivation of iron in vitro induces an aberrant morphological phenotype termed “persistence.” This persistent phenotype develops in response to various immunological and nutritional insults and may contribute to the development of sub-acute Chlamydia-associated chronic diseases in susceptible populations. Given the importance of iron to Chlamydia, relatively little is understood about its acquisition and its role in gene regulation in comparison to other iron-dependent bacteria. Analysis of the genome sequences of a variety of chlamydial species hinted at the involvement of unconventional mechanisms, being that Chlamydia lack many conventional systems of iron homeostasis that are highly conserved in other bacteria. Herein we detail past and current research regarding chlamydial iron biology in an attempt to provide context to the rapid progress of the field in recent years. We aim to highlight recent discoveries and innovations that illuminate the strategies involved in chlamydial iron homeostasis, including the vesicular mode of acquiring iron from the intracellular environment, and the identification of a putative iron-dependent transcriptional regulator that is synthesized as a fusion with a ABC-type transporter subunit. These recent findings, along with the noted absence of iron-related homologs, indicate that Chlamydia have evolved atypical approaches to the problem of iron homeostasis, reinvigorating research into the iron biology of this pathogen.

A vacuolar iron transporter in tulip, TgVit1, is responsible for blue coloration in petal cells through iron accumulation.

Science.gov (United States)

Momonoi, Kazumi; Yoshida, Kumi; Mano, Shoji; Takahashi, Hideyuki; Nakamori, Chihiro; Shoji, Kazuaki; Nitta, Akira; Nishimura, Mikio

2009-08-01

Blue color in flowers is due mainly to anthocyanins, and a considerable part of blue coloration can be attributed to metal-complexed anthocyanins. However, the mechanism of metal ion transport into vacuoles and subsequent flower color development has yet to be fully explored. Previously, we studied the mechanism of blue color development specifically at the bottom of the inner perianth in purple tulip petals of Tulipa gesneriana cv. Murasakizuisho. We found that differences in iron content were associated with the development of blue- and purple-colored cells. Here, we identify a vacuolar iron transporter in T. gesneriana (TgVit1), and characterize the localization and function of this transporter protein in tulip petals. The amino acid sequence of TgVit1 is 85% similar that of the Arabidopsis thaliana vacuolar iron transporter AtVIT1, and also showed similarity to the AtVIT1 homolog in yeast, Ca(2+)-sensitive cross-complementer 1 (CCC1). The gene TgVit1 was expressed exclusively in blue-colored epidermal cells, and protein levels increased with increasing mRNA expression and blue coloration. Transient expression experiments revealed that TgVit1 localizes to the vacuolar membrane, and is responsible for the development of the blue color in purple cells. Expression of TgVit1 in yeast rescued the growth defect of ccc1 mutant cells in the presence of high concentrations of FeSO(4). Our results indicate that TgVit1 plays an essential role in blue coloration as a vacuolar iron transporter in tulip petals. These results suggest a new role for involvement of a vacuolar iron transporter in blue flower color development.

Directed plant cell-wall accumulation of iron: embedding co-catalyst for efficient biomass conversion

Science.gov (United States)

Chien-Yuan Lin; Joseph E. Jakes; Bryon S. Donohoe; Peter N. Ciesielski; Haibing Yang; Sophie-Charlotte Gleber; Stefan Vogt; Shi-You Ding; Wendy A. Peer; Angus S. Murphy; Maureen C. McCann; Michael E. Himmel; Melvin P. Tucker; Hui Wei

2016-01-01

Background: Plant lignocellulosic biomass is an abundant, renewable feedstock for the production of biobased fuels and chemicals. Previously, we showed that iron can act as a co-catalyst to improve the deconstruction of lignocellulosic biomass. However, directly adding iron catalysts into biomass prior to pretreatment is diffusion limited,...

Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.

Directory of Open Access Journals (Sweden)

Quentin Philippot

Full Text Available Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor, storage (ferritin and export (ferroportin genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1 and the ratio between FEV1 and forced vital capacity (FEV1/FVC. The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively. In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative

Nanoparticulate iron(III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans

Science.gov (United States)

Pereira, Dora I.A.; Bruggraber, Sylvaine F.A.; Faria, Nuno; Poots, Lynsey K.; Tagmount, Mani A.; Aslam, Mohamad F.; Frazer, David M.; Vulpe, Chris D.; Anderson, Gregory J.; Powell, Jonathan J.

2014-01-01

Iron deficiency is the most common nutritional disorder worldwide with substantial impact on health and economy. Current treatments predominantly rely on soluble iron which adversely affects the gastrointestinal tract. We have developed organic acid-modified Fe(III) oxo-hydroxide nanomaterials, here termed nano Fe(III), as alternative safe iron delivery agents. Nano Fe(III) absorption in humans correlated with serum iron increase (P solubility. The most promising preparation (iron hydroxide adipate tartrate: IHAT) showed ~80% relative bioavailability to Fe(II) sulfate in humans and, in a rodent model, IHAT was equivalent to Fe(II) sulfate at repleting haemoglobin. Furthermore, IHAT did not accumulate in the intestinal mucosa and, unlike Fe(II) sulfate, promoted a beneficial microbiota. In cellular models, IHAT was 14-fold less toxic than Fe(II) sulfate/ascorbate. Nano Fe(III) manifests minimal acute intestinal toxicity in cellular and murine models and shows efficacy at treating iron deficiency anaemia. From the Clinical Editor This paper reports the development of novel nano-Fe(III) formulations, with the goal of achieving a magnitude less intestinal toxicity and excellent bioavailability in the treatment of iron deficiency anemia. Out of the tested preparations, iron hydroxide adipate tartrate met the above criteria, and may become an important tool in addressing this common condition. PMID:24983890

Studies on the concentrations of iron-55 in South Pacific Ocean water and marine organisms and in the Columbia River. Progress report, 1 April 1975--31 March 1976

International Nuclear Information System (INIS)

Jennings, C.D.

1976-01-01

Progress is reported on studies of the distribution of iron-55 in the marine environment. Direct measurements of iron-55 in seawater and in zooplankton showed that marine organisms concentrate iron-55 in preference to stable iron. Measurements of iron-55 in Pacific sediments gave us an indication of the amount of iron-55 getting through the water column. Measurements in organisms from different depths in the ocean and the measurements in sediments give us a clearer picture of the rate of vertical transport in the ocean. It is also quite clear that the iron-55 in sediments in the equatorial Pacific are concentrated in a very thin surface layer because samples more than a centimeter below the surface were below detectable limits, whereas most surface samples had detectable amounts of iron-55. A series of treatments of Columbia River sediments with hydrochloric acid of strengths 0.1 M, 0.25 M, 1.4 M, 6 M and boiling 6 M respectively, showed that decreasing specific activity results in each subsequent treatment, indicating that the iron-55 can be leached more easily than stable iron. This observation provides some clues to what may be happening to particles in seawater. Organisms may remove from particles the more easily removable iron-55 of higher specific activity, leaving behind particles with a lower specific activity

[Peritoneal fluid iron levels in women with endometriosis].

Science.gov (United States)

Polak, Grzegorz; Wertel, Iwona; Tarkowski, Rafał; Kotarski, Jan

2010-01-01

Endometriosis is characterized by a cyclic hemorrhage within the peritoneal cavity. Accumulating data suggests that iron homeostasis in the peritoneal cavity may be disrupted by endometriosis. The aim of our study was to evaluate iron levels in peritoneal fluid (PF) of women with and without endometriosis. Seventy-five women were studied: 50 women with endometriosis and, as a reference group, 25 patients with functional follicle ovarian cysts. Iron concentrations in the PF were measured using a commercially available colorimetric assay kit. Iron concentrations were significantly higher in PF from women with endometriosis as compared to the reference group. Patients with stages III/IV endometriosis had significantly higher PF iron concentrations than women with stages I/II of the disease. Disrupted iron homeostasis in the peritoneal cavity of women with endometriosis plays a role in the pathogenesis of the disease.

Magnetic study of iron sorbitol

Energy Technology Data Exchange (ETDEWEB)

Lazaro, F.J. E-mail: osoro@posta.unizar.es; Larrea, A.; Abadia, A.R.; Romero, M.S

2002-09-01

A magnetic study of iron sorbitol, an iron-containing drug to treat the iron deficiency anemia is presented. Transmission electron microscopy reveals that the system contains nanometric particles with an average diameter of 3 nm whose composition is close to two-line ferrihydrite. The characterisation by magnetisation and AC susceptibility measurements indicates superparamagnetic behaviour with progressive magnetic blocking starting at 8 K. The quantitative analysis of the magnetic results indicates that the system consists of an assembly of very small magnetic moments, presumably originated by spin uncompensation of the antiferromagnetic nanoparticles, with Arrhenius type magnetic dynamics.

Iron oxides in human spleen.

Science.gov (United States)

Kopáni, Martin; Miglierini, Marcel; Lančok, Adriana; Dekan, Július; Čaplovicová, Mária; Jakubovský, Ján; Boča, Roman; Mrazova, Hedviga

2015-10-01

Iron is an essential element for fundamental cell functions and a catalyst for chemical reactions. Three samples extracted from the human spleen were investigated by scanning (SEM) and transmission electron microscopy (TEM), Mössbauer spectrometry (MS), and SQUID magnetometry. The sample with diagnosis of hemosiderosis (H) differs from that referring to hereditary spherocytosis and the reference sample. SEM reveals iron-rich micrometer-sized aggregate of various structures-tiny fibrils in hereditary spherocytosis sample and no fibrils in hemochromatosis. Hematite and magnetite particles from 2 to 6 μm in TEM with diffraction in all samples were shown. The SQUID magnetometry shows different amount of diamagnetic, paramagnetic and ferrimagnetic structures in the tissues. The MS results indicate contribution of ferromagnetically split sextets for all investigated samples. Their occurrence indicates that at least part of the sample is magnetically ordered below the critical temperature. The iron accumulation process is different in hereditary spherocytosis and hemosiderosis. This fact may be the reason of different iron crystallization.

The Aging of Iron Man

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Azhaar Ashraf

2018-03-01

Full Text Available Brain iron is tightly regulated by a multitude of proteins to ensure homeostasis. Iron dyshomeostasis has become a molecular signature associated with aging which is accompanied by progressive decline in cognitive processes. A common theme in neurodegenerative diseases where age is the major risk factor, iron dyshomeostasis coincides with neuroinflammation, abnormal protein aggregation, neurodegeneration, and neurobehavioral deficits. There is a great need to determine the mechanisms governing perturbations in iron metabolism, in particular to distinguish between physiological and pathological aging to generate fruitful therapeutic targets for neurodegenerative diseases. The aim of the present review is to focus on the age-related alterations in brain iron metabolism from a cellular and molecular biology perspective, alongside genetics, and neuroimaging aspects in man and rodent models, with respect to normal aging and neurodegeneration. In particular, the relationship between iron dyshomeostasis and neuroinflammation will be evaluated, as well as the effects of systemic iron overload on the brain. Based on the evidence discussed here, we suggest a synergistic use of iron-chelators and anti-inflammatories as putative anti-brain aging therapies to counteract pathological aging in neurodegenerative diseases.

The Aging of Iron Man.

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Ashraf, Azhaar; Clark, Maryam; So, Po-Wah

2018-01-01

Brain iron is tightly regulated by a multitude of proteins to ensure homeostasis. Iron dyshomeostasis has become a molecular signature associated with aging which is accompanied by progressive decline in cognitive processes. A common theme in neurodegenerative diseases where age is the major risk factor, iron dyshomeostasis coincides with neuroinflammation, abnormal protein aggregation, neurodegeneration, and neurobehavioral deficits. There is a great need to determine the mechanisms governing perturbations in iron metabolism, in particular to distinguish between physiological and pathological aging to generate fruitful therapeutic targets for neurodegenerative diseases. The aim of the present review is to focus on the age-related alterations in brain iron metabolism from a cellular and molecular biology perspective, alongside genetics, and neuroimaging aspects in man and rodent models, with respect to normal aging and neurodegeneration. In particular, the relationship between iron dyshomeostasis and neuroinflammation will be evaluated, as well as the effects of systemic iron overload on the brain. Based on the evidence discussed here, we suggest a synergistic use of iron-chelators and anti-inflammatories as putative anti-brain aging therapies to counteract pathological aging in neurodegenerative diseases.

Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson's disease.

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Hare, Dominic J; Cardoso, Bárbara Rita; Raven, Erika P; Double, Kay L; Finkelstein, David I; Szymlek-Gay, Ewa A; Biggs, Beverley-Ann

2017-01-01

Iron accumulates gradually in the ageing brain. In Parkinson's disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson's diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson's disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson's disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson's diseases and produce a potential biomarker of Parkinson's disease risk in preclinical individuals.

Iron homeostasis and its disruption in mouse lung in iron deficiency and overload.

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Giorgi, Gisela; D'Anna, María Cecilia; Roque, Marta Elena

2015-10-01

What is the central question of this study? The aim was to explore the role and hitherto unclear mechanisms of action of iron proteins in protecting the lung against the harmful effects of iron accumulation and the ability of pulmonary cells to mobilize iron in iron deficiency. What is the main finding and its importance? We show that pulmonary hepcidin appears not to modify cellular iron mobilization in the lung. We propose pathways for supplying iron to the lung in iron deficiency and for protecting the lung against iron excess in iron overload, mediated by the co-ordinated action of iron proteins, such as divalent metal transporter 1, ZRT-IRE-like-protein 14, transferrin receptor, ferritin, haemochromatosis-associated protein and ferroportin. Iron dyshomeostasis is associated with several forms of chronic lung disease, but its mechanisms of action remain to be elucidated. The aim of the present study was to determine the role of the lung in whole-animal models with iron deficiency and iron overload, studying the divalent metal transporter 1 (DMT1), ZRT-IRE-like protein 14 (ZIP14), transferrin receptor (TfR), haemochromatosis-associated protein (HFE), hepcidin, ferritin and ferroportin (FPN) expression. In each model, adult CF1 mice were divided into the following groups (six mice per group): (i) iron-overload model, iron saccharate i.p. and control group (iron adequate), 0.9% NaCl i.p.; and (ii) iron-deficiency model, induced by repeated bleeding, and control group (sham operated). Proteins were assessed by immunohistochemistry and Western blot. In control mice, DMT1 was localized in the cytoplasm of airway cells, and in iron deficiency and overload it was in the apical membrane. Divalent metal transporter 1 and TfR increased in iron deficiency, without changes in iron overload. ZRT-IRE-like protein 14 decreased in airway cells in iron deficiency and increased in iron overload. In iron deficiency, HFE and FPN were immunolocalized close to the apical membrane

Combined in situ zymography, immunofluorescence, and staining of iron oxide particles in paraffin-embedded, zinc-fixed tissue sections.

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Haeckel, Akvile; Schoenzart, Lena; Appler, Franziska; Schnorr, Joerg; Taupitz, Matthias; Hamm, Bernd; Schellenberger, Eyk

2012-01-01

Superparamagnetic iron oxide particles are used as potent contrast agents in magnetic resonance imaging. In histology, these particles are frequently visualized by Prussian blue iron staining of aldehyde-fixed, paraffin-embedded tissues. Recently, zinc salt-based fixative was shown to preserve enzyme activity in paraffin-embedded tissues. In this study, we demonstrate that zinc fixation allows combining in situ zymography with fluorescence immunohistochemistry (IHC) and iron staining for advanced biologic investigation of iron oxide particle accumulation. Very small iron oxide particles, developed for magnetic resonance angiography, were applied intravenously to BALB/c nude mice. After 3 hours, spleens were explanted and subjected to zinc fixation and paraffin embedding. Cut tissue sections were further processed to in situ zymography, IHC, and Prussian blue staining procedures. The combination of in situ zymography as well as IHC with subsequent Prussian blue iron staining on zinc-fixed paraffin-embedded tissues resulted in excellent histologic images of enzyme activity, protease distribution, and iron oxide particle accumulation. The combination of all three stains on a single section allowed direct comparison with only moderate degradation of fluorescein isothiocyanate-labeled substrate. This protocol is useful for investigating the biologic environment of accumulating iron oxide particles, with excellent preservation of morphology.

Fluid-Attenuated Inversion Recovery Hypointensity of the Pulvinar Nucleus of Patients with Alzheimer Disease: Its Possible Association with Iron Accumulation as Evidenced by the T2 Map

International Nuclear Information System (INIS)

Moon, Won Jin; Roh, Hong Gee; Choi, Jin Woo; Kim, Hee Jin; Han, Seol Heui

2012-01-01

We hypothesized that prominent pulvinar hypointensity in brain MRI represents the disease process due to iron accumulation in Alzheimer disease (AD). We aimed to determine whether or not the pulvinar signal intensity (SI) on the fluid-attenuated inversion recovery (FLAIR) sequences at 3.0T MRI differs between AD patients and normal subjects, and also whether the pulvinar SI is correlated with the T2 map, an imaging marker for tissue iron, and a cognitive scale. Twenty one consecutive patients with AD and 21 age-matched control subjects were prospectively included in this study. The pulvinar SI was assessed on the FLAIR image. We measured the relative SI ratio of the pulvinar to the corpus callosum. The T2 values were calculated from the T2 relaxometry map. The differences between the two groups were analyzed, by using a Student t test. The correlation between the measurements was assessed by the Pearson's correlation test. As compared to the normal white matter, the FLAIR signal intensity of the pulvinar nucleus was significantly more hypointense in the AD patients than in the control subjects (p < 0.01). The pulvinar T2 was shorter in the AD patients than in the control subjects (51.5 ± 4.95 ms vs. 56.5 ± 5.49 ms, respectively, p = 0.003). The pulvinar SI ratio was strongly correlated with the pulvinar T2 (r = 0.745, p < 0.001). When controlling for age, only the pulvinar-to-CC SI ratio was positively correlated with that of the Mini-Mental State Examination (MMSE) score (r = 0.303, p < 0.050). Conversely, the pulvinar T2 was not correlated with the MMSE score (r = 0.277, p = 0.080). The FLAIR hypointensity of the pulvinar nucleus represents an abnormal iron accumulation in AD and may be used as an adjunctive finding for evaluating AD.

Colour Metallography of Cast Iron - Chapter 2: Grey Iron (Ⅱ

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Zhou Jiyang

2009-08-01

Full Text Available Cast iron, as a traditional metal material, has advantages of low total cost, good castability and machinability, good wear resistance and low notch sensitivity, and is still facing tough challenge in quality, property and variety of types etc. Experts and engineers studying and producing iron castings all around world extremely concern this serious challenge. Over more than 30 years, a great of research work has been carried out on how to further improve its property, expand its application and combine cast iron technology with some hi-techs (for example, computer technology. Nevertheless, cast iron is a multi-element and multi-phase alloy and has complex and variety of structures and still has great development potential in structure and property. For further studying and developing cast iron, theoretical research work is important promise, and the study on solidification process and control mechanism of graphite morphology is fundamental for improving property of cast iron and developing new type of cast iron. Metallography of cast iron normally includes two sections: liquid phase transformation and solid phase transformation. The book, Colour Metallography of Cast Iron, uses colour metallography technique to study solidification structures of cast irons: graphite, carbides, austenite and eutectics; and focuses on solidification processes. With progress of modern solidification theory, the control of material solidification process becomes important measure for improving traditional materials and developing new materials. Solidification structure not only influences mechanical and physical properties of cast iron, but also affects its internal quality. The book uses a large amount of colour photos to describe the formation of solidification structures and their relations. Crystallization phenomena, which cannot be displayed with traditional metallography, are presented and more phase transformation information is obtained from these colour

Arsenic rich iron plaque on macrophyte roots - an ecotoxicological risk?

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Taggart, M.A. [School of Biological Sciences, University of Aberdeen, Cruickshank Bld, St Machar Drive, Aberdeen, AB24 3UU (United Kingdom); Instituto de Investigacion en Recursos Cinegeticos, IREC (CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13005 Ciudad Real (Spain)], E-mail: mark.taggart@uclm.es; Mateo, R. [Instituto de Investigacion en Recursos Cinegeticos, IREC (CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13005 Ciudad Real (Spain); Charnock, J.M.; Bahrami, F. [Synchrotron Radiation Department, CCLRC Daresbury Laboratory, Warrington, Cheshire, WA4 4AD (United Kingdom); Green, A.J. [Department of Wetland Ecology, Estacion Biologica de Donana, CSIC, Pabellon del Peru, Avenida Maria Luisa s/n, 41013 Seville (Spain); Meharg, A.A. [School of Biological Sciences, University of Aberdeen, Cruickshank Bld, St Machar Drive, Aberdeen, AB24 3UU (United Kingdom)

2009-03-15

Arsenic is known to accumulate with iron plaque on macrophyte roots. Three to four years after the Aznalcollar mine spill (Spain), residual arsenic contamination left in seasonal wetland habitats has been identified in this form by scanning electron microscopy. Total digestion has determined arsenic concentrations in thoroughly washed 'root + plaque' material in excess of 1000 mg kg{sup -1}, and further analysis using X-ray absorption spectroscopy suggests arsenic exists as both arsenate and arsenite. Certain herbivorous species feed on rhizomes and bulbs of macrophytes in a wide range of global environments, and the ecotoxicological impact of consuming arsenic rich iron plaque associated with such food items remains to be quantified. Here, greylag geese which feed on Scirpus maritimus rhizome and bulb material in areas affected by the Aznalcollar spill are shown to have elevated levels of arsenic in their feces, which may originate from arsenic rich iron plaque. - Accumulation of metals with iron plaque on macrophyte roots in wetlands poses an ecotoxicological risk to certain herbivores.

Evaluation of tumoral enhancement by superparamagnetic iron oxide particles: comparative studies with ferumoxtran and anionic iron oxide nanoparticles

International Nuclear Information System (INIS)

Brillet, P-Y.; Gazeau, F.; Luciani, A.; Bessoud, B.; Cuenod, C.-A.; Siauve, N.; Pons, J.-N.; Poupon, J.; Clement, O.

2005-01-01

This study was designed to compare tumor enhancement by superparamagnetic iron oxide particles, using anionic iron oxide nanoparticles (AP) and ferumoxtran. In vitro, relaxometry and media with increasing complexity were used to assess the changes in r2 relaxivity due to cellular internalization. In vivo, 26 mice with subcutaneously implanted tumors were imaged for 24 h after injection of particles to describe kinetics of enhancement using T1 spin echo, T2 spin echo, and T2 fast spin echo sequences. In vitro, the r2 relaxivity decreased over time (0-4 h) when AP were uptaken by cells. The loss of r2 relaxivity was less pronounced with long (Hahn Echo) than short (Carr-Purcell-Meiboom-Gill) echo time sequences. In vivo, our results with ferumoxtran showed an early T2 peak (1 h), suggesting intravascular particles and a second peak in T1 (12 h), suggesting intrainterstitial accumulation of particles. With AP, the late peak (24 h) suggested an intracellular accumulation of particles. In vitro, anionic iron oxide nanoparticles are suitable for cellular labeling due to a high cellular uptake. Conversely, in vivo, ferumoxtran is suitable for passive targeting of tumors due to a favorable biodistribution. (orig.)

Performance of Iron Plaque of Wetland Plants for Regulating Iron, Manganese, and Phosphorus from Agricultural Drainage Water

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Xueying Jia

2018-01-01

Full Text Available Agricultural drainage water continues to impact watersheds and their receiving water bodies. One approach to mitigate this problem is to use surrounding natural wetlands. Our objectives were to determine the effect of iron (Fe-rich groundwater on phosphorus (P removal and nutrient absorption by the utilization of the iron plaque on the root surface of Glyceria spiculosa (Fr. Schmidt. Rosh. The experiment was comprised of two main factors with three regimes: Fe2+ (0, 1, 20, 100, 500 mg·L−1 and P (0.01, 0.1, 0.5 mg·L−1. The deposition and structure of iron plaque was examined through a scanning electron microscope and energy-dispersive X-ray analyzer. Iron could, however, also impose toxic effects on the biota. We therefore provide the scanning electron microscopy (SEM on iron plaques, showing the essential elements were iron (Fe, oxygen (O, aluminum (Al, manganese (Mn, P, and sulphur (S. Results showed that (1 Iron plaque increased with increasing Fe2+ supply, and P-deficiency promoted its formation; (2 Depending on the amount of iron plaque on roots, nutrient uptake was enhanced at low levels, but at higher levels, it inhibited element accumulation and translocation; (3 The absorption of manganese was particularly affected by iron plague, which also enhanced phosphorus uptake until the external iron concentration exceeded 100 mg·L−1. Therefore, the presence of iron plaque on the root surface would increase the uptake of P, which depends on the concentration of iron-rich groundwater.

Effects of intracellular iron overload on cell death and identification of potent cell death inhibitors.

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Fang, Shenglin; Yu, Xiaonan; Ding, Haoxuan; Han, Jianan; Feng, Jie

2018-06-11

Iron overload causes many diseases, while the underlying etiologies of these diseases are unclear. Cell death processes including apoptosis, necroptosis, cyclophilin D-(CypD)-dependent necrosis and a recently described additional form of regulated cell death called ferroptosis, are dependent on iron or iron-dependent reactive oxygen species (ROS). However, whether the accumulation of intracellular iron itself induces ferroptosis or other forms of cell death is largely elusive. In present study, we study the role of intracellular iron overload itself-induced cell death mechanisms by using ferric ammonium citrate (FAC) and a membrane-permeable Ferric 8-hydroxyquinoline complex (Fe-8HQ) respectively. We show that FAC-induced intracellular iron overload causes ferroptosis. We also identify 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitor GSK2334470 as a potent ferroptosis inhibitor. Whereas, Fe-8HQ-induced intracellular iron overload causes unregulated necrosis, but partially activates PARP-1 dependent parthanatos. Interestingly, we identify many phenolic compounds as potent inhibitors of Fe-8HQ-induced cell death. In conclusion, intracellular iron overload-induced cell death form might be dependent on the intracellular iron accumulation rate, newly identified cell death inhibitors in our study that target ferroptosis and unregulated oxidative cell death represent potential therapeutic strategies against iron overload related diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Overexpression of ZmIRT1 and ZmZIP3 Enhances Iron and Zinc Accumulation in Transgenic Arabidopsis.

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Suzhen Li

Full Text Available Iron and zinc are important micronutrients for both the growth and nutrient availability of crop plants, and their absorption is tightly controlled by a metal uptake system. Zinc-regulated transporters, iron-regulated transporter-like proteins (ZIP, is considered an essential metal transporter for the acquisition of Fe and Zn in graminaceous plants. Several ZIPs have been identified in maize, although their physiological function remains unclear. In this report, ZmIRT1 was shown to be specifically expressed in silk and embryo, whereas ZmZIP3 was a leaf-specific gene. Both ZmIRT1 and ZmZIP3 were shown to be localized to the plasma membrane and endoplasmic reticulum. In addition, transgenic Arabidopsis plants overexpressing ZmIRT1 or ZmZIP3 were generated, and the metal contents in various tissues of transgenic and wild-type plants were examined based on ICP-OES and Zinpyr-1 staining. The Fe and Zn concentration increased in roots and seeds of ZmIRT1-overexpressing plants, while the Fe content in shoots decreased. Overexpressing ZmZIP3 enhanced Zn accumulation in the roots of transgenic plants, while that in shoots was repressed. In addition, the transgenic plants showed altered tolerance to various Fe and Zn conditions compared with wild-type plants. Furthermore, the genes associated with metal uptake were stimulated in ZmIRT1 transgenic plants, while those involved in intra- and inter- cellular translocation were suppressed. In conclusion, ZmIRT1 and ZmZIP3 are functional metal transporters with different ion selectivities. Ectopic overexpression of ZmIRT1 may stimulate endogenous Fe uptake mechanisms, which may facilitate metal uptake and homeostasis. Our results increase our understanding of the functions of ZIP family transporters in maize.

Mercury accumulation and accelerated progression of carotid atherosclerosis: a population-based prospective 4-year follow-up study in men in eastern Finland.

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Salonen, J T; Seppänen, K; Lakka, T A; Salonen, R; Kaplan, G A

2000-02-01

Basic research and our previous studies have suggested that mercury exposure enhances lipid peroxidation and the risk of myocardial infarction, but there are no studies concerning the association between mercury accumulation and atherosclerosis. We therefore investigated whether high hair mercury content is associated with accelerated progression of carotid atherosclerosis, determined by ultrasonographic assessment of common carotid intima-media thickness (IMT), in a prospective study among 1014 men aged 42-60 years. In a linear regression model adjusting for other atherosclerotic risk factors, high hair mercury content was one of the strongest predictors of the 4-year increase in the mean IMT (P2.81 microg/g (fifths) had an IMT increase of 0.105, 0.102, 0.113, 0.107 and 0.140 mm/4 years, respectively (P=0.041 for heterogeneity between groups). The IMT increase was 0.034 mm/4 years (31.9%) greater in the highest fifth than in the other fifths (P<0.05 for the difference). These findings suggest that mercury accumulation in the human body is associated with accelerated progression of carotid atherosclerosis.

Removal of As, Mn, Mo, Se, U, V and Zn from groundwater by zero-valent iron in a passive treatment cell: reaction progress modeling

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Morrison, Stan J.; Metzler, Donald R.; Dwyer, Brian P.

2002-05-01

Three treatment cells were operated at a site near Durango, CO. One treatment cell operated for more than 3 years. The treatment cells were used for passive removal of contamination from groundwater at a uranium mill tailings repository site. Zero-valent iron [Fe(0)] that had been powdered, bound with aluminosilicate and molded into plates was used as a reactive material in one treatment cell. The others used granular Fe(0) and steel wool. The treatment cells significantly reduced concentrations of As, Mn, Mo, Se, U, V and Zn in groundwater that flowed through it. Zero-valent iron [Fe(0)], magnetite (Fe 3O 4), calcite (CaCO 3), goethite (FeOOH) and mixtures of contaminant-bearing phases were identified in the solid fraction of one treatment cell. A reaction progress approach was used to model chemical evolution of water chemistry as it reacted with the Fe(0). Precipitation of calcite, ferrous hydroxide [Fe(OH) 2] and ferrous sulfide (FeS) were used to simulate observed changes in major-ion aqueous chemistry. The amount of reaction progress differed for each treatment cell. Changes in contaminant concentrations were consistent with precipitation of reduced oxides (UO 2, V 2O 3), sulfides (As 2S 3, ZnS), iron minerals (FeSe 2, FeMoO 4) and carbonate (MnCO 3). Formation of a free gas phase and precipitation of minerals contributed to loss of hydraulic conductivity in one treatment cell.

Effect of radioactive iron /sup 59/Fe on the embryogeny of sea-trout (Salmo trutta L. )

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Dabrowski, K; Tucholski, S; Czarnocki, J

1975-01-01

Accumulation and diffusion of /sup 59/Fe in the eggs of Salmo trutta L. were observed under laboratory conditions. The dynamics of iron budget in the egg with developing embryo were determined. Differences were found in the accumulation and elimination of iron depending on the stage of the embryos development in the eggs at the time when they were put into the radionuclide solution and on the strength of its concentration.

Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice.

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Tang, Chih-Hang Anthony; Chang, Shiun; Hashimoto, Ayumi; Chen, Yi-Ju; Kang, Chang Won; Mato, Anthony R; Del Valle, Juan R; Gabrilovich, Dmitry I; Hu, Chih-Chi Andrew

2018-06-01

Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B-cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells that developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL. The MD4/Eμ-TCL1 mice had reduced survival, increased myeloid-derived suppressor cells (MDSC), and decreased numbers of T cells. We tested whether sIgM could contribute to the accumulation of MDSCs by crossing μS -/- mice, which could not produce sIgM, with Eμ-TCL1 mice. The μS -/- /Eμ-TCL1 mice survived longer than Eμ-TCL1 mice and developed decreased numbers of MDSCs which were less able to suppress proliferation of T cells. We targeted the synthesis of sIgM by deleting the function of XBP-1s and showed that targeting XBP-1s genetically or pharmacologically could lead to decreased sIgM, accompanied by decreased numbers and reduced functions of MDSCs in MD4/Eμ-TCL1 mice. Additionally, MDSCs from μS -/- mice grafted with Lewis lung carcinoma were inefficient suppressors of T cells, resulting in slower tumor growth. These results demonstrate that sIgM produced by B cells can upregulate the functions of MDSCs in tumor-bearing mice to aggravate cancer progression. In a mouse model of CLL, production of secretory IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice. Thus, secretory IgM may aggravate the progression of this cancer. Cancer Immunol Res; 6(6); 696-710. ©2018 AACR . ©2018 American Association for Cancer Research.

Photophysiological and photosynthetic complex changes during iron starvation in Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942.

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Jared M Fraser

Full Text Available Iron is an essential component in many protein complexes involved in photosynthesis, but environmental iron availability is often low as oxidized forms of iron are insoluble in water. To adjust to low environmental iron levels, cyanobacteria undergo numerous changes to balance their iron budget and mitigate the physiological effects of iron depletion. We investigated changes in key protein abundances and photophysiological parameters in the model cyanobacteria Synechococcus PCC 7942 and Synechocystis PCC 6803 over a 120 hour time course of iron deprivation. The iron stress induced protein (IsiA accumulated to high levels within 48 h of the onset of iron deprivation, reaching a molar ratio of ~42 IsiA : Photosystem I in Synechococcus PCC 7942 and ~12 IsiA : Photosystem I in Synechocystis PCC 6803. Concomitantly the iron-rich complexes Cytochrome b6f and Photosystem I declined in abundance, leading to a decrease in the Photosystem I : Photosystem II ratio. Chlorophyll fluorescence analyses showed a drop in electron transport per Photosystem II in Synechococcus, but not in Synechocystis after iron depletion. We found no evidence that the accumulated IsiA contributes to light capture by Photosystem II complexes.

Formation of biomineral iron oxides compounds in a Fe hyperaccumulator plant: Imperata cylindrica (L.) P. Beauv.

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Fuente, V; Rufo, L; Juárez, B H; Menéndez, N; García-Hernández, M; Salas-Colera, E; Espinosa, A

2016-01-01

We report a detailed work of composition and location of naturally formed iron biominerals in plant cells tissues grown in iron rich environments as Imperata cylindrica. This perennial grass grows on the Tinto River banks (Iberian Pyritic Belt) in an extreme acidic ecosystem (pH∼2.3) with high concentration of dissolved iron, sulphate and heavy metals. Iron biominerals were found at the cellular level in tissues of root, stem and leaf both in collected and laboratory-cultivated plants. Iron accumulated in this plant as a mix of iron compounds (mainly as jarosite, ferrihydrite, hematite and spinel phases) was characterized by X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS), Mössbauer spectroscopy (MS), magnetometry (SQUID), electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX; TEM-EDX; HRSTEM). A low fraction of phosphorous was detected in this iron hyperaccumulator plant. Root and rhizomes tissues present a high proportion of ferromagnetic iron oxide compounds. Iron oxides-rich zones are localized in electron dense intra and inter-cellular aggregates that appear as dark deposits covering the inner membrane and organelles of the cell. This study aims to contribute to a better understanding of the mechanisms of accumulation, transport, distribution of iron in Imperata cylindrica. Copyright © 2015 Elsevier Inc. All rights reserved.

Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals

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Jesper Hagemeier

2018-01-01

Full Text Available Brain iron homeostasis is known to be disturbed in multiple sclerosis (MS, yet little is known about the association of common gene variants linked to iron regulation and pathological tissue changes in the brain. In this study, we investigated the association of genetic determinants linked to iron regulation with deep gray matter (GM magnetic susceptibility in both healthy controls (HC and MS patients. Four hundred (400 patients with MS and 150 age- and sex-matched HCs were enrolled and obtained 3 T MRI examination. Three (3 single nucleotide polymorphisms (SNPs associated with iron regulation were genotyped: two SNPs in the human hereditary hemochromatosis protein gene HFE: rs1800562 (C282Y mutation and rs1799945 (H63D mutation, as well as the rs1049296 SNP in the transferrin gene (C2 mutation. The effects of disease and genetic status were studied using quantitative susceptibility mapping (QSM voxel-based analysis (VBA and region-of-interest (ROI analysis of the deep GM. The general linear model framework was used to compare groups. Analyses were corrected for age and sex, and adjusted for false discovery rate. We found moderate increases in susceptibility in the right putamen of participants with the C282Y (+6.1 ppb and H63D (+6.9 ppb gene variants vs. non-carriers, as well as a decrease in thalamic susceptibility of progressive MS patients with the C282Y mutation (left: −5.3 ppb, right: −6.7 ppb, p < 0.05. Female MS patients had lower susceptibility in the caudate (−6.0 ppb and putamen (left: −3.9 ppb, right: −4.6 ppb than men, but only when they had a wild-type allele (p < 0.05. Iron-gene linked increases in putamen susceptibility (in HC and relapsing remitting MS and decreases in thalamus susceptibility (in progressive MS, coupled with apparent sex interactions, indicate that brain iron in healthy and disease states may be influenced by genetic factors.

Myelodysplastic syndromes and the role of iron overload.

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Harvey, R Donald

2010-04-01

The epidemiology of myelodysplastic syndromes (MDS) and iron overload, recent clinical findings that highlight the importance of actively managing iron overload, and recommendations for initiating and maintaining iron chelation therapy (ICT) are summarized. MDS are a variety of hematological disorders with differing time courses. Disease morbidities are primarily due to cytopenias and evolution to acute myeloid leukemia. Iron overload is a serious complication in patients with MDS due to the long-term use of red blood cell transfusions in patients with symptomatic anemia. Clinical consequences of iron overload include end-organ damage and dysfunction, an increased frequency of transplant-related complications, and reduced survival rates. To prevent these complications, recommendations for initiating and maintaining ICT should be followed by clinicians caring for patients with MDS and iron overload. As current therapeutic options for patients with MDS do not always reduce the transfusion burden, many patients will still need long-term transfusion therapy. Strategies for the management of iron overload in MDS should be considered early in the disease course and in appropriate patients in order to prevent negative clinical outcomes associated with excessive iron accumulation.

Mineral transformation and biomass accumulation associated with uranium bioremediation at Rifle, Colorado.

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Li, Li; Steefel, Carl I; Williams, Kenneth H; Wilkins, Michael J; Hubbard, Susan S

2009-07-15

Injection of organic carbon into the subsurface as an electron donor for bioremediation of redox-sensitive contaminants like uranium often leads to mineral transformation and biomass accumulation, both of which can alter the flow field and potentially bioremediation efficacy. This work combines reactive transport modeling with a column experiment and field measurements to understand the biogeochemical processes and to quantify the biomass and mineral transformation/accumulation during a bioremediation experiment at a uranium contaminated site near Rifle, Colorado. We use the reactive transport model CrunchFlow to explicitly simulate microbial community dynamics of iron and sulfate reducers, and their impacts on reaction rates. The column experiment shows clear evidence of mineral precipitation, primarily in the form of calcite and iron monosulfide. At the field scale, reactive transport simulations suggest that the biogeochemical reactions occur mostly close to the injection wells where acetate concentrations are highest, with mineral precipitate and biomass accumulation reaching as high as 1.5% of the pore space. This work shows that reactive transport modeling coupled with field data can bean effective tool for quantitative estimation of mineral transformation and biomass accumulation, thus improving the design of bioremediation strategies.

Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo.

Science.gov (United States)

Soe-Lin, Shan; Apte, Sameer S; Andriopoulos, Billy; Andrews, Marc C; Schranzhofer, Matthias; Kahawita, Tanya; Garcia-Santos, Daniel; Ponka, Prem

2009-04-07

Natural resistance-associated macrophage protein 1 (Nramp1) is a divalent metal transporter expressed exclusively in phagocytic cells. We hypothesized that macrophage Nramp1 may participate in the recycling of iron acquired from phagocytosed senescent erythrocytes. To evaluate the role of Nramp1 in vivo, the iron parameters of WT and KO mice were analyzed after acute and chronic induction of hemolytic anemia. We found that untreated KO mice exhibited greater serum transferrin saturation and splenic iron content with higher duodenal ferroportin (Fpn) and divalent metal transporter 1 (DMT1) expression. Furthermore, hepatocyte iron content and hepcidin mRNA levels were dramatically lower in KO mice, indicating that hepcidin levels can be regulated by low-hepatocyte iron stores despite increased transferrin saturation. After acute treatment with the hemolytic agent phenylhydrazine (Phz), KO mice experienced a significant decrease in transferrin saturation and hematocrit, whereas WT mice were relatively unaffected. After a month-long Phz regimen, KO mice retained markedly increased quantities of iron within the liver and spleen and exhibited more pronounced splenomegaly and reticulocytosis than WT mice. After injection of (59)Fe-labeled heat-damaged reticulocytes, KO animals accumulated erythrophagocytosed (59)Fe within their liver and spleen, whereas WT animals efficiently recycled phagocytosed (59)Fe to the marrow and erythrocytes. These data imply that without Nramp1, iron accumulates within the liver and spleen during erythrophagocytosis and hemolytic anemia, supporting our hypothesis that Nramp1 promotes efficient hemoglobin iron recycling in macrophages. Our observations suggest that mutations in Nramp1 could result in a novel form of human hereditary iron overload.

SEALING LARGE-DIAMETER CAST-IRON PIPE JOINTS UNDER LIVE CONDITIONS

Energy Technology Data Exchange (ETDEWEB)

Kiran M. Kothari; Gerard T. Pittard

2004-11-01

- and large-diameter cast iron repair robots to assure their commercial success. Task 4 (Design, Fabricate and Test Patch Setting Robotic Train) progressed to the design of the control electronics and pneumatic system to inflate the bladder robotic patch setting module in the last quarter 5. In this quarter, work has been concentrated on increasing the nitrogen bladder reservoir volume to allow at least two complete patch inflation/patch setting cycles in the event the sleeve does not set all ratchets in the same row on the first attempt. This problem was observed on a few of the repair sleeves that were recently installed during field tests with the small-diameter robotic system. For Task 5 (Design & Fabricate Pipe-Wall Cleaning Robot Train with Pan/Zoom/Tilt Camera) it was observed that it will be necessary to add a stiff brush to push debris away from the immediate vicinity of the bell and spigot joints in mains having low gas velocities. Otherwise, material removed by the cleaning flails (which were found to be very effective in cleaning bell and spigot joints) simply falls to the low side of the pipe and accumulates in a pile. This accumulation can prevent the sleeve from achieving a leak free repair. Similarly, it is also necessary to design a small magnet to capture existing service tap coupons and allow their removal from the inside of the pipe. These coupons were found to cause difficulty in launching and retrieving the small pipe repair robot; one coupon lodged beneath the end of the guide shoe. These new features require redesign of the pipe wall cleaning train and modification to the patch setting train. Task 6 (Design & Build Surface Control and Monitoring System) was previously completed with the control and computer display functions being operated through LabView. However, this must now be re-visited to add control routines for the coupon catcher to be added. This will most likely include a lift-off/place-on magnet translation function. Task 7 (Design

Internal iron biomineralization in Imperata cylindrica, a perennial grass: chemical composition, speciation and plant localization.

Science.gov (United States)

Rodríguez, N; Menéndez, N; Tornero, J; Amils, R; de la Fuente, V

2005-03-01

* The analysis of metal distribution in Imperata cylindrica, a perennial grass isolated from the banks of Tinto River (Iberian Pyritic Belt), an extreme acidic environment with high content in metals, has shown a remarkable accumulation of iron. This property has been used to study iron speciation and its distribution among different tissues and structures of the plant. * Mossbauer (MS) and X-ray diffraction (XRD) were used to determine the iron species, scanning electron microscopy (SEM) to locate iron biominerals among plant tissue structures, and energy-dispersive X-ray microanalysis (EDAX), X-ray fluorescence (TXRF) and inductively coupled plasma emission spectroscopy (ICP-MS) to confirm their elemental composition. * The MS spectral analysis indicated that iron accumulated in this plant mainly as jarosite and ferritin. The presence of jarosite was confirmed by XRD and the distribution of both minerals in structures of different tissues was ascertained by SEM-EDAX analysis. * The convergent results obtained by complementary techniques suggest a complex iron management system in I. cylindrica, probably as a consequence of the environmental conditions of its habitat.

c-Myc over-expression in Ramos Burkitt's lymphoma cell line predisposes to iron homeostasis disruption in vitro

International Nuclear Information System (INIS)

Habel, Marie-Eve; Jung, Daniel

2006-01-01

Burkitt's lymphoma is an aggressive B-cell neoplasm resulting from deregulated c-myc expression. We have previously shown that proliferation of Burkitt's lymphoma cell lines such as Ramos is markedly reduced by iron treatment. It has been shown that iron induces expression of c-myc which, owing to its transcriptional regulatory functions, regulates genes involved in iron metabolism. Transient enhancement of c-myc expression by iron could increase the expression of genes involved in iron incorporation, which could lead to an accumulation of intracellular free iron. Here, we have investigated whether cells with a high basal level of c-Myc were more likely to accumulate free iron. Our results suggest that the basal level of c-Myc in Ramos cells is twofold higher than what is seen in HL-60 cells. Moreover, in Ramos cells, where c-Myc is expressed at a high level, H-ferritin expression is down-regulated, transferrin receptor (CD71) expression is increased, and ferritin translation is inhibited. These modifications in iron metabolism, resulting from the strong basal expression of c-Myc, and amplified by iron addition, could lead to a disruption in homeostasis and consequently to growth arrest

Iron concentrations and distributions in the parkinsonian substantia nigra of aged and young primate models

International Nuclear Information System (INIS)

Ren, M.Q.; Xie, J.P.; Wang, X.S.; Ong, W.Y.; Leong, S.K.; Watt, F.

2001-01-01

Parkinson's disease (PD) is a progressive neuronal degenerative brain disease of the elderly, and is caused by the selective degeneration of neurons in the substantia nigra (SN) region of the brain, resulting in a reduced production of the neurotransmitter dopamine. Iron has been linked to dopaminergic cell death in Parkinson's disease because of its potential to promote free radicals, leading to oxidative stress. The present study is aimed at using the techniques of nuclear microscopy to elucidate the iron concentrations and distributions in the SN of both young and old monkeys following unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioning. A group of three old monkeys (older than 7 years) and a group of three young monkeys (younger than 7 years) were unilaterally MPTP-lesioned (right side) to induce parkinsonism and sacrificed after 35 days. The left side SN was used as a control. This time interval was chosen to correspond to an average 50% loss of dopamine producing cells in the lesioned right side SN. We have observed a significant difference in iron concentrations between the SNs of the young and old monkeys (increasing from an average of 233 to 1092 parts per million dry weight). When comparing the lesioned and non-lesioned SNs of the same animal, we found no significant difference in iron levels for each young monkey. However we have found a slight increase in iron (approximately 10%) between the lesioned SN and control SN for old monkeys. We have also observed that in the SN of younger primates, there is a weak anti-correlation in the SN iron levels with the neuron distribution. In the older monkeys, however, we have observed a proliferation of iron-rich granules, which appear to be more strongly anti-correlated with the distribution of neurons. The iron-cell anti-correlation occurs both in the control as well as the lesioned SN. Our results suggest that iron, particularly in the form of iron-rich deposits, accumulates in specific sites

Effect of iron deficiency on the biodistribution and tumor uptake of Ga-67 citrate in animals: concise communication

International Nuclear Information System (INIS)

Bradley, W.P.; Alderson, P.O.; Weiss, J.F.

1979-01-01

To investigate the effect of iron deficiency on the biodistribution and tumor uptake of Ga-67 citrate, 20 weanling Sprague-Dawley rats were maintained for 6 to 8 weeks on a low-iron diet. Eighteen littermates were maintained on a normal iron diet and served as controls. Animals received 10 μCi Ga-67 citrate, and urine and feces were collected for 48 h. The animals were then killed, tissue samples were obtained, and serum iron and unsaturated iron-binding capacity (UIBC) were measured. The accumulation of Ga-67 in the liver and spleen (% injected dose) was markedly increased in iron-deficient animals and urinary excretion was reduced. Tumor uptake was not significantly different in iron-deficient and control animals, but tumor-to-blood ratios were elevated (p < 0.001) in the iron-deficient animals because of low blood levels of Ga-67. The liver and spleen accumulation of Ga-67 correlated significantly (p < 0.001) with the UIBC. The results show that iron deficiency alters the distribution of Ga-67 citrate, and suggest that the variable liver-spleen uptake seen in clinical Ga-67 images may be explained, in part, by changes in serum iron and UIBC

Plasma protein haptoglobin modulates renal iron loading

DEFF Research Database (Denmark)

Fagoonee, Sharmila; Gburek, Jakub; Hirsch, Emilio

2005-01-01

Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme...... distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting...... morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload....

Colour Metallography of Cast Iron - Chapter 3: Spheroidal Graphite Cast Iron (Ⅳ

Directory of Open Access Journals (Sweden)

Zhou Jiyang

2010-11-01

Full Text Available Cast iron, as a traditional metal material, has advantages of low total cost, good castability and machinability, good wear resistance and low notch sensitivity, and is still facing tough challenge in quality, property and variety of types etc. Experts and engineers studying and producing iron castings all around world extremely concern this serious challenge. Over more than 30 years, a great of research work has been carried out on how to further improve its property, expand its application and combine cast iron technology with some hi-techs (for example, computer technology. Nevertheless, cast iron is a multi-element and multi-phase alloy and has complex and variety of structures and still has great development potential in structure and property. For further studying and developing cast iron, theoretical research work is important promise, and the study on solidification process and control mechanism of graphite morphology is fundamental for improving property of cast iron and developing new type of cast iron. Metallography of cast iron normally includes two sections: liquid phase transformation and solid phase transformation. The book, Colour Metallography of Cast Iron, uses colour metallography technique to study solidification structures of cast irons: graphite, carbides, austenite and eutectics; and focuses on solidification processes. With progress of modern solidification theory, the control of material solidification process becomes important measure for improving traditional materials and developing new materials. Solidification structure not only influences mechanical and physical properties of cast iron, but also affects its internal quality. The book uses a large amount of colour photos to describe the formation of solidification structures and their relations. Crystallization phenomena, which cannot be displayed with traditional metallography, are presented and more phase transformation information is obtained from these colour

Colour Metallography of Cast Iron - Chapter 3: Spheroidal Graphite Cast Iron (Ⅰ

Directory of Open Access Journals (Sweden)

Zhou Jiyang

2010-02-01

Full Text Available Cast iron, as a traditional metal material, has advantages of low total cost, good castability and machinability, good wear resistance and low notch sensitivity, and is still facing tough challenge in quality, property and variety of types etc. Experts and engineers studying and producing iron castings all around world extremely concern this serious challenge. Over more than 30 years, a great of research work has been carried out on how to further improve its property, expand its application and combine cast iron technology with some hi-techs (for example, computer technology. Nevertheless, cast iron is a multi-element and multi-phase alloy and has complex and variety of structures and still has great development potential in structure and property. For further studying and developing cast iron, theoretical research work is important promise, and the study on solidification process and control mechanism of graphite morphology is fundamental for improving property of cast iron and developing new type of cast iron. Metallography of cast iron normally includes two sections: liquid phase transformation and solid phase transformation. The book, Colour Metallography of Cast Iron, uses colour metallography technique to study solidification structures of cast irons: graphite, carbides, austenite and eutectics; and focuses on solidification processes. With progress of modern solidification theory, the control of material solidification process becomes important measure for improving traditional materials and developing new materials. Solidification structure not only influences mechanical and physical properties of cast iron, but also affects its internal quality. The book uses a large amount of colour photos to describe the formation of solidification structures and their relations. Crystallization phenomena, which cannot be displayed with traditional metallography, are presented and more phase transformation information is obtained from these colour

Colour Metallography of Cast Iron - Chapter 4: Vermicular Graphite Cast Iron (Ⅱ

Directory of Open Access Journals (Sweden)

Zhou Jiyang

2011-05-01

Full Text Available Cast iron, as a traditional metal material, has advantages of low total cost, good castability and machinability, good wear resistance and low notch sensitivity, and is still facing tough challenge in quality, property and variety of types etc. Experts and engineers studying and producing iron castings all around world extremely concern this serious challenge. Over more than 30 years, a great of research work has been carried out on how to further improve its property, expand its application and combine cast iron technology with some hi-techs (for example, computer technology. Nevertheless, cast iron is a multi-element and multi-phase alloy and has complex and variety of structures and still has great development potential in structure and property. For further studying and developing cast iron, theoretical research work is important promise, and the study on solidification process and control mechanism of graphite morphology is fundamental for improving property of cast iron and developing new type of cast iron. Metallography of cast iron normally includes two sections: liquid phase transformation and solid phase transformation. The book, Colour Metallography of Cast Iron, uses colour metallography technique to study solidification structures of cast irons: graphite, carbides, austenite and eutectics; and focuses on solidification processes. With progress of modern solidification theory, the control of material solidification process becomes important measure for improving traditional materials and developing new materials. Solidification structure not only influences mechanical and physical properties of cast iron, but also affects its internal quality. The book uses a large amount of colour photos to describe the formation of solidification structures and their relations. Crystallization phenomena, which cannot be displayed with traditional metallography, are presented and more phase transformation information is obtained from these colour

Pro-protein convertases control the maturation and processing of the iron-regulatory protein, RGMc/hemojuvelin

Directory of Open Access Journals (Sweden)

Rotwein Peter

2008-04-01

Full Text Available Abstract Background Repulsive guidance molecule c (RGMc or hemojuvelin, a glycosylphosphatidylinositol-linked glycoprotein expressed in liver and striated muscle, plays a central role in systemic iron balance. Inactivating mutations in the RGMc gene cause juvenile hemochromatosis (JH, a rapidly progressing iron storage disorder with severe systemic manifestations. RGMc undergoes complex biosynthetic steps leading to membrane-bound and soluble forms of the protein, including both 50 and 40 kDa single-chain species. Results We now show that pro-protein convertases (PC are responsible for conversion of 50 kDa RGMc to a 40 kDa protein with a truncated COOH-terminus. Unlike related molecules RGMa and RGMb, RGMc encodes a conserved PC recognition and cleavage site, and JH-associated RGMc frame-shift mutants undergo COOH-terminal cleavage only if this site is present. A cell-impermeable peptide PC inhibitor blocks the appearance of 40 kDa RGMc in extra-cellular fluid, as does an engineered mutation in the conserved PC recognition sequence, while the PC furin cleaves 50 kDa RGMc in vitro into a 40 kDa molecule with an intact NH2-terminus. Iron loading reduces release of RGMc from the cell membrane, and diminishes accumulation of the 40 kDa species in cell culture medium. Conclusion Our results define a role for PCs in the maturation of RGMc that may have implications for the physiological actions of this critical iron-regulatory protein.

Evaluation of constitutive iron reductase (AtFRO2) expression on mineral accumulation and distribution in soybean (Glycine max L.)

Science.gov (United States)

Iron is an important micronutrient in human and plant nutrition. Adequate iron nutrition during crop production is central for assuring appropriate iron concentrations in the harvestable organs, for human food or animal feed. The whole-plant movement of iron involves several processes, including the...

Modern iron replacement therapy: clinical and pathophysiological insights.

Science.gov (United States)

Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa

2018-01-01

Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

Potential involvement of iron in the pathogenesis of peritoneal endometriosis.

Science.gov (United States)

Defrère, S; Lousse, J C; González-Ramos, R; Colette, S; Donnez, J; Van Langendonckt, A

2008-07-01

The aim of this study is to review the current literature associating endometriosis with iron and to discuss the potential causes and consequences of iron overload in the pelvic cavity. Indeed, iron is essential for all living organisms. However, excess iron can result in toxicity and is associated with pathological disorders. In endometriosis patients, iron overload has been demonstrated in the different components of the peritoneal cavity (peritoneal fluid, endometriotic lesions, peritoneum and macrophages). Animal models allow us to gather essential information on the origin, metabolism and effect of iron overload in endometriosis, which may originate from erythrocytes carried into the pelvic cavity mainly by retrograde menstruation. Peritoneal macrophages play an important role in the degradation of these erythrocytes and in subsequent peritoneal iron metabolism. Iron overload could affect a wide range of mechanisms involved in endometriosis development, such as oxidative stress or lesion proliferation. In conclusion, excess iron accumulation can result in toxicity and may be one of the factors contributing to the development of endometriosis. Treatment with an iron chelator could thus be beneficial in endometriosis patients to prevent iron overload in the pelvic cavity, thereby diminishing its deleterious effect.

The role of melatonin on brain iron homeostasis and its relation to Parkinson’s Disease

OpenAIRE

Lai, Hien Tet

2017-01-01

Parkinson’s Disease (PD) is the second most common neurological disorder after Alzheimer’s Disease. The disease will manifest with the loss of up to 70% of the dopaminergic neurons in the Substantia Nigra (SN) region and it mainly affects the elderly. One of the common pathological hallmarks for PD is the excessive iron accumulation within the SN region of the brain. However, the pathogenesis for of the excessive iron levels accumulation in the SN is unclear. The increase in intracellular oxi...

Salinomycin kills cancer stem cells by sequestering iron in lysosomes

Science.gov (United States)

Mai, Trang Thi; Hamaï, Ahmed; Hienzsch, Antje; Cañeque, Tatiana; Müller, Sebastian; Wicinski, Julien; Cabaud, Olivier; Leroy, Christine; David, Amandine; Acevedo, Verónica; Ryo, Akihide; Ginestier, Christophe; Birnbaum, Daniel; Charafe-Jauffret, Emmanuelle; Codogno, Patrice; Mehrpour, Maryam; Rodriguez, Raphaël

2017-10-01

Cancer stem cells (CSCs) represent a subset of cells within tumours that exhibit self-renewal properties and the capacity to seed tumours. CSCs are typically refractory to conventional treatments and have been associated to metastasis and relapse. Salinomycin operates as a selective agent against CSCs through mechanisms that remain elusive. Here, we provide evidence that a synthetic derivative of salinomycin, which we named ironomycin (AM5), exhibits a more potent and selective activity against breast CSCs in vitro and in vivo, by accumulating and sequestering iron in lysosomes. In response to the ensuing cytoplasmic depletion of iron, cells triggered the degradation of ferritin in lysosomes, leading to further iron loading in this organelle. Iron-mediated production of reactive oxygen species promoted lysosomal membrane permeabilization, activating a cell death pathway consistent with ferroptosis. These findings reveal the prevalence of iron homeostasis in breast CSCs, pointing towards iron and iron-mediated processes as potential targets against these cells.

Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

DEFF Research Database (Denmark)

Schonberg, David L; Miller, Tyler E; Wu, Qiulian

2015-01-01

Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue......, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable...

Reducing arsenic accumulation in rice grain through iron oxide amendment

Science.gov (United States)

In this research, we investigated the accumulation of arsenic (As), selenium (Se), molybdenum (Mo), and cadmium (Cd) in rice grain under different soil conditions in standard straighthead-resistant and straighthead-susceptible cultivars, Zhe 733 and Cocodrie, respectively. Results demonstrated that,...

sup(113m)indium-iron chondroitin sulfate colloid for quantitative assessment of the marrow RE function

Energy Technology Data Exchange (ETDEWEB)

Okuyama, S; Ito, Y; Takahashi, K; Sato, T; Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

1975-07-01

sup(113m)In-iron chondroitin sulfate colloid shows a large accumulation in the bone marrow and is suitable for bone marrow imaging. Quantitative assessment of the marrow reticuloendotherial function was performed using this compound. When an appropriate amount of iron carrier was added for adjustment, the rate of accumulation of hyperfunction in the marrow reticuloendotherial system (RES) induced by acute loss of blood increased. Marrow RES hypofunction was efficiently exhibited regardless of the presence or absence of iron carrier. Deposition of sup(113m)In-iron chondroitin sulfate in the spleen increased remarkably in the presence of carrier In. sup(113m)In-iron chondroitin sulfate colloid appears to be suitable for the measurement of the conditions of marrow RES functions. If short half-life nuclide radio-colloids of the present type are clinically applied, it is possible not only to elaborately observe the bone marrow by scintigraphy but also to gradually decrease the absorbed dose of irradiation.

sup(113m)indium-iron chondroitin sulfate colloid for quantitative assessment of the marrow RE function

International Nuclear Information System (INIS)

Okuyama, Shinichi; Ito, Yasuhiko; Takahashi, Kunibumi; Sato, Tachio; Matsuzawa, Taiju

1975-01-01

sup(113m)In-iron chondroitin sulfate colloid shows a large accumulation in the bone marrow and is suitable for bone marrow imaging. Quantitative assessment of the marrow reticuloendotherial function was performed using this compound. When an appropriate amount of iron carrier was added for adjustment, the rate of accumulation of hyperfunction in the marrow reticuloendotherial system (RES) induced by acute loss of blood increased. Marrow RES hypofunction was efficiently exhibited regardless of the presence or absence of iron carrier. Deposition of sup(113m)In-iron chondroitin sulfate in the spleen increased remarkably in the presence of carrier In. sup(113m)In-iron chondroitin sulfate colloid appears to be suitable for the measurement of the conditions of marrow RES functions. If short half-life nuclide radio-colloids of the present type are clinically applied, it is possible not only to elaborately observe the bone marrow by scintigraphy but also to gradually decrease the absorbed dose of irradiation. (Mukohata, S.)

Iron addiction: a novel therapeutic target in ovarian cancer

International Nuclear Information System (INIS)

Basuli, D.

2017-01-01

Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs). The net result of these changes is an accumulation of excess intracellular iron and an augmented dependence on iron for proliferation. A forced reduction in intracellular iron reduces the proliferation of ovarian cancer TICs in vitro, and inhibits both tumor growth and intraperitoneal dissemination of tumor cells in vivo. Some mechanistic studies demonstrate that iron increases metastatic spread by facilitating invasion through expression of matrix metalloproteases and synthesis of interleukin 6 (IL-6). Here, we show that the iron dependence of ovarian cancer TICs renders them exquisitely sensitive in vivo to agents that induce iron-dependent cell death (ferroptosis) as well as iron chelators, and thus creates a metabolic vulnerability that can be exploited therapeutically.

SQUID biosusceptometry in the measurement of hepatic iron

International Nuclear Information System (INIS)

Sheth, Sujit

2003-01-01

Individuals with primary or secondary abnormalities of iron metabolism, such as hereditary hemochromatosis and transfusional iron loading, may develop potentially lethal systemic iron overload. Over time, this excess iron is progressively deposited in the liver, heart, pancreas, and other organs, resulting in cirrhosis, heart disease, diabetes and other disorders. Unless treated, death usually results from cardiac failure. The amount of iron in the liver is the best indicator of the amount of iron in the whole body. At present, the only sure way to measure the amount of iron in the liver is to remove a sample of the liver by biopsy. Iron stored in the liver can be magnetized to a small degree when placed in a magnetic field. The amount of magnetization is measured by our instrument, called a superconducting quantum interference device (SQUID) susceptometer. In patients with iron overload, our previous studies have shown that magnetic measurements of liver iron in patients with iron overload are quantitatively equivalent to biochemical determinations on tissue obtained by biopsy. The safety, ease, rapidity, and comfort of magnetic measurements make frequent, serial studies technically feasible and practically acceptable to patients. (orig.)

Bromine accumulation in acidic black colluvial soils

Science.gov (United States)

Martínez Cortizas, Antonio; Ferro Vázquez, Cruz; Kaal, Joeri; Biester, Harald; Costa Casais, Manuela; Taboada Rodríguez, Teresa; Rodríguez Lado, Luis

2016-02-01

Recent investigations showed that bromine is incorporated to soil organic matter (SOM), its content increasing with humification. But few research was done on its long-term accumulation and the role played by pedogenetic processes, as those involved in organic matter stabilization. We investigated bromine content and distribution in four deep, acidic, organic-rich, Holocene soils from an oceanic area of Western Europe. Bromine concentrations (93-778 μg g-1) in the silt + clay (stabilized as aluminium-OM associations, and to a lesser extent on soil acidity (pH) and iron-OM associations. Thus, at scales of thousands of years, bromine accumulation in acidic soils is linked to the pool of metal-clay-stabilized organic matter.

A comparison of rapid-scanning X-ray fluorescence mapping and magnetic resonance imaging to localize brain iron distribution

International Nuclear Information System (INIS)

McCrea, Richard P.E.; Harder, Sheri L.; Martin, Melanie; Buist, Richard; Nichol, Helen

2008-01-01

The clinical diagnosis of many neurodegenerative disorders relies primarily or exclusively on observed behaviors rather than measurable physical tests. One of the hallmarks of Alzheimer disease (AD) is the presence of amyloid-containing plaques associated with deposits of iron, copper and/or zinc. Work in other laboratories has shown that iron-rich plaques can be seen in the mouse brain in vivo with magnetic resonance imaging (MRI) using a high-field strength magnet but this iron cannot be visualized in humans using clinical magnets. To improve the interpretation of MRI, we correlated iron accumulation visualized by X-ray fluorescence spectroscopy, an element-specific technique with T1, T2, and susceptibility weighted MR (SWI) in a mouse model of AD. We show that SWI best shows areas of increased iron accumulation when compared to standard sequences

Iron Overload and Chelation Therapy in Non-Transfusion Dependent Thalassemia.

Science.gov (United States)

Bou-Fakhredin, Rayan; Bazarbachi, Abdul-Hamid; Chaya, Bachar; Sleiman, Joseph; Cappellini, Maria Domenica; Taher, Ali T

2017-12-20

Iron overload (IOL) due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT), which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient's needs and on the available facilities. Iron chelation therapy (ICT) remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT.

Iron Overload and Chelation Therapy in Non-Transfusion Dependent Thalassemia

Directory of Open Access Journals (Sweden)

Rayan Bou-Fakhredin

2017-12-01

Full Text Available Iron overload (IOL due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT, which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient’s needs and on the available facilities. Iron chelation therapy (ICT remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT.

Anaerobic Copper Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli.

Science.gov (United States)

Tan, Guoqiang; Yang, Jing; Li, Tang; Zhao, Jin; Sun, Shujuan; Li, Xiaokang; Lin, Chuxian; Li, Jianghui; Zhou, Huaibin; Lyu, Jianxin; Ding, Huangen

2017-08-15

While copper is an essential trace element in biology, pollution of groundwater from copper has become a threat to all living organisms. Cellular mechanisms underlying copper toxicity, however, are still not fully understood. Previous studies have shown that iron-sulfur proteins are among the primary targets of copper toxicity in Escherichia coli under aerobic conditions. Here, we report that, under anaerobic conditions, iron-sulfur proteins in E. coli cells are even more susceptible to copper in medium. Whereas addition of 0.2 mM copper(II) chloride to LB (Luria-Bertani) medium has very little or no effect on iron-sulfur proteins in wild-type E. coli cells under aerobic conditions, the same copper treatment largely inactivates iron-sulfur proteins by blocking iron-sulfur cluster biogenesis in the cells under anaerobic conditions. Importantly, proteins that do not have iron-sulfur clusters (e.g., fumarase C and cysteine desulfurase) in E. coli cells are not significantly affected by copper treatment under aerobic or anaerobic conditions, indicating that copper may specifically target iron-sulfur proteins in cells. Additional studies revealed that E. coli cells accumulate more intracellular copper under anaerobic conditions than under aerobic conditions and that the elevated copper content binds to the iron-sulfur cluster assembly proteins IscU and IscA, which effectively inhibits iron-sulfur cluster biogenesis. The results suggest that the copper-mediated inhibition of iron-sulfur proteins does not require oxygen and that iron-sulfur cluster biogenesis is the primary target of anaerobic copper toxicity in cells. IMPORTANCE Copper contamination in groundwater has become a threat to all living organisms. However, cellular mechanisms underlying copper toxicity have not been fully understood up to now. The work described here reveals that iron-sulfur proteins in Escherichia coli cells are much more susceptible to copper in medium under anaerobic conditions than they

Dynamic changes in the distribution of minerals in relation to phytic acid accumulation during rice seed development.

Science.gov (United States)

Iwai, Toru; Takahashi, Michiko; Oda, Koshiro; Terada, Yasuko; Yoshida, Kaoru T

2012-12-01

Phytic acid (inositol hexakisphosphate [InsP(6)]) is the storage compound of phosphorus in seeds. As phytic acid binds strongly to metallic cations, it also acts as a storage compound of metals. To understand the mechanisms underlying metal accumulation and localization in relation to phytic acid storage, we applied synchrotron-based x-ray microfluorescence imaging analysis to characterize the simultaneous subcellular distribution of some mineral elements (phosphorus, calcium, potassium, iron, zinc, and copper) in immature and mature rice (Oryza sativa) seeds. This fine-imaging method can reveal whether these elements colocalize. We also determined their accumulation patterns and the changes in phosphate and InsP(6) contents during seed development. While the InsP(6) content in the outer parts of seeds rapidly increased during seed development, the phosphate contents of both the outer and inner parts of seeds remained low. Phosphorus, calcium, potassium, and iron were most abundant in the aleurone layer, and they colocalized throughout seed development. Zinc was broadly distributed from the aleurone layer to the inner endosperm. Copper localized outside the aleurone layer and did not colocalize with phosphorus. From these results, we suggest that phosphorus translocated from source organs was immediately converted to InsP(6) and accumulated in aleurone layer cells and that calcium, potassium, and iron accumulated as phytic acid salt (phytate) in the aleurone layer, whereas zinc bound loosely to InsP(6) and accumulated not only in phytate but also in another storage form. Copper accumulated in the endosperm and may exhibit a storage form other than phytate.

Finger on the Pulse: Pumping Iron into Chickpea.

Science.gov (United States)

Tan, Grace Z H; Das Bhowmik, Sudipta S; Hoang, Thi M L; Karbaschi, Mohammad R; Johnson, Alexander A T; Williams, Brett; Mundree, Sagadevan G

2017-01-01

Iron deficiency is a major problem in both developing and developed countries, and much of this can be attributed to insufficient dietary intake. Over the past decades several measures, such as supplementation and food fortification, have helped to alleviate this problem. However, their associated costs limit their accessibility and effectiveness, particularly amongst the financially constrained. A more affordable and sustainable option that can be implemented alongside existing measures is biofortification. To date, much work has been invested into staples like cereals and root crops-this has culminated in the successful generation of high iron-accumulating lines in rice and pearl millet. More recently, pulses have gained attention as targets for biofortification. Being secondary staples rich in protein, they are a nutritional complement to the traditional starchy staples. Despite the relative youth of this interest, considerable advances have already been made concerning the biofortification of pulses. Several studies have been conducted in bean, chickpea, lentil, and pea to assess existing germplasm for high iron-accumulating traits. However, little is known about the molecular workings behind these traits, particularly in a leguminous context, and biofortification via genetic modification (GM) remains to be attempted. This review examines the current state of the iron biofortification in pulses, particularly chickpea. The challenges concerning biofortification in pulses are also discussed. Specifically, the potential application of transgenic technology is explored, with focus on the genes that have been successfully used in biofortification efforts in rice.

Finger on the Pulse: Pumping Iron into Chickpea

Directory of Open Access Journals (Sweden)

Grace Z. H. Tan

2017-10-01

Full Text Available Iron deficiency is a major problem in both developing and developed countries, and much of this can be attributed to insufficient dietary intake. Over the past decades several measures, such as supplementation and food fortification, have helped to alleviate this problem. However, their associated costs limit their accessibility and effectiveness, particularly amongst the financially constrained. A more affordable and sustainable option that can be implemented alongside existing measures is biofortification. To date, much work has been invested into staples like cereals and root crops—this has culminated in the successful generation of high iron-accumulating lines in rice and pearl millet. More recently, pulses have gained attention as targets for biofortification. Being secondary staples rich in protein, they are a nutritional complement to the traditional starchy staples. Despite the relative youth of this interest, considerable advances have already been made concerning the biofortification of pulses. Several studies have been conducted in bean, chickpea, lentil, and pea to assess existing germplasm for high iron-accumulating traits. However, little is known about the molecular workings behind these traits, particularly in a leguminous context, and biofortification via genetic modification (GM remains to be attempted. This review examines the current state of the iron biofortification in pulses, particularly chickpea. The challenges concerning biofortification in pulses are also discussed. Specifically, the potential application of transgenic technology is explored, with focus on the genes that have been successfully used in biofortification efforts in rice.

Iron-induced nitric oxide leads to an increase in the expression of ferritin during the senescence of Lotus japonicus nodules.

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Chungopast, Sirinapa; Duangkhet, Mallika; Tajima, Shigeyuki; Ma, Jian Feng; Nomura, Mika

2017-01-01

Iron is an essential nutrient for legume-rhizobium symbiosis and accumulates abundantly in the nodules. However, the concentration of free iron in the cells is strictly controlled to avoid toxicity. It is known that ferritin accumulates in the cells as an iron storage protein. During nodule senescence, the expression of the ferritin gene, Ljfer1, was induced in Lotus japonicus. We investigated a signal transduction pathway leading to the increase of Ljfer1 in the nodule. The Ljfer1 promoter of L. japonicus contains a conserved Iron-Dependent Regulatory Sequence (IDRS). The expression of Ljfer1 was induced by the application of iron or sodium nitroprusside, which is a nitric oxide (NO) donor. The application of iron to the nodule increased the level of NO. These data strongly suggest that iron-induced NO leads to increased expression of Ljfer1 during the senescence of L. japonicus nodules. Copyright © 2016 Elsevier GmbH. All rights reserved.

The physiological functions of iron regulatory proteins in iron homeostasis - an update

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De-Liang eZhang

2014-06-01

Full Text Available Iron regulatory proteins (IRPs regulate the expression of genes involved in iron metabolism by binding to RNA stem-loop structures known as iron responsive elements (IREs in target mRNAs. IRP binding inhibits the translation of mRNAs that contain an IRE in the 5’untranslated region of the transcripts, and increases the stability of mRNAs that contain IREs in the 3'untranslated region of transcripts. By these mechanisms, IRPs increase cellular iron absorption and decrease storage and export of iron to maintain an optimal intracellular iron balance. There are two members of the mammalian IRP protein family, IRP1 and IRP2, and they have redundant functions as evidenced by the embryonic lethality of the mice that completely lack IRP expression (Irp1-/-/Irp2-/- mice, which contrasts with the fact that Irp1-/- and Irp2-/- mice are viable. In addition, Irp2-/- mice also display neurodegenerative symptoms and microcytic hypochromic anemia, suggesting that IRP2 function predominates in the nervous system and erythropoietic homeostasis. Though the physiological significance of IRP1 had been unclear since Irp1-/- animals were first assessed in the early 1990’s, recent studies indicate that IRP1 plays an essential function in orchestrating the balance between erythropoiesis and bodily iron homeostasis. Additionally, Irp1-/- mice develop pulmonary hypertension, and they experience sudden death when maintained on an iron-deficient diet, indicating that IRP1 has a critical role in the pulmonary and cardiovascular systems. This review summarizes recent progress that has been made in understanding the physiological roles of IRP1 and IRP2, and further discusses the implications for clinical research on patients with idiopathic polycythemia, pulmonary hypertension and neurodegeneration.

Dynamic Subcellular Localization of Iron during Embryo Development in Brassicaceae Seeds

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Miguel A. Ibeas

2017-12-01

Full Text Available Iron is an essential micronutrient for plants. Little is know about how iron is loaded in embryo during seed development. In this article we used Perls/DAB staining in order to reveal iron localization at the cellular and subcellular levels in different Brassicaceae seed species. In dry seeds of Brassica napus, Nasturtium officinale, Lepidium sativum, Camelina sativa, and Brassica oleracea iron localizes in vacuoles of cells surrounding provasculature in cotyledons and hypocotyl. Using B. napus and N. officinale as model plants we determined where iron localizes during seed development. Our results indicate that iron is not detectable by Perls/DAB staining in heart stage embryo cells. Interestingly, at torpedo development stage iron localizes in nuclei of different cells type, including integument, free cell endosperm and almost all embryo cells. Later, iron is detected in cytoplasmic structures in different embryo cell types. Our results indicate that iron accumulates in nuclei in specific stages of embryo maturation before to be localized in vacuoles of cells surrounding provasculature in mature seeds.

Purification of Lysosomes Using Supraparamagnetic Iron Oxide Nanoparticles (SPIONs).

Science.gov (United States)

Rofe, Adam P; Pryor, Paul R

2016-04-01

Lysosomes can be rapidly isolated from tissue culture cells using supraparamagnetic iron oxide particles (SPIONs). In this protocol, colloidal iron dextran (FeDex) particles, a type of SPION, are taken up by cultured mouse macrophage cells via the endocytic pathway. The SPIONs accumulate in lysosomes, the end point of the endocytic pathway, permitting the lysosomes to be isolated magnetically. The purified lysosomes are suitable for in vitro fusion assays or for proteomic analysis. © 2016 Cold Spring Harbor Laboratory Press.

Hepatic iron overload following liver transplantation of a C282y homozygous allograft: a case report and literature review.

LENUS (Irish Health Repository)

Dwyer, Jeremy P

2011-11-01

Hereditary haemochromatosis is a common genetic disease associated with progressive iron overload and parenchymal organ damage including liver, pancreas and heart. We report a case of inadvertent transplantation of a liver from a haemochromatosis donor to a 56-year-old Asian female. Progressive iron overload occurred over a 2 year follow up as assessed by liver biopsy and iron studies in the absence of a secondary cause of iron overload, supporting a primary role of liver rather than small intestine in the regulation of iron homeostasis in hereditary haemochromatosis.

Tracking Iron in Multiple Sclerosis: A Combined Imaging and Histopathological Study at 7 Tesla

Science.gov (United States)

Bagnato, Francesca; Hametner, Simon; Yao, Bing; van Gelderen, Peter; Merkle, Hellmut; Cantor, Fredric K.; Lassmann, Hans; Duyn, Jeff H.

2011-01-01

Previous authors have shown that the transverse relaxivity R[subscript 2][superscript *] and frequency shifts that characterize gradient echo signal decay in magnetic resonance imaging are closely associated with the distribution of iron and myelin in the brain's white matter. In multiple sclerosis, iron accumulation in brain tissue may reflect a…

Geology of the Biwabik Iron Formation and Duluth Complex.

Science.gov (United States)

Jirsa, Mark A; Miller, James D; Morey, G B

2008-10-01

The Biwabik Iron Formation is a approximately 1.9 billion year-old sequence of iron-rich sedimentary rocks that was metamorphosed at its eastern-most extent by approximately 1.1 billion year-old intrusions of the Duluth Complex. The metamorphic recrystallization of iron-formation locally produced iron-rich amphiboles and other fibrous iron-silicate minerals. The presence of these minerals in iron-formation along the eastern part of what is known as the Mesabi Iron Range, and their potential liberation by iron mining has raised environmental health concerns. We describe here the geologic setting and mineralogic composition of the Biwabik Iron Formation in and adjacent to the contact metamorphic aureole of the Duluth Complex. The effects of metamorphism are most pronounced within a few kilometers of the contact, and decrease progressively away from it. The contact aureole has been divided into four metamorphic zones-each characterized by the composition and crystal structure of the metamorphic minerals it contains. The recrystallization of iron-formation to iron-rich amphibole minerals (grunerite and cummingtonite) and iron-pyroxene minerals (hedenbergite and ferrohypersthene) is best developed in zones that are most proximal to the Duluth Complex contact.

Effect of Nano Iron and Solupotasse Fertilizers on Accumulation of Nutrient Elements and Quality of Two Onion (Allium cepa Cultivars

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Ali Joghatay

2015-11-01

Full Text Available To study the effect of nano iron and solupotass on agronomic and physiological traits of two onion cultivars, a factorial experiment was conducted in complete randomized block design with 32 treatments and three replications in Joghatai of Khorasan-e- Razavi province, Iran. Treatments consisted of two onion cultivars (red, yellow and four levels (0, 1, 2, 3 kg per hectare of nano iron chelat and four levels of solupotass (0, 5, 10, 15 kg per hectare. Results showed that the effect of nano iron and solupotasse on fresh weight, dry weight, pyrovic acid and macro element (N, P, S contents were significant at %1 levels. Application nano iron, solupotasse to red onion cultivar increased dry weight significantly at the %5 level. Highest onion weight was obtained by using 2 kg nano iron and 15 kg solupotasse (17.3 g. Use of nano iron and solupotasse highly increased the pyruvic acid percentage (1.07 mM. Highest rate of pyruvic acid obtained by application of 3 and 15 kg nano iron and solupotasse respectively. Application of nano iron on the sulfur and nitrogen contents of onion were significant. Use of 2 kg/ha of nano iron exhibited highest increase in these elements. Thus, soil application of 10 kg/ha solupotasse, 3 kg/ha nano iron would highly increase red onion traits mentioned above.

Obesity as an Emerging Risk Factor for Iron Deficiency

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Elmar Aigner

2014-09-01

Full Text Available Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS or nonalcoholic fatty liver disease (NAFLD. This constellation has been named the “dysmetabolic iron overload syndrome (DIOS”. Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity.

Accumulation of magnetic iron oxide nanoparticles coated with variably sized polyethylene glycol in murine tumors

DEFF Research Database (Denmark)

Larsen, Esben Kjær Unmack; Nielsen, Thomas; Wittenborn, Thomas

2012-01-01

Iron oxide nanoparticles have found widespread applications in different areas including cell separation, drug delivery and as contrast agents. Due to water insolubility and stability issues, nanoparticles utilized for biological applications require coatings such as the commonly employed...... polyethylene glycol (PEG). Despite its frequent use, the influence of PEG coatings on the physicochemical and biological properties of iron nanoparticles has hitherto not been studied in detail. To address this, we studied the effect of 333–20 000 Da PEG coatings that resulted in larger hydrodynamic size...

Iron deposition in skin of patients with haemochromatosis

International Nuclear Information System (INIS)

Pinheiro, T.; Silva, J.N.; Alves, L.C.; Filipe, P.

2003-01-01

Haemochromatosis is the most common inherited liver disease in Caucasians and the most common autosomal recessive genetic disorder. It is characterized by inappropriately high iron absorption resulting in progressive iron overload in parenchymal organs such as liver, heart, pancreas, pituitary, joints, and skin. Upon early detection, haemochromatosis can be a manageable chronic disease but, if undetected, is potentially fatal. Skin biopsies were obtained from patients and from healthy donors. Images of the elemental distributions in skin were obtained using nuclear microscopy techniques (nuclear microprobe, NMP). Elemental profiles along skin, and intra-, and extra-cellular iron concentrations, were determined. Results for patients with haemochromatosis were cross-examined with morphologic features and with data obtained for healthy skin. Skin iron content is much increased in patients with haemochromatosis when compared with healthy subjects. Extensive iron deposits are observed at dermis, at the dermo-epidermal interface, at upper epidermis layers and at stratum corneum. Iron deposition was observed preferentially at cell boundaries or at the interstitial matrix

MapA, an iron-regulated, cytoplasmic membrane protein in the cyanobacterium Synechococcus sp. strain PCC7942.

Science.gov (United States)

Webb, R; Troyan, T; Sherman, D; Sherman, L A

1994-08-01

Growth of Synechococcus sp. strain PCC 7942 in iron-deficient media leads to the accumulation of an approximately 34-kDa protein. The gene encoding this protein, mapA (membrane-associated protein A), has been cloned and sequenced (GenBank accession number, L01621). The mapA transcript is not detectable in normally grown cultures but is stably accumulated by cells grown in iron-deficient media. However, the promoter sequence for this gene does not resemble other bacterial iron-regulated promoters described to date. The carboxyl-terminal region of the derived amino acid sequence of MapA resembles bacterial proteins involved in iron acquisition, whereas the amino-terminal end of MapA has a high degree of amino acid identity with the abundant, chloroplast envelope protein E37. An approach employing improved cellular fractionation techniques as well as electron microscopy and immunocytochemistry was essential in localizing MapA protein to the cytoplasmic membrane of Synechococcus sp. strain PCC 7942. When these cells were grown under iron-deficient conditions, a significant fraction of MapA could also be localized to the thylakoid membranes.

Iron-mediated stabilization of soil carbon amplifies the benefits of ecological restoration in degraded lands.

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Silva, Lucas C R; Doane, Timothy A; Corrêa, Rodrigo S; Valverde, Vinicius; Pereira, Engil I P; Horwath, William R

2015-07-01

Recent observations across a 14-year restoration chronosequence have shown an unexpected accumulation of soil organic carbon in strip-mined areas of central Brazil. This was attributed to the rapid plant colonization that followed the incorporation of biosolids into exposed regoliths, but the specific mechanisms involved in the stabilization of carbon inputs from the vegetation remained unclear. Using isotopic and elemental analyses, we tested the hypothesis that plant-derived carbon accumulation was triggered by the formation of iron-coordinated complexes, stabilized into physically protected (occluded) soil fractions. Confirming this hypothesis, we identified a fast formation of microaggregates shortly after the application of iron-rich biosolids, which was characterized by a strong association between pyrophosphate-extractable iron and plant-derived organic matter. The formation of microaggregates preceded the development of macroaggregates, which drastically increased soil carbon content (-140 Mg C/ha) a few years after restoration. Consistent with previous theoretical work, iron-coordinated organic complexes served as nuclei for aggregate formation, reflecting the synergistic effect of biological, chemical, and physical mechanisms of carbon stabilization in developing soils. Nevertheless, iron was not the only factor affecting soil carbon content. The highest carbon accumulation was observed during the period of highest plant diversity (> 30 species; years 3-6), declining significantly with the exclusion of native species by invasive grasses (years 9-14). Furthermore, the increasing dominance of invasive grasses was associated with a steady decline in the concentration of soil nitrogen and phosphorus per unit of accumulated carbon. These results demonstrate the importance of interdependent ecological and biogeochemical processes, and the role of soil-plant interactions in determining the success of restoration efforts. In contrast with previous but

Hereditary iron and copper deposition

DEFF Research Database (Denmark)

Aaseth, Jan; Flaten, Trond Peder; Andersen, Ole

2007-01-01

Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs. The prevalence of primary haemochromatosis is approximately 0.5%, about......, they may be inadequate in patients diagnosed so late that extensive body deposits of metal have been developed. The main research needs in this field are to further clarify molecular mechanisms of disease progression and to develop new chelators that are more effective and less toxic than those presently...

Accumulation of different metals in apple trees organs from an unfertilized orchard

International Nuclear Information System (INIS)

Stanica, F.

1999-01-01

Working in an unfertilized apple orchard, planted on brown-reddish soil in Baneasa - Bucuresti, the accumulation of different metals in trees organs was studied: leaves, vegetative branches, fruit branches and fruits. The samples were taken from 'Golden delicious' variety, planted at 10 meters, 'Idared' variety, planted at 100 meters and 'Akane' variety, planted at 200 meters from the Bucuresti-Ploiesti motorway. Lead accumulation depended on the distance to the pollution source and organ type. In leaves, lead was found even at 100 m from the road border (11.7 ppm in 'Idared' variety). At 10 m the leaves content was much higher (306 ppm, 'Golden delicious'). Because of the specific metabolism selectivity apple trees didn't accumulate lead into fruit branches and fruits. Copper leaves content varied between 5.85 ppm ('Golden delicious') and 16.2 ppm ('Akane') being lower than the fruits content (8.36 ppm 'Idared' - 23.0 ppm 'Golden delicious'). In apple tree fruit branches the Cu accumulation was 2-3 times higher than in the vegetative branches. The same fruit branches accumulated the highest quantity of zinc (between 67.5 and 83.9 ppm). Fruit contents in zinc (10.0-16.9 ppm) were close to the normal value: 15 ppm, but leave contents (43.3-48.7 ppm) were more than doubled compared to the normal range: 15-20 ppm. The 'Idared' variety accumulated the lowest quantity of nickel in all analyzed organs. Iron accumulation was different in function of the analyzed organ, variety and ion type (Fe 2+ , Fe 3+ ). The highest Fe 3+ content was found in 'Golden delicious' leaves: 547 ppm and the highest Fe 2+ content in 'Idared' leaves: 96.0 ppm. The lowest iron content was found in fruits. The manganese content of the analyzed organs varied from 8.32 to 130 ppm. Refs. 4 (author)

Melatonin protects bone marrow mesenchymal stem cells against iron overload-induced aberrant differentiation and senescence.

Science.gov (United States)

Yang, Fan; Yang, Lei; Li, Yuan; Yan, Gege; Feng, Chao; Liu, Tianyi; Gong, Rui; Yuan, Ye; Wang, Ning; Idiiatullina, Elina; Bikkuzin, Timur; Pavlov, Valentin; Li, Yang; Dong, Chaorun; Wang, Dawei; Cao, Yang; Han, Zhenbo; Zhang, Lai; Huang, Qi; Ding, Fengzhi; Bi, Zhengang; Cai, Benzhi

2017-10-01

Bone marrow mesenchymal stem cells (BMSCs) are an expandable population of stem cells which can differentiate into osteoblasts, chondrocytes and adipocytes. Dysfunction of BMSCs in response to pathological stimuli contributes to bone diseases. Melatonin, a hormone secreted from pineal gland, has been proved to be an important mediator in bone formation and mineralization. The aim of this study was to investigate whether melatonin protected against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Here, we found that iron overload induced by ferric ammonium citrate (FAC) caused irregularly morphological changes and markedly reduced the viability in BMSCs. Consistently, osteogenic differentiation of BMSCs was significantly inhibited by iron overload, but melatonin treatment rescued osteogenic differentiation of BMSCs. Furthermore, exposure to FAC led to the senescence in BMSCs, which was attenuated by melatonin as well. Meanwhile, melatonin was able to counter the reduction in cell proliferation by iron overload in BMSCs. In addition, protective effects of melatonin on iron overload-induced dysfunction of BMSCs were abolished by its inhibitor luzindole. Also, melatonin protected BMSCs against iron overload-induced ROS accumulation and membrane potential depolarization. Further study uncovered that melatonin inhibited the upregulation of p53, ERK and p38 protein expressions in BMSCs with iron overload. Collectively, melatonin plays a protective role in iron overload-induced osteogenic differentiation dysfunction and senescence through blocking ROS accumulation and p53/ERK/p38 activation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Colour Metallography of Cast Iron

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Zhou Jiyang

2009-05-01

Full Text Available Cast iron, as a traditional metal material, has advantages of low total cost, good castability and machinability, good wear resistance and low notch sensitivity, and is still facing tough challenge in quality, property and variety of types etc. Experts and engineers studying and producing iron castings all around world extremely concern this serious challenge. Over more than 30 years, a great of research work has been carried out on how to further improve its property, expand its application and combine cast iron technology with some hi-techs (for example, computer technology. Nevertheless, cast iron is a multi-element and multi-phase alloy and has complex and variety of structures and still has great development potential in structure and property. For further studying and developing cast iron, theoretical research work is important promise, and the study on solidification process and control mechanism of graphite morphology is fundamental for improving property of cast iron and developing new type of cast iron.Metallography of cast iron normally includes two sections: liquid phase transformation and solid phase transformation. The book, Colour Metallography of Cast Iron , uses colour metallography technique to study solidification structures of cast irons: graphite, carbides, austenite and eutectics; and focuses on solidification processes. With progress of modern solidification theory, the control of material solidification process becomes important measure for improving traditionalmaterials and developing new materials. Solidification structure not only influences mechanical and physical properties of cast iron, but also affects its internal quality. The book uses a large amount of colour photos to describe the formation of solidification structures and their relations. Crystallization phenomena, which cannot be displayed with traditional metallography, are presented and more phase transformation information is obtained from these colour

Mosses accumulate heavy metals from the substrata of coal ash

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Vukojević Vanja

2005-01-01

Full Text Available Plants that are able to accumulate and tolerate extraordinarily high concentrations of heavy metals (hyperaccumulators can be used for phytoremediation (removal of contaminants from soils or phytomining (growing a crop of plants to harvest the metals. Two moss species, Bryum capillare Hedw. and Ceratodon purpureus Hedw., were tested as potential phytoremedies under in vivo conditions on a coal ash disposal site in the surroundings of Obrenovac (NW Serbia. The content of various heavy metals (iron, manganese zinc, lead, nickel, cadmium, and copper in the mosses and substrata were investigated over a period of three years. Iron and zinc were found to have the highest concentration in the mosses.

Serum iron parameters in liver cirrhosis

Science.gov (United States)

Siregar, G. A.; Maail, W.

2018-03-01

The liver plays a fundamental role in iron homeostasis. Iron parameters change, especially ferritin, need to be evaluated in patients with liver cirrhosis. Serum ferritin could predict the prognosis of patients with decompensated cirrhosis since it reflects immunemediated and infectious stimuli. Ferritin could express the severity of liver disease and possible subsequent complications. Finally, it might reflect an iron overload condition resulting in significant morbidity and early mortality. 70 patients with decompensated liver cirrhosis divided into three Child-Pugh subgroups. Serum iron parameters include serum iron (SI), total iron binding capacity (TIBC) and ferritin was measured in these groups. From these 70 patients, 30 (42.9%) with HbsAg positive, 26 (37.1%) with anti-HCV positive and 14 (20%) with both HbsAg and anti-HCV positive. Of the 70 patients, 14 (20%) had CTP Class A cirrhosis, 17 (24.3%) had CTP Class B cirrhosis, and 39 (55.7%) had CTP C cirrhosis. The median (range) value of serum iron was 36 (10-345) μg/dl, TIBC was 160 (59-520) μg/dl, Ferritin was 253.5 (8-6078) ng/ml and the transferrin saturation was 22.9 (3.65-216.98) %.We found a significant difference in serum ferritin level with CTP score. Ferritin levels increased as Child-Pugh class progressed (p<0.001).

A model for the biological precipitation of Precambrian iron-formation

Science.gov (United States)

Laberge, G. L.

1986-01-01

A biological model for the precipitation of Precambrian iron formations is presented. Assuming an oxygen deficient atmosphere and water column to allow sufficient Fe solubility, it is proposed that local oxidizing environments, produced biologically, led to precipitation of iron formations. It is further suggested that spheroidal structures about 30 mm in diameter, which are widespread in low grade cherty rion formations, are relict forms of the organic walled microfossil Eosphaera tylerii. The presence of these structures suggests that the organism may have had a siliceous test, which allowed sufficient rigidity for accumulation and preservation. The model involves precipitation of ferric hydrates by oxidation of iron in the photic zone by a variety of photosynthetic organisms. Silica may have formed in the frustules of silica secreting organisms, including Eosphaera tylerii. Iron formates formed, therefore, by a sediment rain of biologically produced ferric hydrates and silica and other organic material. Siderite and hematite formed diagenetically on basin floors, and subsequent metamorphism produced magnetite and iron silicates.

Safety assessment of chronic oral exposure to iron oxide nanoparticles

International Nuclear Information System (INIS)

Chamorro, Susana; Vaquero, María Pilar; Brenes, Agustín; Gutiérrez, Lucía; Salas, Gorka; Luengo, Yurena; Verdoy, Dolores; José Teran, Francisco

2015-01-01

Iron oxide nanoparticles with engineered physical and biochemical properties are finding a rapidly increasing number of biomedical applications. However, a wide variety of safety concerns, especially those related to oral exposure, still need to be addressed for iron oxide nanoparticles in order to reach clinical practice. Here, we report on the effects of chronic oral exposure to low doses of γ-Fe 2 O 3 nanoparticles in growing chickens. Animal observation, weight, and diet intake reveal no adverse signs, symptoms, or mortality. No nanoparticle accumulation was observed in liver, spleen, and duodenum, with feces as the main excretion route. Liver iron level and duodenal villi morphology reflect the bioavailability of the iron released from the partial transformation of γ-Fe 2 O 3 nanoparticles in the acid gastric environment. Duodenal gene expression studies related to the absorption of iron from γ-Fe 2 O 3 nanoparticles indicate the enhancement of a ferric over ferrous pathway supporting the role of mucins. Our findings reveal that oral administration of iron oxide nanoparticles is a safe route for drug delivery at low nanoparticle doses. (paper)

HFE gene variants, iron, and lipids: a novel connection in Alzheimer's disease.

Science.gov (United States)

Ali-Rahmani, Fatima; Schengrund, Cara-Lynne; Connor, James R

2014-01-01

Iron accumulation and associated oxidative stress in the brain have been consistently found in several neurodegenerative diseases. Multiple genetic studies have been undertaken to try to identify a cause of neurodegenerative diseases but direct connections have been rare. In the iron field, variants in the HFE gene that give rise to a protein involved in cellular iron regulation, are associated with iron accumulation in multiple organs including the brain. There is also substantial epidemiological, genetic, and molecular evidence of disruption of cholesterol homeostasis in several neurodegenerative diseases, in particular Alzheimer's disease (AD). Despite the efforts that have been made to identify factors that can trigger the pathological events associated with neurodegenerative diseases they remain mostly unknown. Because molecular phenotypes such as oxidative stress, synaptic failure, neuronal loss, and cognitive decline, characteristics associated with AD, have been shown to result from disruption of a number of pathways, one can easily argue that the phenotype seen may not arise from a linear sequence of events. Therefore, a multi-targeted approach is needed to understand a complex disorder like AD. This can be achieved only when knowledge about interactions between the different pathways and the potential influence of environmental factors on them becomes available. Toward this end, this review discusses what is known about the roles and interactions of iron and cholesterol in neurodegenerative diseases. It highlights the effects of gene variants of HFE (H63D- and C282Y-HFE) on iron and cholesterol metabolism and how they may contribute to understanding the etiology of complex neurodegenerative diseases.

Gene Identification and Substrate Regulation Provide Insights into Sulfur Accumulation during Bioleaching with the Psychrotolerant Acidophile Acidithiobacillus ferrivorans

Science.gov (United States)

Liljeqvist, Maria; Rzhepishevska, Olena I.

2013-01-01

The psychrotolerant acidophile Acidithiobacillus ferrivorans has been identified from cold environments and has been shown to use ferrous iron and inorganic sulfur compounds as its energy sources. A bioinformatic evaluation presented in this study suggested that Acidithiobacillus ferrivorans utilized a ferrous iron oxidation pathway similar to that of the related species Acidithiobacillus ferrooxidans. However, the inorganic sulfur oxidation pathway was less clear, since the Acidithiobacillus ferrivorans genome contained genes from both Acidithiobacillus ferrooxidans and Acidithiobacillus caldus encoding enzymes whose assigned functions are redundant. Transcriptional analysis revealed that the petA1 and petB1 genes (implicated in ferrous iron oxidation) were downregulated upon growth on the inorganic sulfur compound tetrathionate but were on average 10.5-fold upregulated in the presence of ferrous iron. In contrast, expression of cyoB1 (involved in inorganic sulfur compound oxidation) was decreased 6.6-fold upon growth on ferrous iron alone. Competition assays between ferrous iron and tetrathionate with Acidithiobacillus ferrivorans SS3 precultured on chalcopyrite mineral showed a preference for ferrous iron oxidation over tetrathionate oxidation. Also, pure and mixed cultures of psychrotolerant acidophiles were utilized for the bioleaching of metal sulfide minerals in stirred tank reactors at 5 and 25°C in order to investigate the fate of ferrous iron and inorganic sulfur compounds. Solid sulfur accumulated in bioleaching cultures growing on a chalcopyrite concentrate. Sulfur accumulation halted mineral solubilization, but sulfur was oxidized after metal release had ceased. The data indicated that ferrous iron was preferentially oxidized during growth on chalcopyrite, a finding with important implications for biomining in cold environments. PMID:23183980

An intracranial aspergilloma with low signal on T2-weighted images corresponding to iron accumulation

Energy Technology Data Exchange (ETDEWEB)

Yamada, K. [Dept. of Radiology, Kyoto Prefectural Univ. of Medicine (Japan); Dept. of Radiology, Univ. of Maryland Medical Center, Baltimore MD (United States); Zoarski, G.H.; Rothman, M.I.; Zagardo, M.T. [Dept. of Radiology, Univ. of Maryland Medical Center, Baltimore MD (United States); Nishimura, T. [Dept. of Radiology, Kyoto Prefectural Univ. of Medicine (Japan); Sun, C.C.J. [Dept. of Pathology, Univ. of Maryland Medical Center, Baltimore MD (United States)

2001-07-01

We present a case of cerebral aspergillosis in an immunocompetent patient. The MRI signal characteristics were compared with the histologic findings. Irregular low-signal zones were demonstrated between the wall of the abscess and the central necrosis on T2-weighted images; the pathology specimen revealed concentrated iron in these transitional zones but no hemosiderin. Iron is an essential element for the growth of fungal hyphae. The low-signal zones may represent the areas where there was active proliferation of aspergillus, and the unique location of the low signal may be a helpful imaging characteristic for the diagnosis of an aspergillus abscess. (orig.)

Aspergillus niger Secretes Citrate to Increase Iron Bioavailability

Science.gov (United States)

Odoni, Dorett I.; van Gaal, Merlijn P.; Schonewille, Tom; Tamayo-Ramos, Juan A.; Martins dos Santos, Vitor A. P.; Suarez-Diez, Maria; Schaap, Peter J.

2017-01-01

Aspergillus niger has an innate ability to secrete various organic acids, including citrate. The conditions required for A. niger citrate overproduction are well described, but the physiological reasons underlying extracellular citrate accumulation are not yet fully understood. One of the less understood culture conditions is the requirement of growth-limiting iron concentrations. While this has been attributed to iron-dependent citrate metabolizing enzymes, this straightforward relationship does not always hold true. Here, we show that an increase in citrate secretion under iron limited conditions is a physiological response consistent with a role of citrate as A. niger iron siderophore. We found that A. niger citrate secretion increases with decreasing amounts of iron added to the culture medium and, in contrast to previous findings, this response is independent of the nitrogen source. Differential transcriptomics analyses of the two A. niger mutants NW305 (gluconate non-producer) and NW186 (gluconate and oxalate non-producer) revealed up-regulation of the citrate biosynthesis gene citA under iron limited conditions compared to iron replete conditions. In addition, we show that A. niger can utilize Fe(III) citrate as iron source. Finally, we discuss our findings in the general context of the pH-dependency of A. niger organic acid production, offering an explanation, besides competition, for why A. niger organic acid production is a sequential process influenced by the external pH of the culture medium. PMID:28824560

MFehi adipose tissue macrophages compensate for tissue iron pertubations in mice.

Science.gov (United States)

Hubler, Merla J; Erikson, Keith M; Kennedy, Arion J; Hasty, Alyssa H

2018-05-16

Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess FFAs and regulation of extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only allows them to function as innate immune cells but also to respond to specific tissue needs, such as iron homeostasis. MFe hi ATMs are a subtype of resident ATMs that we recently identified to have twice the intracellular iron content as other ATMs and elevated expression of iron handling genes. While studies have demonstrated iron homeostasis is important for adipocyte health, little is known about how MFe hi ATMs may respond to and influence AT iron availability. Two methodologies were used to address this question - dietary iron supplementation and intraperitoneal iron injection. Upon exposure to high dietary iron, MFe hi ATMs accumulated excess iron, while the iron content of MFe lo ATMs and adipocytes remained unchanged. In this model of chronic iron excess, MFe hi ATMs exhibited increased expression of genes involved in iron storage. In the injection model, MFe hi ATMs incorporated high levels of iron and adipocytes were spared iron overload. This acute model of iron overload was associated with increased numbers of MFe hi ATMs; 17% could be attributed to monocyte recruitment and 83% to MFe lo ATM incorporation into the MFe hi pool. The MFe hi ATM population maintained its low inflammatory profile and iron cycling expression profile. These studies expand the field's understanding of ATMs and confirm that they can respond as a tissue iron sink in models of iron overload.

Changes in Serum Ferritin and Other Factors Associated with Iron Metabolism During Chronic Hyperbaric Exposure

National Research Council Canada - National Science Library

Gilman, Sara C; Hunter, Jr., W. L; Mooney, L. W

1979-01-01

.... during these simulated dives progressive and correlated increases in serum ferritin and iron occurred. No significant changes were observed in bilirubin, hemoglobin, neurloplasmia, transferrin, cooper, or total iron binding capacity...

Iron and genome stability: An update

International Nuclear Information System (INIS)

Prá, Daniel; Franke, Silvia Isabel Rech; Henriques, João Antonio Pêgas; Fenech, Michael

2012-01-01

Iron is an essential micronutrient which is required in a relatively narrow range for maintaining metabolic homeostasis and genome stability. Iron participates in oxygen transport and mitochondrial respiration as well as in antioxidant and nucleic acid metabolism. Iron deficiency impairs these biological pathways, leading to oxidative stress and possibly carcinogenesis. Iron overload has been linked to genome instability as well as to cancer risk increase, as seen in hereditary hemochromatosis. Iron is an extremely reactive transition metal that can interact with hydrogen peroxide to generate hydroxyl radicals that form the 8-hydroxy-guanine adduct, cause point mutations as well as DNA single and double strand breaks. Iron overload also induces DNA hypermethylation and can reduce telomere length. The current Recommended Dietary Allowances (RDA) for iron, according with Institute of Medicine Dietary Reference Intake (DRI), is based in the concept of preventing anemia, and ranges from 7 mg/day to 18 mg/day depending on life stage and gender. Pregnant women need 27 mg/day. The maximum safety level for iron intake, the Upper Level (UL), is 40–45 mg/day, based on the prevention of gastrointestinal distress associated to high iron intakes. Preliminary evidence indicates that 20 mg/day iron, an intake slightly higher than the RDA, may reduce the risk of gastrointestinal cancer in the elderly as well as increasing genome stability in lymphocytes of children and adolescents. Current dietary recommendations do not consider the concept of genome stability which is of concern because damage to the genome has been linked to the origin and progression of many diseases and is the most fundamental pathology. Given the importance of iron for homeostasis and its potential influence over genome stability and cancer it is recommended to conduct further studies that conclusively define these relationships.

Iron and genome stability: An update

Energy Technology Data Exchange (ETDEWEB)

Pra, Daniel, E-mail: daniel_pra@yahoo.com [PPG em Promocao da Saude, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS (Brazil); PPG em Saude e Comportamento, Universidade Catolica de Pelotas, Pelotas, RS (Brazil); Franke, Silvia Isabel Rech [PPG em Promocao da Saude, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS (Brazil); Henriques, Joao Antonio Pegas [Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS (Brazil); Fenech, Michael [CSIRO Food and Nutritional Sciences, Adelaide, SA (Australia)

2012-05-01

Iron is an essential micronutrient which is required in a relatively narrow range for maintaining metabolic homeostasis and genome stability. Iron participates in oxygen transport and mitochondrial respiration as well as in antioxidant and nucleic acid metabolism. Iron deficiency impairs these biological pathways, leading to oxidative stress and possibly carcinogenesis. Iron overload has been linked to genome instability as well as to cancer risk increase, as seen in hereditary hemochromatosis. Iron is an extremely reactive transition metal that can interact with hydrogen peroxide to generate hydroxyl radicals that form the 8-hydroxy-guanine adduct, cause point mutations as well as DNA single and double strand breaks. Iron overload also induces DNA hypermethylation and can reduce telomere length. The current Recommended Dietary Allowances (RDA) for iron, according with Institute of Medicine Dietary Reference Intake (DRI), is based in the concept of preventing anemia, and ranges from 7 mg/day to 18 mg/day depending on life stage and gender. Pregnant women need 27 mg/day. The maximum safety level for iron intake, the Upper Level (UL), is 40-45 mg/day, based on the prevention of gastrointestinal distress associated to high iron intakes. Preliminary evidence indicates that 20 mg/day iron, an intake slightly higher than the RDA, may reduce the risk of gastrointestinal cancer in the elderly as well as increasing genome stability in lymphocytes of children and adolescents. Current dietary recommendations do not consider the concept of genome stability which is of concern because damage to the genome has been linked to the origin and progression of many diseases and is the most fundamental pathology. Given the importance of iron for homeostasis and its potential influence over genome stability and cancer it is recommended to conduct further studies that conclusively define these relationships.

Plant cell nucleolus as a hot spot for iron.

Science.gov (United States)

Roschzttardtz, Hannetz; Grillet, Louis; Isaure, Marie-Pierre; Conéjéro, Geneviève; Ortega, Richard; Curie, Catherine; Mari, Stéphane

2011-08-12

Many central metabolic processes require iron as a cofactor and take place in specific subcellular compartments such as the mitochondrion or the chloroplast. Proper iron allocation in the different organelles is thus critical to maintain cell function and integrity. To study the dynamics of iron distribution in plant cells, we have sought to identify the different intracellular iron pools by combining three complementary imaging approaches, histochemistry, micro particle-induced x-ray emission, and synchrotron radiation micro X-ray fluorescence. Pea (Pisum sativum) embryo was used as a model in this study because of its large cell size and high iron content. Histochemical staining with ferrocyanide and diaminobenzidine (Perls/diaminobenzidine) strongly labeled a unique structure in each cell, which co-labeled with the DNA fluorescent stain DAPI, thus corresponding to the nucleus. The unexpected presence of iron in the nucleus was confirmed by elemental imaging using micro particle-induced x-ray emission. X-ray fluorescence on cryo-sectioned embryos further established that, quantitatively, the iron concentration found in the nucleus was higher than in the expected iron-rich organelles such as plastids or vacuoles. Moreover, within the nucleus, iron was particularly accumulated in a subcompartment that was identified as the nucleolus as it was shown to transiently disassemble during cell division. Taken together, our data uncover an as yet unidentified although abundant iron pool in the cell, which is located in the nuclei of healthy, actively dividing plant tissues. This result paves the way for the discovery of a novel cellular function for iron related to nucleus/nucleolus-associated processes.

HvZIP7 mediates zinc accumulation in barley (Hordeum vulgare) at moderately high zinc supply

DEFF Research Database (Denmark)

Tiong, Jingwen; Mcdonald, Glenn K.; Genc, Yusuf

2014-01-01

Summary: High expression of zinc (Zn)-regulated, iron-regulated transporter-like protein (ZIP) genes increases root Zn uptake in dicots, leading to high accumulation of Zn in shoots. However, none of the ZIP genes tested previously in monocots could enhance shoot Zn accumulation. In this report...... were also generated to further understand the functions of HvZIP7 in metal transport. HvZIP7 is strongly induced by Zn deficiency, primarily in vascular tissues of roots and leaves, and its protein was localized in the plasma membrane. These properties are similar to its closely related homologs...... in dicots. Overexpression of HvZIP7 in barley plants increased Zn uptake when moderately high concentrations of Zn were supplied. Significantly, there was a specific enhancement of shoot Zn accumulation, with no measurable increase in iron (Fe), manganese (Mn), copper (Cu) or cadmium (Cd). HvZIP7 displays...

Mechanisms of iron sensing and regulation in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Martínez-Pastor, María Teresa; Perea-García, Ana; Puig, Sergi

2017-04-01

Iron is a redox active element that functions as an essential cofactor in multiple metabolic pathways, including respiration, DNA synthesis and translation. While indispensable for eukaryotic life, excess iron can lead to oxidative damage of macromolecules. Therefore, living organisms have developed sophisticated strategies to optimally regulate iron acquisition, storage and utilization in response to fluctuations in environmental iron bioavailability. In the yeast Saccharomyces cerevisiae, transcription factors Aft1/Aft2 and Yap5 regulate iron metabolism in response to low and high iron levels, respectively. In addition to producing and assembling iron cofactors, mitochondrial iron-sulfur (Fe/S) cluster biogenesis has emerged as a central player in iron sensing. A mitochondrial signal derived from Fe/S synthesis is exported and converted into an Fe/S cluster that interacts directly with Aft1/Aft2 and Yap5 proteins to regulate their transcriptional function. Various conserved proteins, such as ABC mitochondrial transporter Atm1 and, for Aft1/Aft2, monothiol glutaredoxins Grx3 and Grx4 are implicated in this iron-signaling pathway. The analysis of a wide range of S. cerevisiae strains of different geographical origins and sources has shown that yeast strains adapted to high iron display growth defects under iron-deficient conditions, and highlighted connections that exist in the response to both opposite conditions. Changes in iron accumulation and gene expression profiles suggest differences in the regulation of iron homeostasis genes.

Responses of Saccharomyces cerevisiae Strains from Different Origins to Elevated Iron Concentrations

Science.gov (United States)

Martínez-Garay, Carlos Andrés; de Llanos, Rosa; Romero, Antonia María; Martínez-Pastor, María Teresa

2016-01-01

Iron is an essential micronutrient for all eukaryotic organisms. However, the low solubility of ferric iron has tremendously increased the prevalence of iron deficiency anemia, especially in women and children, with dramatic consequences. Baker's yeast Saccharomyces cerevisiae is used as a model eukaryotic organism, a fermentative microorganism, and a feed supplement. In this report, we explore the genetic diversity of 123 wild and domestic strains of S. cerevisiae isolated from different geographical origins and sources to characterize how yeast cells respond to elevated iron concentrations in the environment. By using two different forms of iron, we selected and characterized both iron-sensitive and iron-resistant yeast strains. We observed that when the iron concentration in the medium increases, iron-sensitive strains accumulate iron more rapidly than iron-resistant isolates. We observed that, consistent with excess iron leading to oxidative stress, the redox state of iron-sensitive strains was more oxidized than that of iron-resistant strains. Growth assays in the presence of different oxidative reagents ruled out that this phenotype was due to alterations in the general oxidative stress protection machinery. It was noteworthy that iron-resistant strains were more sensitive to iron deficiency conditions than iron-sensitive strains, which suggests that adaptation to either high or low iron is detrimental for the opposite condition. An initial gene expression analysis suggested that alterations in iron homeostasis genes could contribute to the different responses of distant iron-sensitive and iron-resistant yeast strains to elevated environmental iron levels. PMID:26773083

The effects of dietary iron concentration on gastrointestinal and branchial assimilation of both iron and cadmium in zebrafish (Danio rerio)

Energy Technology Data Exchange (ETDEWEB)

Cooper, C.A. [Division of Health and Life Sciences, King' s College London, 150 Stamford Street, London SE1 9NN (United Kingdom)]. E-mail: chris.cooper@ex.ac.uk; Handy, R.D. [School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA (United Kingdom); Bury, N.R. [Division of Health and Life Sciences, King' s College London, 150 Stamford Street, London SE1 9NN (United Kingdom)

2006-08-23

Zebrafish (Danio rerio) were fed either a diet containing 33 mg Fe kg{sup -1} (low) or 95 mg Fe kg{sup -1} (normal) for 10 weeks, after which short-term Cd and Fe uptake by the gastrointestinal tract and gill was assessed. Carcass metal content and transcript levels of the iron importer, Divalent Metal Transporter 1 (DMT1) and an iron exporter, ferroportin1, in both the gastrointestinal tract and gill were also measured. Fish fed the low Fe diet accumulated 13 times more Cd into their livers via the gastrointestinal tract than those fed the normal Fe diet. However, no significant increase in liver Fe accumulation was measured. Concomitantly, when exposed to 48 nmol Cd L{sup -1} fish fed the low Fe diet exhibited a {approx}4-fold increase in Cd accumulation on the gill and in the liver, compared to those fed a normal diet. In addition, fish fed the low Fe diet also significantly accumulated more Fe on the gill (nine-fold increase) and into the carcass (four-fold increase) when exposed to 96 nmol Fe L{sup -1}, compared to fish fed a normal diet. Surprisingly, carcass Fe, Ca and Mg concentrations were increased in fish fed the low Fe diet, which suggests that Fe body levels may not be a good indicator of whether a fish is more or less susceptible to increased non-essential metal accumulation via an Fe uptake pathway. However, significantly elevated transcript levels of DMT1 and ferroportin1 (2.7- and 3.8-fold induction, respectively) were seen in the gastrointestinal tract, and DMT1 in the gills (1.8-fold induction) of zebrafish fed a low Fe diet. The correlation between Cd uptake and DMT1 expression suggests that one route of uptake of Cd, either from the diet or from the water, could be via DMT1.

Performance Comparisons of Improved Regular Repeat Accumulate (RA and Irregular Repeat Accumulate (IRA Turbo Decoding

Directory of Open Access Journals (Sweden)

Ahmed Abdulkadhim Hamad

2017-08-01

Full Text Available In this paper, different techniques are used to improve the turbo decoding of regular repeat accumulate (RA and irregular repeat accumulate (IRA codes. The adaptive scaling of a-posteriori information produced by Soft-output Viterbi decoder (SOVA is proposed. The encoded pilots are another scheme that applied for short length RA codes. This work also suggests a simple and a fast method to generate a random interleaver having a free 4 cycle Tanner graph. Progressive edge growth algorithm (PEG is also studied and simulated to create the Tanner graphs which have a great girth.

Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron

Science.gov (United States)

Shen, Yi; Posavec, Lidija; Bolisetty, Sreenath; Hilty, Florentine M.; Nyström, Gustav; Kohlbrecher, Joachim; Hilbe, Monika; Rossi, Antonella; Baumgartner, Jeannine; Zimmermann, Michael B.; Mezzenga, Raffaele

2017-07-01

Iron-deficiency anaemia (IDA) is a major global public health problem. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods, but the most bioavailable fortificants cause adverse organoleptic changes in foods. Iron nanoparticles are a promising solution in food matrices, although their tendency to oxidize and rapidly aggregate in solution severely limits their use in fortification. Amyloid fibrils are protein aggregates initially known for their association with neurodegenerative disorders, but recently described in the context of biological functions in living organisms and emerging as unique biomaterial building blocks. Here, we show an original application for these protein fibrils as efficient carriers for iron fortification. We use biodegradable amyloid fibrils from β-lactoglobulin, an inexpensive milk protein with natural reducing effects, as anti-oxidizing nanocarriers and colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms a stable protein-iron colloidal dispersion that undergoes rapid dissolution and releases iron ions during acidic and enzymatic in vitro digestion. Importantly, this hybrid shows high in vivo iron bioavailability, equivalent to ferrous sulfate in haemoglobin-repletion and stable-isotope studies in rats, but with reduced organoleptic changes in foods. Feeding the rats with these hybrid materials did not result in abnormal iron accumulation in any organs, or changes in whole blood glutathione concentrations, inferring their primary safety. Therefore, these iron-amyloid fibril hybrids emerge as novel, highly effective delivery systems for iron in both solid and liquid matrices.

Iron Toxicity in the Retina Requires Alu RNA and the NLRP3 Inflammasome

Directory of Open Access Journals (Sweden)

Bradley D. Gelfand

2015-06-01

Full Text Available Excess iron induces tissue damage and is implicated in age-related macular degeneration (AMD. Iron toxicity is widely attributed to hydroxyl radical formation through Fenton’s reaction. We report that excess iron, but not other Fenton catalytic metals, induces activation of the NLRP3 inflammasome, a pathway also implicated in AMD. Additionally, iron-induced degeneration of the retinal pigmented epithelium (RPE is suppressed in mice lacking inflammasome components caspase-1/11 or Nlrp3 or by inhibition of caspase-1. Iron overload increases abundance of RNAs transcribed from short interspersed nuclear elements (SINEs: Alu RNAs and the rodent equivalent B1 and B2 RNAs, which are inflammasome agonists. Targeting Alu or B2 RNA prevents iron-induced inflammasome activation and RPE degeneration. Iron-induced SINE RNA accumulation is due to suppression of DICER1 via sequestration of the co-factor poly(C-binding protein 2 (PCBP2. These findings reveal an unexpected mechanism of iron toxicity, with implications for AMD and neurodegenerative diseases associated with excess iron.

Alleviation of iron toxicity in Schinus terebinthifolius Raddi (Anacardiaceae) by humic substances.

Science.gov (United States)

Dobbss, Leonardo Barros; Dos Santos, Tamires Cruz; Pittarello, Marco; de Souza, Sávio Bastos; Ramos, Alessandro Coutinho; Busato, Jader Galba

2018-04-01

One of the industrial pillars of Espírito Santo state, South East of Brazil, is iron-mining products processing. This activity brings to a high level of coastal pollution due to deposition of iron particulate on fragile ecosystems as mangroves and restinga. Schinus therebinthifolius (aroeira) is a widespread restinga species. This work tested iron toxicity alleviation by vermicompost humic substances (HS) added to aroeira seedlings in hydroponic conditions. Catalase, peroxidase, and ascorbate peroxidase are antioxidant enzymes that work as reactive oxygen species (ROS) scavengers: they increase their activity as an answer to ROS concentration rise that is the consequence of metal accumulation or humic substance stimulation. S. terebinthifolius seedlings treated with HS and Fe augmented their antioxidant enzyme activities significantly less than seedlings treated separately with HS and Fe; their significantly lower Fe accumulation and the slight increase of root and leaf area confirm the biostimulating effect of HS and their role in blocking Fe excess outside the roots. The use of HS can be useful for the recovery of areas contaminated by heavy metals.

The interplay between mitochondrial protein and iron homeostasis and its possible role in ageing.

Science.gov (United States)

Mallikarjun, Venkatesh; Sriram, Ashwin; Scialo, Filippo; Sanz, Alberto

2014-08-01

Free (labile or chelatable) iron is extremely redox-active and only represents a small fraction of the total mitochondrial iron population. Several studies have shown that the proportion of free iron increases with age, leading to increased Fenton chemistry in later life. It is not clear why free iron accumulates in mitochondria, but it does so in parallel with an inability to degrade and recycle damaged proteins that causes loss of mitochondrial protein homeostasis (proteostasis). The increase in oxidative damage that has been shown to occur with age might be explained by these two processes. While this accumulation of oxidative damage has often been cited as causative to ageing there are examples of model organisms that possess high levels of oxidative damage throughout their lives with no effect on lifespan. Interestingly, these same animals are characterised by an outstanding ability to maintain correct proteostasis during their entire life. ROS can damage critical components of the iron homeostasis machinery, while the efficacy of mitochondrial quality control mechanisms will determine how detrimental that damage is. Here we review the interplay between iron and organellar quality control in mitochondrial dysfunction and we suggest that a decline in mitochondrial proteostasis with age leaves iron homeostasis (where several key stages are thought to be dependent on proteostasis machinery) vulnerable to oxidative damage and other age-related stress factors. This will have severe consequences for the electron transport chain and TCA cycle (among other processes) where several components are acutely dependent on correct assembly, insertion and maintenance of iron-sulphur clusters, leading to energetic crisis and death. Copyright © 2014 Elsevier Inc. All rights reserved.

Acquisition and Homeostasis of Iron in Higher Plants and Their Probable Role in Abiotic Stress Tolerance

Directory of Open Access Journals (Sweden)

Durgesh K. Tripathi

2018-02-01

Full Text Available Iron (Fe is a micronutrient that plays an important role in agriculture worldwide because plants require a small amount of iron for its growth and development. All major functions in a plant's life from chlorophyll biosynthesis to energy transfer are performed by Fe (Brumbarova et al., 2008; Gill and Tuteja, 2011. Iron also acts as a major constituent of many plant proteins and enzymes. The acquisition of Fe in plants occurs through two strategies, i.e., strategy I and strategy II (Marschner and Römheld, 1994. Under various stress conditions, Nramp and the YSL gene families help in translocation of Fe, which further acts as a mineral regulatory element and defends plants against stresses. Iron plays an irreplaceable role in alleviating stress imposed by salinity, drought, and heavy metal stress. This is because it activates plant enzymatic antioxidants like catalase (CAT, peroxidase, and an isoform of superoxide dismutase (SOD that act as a scavenger of reactive oxygen species (ROS (Hellin et al., 1995. In addition to this, their deficiency as well as their excess amount can disturb the homeostasis of a plant's cell and result in declining of photosynthetic rate, respiration, and increased accumulation of Na+ and Ca− ions which culminate in an excessive formation of ROS. The short-range order hydrated Fe oxides and organic functional groups show affinities for metal ions. Iron plaque biofilm matrices could sequester a large amount of metals at the soil–root interface. Hence, it has attracted the attention of plant physiologists and agricultural scientists who are discovering more exciting and hidden applications of Fe and its potential in the development of bio-factories. This review looks into the recent progress made in putting forward the role of Fe in plant growth, development, and acclimation under major abiotic stresses, i.e., salinity, drought, and heavy metals.

Iron as a risk factor in neurological diseases

Science.gov (United States)

Galazka-Friedman, Jolanta

2008-02-01

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson’s and Alzheimer’s disease, and progressive supranuclear palsy. Our own studies with the use of Mössbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer’s disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson’s disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

Iron as a risk factor in neurological diseases

International Nuclear Information System (INIS)

Galazka-Friedman, Jolanta

2008-01-01

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson's and Alzheimer's disease, and progressive supranuclear palsy. Our own studies with the use of Moessbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer's disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson's disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

Co-precipitation of phosphate and iron limits mitochondrial phosphate availability in Saccharomyces cerevisiae lacking the yeast frataxin homologue (YFH1).

Science.gov (United States)

Seguin, Alexandra; Santos, Renata; Pain, Debkumar; Dancis, Andrew; Camadro, Jean-Michel; Lesuisse, Emmanuel

2011-02-25

Saccharomyces cerevisiae cells lacking the yeast frataxin homologue (Δyfh1) accumulate iron in the mitochondria in the form of nanoparticles of ferric phosphate. The phosphate content of Δyfh1 mitochondria was higher than that of wild-type mitochondria, but the proportion of mitochondrial phosphate that was soluble was much lower in Δyfh1 cells. The rates of phosphate and iron uptake in vitro by isolated mitochondria were higher for Δyfh1 than wild-type mitochondria, and a significant proportion of the phosphate and iron rapidly became insoluble in the mitochondrial matrix, suggesting co-precipitation of these species after oxidation of iron by oxygen. Increasing the amount of phosphate in the medium decreased the amount of iron accumulated by Δyfh1 cells and improved their growth in an iron-dependent manner, and this effect was mostly transcriptional. Overexpressing the major mitochondrial phosphate carrier, MIR1, slightly increased the concentration of soluble mitochondrial phosphate and significantly improved various mitochondrial functions (cytochromes, [Fe-S] clusters, and respiration) in Δyfh1 cells. We conclude that in Δyfh1 cells, soluble phosphate is limiting, due to its co-precipitation with iron.

Gold-coated iron nanoparticles in transparent Si3N4 matrix thin films

Science.gov (United States)

Sánchez-Marcos, J.; Céspedes, E.; Jiménez-Villacorta, F.; Muñoz-Martín, A.; Prieto, C.

2013-06-01

A new method to prepare thin films containing gold-coated iron nanoparticles is presented. The ternary Fe-Au-Si3N4 system prepared by sequential sputtering has revealed a progressive variation of microstructures from Au/Fe/Au/Si3N4 multilayers to iron nanoparticles. Microstructural characterization by transmission electron microscopy, analysis of the magnetic properties and probing of the iron short-range order by X-ray absorption spectroscopy confirm the existence of a gold-coated iron nanoparticles of 1-2 nm typical size for a specific range of iron and gold contents per layer in the transparent silicon nitride ceramic matrix.

Iron and stony-iron meteorites

DEFF Research Database (Denmark)

Ruzicka, Alex M.; Haack, Henning; Chabot, Nancy L.

2017-01-01

By far most of the melted and differentiated planetesimals that have been sampled as meteorites are metal-rich iron meteorites or stony iron meteorites. The parent asteroids of these meteorites accreted early and differentiated shortly after the solar system formed, producing some of the oldest...... and interpretations for iron and stony iron meteorites (Plate 13.1). Such meteorites provide important constraints on the nature of metal-silicate separation and mixing in planetesimals undergoing partial to complete differentiation. They include iron meteorites that formed by the solidification of cores...... (fractionally crystallized irons), irons in which partly molten metal and silicates of diverse types were mixed together (silicate-bearing irons), stony irons in which partly molten metal and olivine from cores and mantles were mixed together (pallasites), and stony irons in which partly molten metal...

SEALING LARGE-DIAMETER CAST-IRON PIPE JOINTS UNDER LIVE CONDITIONS

Energy Technology Data Exchange (ETDEWEB)

Kiran M. Kothari; Gerard T. Pittard

2005-04-01

robots for cast-iron pipe to assure their commercial success. For Task 4 (Design, Fabricate and Test Patch Setting Robotic Train), previous problems with bladder design and elastomeric material expansion in the large mains were addressed. A new bladder based on a commercially available design was obtained and tested with success. Minor improvements were highlighted during patch-setting tests and are now being pursued. For Task 5 (Design and Fabricate Pipe-Wall Cleaning Robot Train with Pan/Zoom/Tilt Camera), the previous field tests showed clearly that, in mains with low gas velocities, it will be necessary to improve the system's capacity to remove debris from the immediate vicinity of the bell and spigot joints. Otherwise, material removed by the cleaning flails (the flails were found to be very effective in cleaning bell and spigot joints) falls directly to the low side of the pipe and accumulates in a pile. This accumulation can prevent the sleeve from achieving a leak-free repair. Similarly, it is also deemed necessary to design an assembly to capture existing servicetap coupons and allow their removal from the inside of the pipe. Task 6 (Design and Build Surface Control and Monitoring System) was previously completed with the control and computer display functions being operated through LabVIEW. However, this must now be revisited to add control routines for the coupon catcher that will be added. This will most likely include a lift-off/place-on magnet translation function. Task 7 (Design and Fabricate Large Diameter Live Access System) progressed to completing the detailed design for a bolt-on entry fitting for 12-inch diameter cast-iron pipe in the current quarter. The drilling assembly for cutting an access hole through the wall of the gas main was also designed, along with a plug assembly to allow removing all tools from the live main and setting a blind flange on the entry fitting prior to burial. These designs are described in detail in the report. Task

Modulation of iron metabolism in aging and in Alzheimer’s disease: relevance of the choroid plexus.

Directory of Open Access Journals (Sweden)

Sandro Da Mesquita

2012-05-01

Full Text Available Iron is essential for mammalian cellular homeostasis. However, in excess, it promotes free radical formation and is associated with aging-related progressive deterioration and with neurodegenerative disorders such as Alzheimer’s disease (AD. There are no mechanisms to excrete iron, which makes iron homeostasis a very tightly regulated process at the level of the intestinal absorption. Iron is believed to reach the brain through receptor mediated endocytosis of iron-bound transferrin by the brain barriers, the blood-cerebrospinal (CSF fluid barrier, formed by the choroid plexus (CP epithelial cells and the blood-brain barrier formed by the endothelial cells of the brain capillaries. Importantly, the CP epithelial cells are responsible for producing most of the CSF, the fluid that fills the brain ventricles and the subarachnoid space. Recently, the finding that the CP epithelial cells display all the machinery to locally control iron delivery into the CSF may suggest that the general and progressive senescence of the CP may be at the basis of the impairment of regional iron metabolism, iron-mediated toxicity and the increase in inflammation and oxidative stress that occurs with aging and, particularly, in AD.

Deactivation by carbon of iron catalysts for indirect liquefaction

Energy Technology Data Exchange (ETDEWEB)

Bartholomew, C.H.

1990-10-11

This report describes recent progress in a fundamental, three-year investigation of carbon formation and its effects on the activity and selectivity of promoted iron catalysts for Fischer-Tropsch (FT) synthesis, the objectives of which are: determine rates and mechanisms of carbon deactivation of unsupported Fe and Fe/K catalysts during CO hydrogenation over a range of CO concentrations, CO:H{sub 2} ratios, and temperatures; model the rates of deactivation of the same catalysts in fixed-bed reactors. During the thirteenth quarter design of software for a computer-automated reactor system to be used in the kinetic and deactivation studies was continued. Further progress was made toward the completion of the control language, control routines, and software for operating this system. Progress was also made on the testing of the system hardware and software. H{sub 2} chemisorption capacities and activity selectivity data were also measured for three iron catalysts promoted with 1% alumina. 47 refs., 8 figs., 1 tab.

HFE gene variants, iron, and lipids: a novel connection in Alzheimer’s disease

Science.gov (United States)

Ali-Rahmani, Fatima; Schengrund, Cara-Lynne; Connor, James R.

2014-01-01

Iron accumulation and associated oxidative stress in the brain have been consistently found in several neurodegenerative diseases. Multiple genetic studies have been undertaken to try to identify a cause of neurodegenerative diseases but direct connections have been rare. In the iron field, variants in the HFE gene that give rise to a protein involved in cellular iron regulation, are associated with iron accumulation in multiple organs including the brain. There is also substantial epidemiological, genetic, and molecular evidence of disruption of cholesterol homeostasis in several neurodegenerative diseases, in particular Alzheimer’s disease (AD). Despite the efforts that have been made to identify factors that can trigger the pathological events associated with neurodegenerative diseases they remain mostly unknown. Because molecular phenotypes such as oxidative stress, synaptic failure, neuronal loss, and cognitive decline, characteristics associated with AD, have been shown to result from disruption of a number of pathways, one can easily argue that the phenotype seen may not arise from a linear sequence of events. Therefore, a multi-targeted approach is needed to understand a complex disorder like AD. This can be achieved only when knowledge about interactions between the different pathways and the potential influence of environmental factors on them becomes available. Toward this end, this review discusses what is known about the roles and interactions of iron and cholesterol in neurodegenerative diseases. It highlights the effects of gene variants of HFE (H63D- and C282Y-HFE) on iron and cholesterol metabolism and how they may contribute to understanding the etiology of complex neurodegenerative diseases. PMID:25071582

The effect of the administration of iron on Ga-67 uptake in animal tumor and biodistribution

International Nuclear Information System (INIS)

Furukawa, Keiji

1983-01-01

In 1979 Larson reported that the uptake of Ga-67 in tumor cell was preceded by binding of the Ga-67 to transferrin. Since that time there have been many papers concerning changes in Ga-67 accumulation in experimental tumor by administration of iron before and after Ga-67 injection. This study was undertaken in the attempt to discern what changes are produced in Ga-67 images of tumor-bearing rabbits (VX-II) when iron was administered before and after Ga-67 injection. Additionally, the relationships between the change in the serum iron concentration in the tumor tissue in mice bearing Ehrlich's ascites tumor were studied. The following results were obtained. 1) The tumor uptake and biodistribution of Ga-67 following administration of iron in the form of Fesin (saccharated ferric oxide) or ferric-citrate is obviously diminished. This iron administration leads to an elevated excretion of Ga-67 from tumor and other organs except from bone. From this results, it was found that Ga-67 binds somewhat less avidity than iron to various iron transport protein. Accordingly, Ga-67 biodistribution may be markedly influenced by iron-loading. 2) The Ga-67 activity in blood following administration of iron was noted to suddenly markedly decrease. However, 24-48 hours after iron injection the Ga-67 activity in blood gradually increased. This result suggests that the Ga-67 displaced into the extravascular space by iron-loading reentered the vascular space when the iron concentration of serum returned to normal. 3) The accumulation of Ga-67 in the tumor and soft tissues was slightly decreased compared with controls after iron administration. However, the tumor to blood ratio (T/B) of Ga-67 in mice by iron loading was several time greater than that of Ga-67 alone because the clearance of Ga-67 from the blood was more accelated than that of tumor. The large tumor to blood ratio (T/B) would be advantageous in obtaining a more distinct tumor scan. (author)

Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications.

Science.gov (United States)

Regenboog, Martine; van Kuilenburg, André B P; Verheij, Joanne; Swinkels, Dorine W; Hollak, Carla E M

2016-11-01

Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

A role for sex and a common HFE gene variant in brain iron uptake.

Science.gov (United States)

Duck, Kari A; Neely, Elizabeth B; Simpson, Ian A; Connor, James R

2018-03-01

HFE (high iron) is an essential protein for regulating iron transport into cells. Mutations of the HFE gene result in loss of this regulation causing accumulation of iron within the cell. The mutated protein has been found increasingly in numerous neurodegenerative disorders in which increased levels of iron in the brain are reported. Additionally, evidence that these mutations are associated with elevated brain iron challenges the paradigm that the brain is protected by the blood-brain barrier. While much has been studied regarding the role of HFE in cellular iron uptake, it has remained unclear what role the protein plays in the transport of iron into the brain. We investigated regulation of iron transport into the brain using a mouse model with a mutation in the HFE gene. We demonstrated that the rate of radiolabeled iron ( 59 Fe) uptake was similar between the two genotypes despite higher brain iron concentrations in the mutant. However, there were significant differences in iron uptake between males and females regardless of genotype. These data indicate that brain iron status is consistently maintained and tightly regulated at the level of the blood-brain barrier.

Sulfur Cycling in an Iron Oxide-Dominated, Dynamic Marine Depositional System: The Argentine Continental Margin

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Natascha Riedinger

2017-05-01

Full Text Available The interplay between sediment deposition patterns, organic matter type and the quantity and quality of reactive mineral phases determines the accumulation, speciation, and isotope composition of pore water and solid phase sulfur constituents in marine sediments. Here, we present the sulfur geochemistry of siliciclastic sediments from two sites along the Argentine continental slope—a system characterized by dynamic deposition and reworking, which result in non-steady state conditions. The two investigated sites have different depositional histories but have in common that reactive iron phases are abundant and that organic matter is refractory—conditions that result in low organoclastic sulfate reduction rates (SRR. Deposition of reworked, isotopically light pyrite and sulfurized organic matter appear to be important contributors to the sulfur inventory, with only minor addition of pyrite from organoclastic sulfate reduction above the sulfate-methane transition (SMT. Pore-water sulfide is limited to a narrow zone at the SMT. The core of that zone is dominated by pyrite accumulation. Iron monosulfide and elemental sulfur accumulate above and below this zone. Iron monosulfide precipitation is driven by the reaction of low amounts of hydrogen sulfide with ferrous iron and is in competition with the oxidation of sulfide by iron (oxyhydroxides to form elemental sulfur. The intervals marked by precipitation of intermediate sulfur phases at the margin of the zone with free sulfide are bordered by two distinct peaks in total organic sulfur (TOS. Organic matter sulfurization appears to precede pyrite formation in the iron-dominated margins of the sulfide zone, potentially linked to the presence of polysulfides formed by reaction between dissolved sulfide and elemental sulfur. Thus, SMTs can be hotspots for organic matter sulfurization in sulfide-limited, reactive iron-rich marine sedimentary systems. Furthermore, existence of elemental sulfur and iron

Iron overload and HFE gene mutations in Polish patients with liver cirrhosis.

Science.gov (United States)

Sikorska, Katarzyna; Romanowski, Tomasz; Stalke, Piotr; Iżycka-Świeszewska, Ewa; Bielawski, Krzysztof Piotr

2011-06-01

Increased liver iron stores may contribute to the progression of liver injury and fibrosis, and are associated with a higher risk of hepatocellular carcinoma development. Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients. HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins. This study was designed to determine the prevalence of iron overload in relation to HFE gene mutations among Polish patients with liver cirrhosis. Sixty-one patients with liver cirrhosis included in the study were compared with a control group of 42 consecutive patients subjected to liver biopsy because of chronic liver diseases. Liver function tests and serum iron markers were assessed in both groups. All patients were screened for HFE mutations (C282Y, H63D, S65C). Thirty-six of 61 patients from the study group and all controls had liver biopsy performed with semiquantitative assessment of iron deposits in hepatocytes. The biochemical markers of iron overload and iron deposits in the liver were detected with a higher frequency (70% and 47% respectively) in patients with liver cirrhosis. There were no differences in the prevalence of all HFE mutations in both groups. In patients with a diagnosis of hepatocellular carcinoma, no significant associations with iron disorders and HFE gene mutations were found. Iron disorders were detected in patients with liver cirrhosis frequently but without significant association with HFE gene mutations. Only the homozygous C282Y mutation seems to occur more frequently in the selected population of patients with liver cirrhosis. As elevated biochemical iron indices accompanied liver iron deposits more frequently in liver cirrhosis compared to controls with chronic liver disease, there is a need for more extensive studies searching for

Effect of progressive water deficit stress on proline accumulation and ...

African Journals Online (AJOL)

Water deficit stress is one of the important factors limiting chickpea production in arid and semi-arid regions of West Asia and North Africa. When water deficit stress is imposed, different molecular and biochemical responses take place. This study was carried out to investigate proline accumulation and protein profiles of ...

Lactobacillus Decelerates Cervical Epithelial Cell Cycle Progression

Science.gov (United States)

Vielfort, Katarina; Weyler, Linda; Söderholm, Niklas; Engelbrecht, Mattias; Löfmark, Sonja; Aro, Helena

2013-01-01

We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells. PMID:23675492

Lactobacillus decelerates cervical epithelial cell cycle progression.

Directory of Open Access Journals (Sweden)

Katarina Vielfort

Full Text Available We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells.

Update on the use of deferasirox in the management of iron overload

Directory of Open Access Journals (Sweden)

Ali Taher

2009-10-01

Full Text Available Ali Taher,1 Maria Domenica Cappellini21American University of Beirut, Beirut, Lebanon; 2Universitá di Milano, Policlinico Foundation IRCCS, Milan, ItalyAbstract: Regular blood transfusions as supportive care for patients with chronic anemia inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload cause significant morbidity and mortality if not effectively treated with chelation therapy. Based on a comprehensive clinical development program, the once-daily, oral iron chelator deferasirox (Exjade® is approved for the treatment of transfusional iron overload in adult and pediatric patients with various transfusion-dependent anemias, including β-thalassemia and the myelodysplastic syndromes. Deferasirox dose should be titrated for each individual patient based on transfusional iron intake, current iron burden and whether the goal is to decrease or maintain body iron levels. Doses of >30 mg/kg/day have been shown to be effective with a safety profile consistent with that observed at doses <30 mg/kg/day. Recent data have highlighted the ability of deferasirox to decrease cardiac iron levels and to prevent the accumulation of iron in the heart. The long-term efficacy and safety of deferasirox for up to 5 years of treatment have now been established. The availability of this effective and generally well tolerated oral therapy represents a significant advance in the management of transfusional iron overload. Keywords: deferasirox, Exjade, oral, iron chelation, iron overload, cardiac iron 

R2* mapping for brain iron: associations with cognition in normal aging.

Science.gov (United States)

Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

2015-02-01

Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined. Copyright © 2015 Elsevier Inc. All rights reserved.

Applications of biocatalysis in fragrance chemistry: the enantiomers of alpha-, beta-, and gamma-irones.

Science.gov (United States)

Brenna, Elisabetta; Fuganti, Claudio; Serra, Stefano

2008-11-01

The history of iris extracts, and of the isolation and enzyme-mediated synthesis of their odoriferous principle, the "irones", will be used to describe the improvement brought about by chemistry and biocatalysis in the development of natural fragrances. In particular, this tutorial review will discuss how the progress in the field of enzyme chemistry allowed the optimisation of accelerated procedures for the preparation of natural irone extracts, and the synthesis of all the ten isomers of irone, starting from commercial irone alpha.

Role of Serum Iron in the Activation of Lipid Peroxidation in Critical Conditions

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Yu. P. Orlov

2006-01-01

Full Text Available Twenty-four critically ill patients due to generalized purulent peritonitis, pancreatonecrosis, thermal skin injuries, and severe poisoning by acetic acid were examined. The general regularities of the effect of high serum iron concentrations on the health status of patients, on the activity of antioxidative enzymes, and on the initiation of lipid peroxidation (LPO processes, as supported by the values of Fe2+-induced chemiluminescence, were revealed. In critically ill patients, iron metabolism occurs with the overload of a transport protein, such as transferrin, which is caused by intravascular hemolysis and hemoglobin metabolism to ionized iron. The overload of proteins responsible for iron transport leads to the tissue accumulation of free (ferrous and ferric iron that is actively involved in the processes of LPO initiation with excess synthesis of cytotoxic radicals, which in turn accounts for the severity of endotoxicosis.

Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review

Directory of Open Access Journals (Sweden)

Caro J

2002-11-01

Full Text Available Abstract Background Beta thalassemia major requires regular blood transfusions and iron chelation to alleviate the harmful accumulation of iron. Evidence on the efficacy and safety of the available agents, desferrioxamine and deferiprone, is derived from small, non-comparative, heterogeneous observational studies. This evidence was reviewed to quantitatively compare the ability of these chelators to reduce hepatic iron. Methods The literature was searched using Medline and all reports addressing the effect of either chelator on hepatic iron were considered. Data were abstracted independently by two investigators. Analyses were performed using reported individual patient data. Hepatic iron concentrations at study end and changes over time were compared using ANCOVA, controlling for initial iron load. Differences in the proportions of patients improving were tested using χ2. Results Eight of 11 reports identified provided patient-level data relating to 30 desferrioxamine- and 68 deferiprone-treated patients. Desferrioxamine was more likely than optimal dose deferiprone to decrease hepatic iron over the average follow-up of 45 months (odds ratio, 19.0, 95% CI, 2.4 to 151.4. The degree of improvement was also larger with desferrioxamine. Conclusions This analysis suggests that desferrioxamine is more effective than deferiprone in lowering hepatic iron. This comparative analysis – despite its limitations – should prove beneficial to physicians faced with the challenge of selecting the optimal treatment for their patients.

Duodenal Cytochrome b (DCYTB in Iron Metabolism: An Update on Function and Regulation

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Darius J. R. Lane

2015-03-01

Full Text Available Iron and ascorbate are vital cellular constituents in mammalian systems. The bulk-requirement for iron is during erythropoiesis leading to the generation of hemoglobin-containing erythrocytes. Additionally; both iron and ascorbate are required as co-factors in numerous metabolic reactions. Iron homeostasis is controlled at the level of uptake; rather than excretion. Accumulating evidence strongly suggests that in addition to the known ability of dietary ascorbate to enhance non-heme iron absorption in the gut; ascorbate regulates iron homeostasis. The involvement of ascorbate in dietary iron absorption extends beyond the direct chemical reduction of non-heme iron by dietary ascorbate. Among other activities; intra-enterocyte ascorbate appears to be involved in the provision of electrons to a family of trans-membrane redox enzymes; namely those of the cytochrome b561 class. These hemoproteins oxidize a pool of ascorbate on one side of the membrane in order to reduce an electron acceptor (e.g., non-heme iron on the opposite side of the membrane. One member of this family; duodenal cytochrome b (DCYTB; may play an important role in ascorbate-dependent reduction of non-heme iron in the gut prior to uptake by ferrous-iron transporters. This review discusses the emerging relationship between cellular iron homeostasis; the emergent “IRP1-HIF2α axis”; DCYTB and ascorbate in relation to iron metabolism.

Simultaneous alleviation of cadmium and arsenic accumulation in rice by applying zero-valent iron and biochar to contaminated paddy soils.

Science.gov (United States)

Qiao, Jiang-Tao; Liu, Tong-Xu; Wang, Xiang-Qin; Li, Fang-Bai; Lv, Ya-Hui; Cui, Jiang-Hu; Zeng, Xiao-Duo; Yuan, Yu-Zhen; Liu, Chuan-Ping

2018-03-01

The fates of cadmium (Cd) and arsenic (As) in paddy fields are generally opposite; thus, the inconsistent transformation of Cd and As poses large challenges for their remediation. In this study, the impacts of zero valent iron (ZVI) and/or biochar amendments on Cd and As bioavailability were examined in pot trials with rice. Comparison with the untreated soil, both Cd and As accumulation in different rice tissues decreased significantly in the ZVI-biochar amendments and the Cd and As accumulation in rice decreased with increasing ZVI contents. In particular, the concentrations of Cd (0.15 ± 0.01 mg kg -1 ) and As (0.17 ± 0.01 mg kg -1 ) in rice grains were decreased by 93% and 61% relative to the untreated soil, respectively. A sequential extraction analysis indicated that with increasing Fe ratios in the ZVI-biochar mixtures, bioavailable Cd and As decreased, and the immobilized Cd and As increased. Furthermore, high levels of Fe, Cd, and As were detected in Fe plaque of the ZVI-biochar amendments in comparison with the single biochar or single ZVI amendments. The ZVI-biochar mixture may have a synergistic effect that simultaneously reduces Cd and As bioavailability by increasing the formation of amorphous Fe and Fe plaque for Cd and As immobilization. The single ZVI amendment significantly decreased As bioavailability, while the single biochar amendment significantly reduced the bioavailability of Cd compared with the combined amendments. Hence, using a ZVI-biochar mixture as a soil amendment could be a promising strategy for safely-utilizing Cd and As co-contaminated sites in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increasing Provasculature Complexity in the Arabidopsis Embryo May Increase Total Iron Content in Seeds: A Hypothesis

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Hannetz Roschzttardtz

2017-06-01

Full Text Available Anemia due to iron deficiency is a worldwide issue, affecting mainly children and women. Seed iron is a major source of this micronutrient for feeding, however, in most crops these levels are too low to meet daily needs. Thus, increasing iron allocation and its storage in seeds can represent an important step to enhance iron provision for humans and animals. Our knowledge on seed iron homeostasis is mainly based on studies performed in the model plant Arabidopsis thaliana, where iron accumulates in endodermis cells surrounding the embryo provasculature. It has been reported that cotyledon provasculature pattern complexity can be modified, thus we hypothesize that changes in the complexity of embryo vein patterns may affect total iron content in Arabidopsis seeds. This approach could be used as basis to develop strategies aimed to biofortify seeds.

SEALING LARGE-DIAMETER CAST-IRON PIPE JOINTS UNDER LIVE CONDITIONS

Energy Technology Data Exchange (ETDEWEB)

Kiran M. Kothari; Gerard T. Pittard

2005-01-01

-diameter repair robots for cast-iron pipe to assure their commercial success. For Task 4 (Design, Fabricate and Test Patch Setting Robotic Train), work has been directed on increasing the nitrogen bladder reservoir volume to allow at least two complete patch inflation/patch setting cycles in the event the sleeve does not set all ratchets in the same row on the first attempt. This problem was observed on a few of the repair sleeves that were recently installed during field tests with the small-diameter robotic system. For Task 5 (Design & Fabricate Pipe-Wall Cleaning Robot Train with Pan/Zoom/Tilt Camera), the recent field tests showed clearly that, in mains with low gas velocities, it will be necessary to improve the system's capacity to remove debris from the immediate vicinity of the bell and spigot joints. Otherwise, material removed by the cleaning flails (the flails were found to be very effective in cleaning bell and spigot joints) falls directly to the low side of the pipe and accumulates in a pile. This accumulation can prevent the sleeve from achieving a leak-free repair. Similarly, it is also deemed necessary to design an assembly to capture existing service-tap coupons and allow their removal from the inside of the pipe. These coupons were found to cause difficulty in launching and retrieving the small pipe repair robot; for example, one coupon lodged beneath the end of the guide shoe. Designs for new features to accomplish these goals for the large robotic system were pursued and are presented in this report. Task 6 (Design & Build Surface Control and Monitoring System) was previously completed with the control and computer display functions being operated through LabVIEW. However, this must now be revisited to add control routines for the coupon catcher to be added. This will most likely include a lift-off/place-on magnet translation function. Task 7 (Design & Fabricate Large Diameter Live Access System) progressed to completing the detailed design of the entry

Acetate, lactate, propionate, and isobutyrate as electron donors for iron and sulfate reduction in Arctic marine sediments, Svalbard

DEFF Research Database (Denmark)

Finke, Niko; Vandieken, Verona; Jørgensen, Bo Barker

2007-01-01

The contribution of volatile fatty acids (VFA) as e--donors for anaerobic terminal oxidation of organic carbon through iron and sulfate reduction was studied in Arctic fjord sediment. Dissolved inorganic carbon, Fe2+, VFA concentrations, and sulfate reduction were monitored in slurries from...... by alternative e--donors. The accumulation of VFA in the selenate-inhibited 0-2 cm slurry did not enhance iron reduction, indicating that iron reducers were not limited by VFA availability....

Prion Protein Regulates Iron Transport by Functioning as a Ferrireductase

Science.gov (United States)

Singh, Ajay; Haldar, Swati; Horback, Katharine; Tom, Cynthia; Zhou, Lan; Meyerson, Howard; Singh, Neena

2017-01-01

Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal function is unclear. We demonstrate that PrPC is a ferrireductase (FR), and its absence causes systemic iron deficiency in PrP knock-out mice (PrP−/−). When exposed to non-transferrin-bound (NTB) radioactive-iron (59FeCl3) by gastric-gavage, PrP−/− mice absorb significantly more 59Fe from the intestinal lumen relative to controls, indicating appropriate systemic response to the iron deficiency. Chronic exposure to excess dietary iron corrects this deficiency, but unlike wild-type (PrP+/+) controls that remain iron over-loaded, PrP−/− mice revert back to the iron deficient phenotype after 5 months of chase on normal diet. Bone marrow (BM) preparations of PrP−/− mice on normal diet show relatively less stainable iron, and this phenotype is only partially corrected by intraperitoneal administration of excess iron-dextran. Cultured PrP−/− BM-macrophages incorporate significantly less NTB-59Fe in the absence or presence of excess extracellular iron, indicating reduced uptake and/or storage of available iron in the absence of PrPC. When expressed in neuroblastoma cells, PrPC exhibits NAD(P)H-dependent cell-surface and intracellular FR activity that requires the copper-binding octa-peptide-repeat region and linkage to the plasma membrane for optimal function. Incorporation of NTB-59Fe by neuroblastoma cells correlates with FR activity of PrPC, implicating PrPC in cellular iron uptake and metabolism. These observations explain the correlation between PrPC expression and cellular iron levels, and the cause of iron imbalance in sporadic-Creutzfeldt-Jakob-disease brains where PrPC accumulates as insoluble aggregates. PMID:23478311

Lithium Iron Orthosilicate Cathode: Progress and Perspectives

Energy Technology Data Exchange (ETDEWEB)

Ni, Jiangfeng [College; amp, Physics (CECMP), Soochow University, Suzhou 215006, PR China; Jiang, Yu [College; amp, Physics (CECMP), Soochow University, Suzhou 215006, PR China; Bi, Xuanxuan [Chemical; Li, Liang [College; amp, Physics (CECMP), Soochow University, Suzhou 215006, PR China; Lu, Jun [Chemical

2017-07-18

The pursuit of cathodes with a high capacity is remarkably driven by the ever increasing demand of high-energy lithium ion batteries in electronics and transportation. In this regard, polyanionic lithium iron orthosilicate (Li2FeSiO4) offers a promising opportunity because it affords a high theoretical capacity of 331 mAh g–1. However, such a high theoretical capacity of Li2FeSiO4 has frequently been compromised in practice because of the extremely low electronic and ionic conductivity. To address this issue, material engineering strategies to boost the Li storage kinetics in Li2FeSiO4 have proven indispensable. In this Perspective, we will briefly present the structural characteristics, intrinsic physicochemical properties, and electrochemical behavior of Li2FeSiO4. We particularly focus on recent materials engineering of silicates, which is implemented mainly through advanced synthetic techniques and elaborate controls. This Perspective highlights the importance of integrating theoretical analysis into experimental implementation to further advance the Li2FeSiO4 materials.

The effect of iron plaque on uptake and translocation of norfloxacin in rice seedlings grown in paddy soil.

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Yan, Dafang; Ma, Wei; Song, Xiaojing; Bao, Yanyu

2017-03-01

Although the role of iron plaque on rice root surface has been investigated in recent years, its effect on antibiotic uptake remains uncertain. In the study, pot experiment was conducted to investigate the effect of iron plaque on uptake and translocation of norfloxacin (adding 10 and 50 mg·kg -1 treatments) in rice seedlings grown in paddy soil. Iron plaque was induced by adding different amounts of Fe(II) in soil. The results showed that the presence of norfloxacin can decrease the amount of iron plaque induced. After rice with iron plaque induced, norfloxacin was mainly accumulated in iron plaque on root surface, followed by inside root, but its translocation from root to other rice tissues is not observed. Iron plaque played the role of a barrier for norfloxacin uptake into rice roots under high norfloxacin concentration of 50 mg·kg -1 , however not that under low concentration of 10 mg·kg -1 . And the barrier function was the most strongest with adding Fe(II) of 30 mg·kg -1 as combined action of iron plaque and rhizosphere effect. Fluorescence microscope analysis showed that norfloxacin mainly distributed in the outside of root cell, which showed its translocation as apoplastic pathway in rice. Comparing with non-rhizosphere, more norfloxacin was accumulated in rhizosphere soil. Maybe, strong root oxidization (high Eh values) induced more iron oxide formation in rhizosphere and on root surface, which led to norfloxacin's mobility towards to rhizosphere through its strong adsorption of iron oxides and then promoted its uptake by rice on root surface.

Liver iron overloading in captive muriquis (Brachyteles spp.).

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Santos, Stéfanie V; Strefezzi, Ricardo De F; Pissinatti, Alcides; Catão-Dias, José L

2011-04-01

Iron accumulation was investigated qualitatively and quantitatively in the liver of 15 captive Brachyteles spp. Hepatic hemosiderosis index (HHI) was determined as the area percentage of the liver parenchyma occupied by hemosiderin and ferritin deposits, through computerized histomorphometric analysis of Prussian blue-stained histologic sections. All studied animals presented liver hemosiderosis, and HHI ranged from 0.2% to 41.7%. There were no significant differences in HHI between muriqui species or genders, and no correlations were detected among HHI and age, time in captivity or body mass. Iron deposits were accompanied by other hepatic disorders. This is the first study addressing the occurrence and consequences of iron overloading in the liver of muriquis. We propose that hemosiderosis may act as a contribute factor for the development of hepatic injuries. Further studies are advised to clarify the role of diet in the pathogenesis of hemosiderosis in these atelids. © 2010 John Wiley & Sons A/S.

Laboratory assessment of iron status in pregnancy.

LENUS (Irish Health Repository)

Walsh, Thomas

2012-02-01

BACKGROUND: Efforts to improve maternal nutrition during pregnancy prompted an observational study of the occurrence of maternal iron deficiency and its laboratory diagnosis in almost 500 pregnancies. METHODS: In this longitudinal study, the biochemical and haematological iron indices of women (n=492) attending a prenatal clinic in a Dublin maternity hospital were assessed at first booking (mean 15.9 weeks), and after 24 weeks, and 36 weeks of gestation. Full blood counts were measured. Serum ferritin (SF), zinc protoporphyrin (ZPP), and transferrin receptor (sTfR) concentrations were assayed and transferrin receptor index (sTfR-Index) was calculated. The occurrence of low values and their diagnostic values were considered. RESULTS: A high occurrence iron deficiency (ID) at first booking (SF<12 mug\\/L) had increased over six-fold by 24 weeks, and all biochemical iron indices reflected progressive iron depletion right up to term. The WHO recommended anaemia "cut-off" (Hb<110 g\\/L) was insensitive to biochemical iron deficiency at booking, missing over 90% of the low SF values (SF<12 mug\\/L) which were mostly associated with much higher Hb levels. CONCLUSIONS: This study stresses the importance of including a biochemical index of iron status in prenatal screening and supports SF as the best indicator of biochemical ID overall. sTfR was insensitive to iron deficiency in early pregnancy, whereas the sTfR-Index, as a ratio, has the potential to distinguish between ID and physiological anaemia, and may offer stability in the assessment of iron stores from early pregnancy to full term. A policy of early screening of both Hb and SF concentrations is recommended as the minimum requirement for surveillance of maternal iron status in pregnancy.

Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells : Influence of L-Carnosine

NARCIS (Netherlands)

Zhang, Shiqi; Ntasis, Emmanouil; Kabtni, Sarah; van den Born, Jaap; Navis, Gerjan; Bakker, Stephan J. L.; Kraemer, Bernhard K.; Yard, Benito A.; Hauske, Sibylle J.

2016-01-01

Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is

MicroRNAs and liver cancer associated with iron overload: Therapeutic targets unravelled

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Greene, Catherine M; Varley, Robert B; Lawless, Matthew W

2013-01-01

Primary liver cancer is a global disease that is on the increase. Hepatocellular carcinoma (HCC) accounts for most primary liver cancers and has a notably low survival rate, largely attributable to late diagnosis, resistance to treatment, tumour recurrence and metastasis. MicroRNAs (miRNAs/miRs) are regulatory RNAs that modulate protein synthesis. miRNAs are involved in several biological and pathological processes including the development and progression of HCC. Given the poor outcomes with current HCC treatments, miRNAs represent an important new target for therapeutic intervention. Several studies have demonstrated their role in HCC development and progression. While many risk factors underlie the development of HCC, one process commonly altered is iron homeostasis. Iron overload occurs in several liver diseases associated with the development of HCC including Hepatitis C infection and the importance of miRNAs in iron homeostasis and hepatic iron overload is well characterised. Aberrant miRNA expression in hepatic fibrosis and injury response have been reported, as have dysregulated miRNA expression patterns affecting cell cycle progression, evasion of apoptosis, invasion and metastasis. In 2009, miR-26a delivery was shown to prevent HCC progression, highlighting its therapeutic potential. Several studies have since investigated the clinical potential of other miRNAs with one drug, Miravirsen, currently in phase II clinical trials. miRNAs also have potential as biomarkers for the diagnosis of HCC and to evaluate treatment efficacy. Ongoing studies and clinical trials suggest miRNA-based treatments and diagnostic methods will have novel clinical applications for HCC in the coming years, yielding improved HCC survival rates and patient outcomes. PMID:23983424

Innocuous oil as an additive for reductive reactions involving zero valence iron

International Nuclear Information System (INIS)

Cary, J.W.; Cantrell, K.J.

1994-11-01

Reductive reactions involving zero valence iron appear to hold promise for in situ remediation of sites containing chlorinated hydrocarbon solvents and certain reducible metals and radionuclides. Treatment involves the injection of metallic iron and the creation of low levels of dissolved oxygen in the aqueous phase through oxidation of the metallic iron. The use of a biodegradable immiscible and innocuous organic liquid such as vegetable oil as an additive offers several intriguing possibilities. The oil phase creates a large oil-water interface that is immobile with respect to flow in the aqueous phase. This phase will act as a trap for chlorinated hydrocarbons and could potentially increase the reaction efficiency of reductive dehalogenation of chlorinated hydrocarbons by the metallic iron. When iron particles are suspended in the oil before injection they are preferentially held in the oil phase and tend to accumulate at the oil-water interface. Thus oil injection can serve as a mechanism for creating a stable porous curtain of metallic iron in the vadose to maintain a low oxygen environment which will minimize the consumption of the iron by molecular oxygen

Iron and stony-iron meteorites

DEFF Research Database (Denmark)

Benedix, Gretchen K.; Haack, Henning; McCoy, T. J.

2014-01-01

Without iron and stony-iron meteorites, our chances of ever sampling the deep interior of a differentiated planetary object would be next to nil. Although we live on a planet with a very substantial core, we will never be able to sample it. Fortunately, asteroid collisions provide us with a rich...... sampling of the deep interiors of differentiated asteroids. Iron and stony-iron meteorites are fragments of a large number of asteroids that underwent significant geological processing in the early solar system. Parent bodies of iron and some stony-iron meteorites completed a geological evolution similar...... to that continuing on Earth – although on much smaller length- and timescales – with melting of the metal and silicates; differentiation into core, mantle, and crust; and probably extensive volcanism. Iron and stony-iron meteorites are our only available analogues to materials found in the deep interiors of Earth...

Local iron homeostasis in the breast ductal carcinoma microenvironment

International Nuclear Information System (INIS)

Marques, Oriana; Porto, Graça; Rêma, Alexandra; Faria, Fátima; Cruz Paula, Arnaud; Gomez-Lazaro, Maria; Silva, Paula; Martins da Silva, Berta; Lopes, Carlos

2016-01-01

While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. We confirm previous results by showing that breast cancer epithelial cells present an ‘iron-utilization phenotype’ with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an ‘iron-donor’ phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context

Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage

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Shuangying Hao

2016-03-01

Full Text Available Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI following subarachnoid hemorrhage (SAH. This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague–Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

Ferritin gene transcription is regulated by iron in soybean cell cultures.

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Lescure, A M; Proudhon, D; Pesey, H; Ragland, M; Theil, E C; Briat, J F

1991-09-15

Iron-regulated ferritin synthesis in animals is dominated by translational control of stored mRNA; iron-induced transcription of ferritin genes, when it occurs, changes the subunit composition of ferritin mRNA and protein and is coupled to translational control. Ferritins in plants and animals have evolved from a common progenitor, based on the similarity of protein sequence; however, sequence divergence occurs in the C termini; structure prediction suggests that plant ferritin has the E-helix, which, in horse ferritin, forms a large channel at the tetrameric interface. In contemporary plants, a transit peptide is encoded by ferritin mRNA to target the protein to plastids. Iron-regulated synthesis of ferritin in plants and animals appears to be very different since the 50- to 60-fold increases of ferritin protein, previously observed to be induced by iron in cultured soybean cells, is accompanied by an equivalent accumulation of hybridizable ferritin mRNA and by increased transcription of ferritin genes. Ferritin mRNA from iron-induced cells and the constitutive ferritin mRNA from soybean hypocotyls are identical. The iron-induced protein is translocated normally to plastids. Differences in animal ferritin structure coincide with the various iron storage functions (reserve for iron proteins and detoxification). In contrast, the constancy of structure of soybean ferritin, iron-induced and constitutive, coupled with the potential for vacuolar storage of excess iron in plants suggest that rapid synthesis of ferritin from a stored ferritin mRNA may not be needed in plants for detoxification of iron.

Iron overload in patients with myelodysplastic syndromes: An updated overview.

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Moukalled, Nour M; El Rassi, Fuad A; Temraz, Sally N; Taher, Ali T

2018-06-15

Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, related to altered hepcidin and growth differentiation factor-15 levels in the development of hemosiderosis in patients with MDS. In addition to its suggested role in the exacerbation of ineffective erythropoiesis, multiple reports have identified a prognostic implication for the development of iron overload in patients with MDS, with an improvement in overall survival after the initiation of iron chelation therapy. This review includes a detailed discussion of iron overload in patients with MDS whether they are undergoing supportive therapy or curative hematopoietic stem cell transplantation, with a focus on the mechanism, diagnosis, and effect on survival as well as the optimal management of this highly variable complication. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Characterization of iron uptake from hydroxamate siderophores by Chlorella vulgaris

International Nuclear Information System (INIS)

Allnutt, F.C.T.

1985-01-01

Iron uptake by Chlorella vulgaris from ferric-hydroxamate siderophores and the possible production of siderophores by these algae was investigated. No production of siderophores or organic acids was observed. Iron from the two hydroxamate siderophores tested, ferrioximine B (Fe 3+ -DFOB) and ferric-rhodotorulate (Fe 3+ -RA), was taken up at the same rate as iron chelated by citrate or caffeate. Two synthetic chelates, Fe 3+ -EDTA and Fe 3+ -EDDHA, provided iron at a slower rate. Iron uptake was inhibited by 50 μM CCCP or 1 mM vanadate. Cyanide (100 μM KCN) or 25 μM antimycin A failed to demonstrate a link between uptake and respiration. Labeled iron ( 55 Fe) was taken up while labeled ligands ([ 14 C] citrate or RA) were not accumulated. Cation competition from Ni 2+ and Co 2+ observed using Fe 3+ -DFOB and Fe 3+ -RA while iron uptake from Fe 3+ -citrate was stimulated. Iron-stress induced iron uptake from the hydroxamate siderophores. Ferric reduction from the ferric-siderophores was investigated with electron paramagnetic resonance (EPR) and bathophenathroline disulfonate (BPDS). Ferric reduction was induced by iron-stress and inhibited by CCCP. A close correlation between iron uptake and ferric reduction was measured by the EPR method. Ferric reduction measured by the BPDS method was greater than that measure by EPR. BPDS reduction was interpreted to indicate a potential for reduction while EPR measures the physiological rate of reduction. BPDS inhibition of iron uptake and ferricyanide interference with reduction indicate that reduction and uptake occur exposed to the external medium. Presumptive evidence using a binding dose response curve for Fe 3+ -DFOB indicated that a receptor may be involved in this mechanism

PfsR is a key regulator of iron homeostasis in Synechocystis PCC 6803.

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Dan Cheng

Full Text Available Iron is an essential cofactor in numerous cellular processes. The iron deficiency in the oceans affects the primary productivity of phytoplankton including cyanobacteria. In this study, we examined the function of PfsR, a TetR family transcriptional regulator, in iron homeostasis of the cyanobacterium Synechocystis PCC 6803. Compared with the wild type, the pfsR deletion mutant displayed stronger tolerance to iron limitation and accumulated significantly more chlorophyll a, carotenoid, and phycocyanin under iron-limiting conditions. The mutant also maintained more photosystem I and photosystem II complexes than the wild type after iron deprivation. In addition, the activities of photosystem I and photosystem II were much higher in pfsR deletion mutant than in wild-type cells under iron-limiting conditions. The transcripts of pfsR were enhanced by iron limitation and inactivation of the gene affected pronouncedly expression of fut genes (encoding a ferric iron transporter, feoB (encoding a ferrous iron transporter, bfr genes (encoding bacterioferritins, ho genes (encoding heme oxygenases, isiA (encoding a chlorophyll-binding protein, and furA (encoding a ferric uptake regulator. The iron quota in pfsR deletion mutant cells was higher than in wild-type cells both before and after exposure to iron limitation. Electrophoretic mobility shift assays showed that PfsR bound to its own promoter and thereby auto-regulated its own expression. These data suggest that PfsR is a critical regulator of iron homeostasis.

Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease

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Joana Neves

2017-06-01

Full Text Available Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1C326S, increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells. Pulmonary iron overload is associated with oxidative stress, restrictive lung disease with decreased total lung capacity and reduced blood oxygen saturation in homozygous Slc40a1C326S/C326S mice compared to wild-type controls. These findings implicate iron in lung pathology, which is so far not considered a classical iron-related disorder.

Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse

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Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

2016-01-01

The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

Modelling iron mismanagement in neurodegenerative disease in vitro: paradigms, pitfalls, possibilities & practical considerations.

Science.gov (United States)

Healy, Sinead; McMahon, Jill M; FitzGerald, Una

2017-11-01

Although aberrant metabolism and deposition of iron has been associated with aging and neurodegeneration, the contribution of iron to neuropathology is unclear. Well-designed model systems that are suited to studying the putative pathological effect of iron are likely to be essential if such unresolved details are to be clarified. In this review, we have evaluated the utility and effectiveness of the reductionist in vitro platform to study the molecular mechanisms putatively underlying iron perturbations of neurodegenerative disease. The expression and function of iron metabolism proteins in glia and neurons and the extent to which this iron regulatory system is replicated in in vitro models has been comprehensively described, followed by an appraisal of the inherent suitability of different in vitro and ex vivo models that have been, or might be, used for iron loading. Next, we have identified and critiqued the relevant experimental parameters that have been used in in vitro iron loading experiments, including the choice of iron reagent, relevant iron loading concentrations and supplementation with serum or ascorbate, and propose optimal iron loading conditions. Finally, we have provided a synthesis of the differential iron accumulation and toxicity in glia and neurons from reported iron loading paradigms. In summary, this review has amalgamated the findings and paradigms of the published reports modelling iron loading in monocultures, discussed the limitations and discrepancies of such work to critically propose a robust, relevant and reliable model of iron loading to be used for future investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron

Science.gov (United States)

Morgan, Neil V; Westaway, Shawn K; Morton, Jenny E V; Gregory, Allison; Gissen, Paul; Sonek, Scott; Cangul, Hakan; Coryell, Jason; Canham, Natalie; Nardocci, Nardo; Zorzi, Giovanna; Pasha, Shanaz; Rodriguez, Diana; Desguerre, Isabelle; Mubaidin, Amar; Bertini, Enrico; Trembath, Richard C; Simonati, Alessandro; Schanen, Carolyn; Johnson, Colin A; Levinson, Barbara; Woods, C Geoffrey; Wilmot, Beth; Kramer, Patricia; Gitschier, Jane; Maher, Eamonn R; Hayflick, Susan J

2007-01-01

Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis. PMID:16783378

Progressive Retinal Degeneration and Accumulation of Autofluorescent Lipopigments in Progranulin Deficient Mice

Science.gov (United States)

Hafler, Brian P.; Klein, Zoe A.; Zhou, Z. Jimmy; Strittmatter, Stephen M.

2014-01-01

Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn−/− mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

Assessment of intake of iron and nutrients that affect bioavailability of daily food rations of girls

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Anna Broniecka

2014-06-01

Full Text Available INTRODUCTION AND AIM In a human body iron occurs at a level of 3 to 5 g, 60-70 % of which are in hemoglobin, ca. 10% in myoglobin, and ca. 3% are accumulated in enzymes of cellular respiration or enzymes degrading toxic hydrogen peroxide. The other part of iron is accumulated in liver, spleen, kidneys and bone marrow. The dietary deficiency of iron appears at its insufficient level in a diet and at impaired absorption of iron ions present in food products by a body. Groups at an especially high risk of iron deficiencies include, among others, menstruating girls in the pubescence period and women with heavy and irregular menstruations, as well as vegetarians and patients with chronic enteritis. The aim of this study was to evaluate the intake of iron and nutrients that affect its bioavailability from daily food rations of girls. MATERIAL AND METHODS The study included 159 girls aged 17-18, students of high schools in the city of Wroclaw. The study was conducted between November 2010 and ay 2011. Girls were divided into 3 subgroups according to the BMI score. Girls’ diets were analyzed with the method of a direct interview of the last 24 hours before the test and the interview was repeated seven times. RESULTS The present study demonstrated that the intake of iron from food rations of almost all the girls surveyed was below the requirements defined for this age group. Statistically significant differences were noted in the intake of energy and nutrients among the three distinguished subgroups of girls. CONCLUSIONS Food rations of the surveyed girls were characterized by a low, compared to dietary allowances, calorific value, which resulted in deficiencies of nutrients increasing iron bioavailability.

The critical role of Nramp1 in degrading α-synuclein oligomers in microglia under iron overload condition.

Science.gov (United States)

Wu, Kuo-Chen; Liou, Horng-Huei; Kao, Yu-Han; Lee, Chih-Yu; Lin, Chun-Jung

2017-08-01

Oligomeric α-synuclein is a key mediator in the pathogenesis of Parkinson's disease (PD) and is mainly cleared by autophagy-lysosomal pathway, whose dysfunction results in the accumulation and cell-to-cell transmission of α-synuclein. In this study, concomitant with the accumulation of iron and oligomeric α-synuclein, higher expression of a lysosomal iron transporter, natural resistance-associated macrophage protein-1 (Nramp1), was observed in microglia in post-mortem striatum of sporadic PD patients. Using Nramp1-deficient macrophage (RAW264.7) and microglial (BV-2) cells as in-vitro models, iron exposure significantly reduced the degradation rate of the administered human α-synuclein oligomers, which can be restored by the expression of the wild-type, but not mutant (D543N), Nramp1. Likewise, under iron overload condition, mice with functional Nramp1 (DBA/2 and C57BL/6 congenic mice carrying functional Nramp1) had a better ability to degrade infused human α-synuclein oligomers than mice with nonfunctional Nramp1 (C57BL/6) in the brain and microglia. The interplay between iron and Nramp1 exhibited parallel effects on the clearance of α-synuclein and the activity of lysosomal cathepsin D in vitro and in vivo. Collectively, these findings suggest that the function of Nramp1 contributes to microglial degradation of oligomeric α-synuclein under iron overload condition and may be implicated in the pathogenesis of PD. Copyright © 2017 Elsevier Inc. All rights reserved.

Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide Nanoparticles in Mice Following Intraperitoneal Administration

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Binh T. T. Pham

2018-01-01

Full Text Available Nanomedicine is an emerging field with great potential in disease theranostics. We generated sterically stabilized superparamagnetic iron oxide nanoparticles (s-SPIONs with average core diameters of 10 and 25 nm and determined the in vivo biodistribution and clearance profiles. Healthy nude mice underwent an intraperitoneal injection of these s-SPIONs at a dose of 90 mg Fe/kg body weight. Tissue iron biodistribution was monitored by atomic absorption spectroscopy and Prussian blue staining. Histopathological examination was performed to assess tissue toxicity. The 10 nm s-SPIONs resulted in higher tissue-iron levels, whereas the 25 nm s-SPIONs peaked earlier and cleared faster. Increased iron levels were detected in all organs and body fluids tested except for the brain, with notable increases in the liver, spleen, and the omentum. The tissue-iron returned to control or near control levels within 7 days post-injection, except in the omentum, which had the largest and most variable accumulation of s-SPIONs. No obvious tissue changes were noted although an influx of macrophages was observed in several tissues suggesting their involvement in s-SPION sequestration and clearance. These results demonstrate that the s-SPIONs do not degrade or aggregate in vivo and intraperitoneal administration is well tolerated, with a broad and transient biodistribution. In an ovarian tumor model, s-SPIONs were shown to accumulate in the tumors, highlighting their potential use as a chemotherapy delivery agent.

Gold-coated iron nanoparticles in transparent Si{sub 3}N{sub 4} matrix thin films

Energy Technology Data Exchange (ETDEWEB)

Sanchez-Marcos, J. [Consejo Superior de Investigaciones Cientificas, Instituto de Ciencia de Materiales de Madrid (Spain); Cespedes, E. [Keele University, Institute for Science and Technology in Medicine, Guy Hilton Research Centre (United Kingdom); Jimenez-Villacorta, F. [Northeastern University, Department of Chemical Engineering (United States); Munoz-Martin, A. [Universidad Autonoma de Madrid, Centro de Microanalisis de Materiales (Spain); Prieto, C., E-mail: cprieto@icmm.csic.es [Consejo Superior de Investigaciones Cientificas, Instituto de Ciencia de Materiales de Madrid (Spain)

2013-06-15

A new method to prepare thin films containing gold-coated iron nanoparticles is presented. The ternary Fe-Au-Si{sub 3}N{sub 4} system prepared by sequential sputtering has revealed a progressive variation of microstructures from Au/Fe/Au/Si{sub 3}N{sub 4} multilayers to iron nanoparticles. Microstructural characterization by transmission electron microscopy, analysis of the magnetic properties and probing of the iron short-range order by X-ray absorption spectroscopy confirm the existence of a gold-coated iron nanoparticles of 1-2 nm typical size for a specific range of iron and gold contents per layer in the transparent silicon nitride ceramic matrix.

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

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Ewelina Łukaszyk

2015-06-01

Full Text Available Background/Aims: One of the most common causes of anemia of chronic disease (ACD is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. Methods: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP, creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6, hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR, growth differentiation factor-15 (GDF-15 and zonulin. Results: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Conclusion: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency.

Accumulation of BSA in Packed-bed Microfluidics

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Summers, Samantha; Hu, Chuntian; Hartman, Ryan

2012-11-01

Alzheimers and Parkinsons are two diseases that are associated with protein deposition in the brain, causing loss of either cognitive or muscle functioning. Protein deposition diseases are considered progressive diseases since the continual aggregation of protein causes the patient's symptoms to slowly worsen over time. There are currently no known means of treatment for protein deposition diseases. Our goal is to understand the potential for packed-bed microfluidics to study protein accumulation. Measurement of the resistance to flow through micro-scale packed-beds is critical to understanding the process of protein accumulation. Aggregation in bulk is fundamentally different from accumulation on surfaces. Our study attempts to distinguish between either mechanism. The results from our experiments involving protein injection through a microfluidic system will be presented and discussed. Funding received by NSF REU Grant 1062611.

Concentration of 99Tc in seawater by coprecipitation with iron hydroxide

International Nuclear Information System (INIS)

Momoshima, Noriyuki; Eto, Ichiro; Muhammad Sayad; Takashima, Yoshimasa

1991-01-01

A method for accumulation of 99 Tc in seawater has been developed. Technetium tracer in +VII oxidation state was added to the seawater together with reducing agent, potassium pyrosulfite, and coprecipitation agent, ferric chloride. After reduction of Tc(VII) at pH 4, Tc(IV) was coprecipitated as iron hydroxide by addition of sodium hydroxide to pH 9. The reduction and coprecipitation was quantitative and overall recovery of Tc was more than 98%. The green color of iron precipitate formed at pH 9 suggested that Tc(VII) as well as ferric ion was reduced under this condition. Adsorption of Tc(IV), however, was poor for iron hydroxide which was prepared in advance indicating active surface of freshly precipitated iron hydroxide is necessary for quantitative recovery of Tc(IV). A repeating coprecipitation technique was examined for enrichment of Tc in seawater that the same iron was used repeatedly as coprecipitater. After separation of iron hydroxide with Tc(IV) from supernatant, the precipitate was dissolved by addition of acid and then new seawater which contained reducing agent and Tc(VII) was added. Reduction and coprecipitation was again carried out. Good recovery was attained for 7 repeats. The proposed repeating coprecipitation technique was applicable to a large amount of seawater without increasing the amount of iron hydroxide which is subjected to radiochemical analysis. (author)

Iron Refractory Iron Deficiency Anaemia: A Rare Cause of Iron Deficiency Anaemia

LENUS (Irish Health Repository)

McGrath, T

2018-01-01

We describe the case of a 17-month-old boy with a hypochromic microcytic anaemia, refractory to oral iron treatment. After exclusion of dietary and gastrointestinal causes of iron deficiency, a genetic cause for iron deficiency was confirmed by finding two mutations in the TMPRSS6 gene, consistent with a diagnosis of iron-refractory iron deficiency anaemia (IRIDA).

Assessment of irradiated rice bran as iron source

International Nuclear Information System (INIS)

Wada, Heden Katsue

2002-01-01

Rice is the largest cereal crop in Brazil. To obtain the polish grain, its external peel is extracted after abrasive process. As a result, rice bran is obtained. It has low cost and high nutritional level, which has been include into malnourished children feeding. There is a considerable controversy related to the rice bran effect on the prevention and control of undernutrition and iron deficiency. The aim os this study was to assess the availability of in vitro iron of in natura and treated rice brans, after different levels of irradiation were applied. Both sorts of bran had their composition analyzed emphasizing the iron and phytate contents. The microbiological quality of the rice bran was also assessed. The pathogenic microorganisms were destroyed only in the in natura rice bran. As the irradiation level applied on the stabilized bran increased, its lipidic fraction reduced an the progressive destruction of the phytates occurred. The high iron content follow its availability in the rice bran, despite of the irradiation level applied, on the rice bran products and its dietetic preparations. (author)

Antioxidative responses of Elodea nuttallii (Planch.) H. St. John to short-term iron exposure.

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Xing, Wei; Li, Dunhai; Liu, Guihua

2010-01-01

Antioxidative responses of Elodea nuttallii (Planch.) H. St. John to short-term iron exposure were investigated in the study. Results showed that iron accumulation in E. nuttallii was concentration dependent. Growth of E. nuttallii was promoted by low iron concentration (1-10 mg L(-1) [Fe(3+)]), but growth inhibition was observed when iron concentration beyond 10 mg L(-1). The synthesis of protein and pigments increased within 1-10 mg L(-1) [Fe(3+)] range. The activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and glutathione-S-transferase (GST) were up to maximal values at 10 mg L(-1) [Fe(3+)]. High iron concentration inhibited the synthesis of protein and pigments as well as activities of antioxidative enzymes, and accelerated degradation of pigment and production of ROS. Low iron concentration had no significant influences on PSII maximal quantum yield, activity of PSII and relative electron transport rate though PSII. Malondialdehyde (MDA) and proline concentrations were highest at 100 and 1 mg L(-1) [Fe(3+)], respectively. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Comparative Review on Thin Film Growth of Iron-Based Superconductors

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Yoshinori Imai

2017-07-01

Full Text Available Since the discovery of the novel iron-based superconductors, both theoretical and experimental studies have been performed intensively. Because iron-based superconductors have a smaller anisotropy than high-Tc cuprates and a high superconducting transition temperature, there have been a lot of researchers working on the film fabrication of iron-based superconductors and their application. Accordingly, many novel features have been reported in the films of iron-based superconductors, for example, the fabrication of the epitaxial film with a higher Tc than bulk samples, the extraction of the metastable phase which cannot be obtained by the conventional solid state reaction, and so on. In this paper, we review the progress of research on thin film fabrications of iron-based superconductors, especially the four categories: LnFeAs(O,F (Ln = Lanthanide, AEFe2As2 (AE = Alkaline-earth metal, FeCh (Ch = Chalcogen, and FeSe monolayer. Furthermore, we focus on two important topics in thin films of iron-based superconductors; one is the substrate material for thin film growth on the iron-based superconductors, and the other is the whole phase diagram in FeSe1-xTex which can be obtained only by using film-fabrication technique.

Comparative study of radiation damage accumulation in Cu and Fe

International Nuclear Information System (INIS)

Caturla, M.J.; Soneda, N.; Alonso, E.; Wirth, B.D.; Diaz de la Rubia, T.; Perlado, J.M.

2000-01-01

Bcc and fcc metals exhibit significant differences in behavior when exposed to neutron or heavy ion irradiation. Transmission electron microscopy (TEM) observations reveal that damage in the form of stacking fault tetrahedra (SFT) is visible in copper irradiated to very low doses, but that no damage is visible in iron irradiated to the same total dose. In order to understand and quantify this difference in behavior, we have simulated damage production and accumulation in fcc Cu and bcc Fe. We use 20 keV primary knock-on atoms (PKAs) at a homologous temperature of 0.25 of the melting point. The primary damage state was calculated using molecular dynamics (MD) with empirical, embedded-atom interatomic potentials. Damage accumulation was modeled using a kinetic Monte Carlo (kMC) algorithm to follow the evolution of all defects produced in the cascades. The diffusivities and binding energies of defects are input data for this simulation and were either extracted from experiments, the literature, or calculated using MD. MD simulations reveal that vacancy clusters are produced within the cascade core in the case of copper. In iron, most of the vacancies do not cluster during cooling of the cascade core and are available for diffusion. In addition, self-interstitial atom (SIA) clusters are produced in copper cascades but those observed in iron are smaller in number and size. The combined MD/kMC simulations reveal that the visible cluster densities obtained as a function of dose are at least one order of magnitude lower in Fe than in Cu. We compare the results with experimental measurements of cluster density and find excellent agreement between the simulations and experiments when small interstitial clusters are considered to be mobile as suggested by recent MD simulations

A Patient with Beta-Propeller Protein-Associated Neurodegeneration: Treatment with Iron Chelation Therapy

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Shen-Yang Lim

2018-05-01

Full Text Available We present a case of beta-propeller protein-associated neurodegeneration, a form of neurodegeneration with brain iron accumulation. The patient harbored a novel mutation in the WDR45 gene. A detailed video and description of her clinical condition are provided. Her movement disorder phenomenology was characterized primarily by limb stereotypies and gait dyspraxia. The patient’s disability was advanced by the time iron-chelating therapy with deferiprone was initiated, and no clinical response in terms of cognitive function, behavior, speech, or movements were observed after one year of treatment.

The role of iron in the proliferation of Drosophila l(2)mbn cells

Energy Technology Data Exchange (ETDEWEB)

Metzendorf, Christoph [Department of Comparative Physiology, Uppsala University, Norbyvaegen 18A, SE-752 36 Uppsala (Sweden); Lind, Maria I., E-mail: maria.lind@ebc.uu.se [Department of Comparative Physiology, Uppsala University, Norbyvaegen 18A, SE-752 36 Uppsala (Sweden)

2010-09-24

Research highlights: {yields} Establishment of a model system to study the role of iron during proliferation. {yields} Iron deprivation of insect tumorous cell line inhibits cell proliferation. {yields} Iron deprivation causes a reversible cell cycle arrest in G1/S-phase. {yields} Iron deprivation promotes decreased gene expression of cycE. -- Abstract: Iron is essential for life and is needed for cell proliferation and cell cycle progression. Iron deprivation results first in cell cycle arrest and then in apoptosis. The Drosophila tumorous larval hemocyte cell line l(2)mbn was used to study the sensitivity and cellular response to iron deprivation through the chelator desferrioxamine (DFO). At a concentration of 10 {mu}M DFO or more the proliferation was inhibited reversibly, while the amount of dead cells did not increase. FACS analysis showed that the cell cycle was arrested in G1/S-phase and the transcript level of cycE was decreased to less than 50% of control cells. These results show that iron chelation in this insect tumorous cell line causes a specific and coordinated cell cycle arrest.

Altered sterol metabolism in budding yeast affects mitochondrial iron-sulfur (Fe-S) cluster synthesis.

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Ward, Diane M; Chen, Opal S; Li, Liangtao; Kaplan, Jerry; Bhuiyan, Shah Alam; Natarajan, Selvamuthu K; Bard, Martin; Cox, James E

2018-05-17

Ergosterol synthesis is essential for cellular growth and viability of the budding yeast Saccharomyces cerevisiae, and intracellular sterol distribution and homeostasis are therefore highly regulated in this species. Erg25 is an iron-containing C4-methyl sterol oxidase that contributes to the conversion of 4,4-dimethylzymosterol to zymosterol, a precursor of ergosterol. The ERG29 gene encodes an endoplasmic reticulum (ER)-associated protein, and here we identified a role for Erg29 in the methyl sterol oxidase step of ergosterol synthesis. ERG29 deletion resulted in lethality in respiring cells, but respiration-incompetent (Rho- or Rho0) cells survived, suggesting that Erg29 loss leads to accumulation of oxidized sterol metabolites that affect cell viability. Down-regulation of ERG29 expression in Δerg29 cells indeed led to accumulation of methyl sterol metabolites, resulting in increased mitochondrial oxidants and a decreased ability of mitochondria to synthesize iron-sulfur (Fe-S) clusters due to reduced levels of Yfh1, the mammalian frataxin homolog, which is involved in mitochondrial Fe metabolism. Using a high-copy genomic library, we identified suppressor genes that permitted growth of Δerg29 cells on respiratory substrates, and these included genes encoding the mitochondrial proteins Yfh1, Mmt1, Mmt2, and Pet20, which reversed all phenotypes associated with loss of ERG29. Of note, loss of Erg25 also resulted in accumulation of methyl sterol metabolites and also increased mitochondrial oxidants and degradation of Yfh1. We propose that accumulation of toxic intermediates of the methyl sterol oxidase reaction increase mitochondrial oxidants, which affect Yfh1 protein stability. These results indicate an interaction between sterols generated by ER proteins and mitochondrial iron metabolism. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Transformation of vivianite by anaerobic nitrate-reducing iron-oxidizing bacteria.

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Miot, J; Benzerara, K; Morin, G; Bernard, S; Beyssac, O; Larquet, E; Kappler, A; Guyot, F

2009-06-01

In phosphate-rich environments, vivianite (Fe(II)(3)(PO(4))(2), 8H(2)O) is an important sink for dissolved Fe(II) and is considered as a very stable mineral due to its low solubility at neutral pH. In the present study, we report the mineralogical transformation of vivianite in cultures of the nitrate-reducing iron-oxidizing bacterial strain BoFeN1 in the presence of dissolved Fe(II). Vivianite was first transformed into a greenish phase consisting mostly of an amorphous mixed valence Fe-phosphate. This precipitate became progressively orange and the final product of iron oxidation consisted of an amorphous Fe(III)-phosphate. The sub-micrometer analysis by scanning transmission X-ray microscopy of the iron redox state in samples collected at different stages of the culture indicated that iron was progressively oxidized at the contact of the bacteria and at a distance from the cells in extracellular minerals. Iron oxidation in the extracellular minerals was delayed by a few days compared with cell-associated Fe-minerals. This led to strong differences of Fe redox in between these two types of minerals and finally to local heterogeneities of redox within the sample. In the absence of dissolved Fe(II), vivianite was not significantly transformed by BoFeN1. Whereas Fe(II) oxidation at the cell contact is most probably directly catalyzed by the bacteria, vivianite transformation at a distance from the cells might result from oxidation by nitrite. In addition, processes leading to the export of Fe(III) from bacterial oxidation sites to extracellular minerals are discussed including some involving colloids observed by cryo-transmission electron microscopy in the culture medium.

Nitric oxide maintains cell survival of Trichomonas vaginalis upon iron depletion.

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Cheng, Wei-Hung; Huang, Kuo-Yang; Huang, Po-Jung; Hsu, Jo-Hsuan; Fang, Yi-Kai; Chiu, Cheng-Hsun; Tang, Petrus

2015-07-25

Iron plays a pivotal role in the pathogenesis of Trichomonas vaginalis, the causative agent of highly prevalent human trichomoniasis. T. vaginalis resides in the vaginal region, where the iron concentration is constantly changing. Hence, T. vaginalis must adapt to variations in iron availability to establish and maintain an infection. The free radical signaling molecules reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been proven to participate in iron deficiency in eukaryotes. However, little is known about the roles of these molecules in iron-deficient T. vaginalis. T. vaginalis cultured in iron-rich and -deficient conditions were collected for all experiments in this study. Next generation RNA sequencing was conducted to investigate the impact of iron on transcriptome of T. vaginalis. The cell viabilities were monitored after the trophozoites treated with the inhibitors of nitric oxide (NO) synthase (L-NG-monomethyl arginine, L-NMMA) and proteasome (MG132). Hydrogenosomal membrane potential was measured using JC-1 staining. We demonstrated that NO rather than ROS accumulates in iron-deficient T. vaginalis. The level of NO was blocked by MG132 and L-NMMA, indicating that NO production is through a proteasome and arginine dependent pathway. We found that the inhibition of proteasome activity shortened the survival of iron-deficient cells compared with untreated iron-deficient cells. Surprisingly, the addition of arginine restored both NO level and the survival of proteasome-inhibited cells, suggesting that proteasome-derived NO is crucial for cell survival under iron-limited conditions. Additionally, NO maintains the hydrogenosomal membrane potential, a determinant for cell survival, emphasizing the cytoprotective effect of NO on iron-deficient T. vaginalis. Collectively, we determined that NO produced by the proteasome prolonged the survival of iron-deficient T. vaginalis via maintenance of the hydrogenosomal functions. The findings in this

HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues.

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Zukor, Hillel; Song, Wei; Liberman, Adrienne; Mui, Jeannie; Vali, Hojatollah; Fillebeen, Carine; Pantopoulos, Kostas; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Schipper, Hyman M

2009-05-01

Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.

Genetics Home Reference: iron-refractory iron deficiency anemia

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... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons.

Science.gov (United States)

Rodriguez-Rodriguez, Patricia; Sandebring-Matton, Anna; Merino-Serrais, Paula; Parrado-Fernandez, Cristina; Rabano, Alberto; Winblad, Bengt; Ávila, Jesús; Ferrer, Isidre; Cedazo-Minguez, Angel

2017-12-01

Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Iron deficiency regulated OsOPT7 is essential for iron homeostasis in rice.

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Bashir, Khurram; Ishimaru, Yasuhiro; Itai, Reiko Nakanishi; Senoura, Takeshi; Takahashi, Michiko; An, Gynheung; Oikawa, Takaya; Ueda, Minoru; Sato, Aiko; Uozumi, Nobuyuki; Nakanishi, Hiromi; Nishizawa, Naoko K

2015-05-01

The molecular mechanism of iron (Fe) uptake and transport in plants are well-characterized; however, many components of Fe homeostasis remain unclear. We cloned iron-deficiency-regulated oligopeptide transporter 7 (OsOPT7) from rice. OsOPT7 localized to the plasma membrane and did not transport Fe(III)-DMA or Fe(II)-NA and GSH in Xenopus laevis oocytes. Furthermore OsOPT7 did not complement the growth of yeast fet3fet4 mutant. OsOPT7 was specifically upregulated in response to Fe-deficiency. Promoter GUS analysis revealed that OsOPT7 expresses in root tips, root vascular tissue and shoots as well as during seed development. Microarray analysis of OsOPT7 knockout 1 (opt7-1) revealed the upregulation of Fe-deficiency-responsive genes in plants grown under Fe-sufficient conditions, despite the high Fe and ferritin concentrations in shoot tissue indicating that Fe may not be available for physiological functions. Plants overexpressing OsOPT7 do not exhibit any phenotype and do not accumulate more Fe compared to wild type plants. These results indicate that OsOPT7 may be involved in Fe transport in rice.

Deleterious effects of neuronal accumulation of glycogen in flies and mice.

Science.gov (United States)

Duran, Jordi; Tevy, María Florencia; Garcia-Rocha, Mar; Calbó, Joaquim; Milán, Marco; Guinovart, Joan J

2012-08-01

Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant glycogen accumulation in neurons is a hallmark of patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations in genes involved in glycogen metabolism, the role of glycogen accumulation remains elusive. Here, we generated mouse and fly models expressing an active form of GS to force neuronal accumulation of glycogen. We present evidence that the progressive accumulation of glycogen in mouse and Drosophila neurons leads to neuronal loss, locomotion defects and reduced lifespan. Our results highlight glycogen accumulation in neurons as a direct cause of neurodegeneration. Copyright © 2012 EMBO Molecular Medicine.

Effect of dietary iron source and iron status on iron bioavailability tests in the rat

International Nuclear Information System (INIS)

Zhang, D.; Hendricks, D.G.; Mahoney, A.W.

1986-01-01

Weanling male rats were made anemic in 7 days by feeding a low iron diet and bleeding. Healthy rats were fed the low iron diet supplemented with ferrous sulfate (29 ppm Fe). Each group was subdivided and fed for 10 days on test diets containing about 29 ppm iron that were formulated with meat:spinach mixtures or meat:soy mixtures to provided 100:0, 75:25, 50:50, 25:75, or 0:100% of the dietary iron from these sources or from a ferrous sulfate diet. After 3 days on the diets all rats were dosed orally with 2 or 5 micro curries of 59 Fe after a 18 hour fast and refeeding for 1.5 hours. Iron status influenced liver iron, carcass iron, liver radio activity and percent of radioactive dose retained. Diet influenced fecal iron and apparent absorption of iron. In iron bioavailability studies assessment methodology and iron status of the test subject greatly influences the estimates of the value of dietary sources of iron

Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice

International Nuclear Information System (INIS)

Zhang, Pengjun; Yue, Yuanyuan; Pan, Donghui; Yang, Runlin; Xu, Yuping; Wang, Lizhen; Yan, Junjie; Li, Xiaotian; Yang, Min

2016-01-01

Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron-overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with 89 Zr, a long half-life (78.4 h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with 89 Zr directly at pH 5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/μmol. The 89 Zr-MP was stable in human plasma and PBS for at least 48 h. The half-life of 89 Zr-MP was about 15.70 ± 1.74 h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that 89 Zr-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy.

Iron in neurodegenerative disorders: being in the wrong place at the wrong time?

Science.gov (United States)

Apostolakis, Sotirios; Kypraiou, Anna-Maria

2017-11-27

Brain iron deposits have been reported consistently in imaging and histologic examinations of patients with neurodegenerative disorders. While the origins of this finding have not been clarified yet, it is speculated that impaired iron homeostasis or deficient transport mechanisms result in the accumulation of this highly toxic metal ultimately leading to formation of reactive oxygen species and cell death. On the other hand, there are also those who support that iron is just an incidental finding, a by product of neuronal loss. A literature review has been performed in order to present the key findings in support of the iron hypothesis of neurodegeneration, as well as to identify conditions causing or resulting from iron overload and compare and contrast their features with the most prominent neurodegenerative disorders. There is an abundance of experimental and observational findings in support of the hypothesis in question; however, as neurodegeneration is a rare incident of commonly encountered iron-associated disorders of the nervous system, and this metal is found in non-neurodegenerative disorders as well, it is possible that iron is the result or even an incidental finding in neurodegeneration. Understanding the underlying processes of iron metabolism in the brain and particularly its release during cell damage is expected to provide a deeper understanding of the origins of neurodegeneration in the years to come.

Arsenic rich iron plaque on macrophyte roots--an ecotoxicological risk?

Science.gov (United States)

Taggart, M A; Mateo, R; Charnock, J M; Bahrami, F; Green, A J; Meharg, A A

2009-03-01

Arsenic is known to accumulate with iron plaque on macrophyte roots. Three to four years after the Aznalcóllar mine spill (Spain), residual arsenic contamination left in seasonal wetland habitats has been identified in this form by scanning electron microscopy. Total digestion has determined arsenic concentrations in thoroughly washed 'root+plaque' material in excess of 1000 mg kg(-1), and further analysis using X-ray absorption spectroscopy suggests arsenic exists as both arsenate and arsenite. Certain herbivorous species feed on rhizomes and bulbs of macrophytes in a wide range of global environments, and the ecotoxicological impact of consuming arsenic rich iron plaque associated with such food items remains to be quantified. Here, greylag geese which feed on Scirpus maritimus rhizome and bulb material in areas affected by the Aznalcóllar spill are shown to have elevated levels of arsenic in their feces, which may originate from arsenic rich iron plaque.

A legume biofortification quandary: variability and genetic control of seed coat micronutrient accumulation in common beans

Science.gov (United States)

Blair, Matthew W.; Izquierdo, Paulo; Astudillo, Carolina; Grusak, Michael A.

2013-01-01

Common beans (Phaseolus vulgaris L.), like many legumes, are rich in iron, zinc, and certain other microelements that are generally found to be in low concentrations in cereals, other seed crops, and root or tubers and therefore are good candidates for biofortification. But a quandary exists in common bean biofortification: namely that the distribution of iron has been found to be variable between the principal parts of seed; namely the cotyledonary tissue, embryo axis and seed coat. The seed coat represents ten or more percent of the seed weight and must be considered specifically as it accumulates much of the anti-nutrients such as tannins that effect mineral bioavailability. Meanwhile the cotyledons accumulate starch and phosphorus in the form of phytates. The goal of this study was to evaluate a population of progeny derived from an advanced backcross of a wild bean and a cultivated Andean bean for seed coat versus cotyledonary minerals to identify variability and predict inheritance of the minerals. We used wild common beans because of their higher seed mineral concentration compared to cultivars and greater proportion of seed coat to total seed weight. Results showed the most important gene for seed coat iron was on linkage group B04 but also identified other QTL for seed coat and cotyledonary iron and zinc on other linkage groups, including B11 which has been important in studies of whole seed. The importance of these results in terms of physiology, candidate genes and plant breeding are discussed. PMID:23908660

Distribution of implanted ions in seeds and roots of mung bean

International Nuclear Information System (INIS)

Liu Donghua; Wang Wei; Jiang Wusheng; Zhang Zhixiang; Hou Wenqiang; Guo Ximing; Li Yi

1998-01-01

Doses of 1 x 10 16 , and 2 x 10 16 cm -2 and 1 x 10 16 , 2 x 10 16 , 3 x 10 16 and 3.6 x 10 16 cm -2 for iron and copper ions are implanted in dry seeds of mung bean, respectively. The results show that the accumulated-copper and -iron ion amounts in the seeds and roots vary with different doses of ion beam, and the fresh and dry weights of the roots decrease progressively with increasing iron and copper doses, except the treatment of 1 x 10 16 Cu + ions/cm 2 , and the accumulated-copper and -iron ion amounts in the seeds of the different test groups can be correlated with the ion distribution in the roots

Non-transferrin-bound iron (NTBI uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species.

Directory of Open Access Journals (Sweden)

Joao Arezes

Full Text Available Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI. NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.

Iron Deficiency and Anemia Predict Mortality in Patients with Tuberculosis123

Science.gov (United States)

Isanaka, Sheila; Mugusi, Ferdinand; Urassa, Willy; Willett, Walter C.; Bosch, Ronald J.; Villamor, Eduardo; Spiegelman, Donna; Duggan, Christopher; Fawzi, Wafaie W.

2012-01-01

Many studies have documented a high prevalence of anemia among tuberculosis (TB) patients and anemia at TB diagnosis has been associated with an increased risk of death. However, little is known about the factors contributing to the development of TB-associated anemia and their importance in TB disease progression. Data from a randomized clinical trial of micronutrient supplementation in patients with pulmonary TB in Tanzania were analyzed. Repeated measures of anemia with iron deficiency, anemia without iron deficiency, and iron deficiency without anemia were assessed as risk factors for treatment failure, TB recurrence, and mortality. The prevalence of anemia (hemoglobin iron deficiency (mean corpuscular volume , 80 fL). We found no evidence of an association between anemia (with or without iron deficiency) or iron deficiency without anemia at baseline and the risk of treatment failure at 1 mo after initiation. Anemia without iron deficiency was associated with an independent, 4-fold increased risk of TB recurrence [adjusted RR = 4.10 (95% CI = 1.88, 8.91); P Iron deficiency and anemia (with and without iron deficiency) were associated with a 2- to nearly 3-fold independent increase in the risk of death [adjusted RR for iron deficiency without anemia = 2.89 (95% CI = 1.53, 5.47); P = 0.001; anemia without iron deficiency = 2.72 (95% CI = 1.50, 4.93); P = 0.001; iron deficiency anemia = 2.13 (95% CI = 1.10, 4.11); P = 0.02]. Efforts to identify and address the conditions contributing to TB-associated anemia, including iron deficiency, could play an important role in reducing morbidity and mortality in areas heavily affected by TB. PMID:22190024

The actin-binding protein profilin 2 is a novel regulator of iron homeostasis.

Science.gov (United States)

Luscieti, Sara; Galy, Bruno; Gutierrez, Lucia; Reinke, Michael; Couso, Jorge; Shvartsman, Maya; Di Pascale, Antonio; Witke, Walter; Hentze, Matthias W; Pilo Boyl, Pietro; Sanchez, Mayka

2017-10-26

Cellular iron homeostasis is controlled by the iron regulatory proteins (IRPs) 1 and 2 that bind cis -regulatory iron-responsive elements (IRE) on target messenger RNAs (mRNA). We identified profilin 2 ( Pfn2 ) mRNA, which encodes an actin-binding protein involved in endocytosis and neurotransmitter release, as a novel IRP-interacting transcript, and studied its role in iron metabolism. A combination of electrophoretic mobility shift assay experiments and bioinformatic analyses led to the identification of an atypical and conserved IRE in the 3' untranslated region of Pfn2 mRNA. Pfn2 mRNA levels were significantly reduced in duodenal samples from mice with intestinal IRP ablation, suggesting that IRPs exert a positive effect on Pfn2 mRNA expression in vivo. Overexpression of Pfn2 in HeLa and Hepa1-6 cells reduced their metabolically active iron pool. Importantly, Pfn2-deficient mice showed iron accumulation in discrete areas of the brain (olfactory bulb, hippocampus, and midbrain) and reduction of the hepatic iron store without anemia. Despite low liver iron levels, hepatic hepcidin expression remained high, likely because of compensatory activation of hepcidin by mild inflammation. Splenic ferroportin was increased probably to sustain hematopoiesis. Overall, our results indicate that Pfn2 expression is controlled by the IRPs in vivo and that Pfn2 contributes to maintaining iron homeostasis in cell lines and mice. © 2017 by The American Society of Hematology.

Iron absorption in relation to iron status

International Nuclear Information System (INIS)

Magnusson, B.; Bjoern-Rasmussen, E.; Hallberg, L.; Rossander, L.

1981-01-01

The absorption from a 3 mg dose of ferrous iron was measured in 250 male subjects. The absorption was related to the log concentration of serum ferritin in 186 subjects of whom 99 were regular blood donors (r= -0.76), and to bone marrow haemosiderin grading in 52 subjects with varying iron status. The purpose was to try and establish a percentage absorption from such a dose that is representative of subjects who are borderline iron deficient. This information is necessary for food iron absorption studies in order (1) to calculate the absorption of iron from the diet at a given iron status and (2) compare the absorption of iron from different meals studied in different groups of subjects by different investigarors. The results suggest that an absorption of about 40% of a 3 mg reference dose of ferrous iron is given in a fasting state, roughly corresponds to the absorption in borderline-iron-deficient subjects. The results indicate that this 40% absorption value corresponds to a serum ferritin level of 30 μg/l and that food iron absorption in a group of subjects should be expressed preferably as the absorption corresponding to a reference-dose absorption of 45%, or possibly a serum ferritin level of 30 μg/l. (author)

Quantitating Iron in Serum Ferritin by Use of ICP-MS

Science.gov (United States)

Smith, Scott M.; Gillman, Patricia L.

2003-01-01

A laboratory method has been devised to enable measurement of the concentration of iron bound in ferritin from small samples of blood (serum). Derived partly from a prior method that depends on large samples of blood, this method involves the use of an inductively-coupled-plasma mass spectrometer (ICP-MS). Ferritin is a complex of iron with the protein apoferritin. Heretofore, measurements of the concentration of serum ferritin (as distinguished from direct measurements of the concentration of iron in serum ferritin) have been used to assess iron stores in humans. Low levels of serum ferritin could indicate the first stage of iron depletion. High levels of serum ferritin could indicate high levels of iron (for example, in connection with hereditary hemochromatosis an iron-overload illness that is characterized by progressive organ damage and can be fatal). However, the picture is complicated: A high level of serum ferritin could also indicate stress and/or inflammation instead of (or in addition to) iron overload, and low serum iron concentration could indicate inflammation rather than iron deficiency. Only when concentrations of both serum iron and serum ferritin increase and decrease together can the patient s iron status be assessed accurately. Hence, in enabling accurate measurement of the iron content of serum ferritin, the present method can improve the diagnosis of the patient s iron status. The prior method of measuring the concentration of iron involves the use of an atomic-absorption spectrophotometer with a graphite furnace. The present method incorporates a modified version of the sample- preparation process of the prior method. First, ferritin is isolated; more specifically, it is immobilized by immunoprecipitation with rabbit antihuman polyclonal antibody bound to agarose beads. The ferritin is then separated from other iron-containing proteins and free iron by a series of centrifugation and wash steps. Next, the ferritin is digested with nitric acid

Effect of excess iron on oxidative stress and gluconeogenesis through hepcidin during mitochondrial dysfunction.

Science.gov (United States)

Lee, Hyo Jung; Choi, Joo Sun; Lee, Hye Ja; Kim, Won-Ho; Park, Sang Ick; Song, Jihyun

2015-12-01

Excessive tissue iron levels are a risk factor for insulin resistance and type 2 diabetes, which are associated with alterations in iron metabolism. However, the mechanisms underlying this association are not well understood. This study used human liver SK-HEP-1 cells to examine how excess iron induces mitochondrial dysfunction and how hepcidin controls gluconeogenesis. Excess levels of reactive oxygen species (ROS) and accumulated iron due to iron overload induced mitochondrial dysfunction, leading to a decrease in cellular adenosine triphosphate content and cytochrome c oxidase III expression, with an associated increase in gluconeogenesis. Disturbances in mitochondrial function caused excess iron deposition and unbalanced expression of iron metabolism-related proteins such as hepcidin, ferritin H and ferroportin during the activation of p38 mitogen-activated protein kinase (MAPK) and CCAAT/enhancer-binding protein alpha (C/EBPα), which are responsible for increased phosphoenolpyruvate carboxykinase expression. Desferoxamine and n-acetylcysteine ameliorated these deteriorations by inhibiting p38 MAPK and C/EBPα activity through iron chelation and ROS scavenging activity. Based on experiments using hepcidin shRNA and hepcidin overexpression, the activation of hepcidin affects ROS generation and iron deposition, which disturbs mitochondrial function and causes an imbalance in iron metabolism and increased gluconeogenesis. Repression of hepcidin activity can reverse these changes. Our results demonstrate that iron overload is associated with mitochondrial dysfunction and that together they can cause abnormal hepatic gluconeogenesis. Hepcidin expression may modulate this disorder by regulating ROS generation and iron deposition. Copyright © 2015 Elsevier Inc. All rights reserved.

Mineralogy and crystal chemistry of iron in the Timan bauxite and products of their technological processing

Science.gov (United States)

Kotova, O.; Silaev, V.; Lutoev, V.; Vakhrushev, A.

2016-04-01

Mineralogical and geochemical features of two series of samples of typical bauxites from two deposits of Middle Timan mining area (Vezhayu-Vorykva and Svetlinskoe) were studied. The phase composition of ferrous bauxites generally is boehmite, hematite, ultradisperse low-ordered goethite and berthierine. In a boehmite and kaolinite structural impurity of iron to 10%, and in the iron oxidehydroxides aluminum impurity is revealed. On iron content bauxites are subdivided into three mineral types for which quantitative data on valence states of ions of iron and proportions of their distribution last on nonequivalent structural positions in hematite, goethite and berthierine are obtained. Noble metals (Ag, Au, Ir, Rh, Pd) concentrating in bauxites are revealed for the first time. Obtained data can lead to decrease of power consumption during aluminum production and high quality ceramics, to provide production of valuable iron oxide, and also to minimize the ecological harm from accumulation of bauxite wastes.

Evolution and alteration in situ of a massive iron duricrust in Central Africa

Science.gov (United States)

Bitom, Dieudonné; Volkoff, Boris; Abossolo-Angue, Monique

2003-08-01

A soil sequence with iron duricrust is described in an area covered by tropical rain forest in South Cameroon. The dismantling of the iron duricrust is documented through a close observation of a soft duricrust, which corresponds to a transitional stage in the degradation of a massive iron duricrust into a loose nodular horizon. In the initial massive and hematitic duricrust, nodular shapes are progressively formed. The nodules and the internodular matrix remain hematitic. The internodular matrix undergoes goethitization and a pronounced deferruginisation before loosening; the primary structure of the iron duricrust is maintained, however, due to internodular bridges, relics of internodular matrix which escaped the process of goethitization. The iron is gradually released from these hematitic bridges, which become softer. This leads to the collapse of the initial structures of the iron duricrust and to the formation of a loose nodular material with a clayey matrix containing kaolinite and goethite. Many loose nodular horizons, which are found all over Central Africa, may have been formed by such alteration of a former iron duricrust.

An iron-57 Moessbauer spectroscopic study of titania-supported iron- and iron-iridium catalysts

International Nuclear Information System (INIS)

Berry, F.J.; Jobson, S.

1992-01-01

57 Fe Moessbauer spectroscopy shows that titania-supported iron is reduced by treatment in hydrogen at significantly lower temperatures than corresponding silica- and alumina-supported catalysts. The metallic iron formed under hydrogen at 600deg C is partially converted to carbide by treatment in carbon monoxide and hydrogen. In contrast to its alumina- and silica-supported counterparts, the remainder of the titania-supported iron is unchanged by this gaseous mixture. The 57 Fe Moessbauer spectra of EXAFS show that iron and iridium in the titania-supported iron-iridium catalysts are reduced in hydrogen at even lower temperatures and, after treatment at 600deg C, are predominantly present as the iron-iridium alloy. The treatment of these reduced catalysts in carbon monoxide and hydrogen is shown by Moessbauer spectroscopy and EXAFS to induce the segregation of iron from the iron-iridium alloy and its conversion to iron oxide. (orig.)

Soluble Moringa oleifera leaf extract reduces intracellular cadmium accumulation and oxidative stress in Saccharomyces cerevisiae.

Science.gov (United States)

Kerdsomboon, Kittikhun; Tatip, Supinda; Kosasih, Sattawat; Auesukaree, Choowong

2016-05-01

Moringa oleifera leaves are a well-known source of antioxidants and traditionally used for medicinal applications. In the present study, the protective action of soluble M. oleifera leaf extract (MOLE) against cadmium toxicity was investigated in the model eukaryote Saccharomyces cerevisiae. The results showed that this extract exhibited a protective effect against oxidative stress induced by cadmium and H2O2 through the reduction of intracellular reactive oxygen species. Interestingly, not only the co-exposure of soluble MOLE with cadmium but also pretreatment of this extract prior to cadmium exposure significantly reduced the cadmium uptake through an inhibition of Fet4p, a low-affinity iron(II) transporter. In addition, the supplementation of soluble MOLE significantly reduced intracellular iron accumulation in a Fet4p-independent manner. Our findings suggest the potential use of soluble extract from M. oleifera leaves as a dietary supplement for protection against cadmium accumulation and oxidative stress. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice

KAUST Repository

Jeong, Suh Young; Crooks, Daniel R.; Wilson-Ollivierre, Hayden; Ghosh, Manik C.; Sougrat, Rachid; Lee, Jaekwon; Cooperman, Sharon; Mitchell, James B.; Beaumont, Carole; Rouault, Tracey A.

2011-01-01

Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

Iron insufficiency compromises motor neurons and their mitochondrial function in Irp2-null mice

KAUST Repository

Jeong, Suh Young

2011-10-07

Genetic ablation of Iron Regulatory Protein 2 (Irp2, Ireb2), which post-transcriptionally regulates iron metabolism genes, causes a gait disorder in mice that progresses to hind-limb paralysis. Here we have demonstrated that misregulation of iron metabolism from loss of Irp2 causes lower motor neuronal degeneration with significant spinal cord axonopathy. Mitochondria in the lumbar spinal cord showed significantly decreased Complex I and II activities, and abnormal morphology. Lower motor neurons appeared to be the most adversely affected neurons, and we show that functional iron starvation due to misregulation of iron import and storage proteins, including transferrin receptor 1 and ferritin, may have a causal role in disease. We demonstrated that two therapeutic approaches were beneficial for motor neuron survival. First, we activated a homologous protein, IRP1, by oral Tempol treatment and found that axons were partially spared from degeneration. Secondly, we genetically decreased expression of the iron storage protein, ferritin, to diminish functional iron starvation. These data suggest that functional iron deficiency may constitute a previously unrecognized molecular basis for degeneration of motor neurons in mice.

Rapid sedimentation of iron oxyhydroxides in an active hydrothermal shallow semi-enclosed bay at Satsuma Iwo-Jima Island, Kagoshima, Japan

Science.gov (United States)

Kiyokawa, Shoichi; Ueshiba, Takuya

2015-04-01

Hydrothermal activity is common in the fishing port of Nagahama Bay, a small semi-enclosed bay located on the southwest coast of Satsuma Iwo-Jima Island (38 km south of Kyushu Island, Japan). The bay contains red-brown iron oxyhydroxides and thick deposits of sediment. In this work, the high concentration and sedimentation rates of oxyhydroxide in this bay were studied and the sedimentary history was reconstructed. Since dredging work in 1998, a thickness of 1.0-1.5 m of iron oxyhydroxide-rich sediments has accumulated on the floor of the bay. To estimate the volume of iron oxyhydroxide sediments and the amount discharged from hydrothermal vents, sediment traps were operated for several years and 13 sedimentary core samples were collected to reconstruct the 10-year sedimentary history of Nagahama Bay. To confirm the timing of sedimentary events, the core data were compared with meteorological records obtained on the island, and the ages of characteristic key beds were thus identified. The sedimentation rate of iron oxyhydroxide mud was calculated, after correcting for sediment input from other sources. The sediments in the 13 cores from Nagahama Bay consist mainly of iron oxyhydroxide mud, three thick tephra beds, and a topmost thick sandy mud bed. Heavy rainfall events in 2000, 2001, 2002, and 2004-2005 coincide with tephra beds, which were reworked from Iwo-Dake ash deposits to form tephra-rich sediment. Strong typhoon events with gigantic waves transported outer-ocean-floor sediments and supplied quartz, cristobalite, tridymite, and albite sands to Nagahama Bay. These materials were redeposited together with bay sediments as the sandy mud bed. Based on the results from the sediment traps and cores, it is estimated that the iron oxyhydroxide mud accumulated in the bay at the relatively rapid rate of 33.3 cm/year (from traps) and 2.8-4.9 cm/year (from cores). The pore water contents within the sediment trap and core sediments are 73%-82% and 47%-67%, respectively

SEALING LARGE-DIAMETER CAST-IRON PIPE JOINTS UNDER LIVE CONDITIONS

Energy Technology Data Exchange (ETDEWEB)

Kiran M. Kothari; Gerard T. Pittard

2004-04-01

Utilities in the U.S. operate over 75,000 km (47,000 miles) of old cast-iron pipes for gas distribution. The bell-and-spigot joints that connect pipe sections together tend to leak as these pipes age. Current repair practices are costly and highly disruptive. The objective of this program is to design, test and commercialize a robotic system capable of sealing multiple cast-iron bell and spigot joints from a single pipe entry point. The proposed system will perform repairs while the pipe remains in service by traveling through the pipe, cleaning each joint surface, and installing a stainless-steel sleeve lined with an epoxy-impregnated felt across the joint. This approach will save considerable time and labor, avoid traffic disruption, and eliminate any requirement to interrupt service to customers (which would result in enormous expense to utilities). Technical challenges include: (1) repair sleeves must compensate for diametric variation and eccentricity of cast-iron pipes; (2) the assembly must travel long distances through pipes containing debris; (3) the pipe wall must be effectively cleaned in the immediate area of the joint to assure good bonding of the sleeve; and (4) an innovative bolt-on entry fitting is required to conduct repair operations on live mains. The development effort is divided into eleven tasks. Task 1--Program Management and Task 2--were completed in prior quarters while Task 3--Design and Fabricate Ratcheting Stainless-Steel Repair Sleeves has progressed to installing prototype sleeves in cast iron test pipe segments. Efforts in this quarter continued to focus on Tasks 4--8, with significant progress made in each. Task 4 (Design, Fabricate and Test Patch Setting Robotic Train) progressed to the design of the control electronics and pneumatic system to inflate the bladder robotic patch setting module. Task 5 (Design & Fabricate Pipe-Wall Cleaning Robot Train with Pan/Zoom/Tilt Camera) continued with additional in-pipe testing required to

Iron phosphate nanoparticles for food fortification: Biological effects in rats and human cell lines.

Science.gov (United States)

von Moos, Lea M; Schneider, Mirjam; Hilty, Florentine M; Hilbe, Monika; Arnold, Myrtha; Ziegler, Nathalie; Mato, Diogo Sales; Winkler, Hans; Tarik, Mohamed; Ludwig, Christian; Naegeli, Hanspeter; Langhans, Wolfgang; Zimmermann, Michael B; Sturla, Shana J; Trantakis, Ioannis A

2017-05-01

Nanotechnology offers new opportunities for providing health benefits in foods. Food fortification with iron phosphate nanoparticles (FePO 4 NPs) is a promising new approach to reducing iron deficiency because FePO 4 NPs combine high bioavailability with superior sensory performance in difficult to fortify foods. However, their safety remains largely untested. We fed rats for 90 days diets containing FePO 4 NPs at doses at which iron sulfate (FeSO 4 ), a commonly used food fortificant, has been shown to induce adverse effects. Feeding did not result in signs of toxicity, including oxidative stress, organ damage, excess iron accumulation in organs or histological changes. These safety data were corroborated by evidence that NPs were taken up by human gastrointestinal cell lines without reducing cell viability or inducing oxidative stress. Our findings suggest FePO 4 NPs appear to be as safe for ingestion as FeSO 4 .

Biomarkers of Hypochromia: The Contemporary Assessment of Iron Status and Erythropoiesis

Directory of Open Access Journals (Sweden)

Eloísa Urrechaga

2013-01-01

Full Text Available Iron status is the result of the balance between the rate of erythropoiesis and the amount of the iron stores. Direct consequence of an imbalance between the erythroid marrow iron requirements and the actual supply is a reduction of red cell hemoglobin content, which causes hypochromic mature red cells and reticulocytes. The diagnosis of iron deficiency is particularly challenging in patients with acute or chronic inflammatory conditions because most of the biochemical markers for iron metabolism (serum ferritin and transferrin are affected by acute phase reaction. For these reasons, interest has been generated in the use of erythrocyte and reticulocyte parameters, available on the modern hematology analyzers. Reported during blood analysis routinely performed on the instrument, these parameters can assist in early detection of clinical conditions (iron deficiency, absolute, or functional; ineffective erythropoiesis, including iron restricted or thalassemia, without additional cost. Technological progress has meant that in recent years modern analyzers report new parameters that provide further information from the traditional count. Nevertheless these new parameters are exclusive of each manufacturer, and they are patented. This is an update of these new laboratory test biomarkers of hypochromia reported by different manufactures, their meaning, and clinical utility on daily practice.

Iron status of pregnant Filipino women as measured by serum ferritin.

Science.gov (United States)

Perlas, L A; Kuizon, M D; Tajaon, R T; Desnacido, J A

1992-12-01

Iron status of pregnant women at different stages of pregnancy was evaluated by comparing values for hemoglobin (Hb), red cell indices, serum iron (SI), transferrin saturation (TS) and serum ferritin (SF) values with those of a group of non-pregnant women of comparable age and socio-economic status. Mean SF values on the second and third trimesters (9.3 +/- 2.60 ng/ml and 7.1 +/- 2.19 ng/ml) were significantly lower compared to that in the first trimester (22.6 +/- 2.20 ng/ml). These levels were also lower than that found in the non-pregnant controls. The trend was the same for TS. Hemoglobin levels of the pregnant subjects were significantly lower than those of the non-pregnant women. Prevalence of iron deficiency based on SF < 12.0 ng/ml and TS < 16.0% was highest at term and lowest during the first trimester indicating a decrease in iron stores as pregnancy progressed. Sensitivity for each of the iron parameters was computed, and it was found that for the diagnosis of iron deficiency in pregnant women, SF has a greater sensitivity than TS, SI, MCV and MCH.

Peculiarities of antioxidant system and iron metabolism in organism during development of tumor resistance to cisplatin.

Science.gov (United States)

Chekhun, V F; Lozovska, Y V; Burlaka, A P; Lukyanova, N Y; Todor, I N; Naleskina, L A

2014-09-01

To study in vivo the peculiarities of changes of iron metabolism and antioxidant system in dynamics of growth of Guerin carcinoma with different sensitivity to cisplatin. In order to evaluate the content of metallothionein-1 (MT-1) in tumor homogenates and blood serum of rats with cisplatin-sensitive and cisplatin-resistant Guerin carcinoma the immunoenzyme method was used. The evaluation of ceruloplasmin activity, content of "free iron" complexes, superoxide and NO-generating acti-vity of NADPH-oxidase and iNOS activity in neutrophils, blood serum and tumor homogenates was measured by EPR-spectro-scopy. Maximal accumulation of MT-1 in blood serum and tumor, more pronounced in resistant strain, at the border of latent and exponential phase of growth has been shown that is the evidence of protective role of this protein in the respect to the generation of free radical compounds. It has been determined that in animals with cisplatin-resistant strain of Guerin carcinoma, increase of "free iron" complexes is more apparent both on the level of tumor and organism on the background on increase of CP/TR ratio that is the consequence of organism antioxidant protection system disorder. Mentioned changes in metabolism of iron with its accumulation in tumor and further reprogramming of mitochondria metabolism and activity of NADPH-oxidase for non-transformed cells are favorable conditions for the formation of oxidative phenotype of tumor.

HFE Gene Mutations and Iron Status in 100 Healthy Polish Children.

Science.gov (United States)

Kaczorowska-Hac, Barbara; Luszczyk, Marcin; Antosiewicz, Jedrzej; Ziolkowski, Wieslaw; Adamkiewicz-Drozynska, Elzbieta; Mysliwiec, Malgorzata; Milosz, Ewa; Kaczor, Jan J

2017-07-01

Iron participates in oxygen transport, energetic, metabolic, and immunologic processes. There are 2 main causes of iron overload: hereditary hemochromatosis which is a primary cause, is a metabolic disorder caused by mutations of genes that control iron metabolism and secondary hemochromatosis caused by multitransfusions, chronic hemolysis, and intake of iron rich food. The most common type of hereditary hemochromatosis is caused by HFE gene mutation. In this study, we analyzed iron metabolism in 100 healthy Polish children in relation to their HFE gene status. The wild-type HFE gene was predominant being observed in 60 children (60%). Twenty-five children (25%), presented with heterozygotic H63D mutation, and 15 children (15%), presented with other mutations (heterozygotic C282Y and S65C mutation, compound heterozygotes C282Y/S65C, C282Y/H63D, H63D homozygote). The mean concentration of iron, the level of ferritin, and transferrin saturation were statistically higher in the group of HFE variants compared with the wild-type group. H63D carriers presented with higher mean concentration of iron, ferritin levels, and transferrin saturation compared with the wild-type group. Male HFE carriers presented with higher iron concentration, transferrin saturation, and ferritin levels than females. This preliminary investigation demonstrates allelic impact on potential disease progression from childhood.

The Nutraceutic Silybin Counteracts Excess Lipid Accumulation and Ongoing Oxidative Stress in an In Vitro Model of Non-Alcoholic Fatty Liver Disease Progression

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Giulia Vecchione

2017-09-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD is a major cause of liver-related morbidity and mortality. Oxidative stress and release of pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα, are major consequences of hepatic lipid overload, which can contribute to progression of NAFLD to non-alcoholic steatohepatitis (NASH. Also, mitochondria are involved in the NAFLD pathogenesis for their role in hepatic lipid metabolism. Definitive treatments for NAFLD/NASH are lacking so far. Silybin, the extract of the milk thistle seeds, has previously shown beneficial effects in NAFLD. Sequential exposure of hepatocytes to high concentrations of fatty acids (FAs and TNFα resulted in fat overload and oxidative stress, which mimic in vitro the progression of NAFLD from simple steatosis (SS to steatohepatitis (SH. The exposure to 50 µM silybin for 24 h reduced fat accumulation in the model of NAFLD progression. The in vitro progression of NAFLD from SS to SH resulted in reduced hepatocyte viability, increased apoptosis and oxidative stress, reduction in lipid droplet size, and up-regulation of IκB kinase β-interacting protein and adipose triglyceride lipase expressions. The direct action of silybin on SS or SH cells and the underlying mechanisms were assessed. Beneficial action of silybin was sustained by changes in expression/activity of peroxisome proliferator-activated receptors and enzymes for FA oxidation. Moreover, silybin counteracted the FA-induced mitochondrial damage by acting on complementary pathways: (i increased the mitochondrial size and improved the mitochondrial cristae organization; (ii stimulated mitochondrial FA oxidation; (iii reduced basal and maximal respiration and ATP production in SH cells; (iv stimulated ATP production in SS cells; and (v rescued the FA-induced apoptotic signals and oxidative stress in SH cells. We provide new insights about the direct protective effects of the nutraceutic silybin on hepatocytes

Mutation in HFE gene decreases manganese accumulation and oxidative stress in the brain after olfactory manganese exposure.

Science.gov (United States)

Ye, Qi; Kim, Jonghan

2016-06-01

Increased accumulation of manganese (Mn) in the brain is significantly associated with neurobehavioral deficits and impaired brain function. Airborne Mn has a high systemic bioavailability and can be directly taken up into the brain, making it highly neurotoxic. While Mn transport is in part mediated by several iron transporters, the expression of these transporters is altered by the iron regulatory gene, HFE. Mutations in the HFE gene are the major cause of the iron overload disorder, hereditary hemochromatosis, one of the prevalent genetic diseases in humans. However, whether or not HFE mutation modifies Mn-induced neurotoxicity has not been evaluated. Therefore, our goal was to define the role of HFE mutation in Mn deposition in the brain and the resultant neurotoxic effects after olfactory Mn exposure. Mice carrying the H67D HFE mutation, which is homologous to the H63D mutation in humans, and their control, wild-type mice, were intranasally instilled with MnCl2 with different doses (0, 0.2, 1.0 and 5.0 mg kg(-1)) daily for 3 days. Mn levels in the blood, liver and brain were determined using inductively-coupled plasma mass spectrometry (ICP-MS). H67D mutant mice showed significantly lower Mn levels in the blood, liver, and most brain regions, especially in the striatum, while mice fed an iron-overload diet did not. Moreover, mRNA expression of ferroportin, an essential exporter of iron and Mn, was up-regulated in the striatum. In addition, the levels of isoprostane, a marker of lipid peroxidation, were increased in the striatum after Mn exposure in wild-type mice, but were unchanged in H67D mice. Together, our results suggest that the H67D mutation provides decreased susceptibility to Mn accumulation in the brain and neurotoxicity induced by inhaled Mn.

Mössbauer spectroscopy and the understanding of the role of iron in neurodegeneration

Science.gov (United States)

Friedman, A.; Galazka-Friedman, J.

2017-11-01

The possible role of iron in neurodegeneration may be related to the oxidative stress, triggered by Fenton reaction. In this reaction hydroxyl free radical production is generated by divalent iron. Motor symptoms of Parkinson's disease depend on the destruction of substantia nigra (SN). As the substantive questions were: 1/ what is the concentration of iron in the samples, 2/ what is the proportion of divalent vs. trivalent iron in the samples, and 3/ what is the iron-binding compound, it seemed appropriate to use Mössbauer spectroscopy to answer those questions. We found no difference in the concentration of total iron between PD and control, with the ratio of iron in PD vs. control being 1.00 ± 0.13. The divalent iron could not exceed 5% of the total iron. The main iron-binding compound in SN, both in PD and control is ferritin. Our further studies of ferritin in parkinsonian SN demonstrated a decrease, compared to control, of L-ferritin involved in the storage of iron within ferritin. This could allow an efflux of iron from the ferritin shell and an increase of non-ferritin iron in PD SN, which was confirmed by us. Mössbauer studies in Alzheimer showed slightly higher concentration of iron in hippocampal cortex with significantly higher concentrations of L and H ferritins compared to control. In atypical parkinsonism, progressive supranuclear palsy, higher concentration of iron was found in globus pallidus and SN compared to control. Mössbauer spectroscopy may play crucial role in further studies of human neurodegeneration.

Colour Metallography of Cast Iron - Chapter 1: Introduction (Ⅰ

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Zhou Jiyang

2009-02-01

Full Text Available Cast iron, as a traditional metal material, has advantages of low total cost, good castability and machinability, good wear resistance and low notch sensitivity, and is still facing tough challenge in quality, property and variety of types etc. Experts and engineers studying and producing iron castings all around world extremely concern this serious challenge. Over more than 30 years, a great of research work has been carried out on how to further improve its property, expand its application and combine cast iron technology with some hi-techs (for example, computer technology. Nevertheless, cast iron is a multi-element and multi-phase alloy and has complex and variety of structures and still has great development potential in structure and property. For further studying and developing cast iron, theoretical research work is important promise, and the study on solidification process and control mechanism of graphite morphology is fundamental for improving property of cast iron and developing new type of cast iron. Metallography of cast iron normally includes two sections: liquid phase transformation and solid phase transformation. The book, Colour Metallography of Cast Iron, uses colour metallography technique to study solidification structures of cast irons: graphite, carbides, austenite and eutectics; and focuses on solidification processes. With progress of modern solidification theory, the control of material solidification process becomes important measure for improving traditional materials and developing new materials. Solidification structure not only influences mechanical and physical properties of cast iron, but also affects its internal quality. The book uses a large amount of colour photos to describe the formation of solidification structures and their relations. Crystallization phenomena, which cannot be displayed with traditional metallography, are presented and more phase transformation information is obtained from these colour

Dynamic changes in radial oxygen loss and iron plaque formation and their effects on Cd and As accumulation in rice (Oryza sativa L.).

Science.gov (United States)

Wang, Xun; Yao, Haixin; Wong, Ming Hung; Ye, Zhihong

2013-12-01

Temporal variations and correlations between radial oxygen loss (ROL), iron (Fe) plaque formation, cadmium (Cd) and arsenic (As) accumulation were investigated in two rice cultivars at four different growth stages based upon soil pot and deoxygenated solution experiments. The results showed that there were significant differences in ROL (1.1-16 μmol O(2) plant(-1) h(-1)), Fe plaque formation (4,097-36,056 mg kg(-1)), Cd and As in root tissues (Cd 77-162 mg kg(-1); As 49-199 mg kg(-1)) and Fe plaque (Cd 0.4-24 mg kg(-1); As 185-1,396 mg kg(-1)) between these growth stages. ROL and Fe plaque increased dramatically from tillering to ear emergence stages and then were much reduced at the grain-filling stage. Furthermore, significantly positive correlations were detected between ROL and concentrations of Fe, Cd and As in Fe plaque. Our study indicates that increased Fe plaque forms on rice roots at the ear emergence stage due to the increased ROL. This stage could therefore be an important period to limit the transfer and distribution of Cd and As in rice plants when growing in soils contaminated with these toxic elements.

Higher iron bioavailability of a human-like collagen iron complex.

Science.gov (United States)

Zhu, Chenhui; Yang, Fan; Fan, Daidi; Wang, Ya; Yu, Yuanyuan

2017-07-01

Iron deficiency remains a public health problem around the world due to low iron intake and/or bioavailability. FeSO 4 , ferrous succinate, and ferrous glycinate chelate are rich in iron but have poor bioavailability. To solve the problem of iron deficiency, following previous research studies, a thiolated human-like collagen-ironcomplex supplement with a high iron content was prepared in an anaerobic workstation. In addition, cell viability tests were evaluated after conducting an MTT assay, and a quantitative analysis of the thiolated human-like collagen-iron digesta samples was performed using the SDS-PAGE method coupled with gel filtration chromatography. The iron bioavailability was assessed using Caco-2 cell monolayers and iron-deficiency anemia mice models. The results showed that (1) one mole of thiolated human-like collagen-iron possessed approximately 35.34 moles of iron; (2) thiolated human-like collagen-iron did not exhibit cytotoxity and (3) thiolated human-like collagen- iron digesta samples had higher bioavailability than other iron supplements, including FeSO 4 , ferrous succinate, ferrous glycine chelate and thiolated human-like collagen-Fe iron. Finally, the iron bioavailability was significantly enhanced by vitamin C. These results indicated that thiolated human-like collagen-iron is a promising iron supplement for use in the future.

Adrenaline and triiodothyronine modify the iron handling in the freshwater air-breathing fish Anabas testudineus Bloch: role of ferric reductase in iron acquisition.

Science.gov (United States)

Rejitha, V; Peter, M C Subhash

2013-01-15

The effects of in vivo adrenaline and triiodothyronine (T(3)) on ferric reductase (FR) activity, a membrane-bound enzyme that reduces Fe(III) to Fe(II) iron, were studied in the organs of climbing perch (Anabas testudineus Bloch). Adrenaline injection (10 ng g(-1)) for 30 min produced significant inhibition of FR activity in the liver and kidney and that suggests a role for this stress hormone in iron acquisition in this fish. Short-term T(3) injection (40 ng g(-1)) reduced FR activity in the gills of fed fish but not in the unfed fish. Similar reduction of FR activity was also obtained in the intestine and kidney of fed fish after T(3) injection. Feeding produced pronounced decline in FR activity in the spleen but T(3) challenge in fed and unfed fish increased its activity in this iron storing organ and that point to the sensitivity of FR system to feeding activity. The in vitro effects of Fe on FR activity in the gill explants of freshwater fish showed correlations of FR with Na(+), K(+)-ATPase and H(+)-ATPase activities. Substantial increase in the FR activity was found in the gill explants incubated with all the tested doses of Fe(II) iron (1.80, 3.59 and 7.18 μM) and Fe(III) iron (1.25, 2.51 and 5.02 μM) and this indicate that FR and Na pump activity are positively correlated. On the contrary, substantial reduction of gill H(+)-ATPase activity was found in the gill explants incubated with Fe(II) iron and Fe(III) iron indicating that perch gills may not require a high acidic microenvironment for the reduction of Fe(III) iron. Accumulation of iron in the gill explants after Fe(III) iron incubation implies a direct relationship between Fe acquisition and FR activity in this tissue. The inverse correlation between FR activity and H(+)-ATPase activity in Fe(II) or Fe(III) loaded gills and the significant positive correlations of FR activity with total [Fe] content in the Fe(III) loaded gills substantiate that FR which shows sensitivity to sodium and proton pumps

Low energy current accumulator for high-energy proton rings

International Nuclear Information System (INIS)

Month, M.

1977-01-01

Building current in high-energy p-p colliding beam machines is most appropriately done in a low-energy (small circumference) current accumulator. Three significant factors favor such a procedure: First, large rings tend to be susceptible to unstable longitudinal density oscillations. These can be avoided by pumping up the beam in the accumulator. When the current stack is injected into the storage ring, potentially harmful instability is essentially neutralized. Second, high-field magnets characteristic of future high energy proton rings are designed with superconducting coils within the iron magnetic shield. This means coil construction and placement errors propagate rapidly within the beam aperture. An intermediate ''stacking ring'' allows the minimum use of the superconducting ring aperture. Finally, the coils are vulnerable to radiation heating and possible magnet quenching. By minimizing beam manipulaion in the superconducting environment and using only the central portion of the beam aperture, coil vulnerability can be put at a minimum

Arsenic content in pteridophytes from the Iron Quadrangle, Minas Gerais, Brazil

International Nuclear Information System (INIS)

Uemura, George; Menezes, Maria Angela de Barros C.; Silva, Lucilene Guerra e; Isaias, Rosy Mary dos Santos; Salino, Alexandre

2005-01-01

Natural arsenic contamination is a cause for concern in many countries of the world and, in Brazil, specially in the Iron Quadrangle area, where mining activities contributed to aggravate natural contamination of this area. The discovery that a fern, Pteris vitata, hyperaccumulates arsenic led to the search of other pteridophytes species with such capacity, due to their possible use for phytoremediation of contaminated areas. In the literature cited, arsenic amounts were measured by atomic absorption, using leaf and roots samples; and only one species (Pityrogramma calomelanos) had the arsenic content of its spores measured. In a preliminary study, ferns samples from the Iron Quadrangle region were collected, identified and had their leaves processed for measurement of their arsenic content through Neutron Activation Analysis - method k 0 ; also, spores of Pteris vitata had their arsenic content measured. The results showed that: spores of P. vitata present arsenic accumulation and another fern species was found to accumulate arsenic (Adiantum raddianum). Other species that were screened confirm that, among the families of ferns already studied, species from the family Pteridaceae seems the most promising for arsenic phytoremediation purposes. Considering that two species that showed arsenic accumulation in their leaves, also presented high arsenic content in their spores, it might fasten the selection if the spores of different fern species from contaminated sites are screened first, making the process of species selection for phytoremediation faster and more efficient. (author)

Arsenic content in pteridophytes from the Iron Quadrangle, Minas Gerais, Brazil

Energy Technology Data Exchange (ETDEWEB)

Uemura, George; Menezes, Maria Angela de Barros C.; Silva, Lucilene Guerra e [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Belo Horizonte, MG (Brazil)]. E-mail: george@cdtn.br; menezes@cdtn.br; leneguerra@bol.com.br; Isaias, Rosy Mary dos Santos; Salino, Alexandre [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Botanica]. E-mail: rosy@icb.ufmg.br; salino@mono.icb.ufmg.br

2005-07-01

Natural arsenic contamination is a cause for concern in many countries of the world and, in Brazil, specially in the Iron Quadrangle area, where mining activities contributed to aggravate natural contamination of this area. The discovery that a fern, Pteris vitata, hyperaccumulates arsenic led to the search of other pteridophytes species with such capacity, due to their possible use for phytoremediation of contaminated areas. In the literature cited, arsenic amounts were measured by atomic absorption, using leaf and roots samples; and only one species (Pityrogramma calomelanos) had the arsenic content of its spores measured. In a preliminary study, ferns samples from the Iron Quadrangle region were collected, identified and had their leaves processed for measurement of their arsenic content through Neutron Activation Analysis - method k{sub 0}; also, spores of Pteris vitata had their arsenic content measured. The results showed that: spores of P. vitata present arsenic accumulation and another fern species was found to accumulate arsenic (Adiantum raddianum). Other species that were screened confirm that, among the families of ferns already studied, species from the family Pteridaceae seems the most promising for arsenic phytoremediation purposes. Considering that two species that showed arsenic accumulation in their leaves, also presented high arsenic content in their spores, it might fasten the selection if the spores of different fern species from contaminated sites are screened first, making the process of species selection for phytoremediation faster and more efficient. (author)

The memory of iron stress in strawberry plants.

Science.gov (United States)

Gama, Florinda; Saavedra, Teresa; da Silva, José Paulo; Miguel, Maria Graça; de Varennes, Amarilis; Correia, Pedro José; Pestana, Maribela

2016-07-01

To provide information towards optimization of strategies to treat Fe deficiency, experiments were conducted to study the responses of Fe-deficient plants to the resupply of Fe. Strawberry (Fragaria × ananassa Duch.) was used as model plant. Bare-root transplants of strawberry (cv. 'Diamante') were grown for 42 days in Hoagland's nutrient solutions without Fe (Fe0) and containing 10 μM of Fe as Fe-EDDHA (control, Fe10). For plants under Fe0 the total chlorophyll concentration of young leaves decreased progressively on time, showing the typical symptoms of iron chlorosis. After 35 days the Fe concentration was 6% of that observed for plants growing under Fe10. Half of plants growing under Fe0 were then Fe-resupplied by adding 10 μM of Fe to the Fe0 nutrient solution (FeR). Full Chlorophyll recovery of young leaves took place within 12 days. Root ferric chelate-reductase activity (FCR) and succinic and citric acid concentrations increased in FeR plants. Fe partition revealed that FeR plants expressively accumulated this nutrient in the crown and flowers. This observation can be due to a passive deactivation mechanism of the FCR activity, associated with continuous synthesis of succinic and citric acids at root level, and consequent greater uptake of Fe. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body.

Directory of Open Access Journals (Sweden)

Christal A Worthen

2014-03-01

Full Text Available Fine tuning of body iron is required to prevent diseases such as iron-overload and anemia. The putative iron-sensor, transferrin receptor 2 (TfR2, is expressed in the liver and mutations in this protein result in the iron-overload disease Type III hereditary hemochromatosis (HH. With the loss of functional TfR2, the liver produces about two-fold less of the peptide hormone hepcidin, which is responsible for negatively regulating iron uptake from the diet. This reduction in hepcidin expression leads to the slow accumulation of iron in the liver, heart, joints, and pancreas and subsequent cirrhosis, heart disease, arthritis, and diabetes. TfR2 can bind iron-loaded transferrin in the bloodstream, and hepatocytes treated with transferrin respond with a two-fold increase in hepcidin expression through stimulation of the BMP-signaling pathway. Loss of functional TfR2 or its binding partner, the original HH protein (HFE, results in a loss of this transferrin-sensitivity. While much is known about the trafficking and regulation of TfR2, the mechanism of its transferrin-sensitivity through the BMP-signaling pathway is still not known.

Structural transformations of heat-treated bacterial iron oxide

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, Hideki, E-mail: hideki-h@cc.okayama-u.ac.jp [Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530 (Japan); JST, CREST, Okayama 700-8530 (Japan); Fujii, Tatsuo [Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530 (Japan); Kohara, Shinji [Japan Synchrotron Radiation Research Institute, Sayo, Hyogo 679-5198 (Japan); Nakanishi, Koji [Office of Society-Academia Collaboration for Innovation, Kyoto University, Uji 611-0011 (Japan); Yogi, Chihiro [SR Center, Ritsumeikan University, Kusatsu, Shiga 525-8577 (Japan); Peterlik, Herwig [Faculty of Physics, University of Vienna, A-1090 Vienna (Austria); Nakanishi, Makoto [Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530 (Japan); Takada, Jun [Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530 (Japan); JST, CREST, Okayama 700-8530 (Japan)

2015-04-01

A bacterial siliceous iron oxide microtubule (diameter: ca. 1 μm, 15Fe{sub 2}O{sub 3}·8SiO{sub 2}·P{sub 2}O{sub 5}·30H{sub 2}O) produced by Leptothrix ochracea was heat treated in air and its structural transformation was investigated in detail by microscopy, diffractometry, and spectroscopy. Although the heat-treated bacterial iron oxide retained its original microtubular structure, its nanoscopic, middle-range, and local structures changed drastically. Upon heat treatment, nanosized pores were formed and their size changed depending on temperature. The Fe–O–Si linkages were gradually cleaved with increasing temperature, causing the progressive separation of Fe and Si ions into iron oxide and amorphous silicate phases, respectively. Concomitantly, global connectivity and local structure of FeO{sub 6} octahedra in the iron oxide nanoparticles systematically changed depending on temperature. These comprehensive investigations clearly revealed various structural changes of the bacterial iron oxide which is an important guideline for the future exploration of novel bio-inspired materials. - Highlights: • Structural transformation of a bacterial iron oxide microtubule was investigated. • Si–O–Fe was cleaved with increasing temperature to form α-Fe{sub 2}O{sub 3}/silicate composite. • Crystallization to 2Fh started at 500 °C to give α-Fe{sub 2}O{sub 3} >700 °C. • FeO{sub 6} octahedra were highly distorted <500 °C. • Formation of face-sharing FeO{sub 6} was promoted >500 °C, releasing the local strain of FeO{sub 6}.