Haemochromatosis and HLA--H

The recently identified can didate gene, HLA-H, for haemochromatosis (HH) by Feder et al. generated considerable scientific interest coupled with a degree of uncertainty about the likely involvement of this gene in this common iron metabolism disorder, Feder et al. found a single point mutation resulting in an amino acid substitution (C282Y) that was homozygous in 148 (83%) of their patients, heterozygous in 9 patients (5%) but completely absent in 21 patients (12%). They proposed that the lack of a causative mutation in HLA-H in 12% of their patients was because these cases were not linked to chromosome 6p. A significant weakness in this argument is that all familial studies of the disorder so far have concluded that HH is due to a single major HLA-linked gene5-7. The ultimate test for a candidate gene is the clear segregation of a mutation with the disorder in all patients. Thus, some of the uncertainty surrounding the role of HLA-H in HH may be resolved by the identification of complete concordance of the C282Y mutation (or some other mutation) in HLA H with disease status in HH families. One potential problem in the design of such an experimental analysis is that a number of studies have shown the presence of a predominant ancestral haplotype in all HH populations examined: Australian, French, Italian, UK and US Thus in the analysis of a putative causative mutation, it is important to include families with...

Iron biogeochemistry and associated greenhouse gas evolution in a forested subtropical Australian coastal catchment : Poona Creek, Southeast Queensland

Iron (Fe) is the fourth most abundant element in the Earth’s crust. Excess Fe mobilization from terrestrial into aquatic systems is of concern for deterioration of water quality via biofouling and nuisance algal blooms in coastal and marine systems. Substantial Fe dissolution and transport involve alternate Fe(II) oxidation followed by Fe(III) reduction, with a diversity of Bacteria and Archaea acting as the key catalyst. Microbially-mediated Fe cycling is of global significance with regard to cycles of carbon (C), sulfur (S) and manganese (Mn). However, knowledge regarding microbial Fe cycling in circumneutral-pH habitats that prevail on Earth has been lacking until recently. In particular, little is known regarding microbial function in Fe cycling and associated Fe mobilization and greenhouse (CO2 and CH4, GHG) evolution in subtropical Australian coastal systems where microbial response to ambient variations such as seasonal flooding and land use changes is of concern. Using the plantation-forested Poona Creek catchment on the Fraser Coast of Southeast Queensland (SEQ), this research aimed to 1) study Fe cycling-associated bacterial populations in diverse terrestrial and aquatic habitats of a representative subtropical coastal circumneutral-pH (4–7) ecosystem; and 2) assess potential impacts of Pinus plantation forestry practices on microbially-mediated Fe mobilization, organic C mineralization and associated GHG evolution in coastal SEQ. A combination of wet-chemical extraction, undisturbed core microcosm, laboratory bacterial cultivation, microscopy and 16S rRNA-based molecular phylogenetic techniques were employed. The study area consisted primarily of loamy sands, with low organic C and dissolved nutrients. Total reactive Fe was abundant and evenly distributed within soil 0–30 cm profiles. Organic complexation primarily controlled Fe bioavailability and forms in well-drained plantation soils and water-logged, native riparian soils, whereas tidal flushing exerted a strong “seawater effect” in estuarine locations and formed a large proportion of inorganic Fe(III) complexes. There was a lack of Fe(II) sources across the catchment terrestrial system. Mature, first-rotation plantation clear-felling and second-rotation replanting significantly decreased organic matter and poorly crystalline Fe in well-drained soils, although variations in labile soil organic C fractions (dissolved organic C, DOC; and microbial biomass C, MBC) were minor. Both well-drained plantation soils and water-logged, native-vegetation soils were inhabited by a variety of cultivable, chemotrophic bacterial populations capable of C, Fe, S and Mn metabolism via lithotrophic or heterotrophic, (micro)aerobic or anaerobic pathways. Neutrophilic Fe(III)-reducing bacteria (FeRB) were most abundant, followed by aerobic, heterotrophic bacteria (heterotrophic plate count, HPC). Despite an abundance of FeRB, cultivable Fe(II)-oxidizing bacteria (FeOB) were absent in associated soils. A lack of links between cultivable Fe, S or Mn bacterial densities and relevant chemical measurements (except for HPC correlated with DOC) was likely due to complex biogeochemical interactions. Neither did variations in cultivable bacterial densities correlate with plantation forestry practices, despite total cultivable bacterial densities being significantly lower in estuarine soils when compared with well-drained plantation soils and water-logged, riparian native-vegetation soils. Given that bacterial Fe(III) reduction is the primary mechanism of Fe oxide dissolution in soils upon saturation, associated Fe mobilization involved several abiotic and biological processes. Abiotic oxidation of dissolved Fe(II) by Mn appeared to control Fe transport and inhibit Fe dissolution from mature, first-rotation plantation soils post-saturation. Such an effect was not observed in clear-felled and replanted soils associated with low SOM and potentially low Mn reactivity. Associated GHG evolution post-saturation mainly involved variable CO2 emissions, with low, but consistently increasing CH4 effluxes in mature, first-rotation plantation soil only. In comparison, water-logged soils in the riparian native-vegetation buffer zone functioned as an important GHG source, with high potentials for Fe mobilization and GHG, particularly CH4 emissions in riparian loam soils associated with high clay and crystalline Fe fractions. Active Fe–C cycling was unlikely to occur in lower-catchment estuarine soils associated with low cultivable bacterial densities and GHG effluxes. As a key component of bacterial Fe cycling, neutrophilic FeOB widely occurred in diverse aquatic, but not terrestrial, habitats of the catchment study area. Stalked and sheathed FeOB resembling Gallionella and Leptothrix were limited to microbial mat material deposited in surface fresh waters associated with a circumneutral-pH seep, and clay-rich soil within riparian buffer zones. Unicellular, Sideroxydans-related FeOB (96% sequence identity) were ubiquitous in surface and subsurface freshwater environments, with highest abundance in estuary-adjacent shallow coastal groundwater water associated with redox transition. The abundance of dissolved C and Fe in the groundwater-dependent system was associated with high numbers of cultivable anaerobic, heterotrophic FeRB, microaerophilic, putatively lithotrophic FeOB and aerobic, heterotrophic bacteria. This research represents the first study of microbial Fe cycling in diverse circumneutral-pH environments (terrestrial–aquatic, freshwater–estuarine, surface–subsurface) of a subtropical coastal ecosystem. It also represents the first study of its kind in the southern hemisphere. This work highlights the significance of bacterial Fe(III) reduction in terrestrial, and bacterial Fe(II) oxidation in aquatic catchment Fe cycling. Results indicate the risk of promotion of Fe mobilization due to plantation clear-felling and replanting, and GHG emissions associated with seasonal water-logging. Additional significant outcomes were also achieved. The first direct evidence for multiple biomineralization patterns of neutrophilic, microaerophilic, unicellular FeOB was presented. A putatively pure culture, which represents the first cultivable neutrophilic FeOB from the southern hemisphere, was obtained as representative FeOB ubiquitous in diverse catchment aquatic habitats.

Bacterially mediated iron cycling and associated biogeochemical processes in a subtropical shallow coastal aquifer: implications for groundwater quality

Bacterially mediated iron redox cycling exerts a strong influence on groundwater geochemistry, but few studies have investigated iron biogeochemical processes in coastal alluvial aquifers from a microbiological viewpoint. The shallow alluvial aquifer located adjacent to Poona estuary on the subtropical Southeast Queensland coast represents a redox-stratified system where iron biogeochemical cycling potentially affects water quality. Using a 300 m transect of monitoring wells perpendicular to the estuary, we examined groundwater physico-chemical conditions and the occurrence of cultivable bacterial populations involved in iron (and manganese, sulfur) redox reactions in this aquifer. Results showed slightly acidic and near-neutral pH, suboxic conditions and an abundance of dissolved iron consisting primarily of iron(II) in the majority of wells. The highest level of dissolved iron(III) was found in a well proximal to the estuary most likely a result of iron curtain effects due to tidal intrusion. A number of cultivable, (an)aerobic bacterial populations capable of diverse carbon, iron, or sulfur metabolism coexisted in groundwater redox transition zones. Our findings indicated aerobic, heterotrophic respiration and bacterially mediated iron/sulfur redox reactions were integral to carbon cycling in the aquifer. High abundances of dissolved iron and cultivable iron and sulfur bacterial populations in estuary-adjacent aquifers have implications for iron transport to marine waters. This study demonstrated bacterially mediated iron redox cycling and associated biogeochemical processes in subtropical coastal groundwaters using culture-based methods.

The influence of vegetation and soil type on the speciation of iron in soil water

Soluble organic matter derived from exotic Pinus species has been shown to form stronger complexes with iron (Fe) than that derived from most native Australian species. It has also been proposed that the establishment of exotic Pinus plantations in coastal southeast Queensland may have enhanced the solubility of Fe in soils by increasing the amount of organically complexed Fe, but this remains inconclusive. In this study we test whether the concentration and speciation of Fe in soil water from Pinus plantations differs significantly from soil water from native vegetation areas. Both Fe redox speciation and the interaction between Fe and dissolved organic matter (DOM) were considered; Fe - DOM interaction was assessed using the Stockholm Humic Model. Iron concentrations (mainly Fe 2+) were greatest in the soil waters with the greatest DOM content collected from sandy podosols (Podzols), where they are largely controlled by redox potential. Iron concentrations were small in soil waters from clay and iron oxide-rich soils, in spite of similar redox potentials. This condition is related to stronger sorption on to the reactive clay and iron oxide mineral surfaces in these soils, which reduces the amount of DOM available for electron shuttling and microbial metabolism, restricting reductive dissolution of Fe. Vegetation type had no significant influence on the concentration and speciation of iron in soil waters, although DOM from Pinus sites had greater acidic functional group site densities than DOM from native vegetation sites. This is because Fe is mainly in the ferrous form, even in samples from the relatively well-drained podosols. However, modelling suggests that Pinus DOM can significantly increase the amount of truly dissolved ferric iron remaining in solution in oxic conditions. Therefore, the input of ferrous iron together with Pinus DOM to surface waters may reduce precipitation of hydrous ferric oxides (ferrihydrite) and increase the flux of dissolved Fe out of the catchment. Such inputs of iron are most probably derived from podosols planted with Pinus.

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10−8) loci, some including known iron-related genes (​HFE, ​SLC40A1, ​TF, ​TFR2, ​TFRC, ​TMPRSS6) and others novel (​ABO, ​ARNTL, ​FADS2, ​NAT2, ​TEX14). SNPs at ​ARNTL, ​TF, and ​TFR2 affect iron markers in ​HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)) and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

Tris[4,4,4-trifluoro-1-(2-thienyl)butane-1,3-dionato]aluminium(III)-tris[4,4,4-trifluoro-1-(2-thienyl)butane-1,3-dionato]iron(III) (3/1)

In the title compound, [Al(C8H4F3O2S)3]3[Fe(C8H4F3O2S)3], the metal centre is statistically occupied by AlIII and FeIII cations in a 3:1 ratio. The metal centre is within an octahedral O6 donor set defined by three chelating substituted acetoacetonate anions. The ligands are arranged around the periphery of the molecule with a mer geometry of the S atoms.