Sodium removal from bauxite desilication product (sodalite) aided by chelating effects of inorganic and organic acids.

Dealkalization is a prerequisite to converting bauxite residue into non-hazardous materials that can be used for various upcycling applications. Structural alkali (Na+) lodged inside the densely packed aluminosilicate-cages of sodalite, the dominant desilication product from refining alumina, is a common culprit in the persistence of strong alkalinity of bauxite residue. The present study unravelled chemical and mineralogical processes involved in sodalite dealkalization, driven by organic and inorganic acids. These acids have different H+ dissociation coefficients and their anions have different chelation abilities with surface metal atoms of aluminosilicate minerals. The efficacy of sodium removal by exposure to the acids was found not only dependent on the acid strength (pKa), but also on the chelating property of dissociated conjugate anions. Following an initial H+-Na+ exchange, Na+ removal from sodalite was correlated with partial hydrolysis of aluminosilicate network and resultant chelating reactions with acid anions. The selection of organic and inorganic acids whose conjugate bases possess good chelating capability in the pH buffer zone 7-9 (e.g., oxalate or phosphate), would provide significant aid to the dealkalization process. The findings in this study are crucial in understanding the conversion of bauxite residue into a soil-like growth media (technosol) for sustainable mined land rehabilitation.

Adaptive growth and acidogenic fermentation performance of haloalkaliphilic bacterial communities enriched from biofilms colonising strongly alkaline and saline bauxite residue.

The present study aimed to characterise the adaptive growth and acidogenic fermentation performance of haloalkaliphilic bacteria sourced from field biofilms colonising seawater-treated bauxite residue, under moderate and extremely alkaline pH conditions (8.5 to 10.8) and coupled saline (EC ≈ 50 mS/cm) conditions. The haloalkaliphilic bacterial communities demonstrated strong adaptiveness to the increasing pH from 8.5 to 10.8. The dominant groups were Exiguobacterales and Bacillales at pH 8.5 and 10, but Lactobacillales and Bacillales at pH 10.8. The exposure to pH 10.8 initially delayed bacterial growth in the first 24 h, but which rapidly recovered to a peak rate at 48 h similar to that in the pH 10 treatment. Correspondingly, lactic acid concentration at pH 10.8 rapidly rose to as high as >2000 mg/L at 48 h. Bacterial growth and organic acid production were positively related to carbohydrate supply. Overall, these bacterial groups fermented glucose to produce mainly lactic acid (>80 %) and other acids (such as acetic acid, formic acid, and succinic acid), leading to 0.5-2.0 units of pH reduction, despite the strong buffering capacity in the culture solution. The bacteria could up-regulate their phosphatase activity to mineralise the organic P in the basal nutrient broth, but increasing soluble phosphate-P at a 1:10 of glucose-C was beneficial. The biofilm-sourced bacteria communities contained redundant fermentative haloalkaliphilic groups which were adaptive to strongly alkaline pH and saline conditions.

Sediment spiking and equilibration procedures to achieve partitioning of uranium similar to contamination in tropical wetlands near a mine site.

The derivation of sediment quality guideline values (SQGVs) presents significant challenges. Arguably the most important challenge is to conduct toxicity tests using contaminated sediments with physico-chemistry that represents real-world scenarios. We used a novel metal spiking method for an experiment that ultimately aims to derive a uranium SQGV. Two pilot studies were conducted to inform the final spiking design, i.e. percolating a uranyl sulfate solution through natural wetland sediments. An initial pilot study that used extended mixing equilibration phases produced hardened sediments not representative of natural sediments. A subsequent percolation method produced sediment with similar texture to natural sediment and was used as the method for spiking the sediments. The range of total recoverable uranium (TR-U) concentrations achieved was 8-3200 mg/kg. This reflected the concentrations found in natural wetlands and water management ponds found on a uranium mine site and was above natural levels. Dilute-acid extractable uranium (AE-U) concentrations were >80% of total concentrations, indicating that much of the uranium in the spiked sediment was labile and potentially bioavailable. The portion of TR-U extractable as AE-U was similar at the start and end of the 4.5-month field-deployment. Porewater uranium (PW-U) analyses indicated that partition coefficients (Kd) were 2000-20,000 L/kg, and PW-U was greater in post- than pre-field-deployed samples when TR-U was ≤1500 mg/kg, indicating the binding became weaker during the field-deployment period. At higher spiked-U concentrations, the PW-U was lower post-field-deployment. Comparing the physico-chemical data of the spiked sediments with environmental monitoring data from sediments in the vicinity of a uranium mining operation indicated that they were representative of sediments contaminated by mining and that the U-spiked sediments had a clear U concentration gradient. This confirmed the suitability of the spiking procedure for preparing sediments that were suitable for deriving a SQGV for uranium.

Soil uranium concentration at Ranger Uranium Mine Land Application Areas drives changes in the bacterial community.

Soil microorganisms may respond to metal stress by a shift in the microbial community from metal sensitive to metal resistant microorganisms. We assessed the bacterial community from low (2-20 mg kg-1), medium (200-400 mg kg-1), high (500-900 mg kg-1) and very high (>900 mg kg-1) uranium soils at Ranger Uranium Mine in northern Australia through pyrosequencing. Proteobacteria (28.85%) was the most abundant phylum at these sites, followed by Actinobacteria (9.31%), Acidobacteria (7.33%), Verrucomicrobia (2.11%), Firmicutes (2.02%), Chloroflexi (1.11%), Cyanobacteria (0.93%), Planctomycetes (0.82%), Bacteroidetes (0.46%) and Candidate_division_WS3 (Latescibacteria) (0.21%). However, 46.79% of bacteria were unclassified. Bacteria at low U soils differed from soils with elevated uranium. Bacterial OTUs closely related to Kitasatospora spp., Sphingobacteria spp. and Rhodobium spp. were only present at higher uranium concentrations and the bacterial community also changed with seasonal and temporal changes in soil uranium and physicochemical variables. This study using next generation sequencing in association with environmental variables at a uranium mine has laid a foundation for further studies of soil-microbe-metal interactions which may be useful for developing sustainable management and rehabilitation strategies. Furthermore, bacterial species associated with higher uranium may serve as useful indicators of uranium contamination in the wet-dry tropics.

Land application of mine water causes minimal uranium loss offsite in the wet-dry tropics: Ranger Uranium Mine, Northern Territory, Australia.

Ranger Uranium Mine (RUM) is situated in the wet-dry tropics of Northern Australia. Land application (irrigation) of stockpile (ore and waste) runoff water to natural woodland on the mine lease is a key part of water management at the mine. Consequently, the soil in these Land Application Areas (LAAs) presents a range of uranium (U) and other metals concentrations. Knowledge of seasonal and temporal changes in soil U and physicochemical parameters at RUM LAAs is important to develop suitable management and rehabilitation strategies. Therefore, soil samples were collected from low, medium, high and very high U sites at RUM LAAs for two consecutive years and the effect of time and season on soil physicochemical parameters particularly U and other major solutes applied in irrigation water was measured. Concentrations of some of the solutes applied in the irrigation water such as sulphur (S), iron (Fe) and calcium (Ca) showed significant seasonal and temporal changes. Soil S, Fe and Ca concentration decreased from year 1 to year 2 and from dry to wet seasons during both years. Soil U followed the same pattern except that we recorded an increase in soil U concentrations at most of the RUM LAAs after year 2 wet season compared to year 2 dry season. Thus, these sites did not show a considerable decrease in soil U concentration from year 1 to year 2. Sites which contained elevated U after wet season 2 also had higher moisture content which suggests that pooling of U containing rainwater at these sites may be responsible for elevated U. Thus, U may be redistributed within RUM LAAs due to surface water movement. The study also suggested that a decrease in U concentrations in LAA soils at very high U (>900 mg kg(-1)) sites is most likely due to transport of particulate matter bound U by surface runoff and U may not be lost from the surface soil due to vertical movement through the soil profile. Uranium attached to particulate matter may reduce its potential for environmental impact. These findings suggest that U is effectively adsorbed by the soils and thus land application may serve as a useful tool for U management in the wet-dry tropics of northern Australia.

Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling.

Mitochondrial Ca(2+) uptake has key roles in cell life and death. Physiological Ca(2+) signaling regulates aerobic metabolism, whereas pathological Ca(2+) overload triggers cell death. Mitochondrial Ca(2+) uptake is mediated by the Ca(2+) uniporter complex in the inner mitochondrial membrane, which comprises MCU, a Ca(2+)-selective ion channel, and its regulator, MICU1. Here we report mutations of MICU1 in individuals with a disease phenotype characterized by proximal myopathy, learning difficulties and a progressive extrapyramidal movement disorder. In fibroblasts from subjects with MICU1 mutations, agonist-induced mitochondrial Ca(2+) uptake at low cytosolic Ca(2+) concentrations was increased, and cytosolic Ca(2+) signals were reduced. Although resting mitochondrial membrane potential was unchanged in MICU1-deficient cells, the mitochondrial network was severely fragmented. Whereas the pathophysiology of muscular dystrophy and the core myopathies involves abnormal mitochondrial Ca(2+) handling, the phenotype associated with MICU1 deficiency is caused by a primary defect in mitochondrial Ca(2+) signaling, demonstrating the crucial role of mitochondrial Ca(2+) uptake in humans.

Fungi outcompete bacteria under increased uranium concentration in culture media.

As a key part of water management at the Ranger Uranium Mine (Northern Territory, Australia), stockpile (ore and waste) runoff water was applied to natural woodland on the mine lease in accordance with regulatory requirements. Consequently, the soil in these Land Application Areas (LAAs) presents a range of uranium concentrations. Soil samples were collected from LAAs with different concentrations of uranium and extracts were plated onto LB media containing no (0 ppm), low (3 ppm), medium (250 ppm), high (600 ppm) and very high (1500 ppm) uranium concentrations. These concentrations were similar to the range of measured uranium concentrations in the LAAs soils. Bacteria grew on all plates except for the very high uranium concentrations, where only fungi were recovered. Identifications based on bacterial 16S rRNA sequence analysis showed that the dominant cultivable bacteria belonged to the genus Bacillus. Members of the genera Paenibacillus, Lysinibacillus, Klebsiella, Microbacterium and Chryseobacterium were also isolated from the LAAs soil samples. Fungi were identified by sequence analysis of the intergenic spacer region, and members of the genera Aspergillus, Cryptococcus, Penicillium and Curvularia were dominant on plates with very high uranium concentrations. Members of the Paecilomyces and Alternaria were also present but in lower numbers. These findings indicate that fungi can tolerate very high concentrations of uranium and are more resistant than bacteria. Bacteria and fungi isolated at the Ranger LAAs from soils with high concentrations of uranium may have uranium binding capability and hence the potential for uranium bioremediation.

Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based approach--part 2.

Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo[1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors.

Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: a template-based approach--part 1.

The synthesis and hit-to-lead SAR development of a pyrazolo[1,5-a]pyrimidine hit 4 is described leading to a series of potent, selective CHK1 inhibitors such as compound 17r. In the Letter, the further utility of the pyrazolo[1,5-a]pyrimidine template for the development of potent, selective kinase inhibitors is detailed.

Synthesis and structure-activity relationship of aminopyrimidine IKK2 inhibitors.

The synthesis and structure-activity relationship of a novel series of aminopyrimidines are exemplified. Results of key compounds from within this series in the E-selectin reporter cell assay are also reported.

IRAK-4 inhibitors. Part III: a series of imidazo[1,2-a]pyridines.

Following the identification of a potent IRAK inhibitor through routine project cross screening, a novel class of IRAK-4 inhibitor was established. The SAR of imidazo[1,2-a]pyridino-pyridines and benzimidazolo-pyridines was explored.

Structure-guided discovery of cyclin-dependent kinase inhibitors.

CDK2 inhibitors containing the related bicyclic heterocycles pyrazolopyrimidines and imidazopyrazines were discovered through high-throughput screening. Crystal structures of inhibitors with these bicyclic cores and two more related ones show that all but one have a common binding mode featuring two hydrogen bonds (H-bonds) to the backbone of the kinase hinge region. Even though ab initio computations indicated that the imidazopyrazine core would bind more tightly to the hinge, pyrazolopyrimidines gain an advantage in potency through participation of N4 in an H-bond network involving two catalytic residues and bridging water molecules. Further insight into inhibitor/CDK2 interactions was gained from analysis of additional crystal structures. Significant gains in potency were obtained by optimizing the fit of hydrophobic substituents to the gatekeeper region of the ATP binding site. The most potent inhibitors have good selectivity.

Dynamics of arsenic in the mining sites of Pine Creek Geosyncline, Northern Australia.

The transportation and fixation of arsenic (As) in soil and sediments from five mine sites within the Pine Creek Geosyncline, Northern Territory, were examined based on measurements of operationally-defined fractions of As in soils, sediment and evaporates. Arsenic was mainly retained in sediments in the form iron arsenate (Fe-As). In wetland systems, As was retained as Fe-As together with calcium arsenate (Ca-As) from alkaline groundwater and organic-bound As from detrital material. In retention ponds As was retained as Fe-As, Ca-As and residual As (Res-As) up to 1700 mg/kg. Sediment traps can retain As from alkaline and acidic source seepages. The retention of Res-As and other mineral particulates during erosional or controlled process water discharges was associated with high Fe-As and organic-bound As in sediment. Arsenic was retained as Fe-As, Ca-As and residual As in 100 year old tailings at Millar's Battery, Union Reefs mine nearby McKinlay River and the small copper mine lease MLN 95 adjacent Copperfield Creek nearby Pine Creek. Natural geo-mobilisation of As was observed in upstream sediments at Copperfield Creek (5-8 mg/kg), Mt. Bundey Creek (10-12 mg/kg), upstream Ryan's Creek (10-12 mg/kg) and downstream East branch Ryan's Creek (7 mg/kg). Erosion of As-containing mineralisation was observed in the McKinlay River upstream and downstream (23-26 mg/kg) and upstream Ryan's Creek boundary of the Goodall mine lease MLN 1049 (24-40 mg/kg). Overall, As was mainly retained in sediments in the form Fe-As. The concentration data for As were used to propose mechanisms of As dispersion and retention occurring at the various mine sites that can be utilised for future mine water management design to minimise As dispersion.

Vegetation fires, particulate air pollution and asthma: a panel study in the Australian monsoon tropics.

We examined the relationship between particulate matter (PM) <10 and <2.5 microns in diameter (PM10 and PM2.5) generated by vegetation fires and daily health outcomes in 251 adults and children with asthma over a 7-month period. Data were analysed using generalized estimating equations adjusted for potential environmental confounders, autocorrelation, weekends and holidays. PM10 ranged from 2.6 - 43.3 microg m-3and was significantly associated with onset of asthma symptoms, commencing oral steroid medication, the mean daily symptom count and the mean daily dose of reliever medication. Similar results were found for PM2.5. No associations were found with the more severe outcomes of asthma attacks, increased health care attendances or missed school/work days. These results help fill a gap in the evidence about the population health impacts of lower levels of pollution characteristic of deliberate landscape burning to control fuel loads versus the better documented risks of more intense and severely polluting wildfires.

The uptake of uranium by Eleocharis dulcis (Chinese water chestnut) in the Ranger Uranium Mine constructed wetland filter.

Eleocharis dulcis has proliferated in a constructed wetland used to treat uranium mine runoff water, where it rapidly accumulates significant quantities of uranium (U) in its roots and relatively little in its stems. We investigated the mechanism of U uptake and accumulation by E. dulcis using field-sampling techniques and microcosm test work. Results from the microcosm trials and outcomes from statistical tests of field sampled macrophyte, water and sediment indicate that the primary source of U for E. dulcis is the water column. Basipetal translocation of U to the plant's roots was indicated by significant correlations between the U content of stems, taproots and rhizomes and XPS detection of U inside root segments. U sequestering from sediment interstitial water by Fe hydroxides on root surfaces was also evident. No basipetal translocation was evident following the 28-day duration of the microcosm experiments, indicating that it is a longer-term process.