The environmental and geomorphological impacts of historical gold mining in the Ohinemuri and Waihou river catchments, Coromandel, New Zealand

Between 1875 and 1955 approximately 250,000 Mg yr− 1 of mercury-, arsenic-, and cyanide-contaminated mine tailings were discharged directly into the Ohinemuri River and its tributaries, in the Coromandel Region, North Island, New Zealand. A devastating flood on 14 January 1907 deposited large amounts of mine waste across the floodplain of the Ohinemuri and Waihou rivers in the vicinity of the township of Paeroa. The 1907 mine-waste flood deposit was located as a dirty yellow silt in cores and floodplain profiles, with a thickness ranging from 0.15–0.50 m. Geochemical analysis of the mine waste shows elevated concentrations of Pb (~ 200–570 mg kg− 1) and As (~ 30–80 mg kg− 1), compared to early Holocene background concentrations (Pb < 30 mg kg− 1; As < 17 mg kg− 1). Bulk sediment samples recovered from the river channel and overbank deposits also show elevated concentrations of Pb (~ 110 mg kg− 1), Zn (~ 140–320 mg kg− 1), Ag (~ 3 mg kg− 1), and Hg (~ 0.4 mg kg− 1). Using the mine-waste deposit as a chronological marker shows that sedimentation rates increased from ~ 0.2 mm yr− 1 in the early Holocene, to 5.5–26.8 mm yr− 1 following the 1907 flood. Downstream trends in the thickness of the flood deposit show that local-scale geomorphic factors are a significant influence on the deposition of mine waste in such events. Storage of mine waste is greatest in the upstream reaches of the floodplain. The volume of mine waste estimated to be stored in the Ohinemuri floodplain is ~ 1.13 M m3, an order of magnitude larger than recent well-publicised tailings-dam failures, such as the 1996 South America Porco, 2000 Romanian Baia Mare and Baia Borsa accidents, and constituted, and was recognised at the time, a significant geomorphological and environmental event. The mine-waste material remains in the floodplain today, representing a sizable legacy store of contaminant metals and metalloids that pose a long-term risk to the Ohinemuri and Waihou ecosystems

Understanding the antimicrobial mechanism of TiO2-based nanocomposite films in a pathogenic bacterium

Titania (TiO2)-based nanocomposites subjected to light excitation are remarkably effective in eliciting microbial death. However, the mechanism by which these materials induce microbial death and the effects that they have on microbes are poorly understood. Here, we assess the low dose radical-mediated TiO2 photocatalytic action of such nanocomposites and evaluate the genome/proteome-wide expression profiles of Pseudomonas aeruginosa PAO1 cells after two minutes of intervention. The results indicate that the impact on the gene-wide flux distribution and metabolism is moderate in the analysed time span. Rather, the photocatalytic action triggers the decreased expression of a large array of genes/proteins specific for regulatory, signalling and growth functions in parallel with subsequent selective effects on ion homeostasis, coenzyme-independent respiration and cell wall structure. The present work provides the first solid foundation for the biocidal action of titania and may have an impact on the design of highly active photobiocidal nanomaterial

Acute and delayed sulfur mustard toxicity; novel mechanisms and future studies

Sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. The toxicity of SM as an incapacitating agent is of much greater importance than its ability to cause lethality. Acute toxicity of SM is related to reactive oxygen and nitrogen species, DNA damage, poly(ADP-ribose) polymerase activation and energy depletion within the affected cell. Therefore melatonin shows beneficial effects against acute SM toxicity in a variety of manner. It scavenges most of the oxygen- and nitrogen-based reactants, inhibits inducible nitric oxide synthase, repairs DNA damage and restores cellular energy depletion. The delayed toxicity of SM however, currently has no mechanistic explanation. We propose that epigenetic aberrations may be responsible for delayed detrimental effects of mustard poisoning. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to genetic mutations, epimutations can also involve in the pathogenesis of a variety of human diseases. Several actions of melatonin are now delineated by epigenetic actions including modulation of histone acetylation and DNA methylation. Future studies are warranted to clarify whether epigenetic mechanisms are involved in pathogenesis of delayed sulfur mustard toxicity and melatonin alleviates delayed toxicity of this warfare agent

Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the <it>CCR5 </it>gene leads to a non-functional receptor. A negative association between the <it>CCR5Δ32 </it>and rheumatoid arthritis (RA) has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA), an association with CCR5 was recently reported. The purpose of this study was to investigate if the <it>CCR5Δ32 </it>polymorphism is associated with RA or JIA in Norwegian cohorts.</p> <p>Methods</p> <p>853 RA patients, 524 JIA patients and 658 controls were genotyped for the <it>CCR5Δ32 </it>polymorphism.</p> <p>Results</p> <p>The <it>CCR5Δ32 </it>allele frequency was 11.5% in the controls vs. 10.4% in RA patients (OR = 0.90; <it>P </it>= 0.36) and 9.7% in JIA patients (OR = 0.85; <it>P </it>= 0.20). No decreased homozygosity was observed for <it>CCR5Δ32</it>, as previously suggested.</p> <p>Conclusion</p> <p>Our data do not support an association between the <it>CCR5Δ32 </it>allele and Norwegian RA or JIA patients. Combining our results with those from a recently published meta-analysis still provide evidence for a role for <it>CCR5Δ32 </it>in RA, albeit substantially weaker than the effect first reported.</p

Integrating geospatial information into fire risk assessment

Fire risk assessment should take into account the most relevant components associated to fire occurrence. To estimate when and where the fire will produce undesired effects, we need to model both (a) fire ignition and propagation potential and (b) fire vulnerability. Following these ideas, a comprehensive fire risk assessment system is proposed in this paper, which makes extensive use of geographic information technologies to offer a spatially explicit evaluation of fire risk conditions. The paper first describes the conceptual model, then the methods to generate the different input variables, the approaches to merge those variables into synthetic risk indices and finally the validation of the outputs. The model has been applied at a national level for the whole Spanish Iberian territory at 1-km2 spatial resolution. Fire danger included human factors, lightning probability, fuel moisture content of both dead and live fuels and propagation potential. Fire vulnerability was assessed by analysing values-at-risk and landscape resilience. Each input variable included a particular accuracy assessment, whereas the synthetic indices were validated using the most recent fire statistics available. Significant relations (P < 0.001) with fire occurrence were found for the main synthetic danger indices, particularly for those associated to fuel moisture content conditions.Peer reviewe

What to consider when pseudohypoparathyroidism is ruled out: IPPSD and differential diagnosis

Background: Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright''s hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. Methods: We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. Results: A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. Conclusions: This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes

Human Vav1 Expression in Hematopoietic and Cancer Cell Lines Is Regulated by c-Myb and by CpG Methylation

Vav1 is a signal transducer protein that functions as a guanine nucleotide exchange factor for the Rho/Rac GTPases in the hematopoietic system where it is exclusively expressed. Recently, Vav1 was shown to be involved in several human malignancies including neuroblastoma, lung cancer, and pancreatic ductal adenocarcinoma (PDA). Although some factors that affect vav1 expression are known, neither the physiological nor pathological regulation of vav1 expression is completely understood. We demonstrate herein that mutations in putative transcription factor binding sites at the vav1 promoter affect its transcription in cells of different histological origin. Among these sites is a consensus site for c-Myb, a hematopoietic-specific transcription factor that is also found in Vav1-expressing lung cancer cell lines. Depletion of c-Myb using siRNA led to a dramatic reduction in vav1 expression in these cells. Consistent with this, co-transfection of c-Myb activated transcription of a vav1 promoter-luciferase reporter gene construct in lung cancer cells devoid of Vav1 expression. Together, these results indicate that c-Myb is involved in vav1 expression in lung cancer cells. We also explored the methylation status of the vav1 promoter. Bisulfite sequencing revealed that the vav1 promoter was completely unmethylated in human lymphocytes, but methylated to various degrees in tissues that do not normally express vav1. The vav1 promoter does not contain CpG islands in proximity to the transcription start site; however, we demonstrated that methylation of a CpG dinucleotide at a consensus Sp1 binding site in the vav1 promoter interferes with protein binding in vitro. Our data identify two regulatory mechanisms for vav1 expression: binding of c-Myb and CpG methylation of 5′ regulatory sequences. Mutation of other putative transcription factor binding sites suggests that additional factors regulate vav1 expression as well