Search

Huntington's disease (HD) is an incurable inherited brain disorder characterized by massive degeneration of striatal neurons, which correlates with abnormal accumulation of misfolded mutant huntingtin (mHTT) protein. Research on HD has been hampered by the inability to study early dysfunction and progressive degeneration of human striatal neurons in vivo. To investigate human pathogenesis in a physiologically relevant context, we transplanted human pluripotent stem cell-derived neural progenitor cells (hNPCs) from control and HD patients into the striatum of newborn mice. Chimeric mice were subjected to behavioral testing and implanted human cells were examined by immunohistochemistry and electron microscopy. Most hNPCs differentiated into striatal neurons that projected to their target areas and established synaptic connections within the host basal ganglia circuitry. Remarkably, HD human striatal neurons first developed mHTT oligomers, which primarily targeted endoplasmic reticulum, mitochondria and nuclear membrane to cause structural alterations. Furthermore, HD human cells secreted extracellular vesicles containing mHTT oligomers, which were internalized by non-mutated mouse striatal neurons triggering cell death. We conclude that interaction of mHTT oligomers with key cellular organelles initially drives disease progression in HD patients, and that mHTT oligomers within extracellular vesicles contribute to spread the disease in a non-cell autonomous manner.

In the Valongo Belt, with an extension of about 90 km, located very close to Porto, northern Portugal, dozens of ore deposits of various metallic minerals and coal were exploited in the 19th and 20th centuries. One of the metals most intensely exploited was antimony, with or without associated gold mineralization. This research intends to verify the extent of the current environmental legacy of ancient antimony mining. A typical old mine was selected. The main objectives were to verify whether the environmental legacy still manifests today, how natural processes contributed to an environmental dispersion of the mining footprint and whether the environmental legacy was absorbed by developments in a new landscape modified by anthropic activities. The topography of the area was captured using a Light Detection and Ranging (LIDAR) based drone system. The regional background was characterized by the geo-referenced chemical analysis of 157 soil samples, collected in a 35 × 35 m grid. The former mining area was characterized by 58 supplementary samples. The mining area is distinct from the background by higher antimony and zinc levels, constituting two distinct populations, as confirmed by statistical tests. In the samples collected in the industrial zone, six elements were considered contaminants: As, Cu, Mo, Sb, Sn and Zn. The concentrations of these elements were statistically examined using multivariate statistical analyses (principal component analysis and correspondence analysis). The main conclusions are: (a) the mining heritage area is discernible from the highly mineralized background; (b) in the mining zone, it is possible to distinguish the processing industrial area from the waste rock storage; (c) the natural processes of environmental dispersion were of little relevance; (d) the environmental legacy was smoothed and mostly incorporated into the new post-industrial landscape created by anthropic activities.

The characterization of historical mine tailings provides important information for land-management decisions, in particular when considering potential reprocessing activities or the development of an environmental protection program. In addition, outcomes from such characterization may define the scope for a more detailed investigation. The present work describes the characterization of the waste material from the Cabeço do Pião tailings impoundment performed within the project ReMinE: Improve Resource Efficiency and Minimize Environmental Footprint. The purpose of the work was to investigate alternative mine waste management options such as the extraction of valuable resources from an environmental liability. The study involved the collection of 41 samples at different locations at two different depths, physical and chemical characterization of the wastes, natural leaching tests, and potential for acid generation. The results showed that, apart from the potential instability of the dyke (with an average slope of 35°), the drained solutions flowing by percolation contain very small particles with high arsenic contents that are being incorporated into the river sediments. In addition, these very fine-grained materials are available for the transport by the wind creating secondary sources of environmental contamination. This data is fundamental for economic and environmental assessment of the two main alternatives, reprocessing or removal.

The present work was developed in the scope of ERA-MIN/0007/2015 REMinE project, aiming recover of valuable metals through reprocessing of abandoned mine waste deposits. Cabeco do Piao site, the Portuguese case study in this project, is an old tailings disposal whose property was transferred from Panasqueira Mine to the Municipality of Fundao. The material deposited in the dam constitutes a risk to the environment, in particular to Zezere’s river that flows close to the bottom of the tailings pile and is a relevant contributor for the supply of drinking water. The study area was sampled at two different depths according to a regular grid. About fifty samples were collected and analyzed by X-ray fluorescence. The multivariate analysis of the chemical and the particle size data, allowed to establish mineralogical associations, proving to be a useful planning tool in a future selective re-mining of the tailings pile. Information extracted from the results of the principal component analysis was corroborated by the results of the geostatistical techniques applied to the analytical data.

Today, various methods such as bioleaching are increasingly used to remove toxic and reuse useful metals from low-grade ores and tailings. Bioleaching is an ecologically based technique carried by iron or sulfur-oxidizing bacteria, which convert insoluble metal sulfide to soluble metal sulfate. The purpose of this study was to test and compare two different methods, including Flask and Column experiments, to remove Zinc, Copper, Arsenic, and Iron. The materials were the same in both tests; inoculum came from the tailings of Neves-Corvo Mine, and the mineral sample was collected from Panasqueira Wolfram-Tin mine. Firstly, the cultures were tested for metal resistance and adapted by 3-day transference, adding sodium thiosulfate as an energy source supplement. Secondly, bioleaching tests were conducted in Flasks and Columns in 35 and 30 days, respectively. Finally, samples were taken to evaluate particle size, chemical compositions, bacterial growth, pH, oxidation–reduction potential (ORP), sulfate concentration, and metal content in the leachate. Besides, the Scanning Electron Microscope (SEM) pictures proved the existence of bacterial cells during the bioleaching tests. The results indicated that the Flask tests were superior to Column experiments in removing Zinc, Arsenic, and Copper from the mineral ore samples. However, Column experiments showed better results in the recovery of Iron in comparison with Flask tests.

Cizolirtine is a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence. To assess its carcinogenic potential, cizolirtine was administered by oral route once daily for up to 104 weeks to CD-1 mice at doses of 40, 90, or 200 mg/kg/day, and to Han Wistar rats at doses of 40, 90 or 200 mg/kg/day to males and 40, 110 or 160 mg/kg/day to females. There were treatment-related neoplastic findings both in mice and rats. In mice, administration of cizolirtine was associated to an increase in skin fibrosarcomas and sarcomas among high-dose males, considered secondary to increased aggression and specific to the animal model. In rats, there was an increased incidence of liver adenomas in males and females, and carcinomas in males, in association with an increased incidence of hepatocyte hypertrophy, vacuolation and clear cell foci, and considered related to sustained long-term enzyme induction resulting in increased liver metabolism and associated hypertrophic changes. The observed neoplastic findings in mouse skin and rat liver after life-time oral administration of cizolirtine are considered related to rodent-specific non-genotoxic mechanisms of questionable relevance to man.

The analysis of the genotoxic potential of cizolirtine, a compound being developed as a drug for analgesia and for urinary incontinence, was carried out using a battery of in vitro and in vivo assays as recommended in the guidelines for medicinal products. Negative results were obtained in an Ames test (up to 5000 µg/plate), in a Mouse Lymphoma assay (up to 2000 µg/ml) and in a single dose mouse bone marrow micronucleus assay (up to 300 mg/kg). In a human lymphocyte chromosome aberration assay, a slight statistical increase in the frequency of cells with chromosome aberrations including gaps was reported for the concentrations of 200 and 1600 μg/ml at the 24-h sampling time. This minor increase in chromosome aberrations was considered of questionable biological relevance since it was moderate, was within the laboratory historical control values, did no show a dose-dependent effect and was not observed at similar concentrations in a repeat assay. Taking into considerations the results obtained in the different in vitro and in vivo assays and a weight-of-evidence analysis, it suggests that cizolirtine would not pose a genotoxic risk when administered to humans.

Cizolirtine, a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence, was orally administered for 26-weeks to rats at dosages of 20, 60 and 200 mg/kg/day. Clinical signs were limited to post-dosing salivation and brown staining on head and muzzle. There were slight decreases in bodyweight gain and slight increases in water consumption among cizolirtine-treated animals. Slight increases in plasma alkaline phosphatase activity, and cholesterol and phospholipid concentrations were observed in mid- and/or high-dose animals. Low urinary volume, pH and sodium and potassium outputs were observed after 12-weeks, and low urinary pH, low sodium and high potassium outputs at end of treatment. Increased relative (to bodyweight) liver weight was observed in high-dose animals. Treated males and high-dose females showed a dose-related increase in the incidence and severity of periacinar hepatocytic hypertrophy and midzonal/periacinar hepatocytic fat vacuolization. Increased incidences of hepatic clear cell foci were observed in all cizolirtine-treated male groups and, to a lesser extent, in treated females. Ovaries of treated females showed a dose-dependent increased incidence of absent corpora lutea and, occasionally, follicular cysts. The dosages of 20 and 60 mg/kg/day were considered as the No-Observed-Adverse-Effect Levels for males and females, respectively.

It is known since the end of the XIX century that bromine is an excellent leaching reagent for gold but the research concerning its potential application as an alternative reagent has been relatively despised, mainly because elemental bromine is hazardous and extremely difficult to store or transport in safe conditions. We performed experimental tests in order to assess the feasibility of bromine produced in-situ, in the leaching reactor, to dissolve gold using ore samples from the unexploited Portuguese mine of Castromil. The reagents used in the production of bromine (NaBr, NaOCl and HCl) can be more safely stored than bromine. The ore sample was crushed and grinded in order to produce a particle size distribution (D80 = 0.48 mm) that would guarantee that most of the gold and electrum would be liberated in accordance with previous mineralogical studies. The following operating conditions were assessed: temperature, solid/liquid ratio, composition of the leaching reagent, stirring speed, residence time, effect of pretreatments and the addition of oxidants to the bromine solution. The highest gold dissolution (89%) was achieved with a previous roasting, although the simultaneous addition of H2O2 and FeCl3 allows for a similar recovery (80%) with much lower environmental impact. These results were achieved with the following leaching solution: 4.4 g NaBr, 30 mL NaOCl, 42 mL HCl and 28 mL H2O and with the following operating conditions: a solid/liquid ratio of 1, temperature around 95 °C, stirring speed of 450 rpm, natural reaction pH and a leaching time of 4 h. The comparison between bromine, cyanide and thiosulfate leaching for the same ore indicates that bromine is a good technical alternative for leaching this gold ore. The following advantages may be stressed: fast dissolution rate, non-toxic reagents, it does not require the use of pH regulator and can be performed with low quantities of leaching solution.

The mining waste and tailing dam are object of discussion due to the accidents that occur due to a lack of control or due to interest in the remaining minerals present in these materials. Most of the old tailings dams have high contents of heavy metals which could represent potential risks to the environment or be an alternative source of some critical raw materials. The case study of the Cabeço do Pião dam in Central Portugal involved tailings from a processing plant that belonged to the Panasqueira Mine Complex, which has been in operation for over 120 years. Waste rock and mining tailings were deposited in the area until 1995, and they represent an environmental liability for the local population due to their high content of toxic metals. Tailings reprocessing can be considered as a solution that minimizes social and environmental impacts, recovers some essential minerals, such as Zn, W, and Cu which can help to offset investments made. The project design involves several stages of metal concentration, determined by experiments, as well as a model of the process. The overall model will take into account technological constraints, social-economic conditions and environmental impacts. A preliminary result of an optimization study of the kinetic approach is presented in this piece of work. Keywords: Tailings, Multi-criteria optimization, Reprocessing, Zinc and tungsten

The FAME (Flexible and Mobile Economic Processing Technologies) project targets the development of flexible and economic processing technologies for small and low-grade European ore deposits with complex mineralogy, targeting greisen, skarn and pegmatite ores. Amongst the valuable elements to be recovered are W, Sn, Li and minor constituents like In, Ge, Ga, Nb or Ta. To improve the processing of by-product sulfides to recover critical elements like In or Ga and to develop innovative processing strategies for raw materials, biohydrometallurgical technologies are investigated. There are different approaches in FAME for the biohydrometallurgical recovery of valuable metals from low grade ores: 1) the extraction of Li from zinnwaldite and lepidolite, 2) the heap leaching of low grade sulfide ore unsuitable for conventional processing to recover Zn and In, and 3) the bioleaching of sulfide concentrates in a two-stage tank process for recovery of Zn and Cu. So far the most promising results were achieved for heap-leaching of low-grade Zn-In ores achieving 7.4 ppm In in the leaching solution and for Li extraction (28%) from zinnwaldite.

In a circular economy concept, where more than 300 million tons of mining and quarrying wastes are produced annually, those are valuable resources, supplying metals that are extracted today by other processes, if innovative methods and processes for efficient extraction of these elements are applied. This work aims to assess microbiological and chemical spatial distribution within two tailing basins from a tungsten mine, using a MiSeq approach targeting the 16S rRNA gene, to relate microbial composition and function with chemical variability, thus, providing information to enhance the efficiency of the exploitation of these secondary sources. The tailings sediments core microbiome comprised members of family Anaerolineacea and genera Acinetobacter, Bacillus, Cellulomonas, Pseudomonas, Streptococcus and Rothia, despite marked differences in tailings physicochemical properties. The higher contents of Al and K shaped the community of Basin 1, while As-S-Fe contents were correlated with the microbiome composition of Basin 2. The predicted metabolic functions of the microbiome were rich in genes related to metabolism pathways and environmental information processing pathways. An in-depth understanding of the tailings microbiome and its metabolic capabilities can provide a direction for the management of tailings disposal sites and maximize their potential as secondary resources.

Demand growth for metallic minerals has been faced with the need for new techniques and improving technologies for all mining life-cycle operations. Nowadays, the exploitation of old tailings and mine-waste facilities could be a solution to this demand, with economic and environmental advantages. The Panasqueira Mine has been operating for more than a century, extracting tungsten and tin ore. Its first processing plant, &ldquo, Rio&rdquo, was located near the Z&ecirc, rere river, where mineral-processing residues were deposited on the top hillside on the margin of this river in the Cabe&ccedil, o do Pi&atilde, o tailings dam. The lack of maintenance and monitoring of this enormous structure in the last twenty years represents a high risk to the environment and the population of the surrounding region. A field-sample campaign allowed the collection of data, and resulted from laboratory tests to use regression optimization. Re-mining the tailings by hydrometallurgical methods was considered to satisfy the two conditions of metal demand and environmental risk. The metal content in Cabe&ccedil, o was shown be enough for environmental restoration. The re-mining solution was studied, taking into account the technical, economic, social, and environmental aspects.

The growth of demand for metallic minerals has faced with the need for new techniques and improving technologies for all mine life cycle operations. Nowadays, the exploitation of old tailings and mine wastes facilities could represent a solution to this demand, with economic and environmental advantages. W-Sn Panasqueira Mine has been operating for more than 100 years. Its first processing plant “Rio” was located near Zêrere river being the mineral processing residues deposited on the top hillside on the margin of this river in Cabeço do Pião tailings dam. The lack of maintenance and monitoring of this enormous structure in the last twenty years represents high risks to the environment and population of the surrounding region. The re-mining of the tailings by hydrometallurgical methods was considered, in order to satisfy these two enounced conditions - metals demand and environmental risk, aiming for the sale of the metal to pay the environmental intervention. Field samples campaign allowed collecting data and results from laboratory tests driving to use regression optimization. The re-mining solution was studied, taking into account the technical, economic, social, and environmental aspects.

The present work is the first report characterising bacterial communities recovered from sulphide ore from a Portuguese active mine (Neves-Corvo) and collecting samples from three independent processing stages (feed/tailings/paste), at three sampling periods over 15 months. The recovered bacterial communities demonstrated low richness and heterogeneity (intra/inter-samples). Neutrophile sulphur-oxidising chemolithoautotrophs (e.g., Thiobacillus, Halothiobacillus, Thiomicrospira) were the most abundant organisms found across all samples. The presence of these primary producers may explain the occurrence of mixotrophs and facultative chemolithoheterotrophs/chemoorganoheterotrophs (e.g., Limnobacter, Paracoccus, Marinobacter, Alishewanella, Pseudomonas) in these non-acidic (4.6 8.7), pyrite-rich environments. The capacity of the surviving bacterial community following ore processing (tailings) to solubilise metals from mine wastes was also assessed. After 65 days at room temperature and in the presence of thiosulphate as an additional energy source, the tailings’ bacterial community solubilised pollutants detected in acid mine drainage waters, namely As (96%), Cd (58%), Cu (24%) and Zn (56%) with the concomitant decrease of pH from 7.4 to 1.8. The low solubilisation efficiencies obtained for copper, zinc, and cadmium indicate a limited technological potential of these communities. However, their ability to significantly mobilise noxious pollutants from the mine wastes to the liquid medium, particularly for As, raises environmental concern. This finding should increase awareness among stakeholders for the need to increase studies at field scale, in real scenarios.

The average global recovery rates for processing scheelite ores by physical methods are normally in the range 50 to 70%, and it is problematic to attain a minimum grade of 60% WO3 in the concentrates without penalizing further this yield. Direct hydrometallurgical processing of low-grade concentrates or medium- to high-grade ores may become an interesting global economic alternative as it allows increasing the recovery rate, avoiding major penalizations due to the grade of the concentrate and increasing the added value of the final product. Leaching of scheelite by sodium carbonate presents several advantages such as its selectivity regarding the dissolution of troubling metals like iron and aluminium, allowing for a simple and flexible process diagram. However, it has the disadvantage that it is performed at high temperature and pressure with a high consumption of reagents. The feasibility of leaching is appraised by the extraction yield and selectivity, but also by the operating cost. Considering these aspects, a relevant objective of the research was to transform alkaline pressure leaching into a feasible processing alternative directly applicable to both medium- and high-grade ores and simultaneously to low- and high-grade concentrates produced by physical methods. The research used ore samples and low-grade concentrates from a typical skarn orebody as well as high-grade concentrates from a chalcopyrite-scheelite orebody. Different operating conditions were tested. Temperature, pressure and reagent concentration showed to be fundamental, but not exclusive, in determining the leaching behaviour. The operating conditions are milder than the ones generally proposed in the literature or currently in use in industry, but with higher carbonate consumptions. The research was oriented towards potential industrial implementation allowing for the application of optimization methods and straight scale-up to pilot-plan design and project.

Huntington’s disease (HD) is a hereditary neurodegenerative disorder mainly characterized by striatal atrophy and degeneration of medium spiny neurons (MSNs). Although mouse models have provided a substantial amount of information about HD, they show important limitations for understanding the pathogenesis in humans. Current in vitro HD human models can recapitulate some disease phenotypes, but they are not useful for studying long-term differentiation, aging and the establishment of brain connections. Interestingly, new in vivo chimeric models using HD patient-derived induced pluripotent stem cells (iPSCs) transplanted into mice could avoid these shortcomings, by allowing cell differentiation and aging within a physiologically relevant environment. We have transplanted iPSC-derived telencephalic progenitors from healthy subjects and HD patients into the mouse developing forebrain, at both embryonic and neonatal stages. At these early ages, patterning cues present in the host developing brain act to instruct specific cell fates and play a key role in determining the migration, connectivity and functional integration of engrafted cells. Following transplantation into the mouse neonatal striatum, the vast majority of cells express CTIP2, including a subpopulation co-expressing DARPP-32, indicative of MSN identity. Furthermore, human iPSC-derived differentiated neurons sent axons towards MSN targets and were able to establish synapses, suggesting functional integration within the basal ganglia circuitry. Remarkably, transplanted cells survived up to 5 months and HD cells recapitulated human HD pathology, as evidenced by altered autophagy, mutant huntingtin aggregation and striatal degeneration. Preliminary results from in utero transplantation into the lateral ventricles of E14.5 embryos, show a wider dispersion of grafted cells compared to neonatal transplantation. Moreover, HD cells display increased branching one month after grafting. In summary, we conclude that human iPSC-mouse chimeras are a useful tool for modeling human HD in vivo.

The FAME (Flexible and Mobile Economic Processing Technologies) project targets the development of flexible and economic processing technologies for small and low-grade European ore deposits with complex mineralogy, targeting greisen, skarn and pegmatite ores. Amongst the valuable elements to be recovered are W, Sn, Li and minor constituents like In, Ge, Ga, Nb or Ta. To improve the processing of by-product sulfides to recover critical elements like In or Ga and to develop innovative processing strategies for raw materials, biohydrometallurgical technologies are investigated. There are different approaches in FAME for the biohydrometallurgical recovery of valuable metals from low grade ores: 1) the extraction of Li from zinnwaldite and lepidolite, 2) the heap leaching of low grade sulfide ore unsuitable for conventional processing to recover Zn and In, and 3) the bioleaching of sulfide concentrates in a two-stage tank process for recovery of Zn and Cu. So far the most promising results were achieved for heap-leaching of low-grade Zn-In ores achieving 7.4 ppm In in the leaching solution and for Li extraction (28%) from zinnwaldite. (c) 2017 Trans Tech Publications, Switzerland.

Panasqueira Mine (Portugal) has been mainly exploited for wolframite, cassiterite and chalcopyrite (W, Sn, Cu). Through the detailed and careful characterization of tailings with different mineralogy, new invaluable insights into the weathering characteristics of many different minerals will be received, making possible proper risk assessments, and predict which type of tailings might pose severe future environmental risk namely to the Zêzere river. The Zêzere River is an important river and is under the Cabeço do Pião tailings influence. The knowledge and methods acquired will lead to a conceptual model working as guidance to a more sustainable mining in the hereafter., This work of the project Remine was funded with public national funds from FCT under the programme for International Cooperation ERA-NET, supported by ERA-MIN (2011-2015) funded under the EU 7th Framework Programme FP7-NMP having also for partners the Technical University of Luleå (Sweden) and the National Institute for Metals and Radioactive Resources (INCDMRR), Romania., info:eu-repo/semantics/publishedVersion