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Vazquez M.C.,University of Santiago de Chile | Martinez P.,University of Santiago de Chile | Alvarez A.R.,University of Santiago de Chile | Gonzalez M.,University of Chile | And 4 more authors.
BioMetals | Year: 2012

Niemann-Pick type C disease (NPC) is a hereditary neurovisceral atypical lipid storage disorder produced by mutations in the NPC1 and NPC2 genes. The disease is characterized by unesterified cholesterol accumulation in late endosomal/lysosomal compartments and oxidative stress. Themost affected tissues are the cerebellum and the liver. The lysotropic drug U18666A (U18) has been widely used as a pharmacological model to induce the NPC phenotype in several cell culture lines. It has already been reported that there is an increase in copper content in hepatoma Hu7 cells treated with U18.We confirmed this result with another human hepatoma cell line, HepG2, treatedwithU18 and supplemented with copper in the media. However, in mouse hippocampal primary cultures treated under similar conditions, we did not find alterations in copper content. We previously reported increased copper content in the liver of Npc1-/- mice compared to control animals. Here, we extended the analysis to the copper content in the cerebella, the plasma and the bile ofNPC1 deficientmice.We did not observe a significant change in copper content in the cerebella, whereas we found increased copper content in the plasma and decreased copper levels in the bile of Npc1-/- mice. Finally, we also evaluated the plasma content of ceruloplasmin, and we found an increase in this primary copper-binding protein in Npc1-/- mice. These results indicate cell-type dependence of copper accumulation in NPC disease and suggest that copper transport imbalance may be relevant to the liver pathology observed in NPC disease. © 2012 Springer Science+Business Media, LLC.


Latorre M.,University of Chile | Galloway-Pena J.,University of Houston | Roh J.H.,University of Houston | Budinich M.,Center for Mathematical Modeling | And 6 more authors.
Metallomics | Year: 2014

A global transcriptional regulatory network was generated in the pathogenic bacterium Enterococcus faecalis in order to understand how this organism can activate and coordinate its expression at different copper concentrations. The topological evaluation of the network showed common patterns described in other organisms. Integrating microarray experiments allowed the identification of two sub-networks activated at low (0.05 mM CuSO4) and high (0.5 mM CuSO4) concentrations of copper. The analysis indicates the presence of specific functionally activated modules induced by copper levels, highlighting the regulons LysR and ArgR as global regulators and CopY, Fur and LexA as local regulators. Taking advantage of the fact that E. faecalis presented a homeostatic module, we produced an in vivo intervention by removing this system from the cell without affecting the connectivity of the global transcriptional network. This strategy led us to find that this bacterium can reconfigure its gene expression to maintain cellular homeostasis, activating new modules principally related to glucose metabolism and transcriptional processes. Finally, these results position E. faecalis as the most complete and controllable systemic model organism for copper homeostasis available to date. © 2014 The Royal Society of Chemistry.


Correa R.,Center for Mathematical Modeling | Hantoute A.,University of Chile | Perez-Aros P.,University of Chile
SIAM Journal on Optimization | Year: 2016

Using techniques of convex analysis, we provide a direct proof of a recent characterization of convexity given in the setting of Banach spaces in [J. Saint Raymond, J. Nonlinear Convex Anal., 14(2013), pp. 253-262]. Our results also extend this characterization to locally convex spaces under weaker conditions. © 2016 Societ y for Industrial and Applied Mathematics.


Latorre M.,University of Chile | Olivares F.,University of Chile | Reyes-Jara A.,BioSigma S.A. | Lopez G.,Autonomous University of the State of Hidalgo | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

Copper is a micronutrient that is required for proper metabolic functioning of most prokaryotic and eukaryotic organisms. To sustain an adequate supply of copper, a cell requires molecular mechanisms that control the metal content to avoid copper toxicity. This toxicity comes primarily from the reactivity of copper, which can lead to the generation of free radicals. In bacteria, two independent systems are responsible for maintaining the balance of copper within the cells (Cop and Cut family proteins). Previous studies describe CutC as a member of the Cut family that is probably involved in copper homeostasis. However, the role of CutC in copper homeostasis is still unclear. In this work, a homolog of CutC was studied in Enterococcus faecalis, a bacterial model for copper homeostasis. The molecular 3D model of efCutC shows the presence of triose phosphate isomerase (TIM) barrel motifs, previously described in CutC crystals from other organisms, which illustrates the conservation of amino acids with the potential ability to coordinate copper. Through quantitative real-time PCR (qPCR), it was demonstrated that efcutC expression is induced late by copper stimulus, Interestingly this transcriptional response directly correlates with a significant increase in the intracellular copper concentration when the protein is absent in the bacteria, suggesting its participation in mechanisms related to efflux of the metal. Our results describe efCutC as a protein able to respond transcriptionally to copper and to participate in the control of copper homeostasis in E. faecalis. This bacterium is the first reported organism containing a cop operon and an active member of the Cut protein family. © 2011 Elsevier Inc.


Bobadilla-Fazzini R.A.,BioSigma S.A | Cortes M.P.,CNRS Mathematics Laboratory | Cortes M.P.,University of Chile | Maass A.,University of Chile | And 2 more authors.
AMB Express | Year: 2014

Currently more than 90% of the world’s copper is obtained through sulfide mineral processing. Among the copper sulfides, chalcopyrite is the most abundant and therefore economically relevant. However, primary copper sulfide bioleaching is restricted due to high ionic strength raffinate solutions and particularly chloride coming from the dissolution of ores. In this work we describe the chalcopyrite bioleaching capacity of Sulfobacillus thermosulfidooxidans strain Cutipay (DSM 27601) previously described at the genomic level (Travisany et al. (2012) Draft genome sequence of the Sulfobacillus thermosulfidooxidans Cutipay strain, an indigenous bacterium isolated from a naturally extreme mining environment in Northern Chile. J Bacteriol 194:6327–6328). Bioleaching assays with the mixotrophic strain Cutipay showed a strong increase in copper recovery from chalcopyrite concentrate at 50°C in the presence of chloride ion, a relevant inhibitory element present in copper bioleaching processes. Compared to the abiotic control and a test with Sulfobacillus acidophilus DSM 10332, strain Cutipay showed an increase of 42 and 69% in copper recovery, respectively, demonstrating its high potential for chalcopyrite bioleaching. Moreover, a genomic comparison highlights the presence of the 2-Haloacid dehalogenase predicted-protein related to a potential new mechanism of chloride resistance in acidophiles. This novel and industrially applicable strain is under patent application CL 2013–03335. © 2014, Bobadilla-Fazzini et al.; licensee Springer.


Bobadilla Fazzini R.A.,BioSigma S.A. | Cortes M.P.,CNRS Mathematics Laboratory | Cortes M.P.,University of Chile | Padilla L.,BioSigma S.A. | And 7 more authors.
Biotechnology and Bioengineering | Year: 2013

The prokaryotic oxidation of reduced inorganic sulfur compounds (RISCs) is a topic of utmost importance from a biogeochemical and industrial perspective. Despite sulfur oxidizing bacterial activity is largely known, no quantitative approaches to biological RISCs oxidation have been made, gathering all the complex abiotic and enzymatic stoichiometry involved. Even though in the case of neutrophilic bacteria such as Paracoccus and Beggiatoa species the RISCs oxidation systems are well described, there is a lack of knowledge for acidophilic microorganisms. Here, we present the first experimentally validated stoichiometric model able to assess RISCs oxidation quantitatively in Acidithiobacillus thiooxidans (strain DSM 17318), the archetype of the sulfur oxidizing acidophilic chemolithoautotrophs. This model was built based on literature and genomic analysis, considering a widespread mix of formerly proposed RISCs oxidation models combined and evaluated experimentally. Thiosulfate partial oxidation by the Sox system (SoxABXYZ) was placed as central step of sulfur oxidation model, along with abiotic reactions. This model was coupled with a detailed stoichiometry of biomass production, providing accurate bacterial growth predictions. In silico deletion/inactivation highlights the role of sulfur dioxygenase as the main catalyzer and a moderate function of tetrathionate hydrolase in elemental sulfur catabolism, demonstrating that this model constitutes an advanced instrument for the optimization of At. thiooxidans biomass production with potential use in biohydrometallurgical and environmental applications. © 2013 Wiley Periodicals, Inc.


Soto G.,Center for Mathematical Modeling | Fontbona J.,Center for Mathematical Modeling | Cortez R.,Center for Mathematical Modeling | Mujica L.,Mining Information Communications and Monitoring Micomo
Measurement: Journal of the International Measurement Confederation | Year: 2016

Strain measurement using BOTDR (Brillouin Optical Time-Domain Reflectometry) is nowadays a standard tool for structural health monitoring. In this context, weak data quality and noise, usually owed to defective fiber installation, hinders discriminating actual level shifts from outliers and might entail a biased risk assessment. We propose a novel online adaptive algorithm for strain profile estimation in strain time series with abrupt and gradual changes and missing data. It relies on a convolution filter in Brillouin spectrum domain and a smoothing technique in time domain. In simulated data, the convolution filter is shown to reduce strain measurement uncertainty by up to 8 times the strain resolution. The two-stage method is illustrated with systematic outliers removal from real data of a Chilean copper mine and the improvement of the associated gain spectrum quality by up to 18 dB in SNR terms. © 2016 Elsevier Ltd

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