Spectroscopic study of the interaction of actinomycin D with oligonucleotides carrying the central base sequences -XGCY- and -XGGCCY- using multivariate methods

10 pages, 5 figures, 1 table.-- PMID: 17123067 [PubMed].-- Published online Nov 23, 2006.Supporting information (4 pages, 3 suppl. figures) available at: http://www.springerlink.com/content/870650451902431q/MediaObjects/216_2006_946_MOESM1_ESM.docThe interactions of actinomycin D (ACTD) with the oligonucleotides 5′-CAAAGCTTTG-3′, 5′-CATGGC CATG-3′ and 5′-TATGGCCATA-3′ were investigated by means of acid–base titrations and mole-ratio and melting experiments monitored by molecular absorption and circular dichroism (CD) spectroscopies. For each experiment, CD and molecular absorption spectra were recorded at each point in the experiment, and later analyzed via appropriate multivariate data analysis methods. The study of the interactions between these oligonucleotides and ACTD at 25°C showed the formation of an interaction complex with a stoichiometry of 1:1 (ACTD:duplex) and values for the log(formation constant) of 5.1 ± 0.3, 6.4 ± 0.2, and 5.6 ± 0.2, respectively. An additional interaction complex at higher temperatures was also detected, which might be related to the single-stranded forms of the oligonucleotides.We acknowledge two grants from the Spanish Ministerio de Educación y Ciencia (projects BFU2004-02048/BMC and BQU2003-0191).Peer reviewe

Epithelial-to-mesenchymal transition involves triacylglycerol accumulation in DU145 prostate cancer cells

Epithelial to mesenchymal transition (EMT) is a biological process that plays a crucial role in cancer metastasis. Although studies regarding the EMT mechanisms are usual in terms of gene expression and protein functions, little is known about the involvement of lipids in EMT. In this work, an untargeted lipidomic analysis was performed to reveal which lipids are involved in the EMT process. DU145 prostate cancer cells were treated with TNFα, a well-known EMT inducer. After 6 hours of treatment, a decrease of cell membrane E-cadherin as well as a reduction in its gene expression were observed. Also, the mesenchymal markers Vimentin and Snail were up-regulated, suggesting that EMT started below 6 hours of treatment. Lipid extracts of untreated and TNFα-treated cells at short times were analyzed using ultra-performance liquid chromatography coupled to high-resolution mass spectrometry (UPLC-MS). Multivariate data analysis methods were applied to decipher which lipids presented significant changes after EMT induction. Among the results obtained, a significant increase of twelve unsaturated triacylglycerides (TAGs) was observed. This increase of TAGs was also observed for cells treated with TGFβ (another EMT inducer), suggesting that this feature is a common mechanism in the EMT process. In conclusion, this work reported for the first time a TAG accumulation through EMT induction. These TAG lipids could play a key role in providing cells with the energy, cell membrane components and signaling lipids necessary to guarantee the enhanced cell migration and proliferation of metastatic cells.This work was supported by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement 320737. J.J acknowledges a CSIC JAE-Doc contract cofounded by FSE.Peer reviewe

Caracterització i estudi de procedència de l’alabastre del retaule de l’altar major de Poblet

S’ha realitzat la caracterització del material petri usat en l’execució del retaule de l’altar major de Poblet, esculpit en guix alabastrí, des dels punts de vista mineralògic, petrològic i geoquímic, mitjançant l’observació macroscòpica i microscòpica (microscòpia òptica de transmissió electrònica de rastreig) i la difracció de raigs X. Els resultats revelen que aquest alabastre és, en força àrees del retaule, de molt bona qualitat, si bé presenta abundants components que evidencien un descens en la seva puresa en algunes àrees. La caracterització geoquímica d’algunes mostres d’alabastre mitjançant l’estudi de les composicions isotòpiques del sofre i l’oxigen del sulfat del guix, ha permès recolzar analíticament la teoria coneguda documentalment sobre la procedència dels alabastres del retaule de l’altar major de Poblet de la zona de Sarra

1H NMR metabolomic study of auxotrophic starvation in yeast using Multivariate Curve Resolution-Alternating Least Squares for Pathway Analysis

Disruption of specific metabolic pathways constitutes the mode of action of many known toxicants and it is responsible for the adverse phenotypes associated to human genetic defects. Conversely, many industrial applications rely on metabolic alterations of diverse microorganisms, whereas many therapeutic drugs aim to selectively disrupt pathogens' metabolism. In this work we analyzed metabolic changes induced by auxotrophic starvation conditions in yeast in a non-targeted approach, using one-dimensional proton Nuclear Magnetic Resonance spectroscopy (1H NMR) and chemometric analyses. Analysis of the raw spectral datasets showed specific changes linked to the different stages during unrestricted yeast growth, as well as specific changes linked to each of the four tested starvation conditions (L-methionine, L-histidine, L-leucine and uracil). Analysis of changes in concentrations of more than 40 metabolites by Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) showed the normal progression of key metabolites during lag, exponential and stationary unrestricted growth phases, while reflecting the metabolic blockage induced by the starvation conditions. In this case, different metabolic intermediates accumulated over time, allowing identification of the different metabolic pathways specifically affected by each gene disruption. This synergy between NMR metabolomics and molecular biology may have clear implications for both genetic diagnostics and drug development. © The Author(s) 2016.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 320737. We also thank Dr. Yolanda Pérez for her helpful recommendations on setting up the acquisition parameters for some of the NMR experiments.Peer reviewe

Perfluoroalkylated substances effects in Xenopus laevis A6 kidney epithelial cells determined by ATR-FTIR spectroscopy and chemometric analysis

The effects of four perfluoroalkylated substances (PFASs), namely, perfluorobutanesulfonate (PFBS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS) and perfluorononanoic acid (PFNA) were assessed in Xenopus laevis A6 kidney epithelial cells by attenuated total reflection Fouriertransform infrared (ATR-FTIR) spectroscopy and chemometric analysis. Principal component analysis-linear discriminant analysis (PCA-LDA) was used to visualize wavenumber-related alterations and ANOVA-simultaneous component analysis (ASCA) allowed data processing considering the underlying experimental design. Both analyses evidenced a higher impact of low-dose PFAS-treatments (10-9 M) on A6 cells forming monolayers, while there was a larger influence of high-dose PFAS-treatments (10-5 M) on A6 cells differentiated into dome structures. The observed dose-response PFAS-induced effects were to some extent related to their cytotoxicity: the EC50-values of most influent PFAS-treatments increased (PFOS<PFNA<PFOA<<PFBS), higherdoses of these chemicals induced a larger impact. Major spectral alterations were mainly attributed to DNA/RNA, secondary protein structure, lipids and fatty acids. Finally, PFOS and PFOA caused a decrease in A6 cell numbers compared to controls, whereas PFBS and PFNA did not significantly change cell population levels. Overall, this work highlights the ability of PFASs to alter A6 cells, whether forming monolayers or differentiated into dome structures, and the potential of PFOS and PFOA to induce cell death

Usefulness of Bayesian networks in epidemiological studies

Introduction: Bayesian networks are a form of statistical modelling, which has been widely used in fields like clinical decision, systems biology, human immunodeficiency virus (HIV) and influenza research, analyses of complex disease systems, interactions between multiple diseases and, also, in diagnostic diseases. The present study aimed to show the usefulness of Bayesian networks (BNs) in epidemiological studies. Material and Methods: 3,993 subjects (men 1,758, women 2,235) belonging to the public productive sector from the Balearic Islands (Spain), which were active workers, constitute the data set. Results: A BN was built from a dataset composed of twelve relevant features in cardiovascular disease epidemiology. Furthermore, the structure and parameters were learnt with GeNIe 2.0 tool. Taking into account the main topological properties some features were optimized, obtaining a hypothesized scenario where the likelihoods of the different features were updated and the adequate conclusions were established. Conclusions: Bayesian networks allow us to obtain a hypothetical scenario where the probabilities of the different features are updated according to the evidence that is introduced. This fact makes Bayesian networks a very attractive tool.Introducción: Las redes Bayesianas son una forma de modelización estadística, las cuales han sido ampliamente utilizadas en campos como la decisión clínica, biología de sistemas, virus de inmunodeficiencia humana (VIH) e investigación en influenza, análisis de sistemas de enfermedades complejos, interacciones entre múltiples enfermedades y, también, en enfermedades de diagnóstico. Este estudio tiene como objetivo mostrar la utilidad de las redes Bayesianas en estudios epidemiológicos. Material y Métodos: 3,993 individuos (hombres 1,758, mujeres 2,235) pertenecientes al sector productivo público de las Islas Baleares (España), los cuales eran trabajadores activos, constituyen la base de datos. Resultados: Una red Bayesiana se ha obtenido a partir de una base de datos compuesta de doce características relevantes de la epidemiología de la enfermedad cardiovascular. Por otra parte, la estructura y los parámetros se han obtenido con la herramienta Genie 2.0. Teniendo en cuenta las principales propiedades topológicas algunas características fueron optimizadas. Conclusiones: Las redes Bayesianas permiten obtener un escenario hipotético donde las probabilidades de las diferentes características se van actualizando de acuerdo con la evidencia introducida. Este hecho hace de las redes Bayesianas una herramienta muy atractiva, además permite establecer diversas conclusiones

Mineralogy and distribution of critical elements in the Sn–W–Pb–Ag–Zn Huanuni deposit, Bolivia

The polymetallic Huanuni deposit, a world-class tin deposit, is part of the Bolivian tin belt. As a likely case for a “mesothermal” or transitional deposit between epithermal and porphyry Sn types (or shallow porphyry Sn), it represents a case that contributes significantly to the systematic study of the distribution of critical elements within the “family” of Bolivian tin deposits. In addition to Sn, Zn and Ag, further economic interest in the area resides in its potential in critical elements such as In, Ga and Ge. This paper provides the first systematic characterisation of the complex mineralogy and mineral chemistry of the Huanuni deposit with the twofold aim of identifying the mineral carriers of critical elements and endeavouring plausible metallogenic processes for the formation of this deposit, by means of a multi-methodological approach. With In concentrations consistently over 2000 ppm, the highest potential for relevant concentrations in this metal resides in widespread tin minerals (cassiterite and stannite) and sphalerite. Hypogene alteration assemblages are hardly developed due to the metasedimentary nature of host rocks, but the occurrence of potassium feldspar, schorl, pyrophyllite and dickite as vein material stand for potassic to phyllic or advanced argillic alteration assemblages and relatively high-temperature (and low pH) mineralising fluids. District-scale mineralogical zonation suggests a thermal zonation with decreasing temperatures from the central to the peripheral areas. A district-scale zonation has been also determined for d34SVCDT values, which range -7.2‰ to 0.2‰ (mostly -7‰ to -5‰) in the central area and -4.2‰ to 1.0‰ (mainly constrained between -2‰ and 1‰) in peripheral areas. Such values stand for magmatic and metasedimentary sources for sulfur, and their spatial zoning may be related to differential reactivity between mineralising fluids and host rocks, outwardly decreasing from the central to the peripheral areasPeer ReviewedPostprint (published version

MINROCIND una eina d'aprenentatge presencial e interactiva dels jaciments de roques i minerals industrials a Catalunya. Eina d'aprenentatge presencial i/o interactiu en el àmbit dels ensenyaments de la mineralogia i petrologia aplicada

Es tracta d'un material i eina didàctica a la vegada. Té doncs una doble vesant: a) una part física constituïda per una mostra de roca polida i una làmina prima de la mateixa roca, per a ser utilitzada a l'hora de pràctiques a classe; i b) una part virtual formada per una base de dades interactiva on els estudiants trobaran fitxes amb les característiques bàsiques de la roca, i la descripció de les pedreres més importants on es troben i la seva importància com a recurs econòmic, com a roca ornamental i/o industrial