Lipid storage and autophagy in melanoma cancer cells

Cancer stem cells (CSC) represent a key cellular subpopulation controlling biological features such as cancer progression in all cancer types. By using melanospheres established from human melanoma patients, we compared less differentiated melanosphere-derived CSC to differentiating melanosphere-derived cells. Increased lipid uptake was found in melanosphere-derived CSC vs. differentiating melanosphere-derived cells, paralleled by strong expression of lipogenic factors Sterol Regulatory Element-Binding Protein-1 (SREBP-1) and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ). An inverse relation between lipid-storing phenotype and autophagy was also found, since microtubule-associated protein 1A/1B-Light Chain 3 (LC3) lipidation is reduced in melanosphere-derived CSC. To investigate upstream autophagy regulators, Phospho-AMP activated Protein Kinase (P-AMPK) and Phospho-mammalian Target of Rapamycin (P-mTOR) were analyzed; lower P-AMPK and higher P-mTOR expression in melanosphere-derived CSC were found, thus explaining, at least in part, their lower autophagic activity. In addition, co-localization of LC3-stained autophagosome spots and perilipin-stained lipid droplets was demonstrated mainly in differentiating melanosphere-derived cells, further supporting the role of autophagy in lipid droplets clearance. The present manuscript demonstrates an inverse relationship between lipid-storing phenotype and melanoma stem cells differentiation, providing novel indications involving autophagy in melanoma stem cells biology

TLR3 engagement induces IRF-3-dependent apoptosis in androgen-sensitive prostate cancer cells and inhibits tumour growth in vivo

Toll-like receptors (TLRs) are a family of highly conserved transmembrane proteins expressed in epithelial and immune cells that recognize pathogen associated molecular patterns. Besides their role in immune response against infections, numerous studies have shown an important role of different TLRs in cancer, indicating these receptors as potential targets for cancer therapy. We previously demonstrated that the activation of TLR3 by the synthetic double-stranded RNA analogue poly I:C induces apoptosis of androgen-sensitive prostate cancer (PCa) LNCaP cells and, much less efficiently, of the more aggressive PC3 cell line. Therefore, in this study we selected LNCaP cells to investigate the mechanism of TLR3-mediated apoptosis and the in vivo efficacy of poly I:C-based therapy. We show that interferon regulatory factor-3 (IRF-3) signalling plays an essential role in TLR3-mediated apoptosis in LNCaP cells through the activation of the intrinsic and extrinsic apoptotic pathways. Interestingly, hardly any apoptosis was induced by poly I:C in normal prostate epithelial cells RWPE-1. We also demonstrate for the first time the direct anticancer effect of poly I:C as a single therapeutic agent in a well-established human androgen-sensitive PCa xenograft model, by showing that tumour growth is highly impaired in poly I:C-treated immunodeficient mice. Immunohistochemical analysis of PCa xenografts highlights the antitumour role of poly I:C in vivo both on cancer cells and, indirectly, on endothelial cells. Notably, we show the presence of TLR3 and IRF-3 in both human normal and PCa clinical samples, potentially envisaging poly I:C-based therapy for PCa

Metal release under anaerobic conditions of urban soils of four European cities

Urban soil contamination may represent an environmental threat in view of their proximity to humans. The ecological homogenization of urban areas has been postulated, and as the sources of pollution are the same in most European cities, it is possible that soil contamination is another factor of convergence. The current climate change with consequent increase of extreme rain events may affect the mobility of potentially toxic elements (PTE) thus increasing the risks. If the soil is submerged, Eh decreases and causes the solubilization of Fe and Mn oxides, which are important carriers of PTE. We compared the release of Cu, Pb, and Zn from 48 soils of four cities (namely Glasgow, Ljubljana, Sevilla, and Torino) when submerged for up to 30 days. A decrease of the redox potential was observed in all soils after a few days and an increase of Mn and then Fe in solution. Cu, Pb, and Zn were consequently released to the solution according to the general soil contamination. Despite the marked differences in soil properties, the reaction to anaerobiosis appeared to be similar in all samples indicating that waterlogging of urban soil contaminated with PTE may pose a serious environmental risk and substantiating the hypothesis of ecological convergence

Interference coloration as an anti-predator defence

Interference coloration, in which the perceived colour varies predictably with the angle of illumination or observation, is extremely widespread across animal groups. However, despite considerable advances in our understanding of the mechanistic basis of interference coloration in animals, we still have a poor understanding of its function. Here, I show, using avian predators hunting dynamic virtual prey, that the presence of interference coloration can significantly reduce a predator's attack success. Predators required more pecks to successfully catch interference-coloured prey compared with otherwise identical prey items that lacked interference coloration, and attacks against prey with interference colours were less accurate, suggesting that changes in colour or brightness caused by prey movement hindered a predator's ability to pinpoint their exact location. The pronounced antipredator benefits of interference coloration may explain why it has evolved independently so many times. © 2015 The Author(s) Published by the Royal Society. All rights reserved

An equilibrium model for RFP plasmas in the presence of resonant tearing modes

The equilibrium of a finite-beta RFP plasma in the presence of saturated-amplitude tearing modes is investigated. The singularities of the MHD force balance equation JXB=grad(p) at the modes rational surfaces are resolved through a proper regularization of the zeroth-order (equilibrium) profiles, by setting to zero there the gradient of the pressure and parallel current density. An equilibrium model, which satisfies the regularization rule at the various rational surfaces, is developed. The comparison with the experimental data from the Reversed Field eXperiment (RFX) gives encouraging results. The model provides an easy tool for magnetic analysis: many aspects of the perturbations can be analyzed and reconstructed.Comment: Final accepted version. 36 page

Progress on Radio Frequency Auxiliary Heating System Designs in ITER

ITER will require over 100 MW of auxiliary power for heating, on- and off-axis current drive, accessing the H-mode, and plasma shut-down. The Electron Cyclotron Range of Frequencies (ECRF) and Ion Cyclotron Range of Frequencies (ICRF) are two forms of Radio Frequency (RF) auxiliary power being developed for these applications. Design concepts for both the ECRF and ICRF systems are presented, key features and critical design issues are discussed, and projected performances outlined

Membranas híbridas de polieterimida-sílice. Caracterización por espectroscopia de IR y MEB.

Se prepararon membranas híbridas de polieterimida-sílice por incorporación de nanopartículas de sílice a la solución polimérica y a través de la generación del relleno inorgánico empleando la técnica sol-gel. Las membranas híbridas obtenidas fueron caracterizadas por FTIR, MEB y MEB-EDS. Los estudios de FTIR permitieron realizar un seguimiento del grado de hidrólisis del alcóxido metálico precursor (TEOS) y analizar la interacción existente entre la sílice generada y el polímero. Las imágenes de MEB reflejaron la evolución de la morfología de las membranas frente a modificaciones producidas durante la síntesis tales como la incorporación de un agente de acoplamiento, la polimerización de TEOS in situ, el incremento del contenido de sílice y el efecto de la redisolución de las membranas sintetizadas. El análisis químico elemental de las membranas híbridas usando EDS, permitió corroborar la presencia de partículas de sílice en las membranas, a través de la observación de la intensidad del pico correspondiente al silicio

Identification of Differentially Expressed MicroRNAs in Osteosarcoma

A limited number of reports have investigated the role of microRNAs in osteosarcoma. In this study, we performed miRNA expression profiling of osteosarcoma cell lines, tumor samples, and normal human osteoblasts. Twenty-two differentially expressed microRNAs were identified using high throughput real-time PCR analysis, and 4 (miR-135b, miR-150, miR-542-5p, and miR-652) were confirmed and validated in a different group of tumors. Both miR-135b and miR-150 have been previously shown to be important in cancer. We hypothesize that dysregulation of differentially expressed microRNAs may contribute to tumorigenesis. They might also represent molecular biomarkers or targets for drug development in osteosarcoma

CO2 and Rn degassing from the natural analog of Campo de Calatrava (Spain): Implications for monitoring of CO2 storage sites

Natural analogs offer a valuable opportunity to investigate the long-term impacts associated with thepotential leakage in geological storage of CO2.Degassing of CO2and radon isotopes (222Rn?220Rn) from soil, gas vents and thermal water dischargeswas investigated in the natural analog of Campo de Calatrava Volcanic Field (CCVF; Central Spain) todetermine the CO2?Rn relationships and to assess the role of CO2as carrier gas for radon. Furthermore,radon measurements to discriminate between shallow and deep gas sources were evaluated under theperspective of their applicability in monitoring programs of carbon storage projects.CO2flux as high as 5000 g m?2d?1and222Rn activities up to 430 kBq m?3were measured;220Rn activi-ties were one order of magnitude lower than those of222Rn. The222Rn/220Rn ratios were used to constrainthe source of the Campo de Calatrava soil gases since a positive correlation between radon isotopic ratiosand CO2fluxes was observed. Thus, in agreement with previous studies, our results indicate a deepmantle-related origin of CO2for both free and soil gases, suggesting that carbon dioxide is an efficientcarrier for Rn. Furthermore, it was ascertained that the increase of222Rn in the soil gases was likely pro-duced by two main processes: (i) direct transport by a carrier gas, i.e., CO2and (ii) generation at shallowlevel due to the presence of relatively high concentrations of dissolved U and Ra in the thermal aquiferof Campo de Calatrava.The diffuse CO2soil flux and radon isotopic surveys carried out in the Campo de Calatrava VolcanicFields can also be applicable to geochemical monitoring programs in CCS (Carbon Capture and Storage)areas as these parameters are useful to: (i) constrain CO2leakages once detected and (ii) monitor both theevolution of the leakages and the effectiveness of subsequent remediation activities. These measurementscan also conveniently be used to detect diffuse leakages