In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma.

Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain tissue after its oral administration in Compritol® and Precirol® lipid nanoparticles (LN). The high accumulation of edelfosine in brain was due to the inhibition of P-glycoprotein by Tween® 80, as verified using a P-glycoprotein drug interaction assay. Moreover, these LN were tested in vitro against the C6 glioma cell line, which was later employed to establish an in vivo xenograft mouse model of glioma. In vitro studies revealed that edelfosine-loaded LN induced an antiproliferative effect in C6 glioma cell line. In addition, in vivo oral administration of drug-loaded LN in NMRI nude mice bearing a C6 glioma xenograft tumor induced a highly significant reduction in tumor growth (p<0.01) fourteen days after the beginning of the treatment. Our results showed that Tween® 80 coated Compritol® and Precirol® LN can effectively inhibit the growth of C6 glioma cells in vitro and suggest that edelfosine-loaded LN represent an attractive option for the enhancement of antitumor activity on brain tumors in vivo

Lipid nanoparticles for alkyl lysophospholipid edelfosine encapsulation: development and in vitro characterization

The ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, edelfosine (ET-18-OCH3) is the prototype molecule of a promising class of antitumour drugs named alkyl–lysophospholipid analogues (ALPs) or antitumor ether lipids. This drug presents a very important drawback as can be the dose depending haemolysis when administered intravenously. Lipid nanoparticles have been lately proposed for different drug encapsulation as an alternative to other controlled release delivery systems, such as liposomes or polymeric nanoparticles. The aim of this study was to develop a lipid nanoparticulate system that would decrease systemic toxicity as well as improve the therapeutic potential of the drug. Lipids employed were Compritol® 888 ATO and stearic acid. The nanoparticles were characterized by photon correlation spectroscopy for size and size distribution, and atomic force microscopy (AFM) was used for the determination of morphological properties. By both differential scanning calorimetry (DSC) and X-ray diffractometry, crystalline behaviour of lipids and drug was assessed. The drug encapsulation efficiency and the drug release kinetics under in vitro conditions were measured by HPLC–MS. It was concluded that Compritol® presents advantages as a matrix material for the manufacture of the nanoparticles and for the controlled release of edelfosine

The AMBRE Project: Stellar parameterisation of the ESO:FEROS archived spectra

The AMBRE Project is a collaboration between the European Southern Observatory (ESO) and the Observatoire de la Cote d'Azur (OCA) that has been established in order to carry out the determination of stellar atmospheric parameters for the archived spectra of four ESO spectrographs. The analysis of the FEROS archived spectra for their stellar parameters (effective temperatures, surface gravities, global metallicities, alpha element to iron ratios and radial velocities) has been completed in the first phase of the AMBRE Project. From the complete ESO:FEROS archive dataset that was received, a total of 21551 scientific spectra have been identified, covering the period 2005 to 2010. These spectra correspond to ~6285 stars. The determination of the stellar parameters was carried out using the stellar parameterisation algorithm, MATISSE (MATrix Inversion for Spectral SynthEsis), which has been developed at OCA to be used in the analysis of large scale spectroscopic studies in galactic archaeology. An analysis pipeline has been constructed that integrates spectral reduction and radial velocity correction procedures with MATISSE in order to automatically determine the stellar parameters of the FEROS spectra. Stellar atmospheric parameters (Teff, log g, [M/H] and [alpha/Fe]) were determined for 6508 (30.2%) of the FEROS archived spectra (~3087 stars). Radial velocities were determined for 11963 (56%) of the archived spectra. 2370 (11%) spectra could not be analysed within the pipeline. 12673 spectra (58.8%) were analysed in the pipeline but their parameters were discarded based on quality criteria and error analysis determined within the automated process. The majority of these rejected spectra were found to have broad spectral features indicating that they may be hot and/or fast rotating stars, which are not considered within the adopted reference synthetic spectra grid of FGKM stars.Comment: 28 pages, 28 figures, 9 table

A simple approach to obtain hybrid Au-loaded polymeric nanoparticles with a tunable metal load

A new strategy to nanoengineer multi-functional polymer-metal hybrid nanostructures is reported. By using this protocol the hurdles of most of the current developments concerning covalent and non-covalent attachment of polymers to preformed inorganic nanoparticles (NPs) are overcome. The strategy is based on the in situ reduction of metal precursors using the polymeric nanoparticle as a nanoreactor. Gold nanoparticles and poly(dl-lactic-co-glycolic acid), PLGA, are located in the core and shell, respectively. This novel technique enables the production of PLGA NPs smaller than 200 nm that bear either a single encapsulated Au NP or several smaller NPs with tunable sizes and a 100% loading efficiency. In situ reduction of Au ions inside the polymeric NPs was achieved on demand by using heat to activate the reductive effect of citrate ions. In addition, we show that the loading of the resulting Au NPs inside the PLGA NPs is highly dependent on the surfactant used. Electron microscopy, laser irradiation, UV-Vis and fluorescence spectroscopy characterization techniques confirm the location of Au nanoparticles. These promising results indicate that these hybrid nanomaterials could be used in theranostic applications or as contrast agents in dark-field imaging and computed tomography

Efficacy of edelfosine lipid nanoparticles in breast cancer cells

Breast cancer is a heterogeneous group of neoplasms predominantly originating in the terminal duct lobular units. It represents the leading cause of cancer death in women and the survival frequencies for patients at advanced stages of the disease remain low. New treatment options need to be researched to improve these rates. The anti-tumor ether lipid edelfosine (ET) is the prototype of a novel generation of promising anticancer drugs. However, it presents several drawbacks for its use in cancer therapy, including gastrointestinal and hemolytic toxicity and low oral bioavailability. To overcome these obstacles, ET was encapsulated in Precirol ATO 5 lipid nanoparticles (ET-LN), and its anti-tumor potential was in vitro tested in breast cancer. The formulated ET-LN were more effective in inhibiting cell proliferation and notably decreased cell viability, showing that the cytotoxic effect of ET was considerably enhanced when ET was encapsulated. In addition, ET and ET-LN were able to promote cell cycle arrest at G1 phase. Moreover, although both treatments provoked an apoptotic effect in a time-dependent manner, such anti-tumor effects were noticeably improved with ET-LN treatment. Therefore, our results indicate that encapsulating ET in LN played an essential role in improving the efficacy of the drug

The Open Cluster Chemical Abundances from Spanish Observatories survey (OCCASO)

We present the motivation, design and current status of the Open Cluster Chemical Abundances from Spanish Observatories survey (OCCASO). Using the high resolution spectroscopic facilities available at Spanish observatories, OCCASO will derive chemical abundances in a sample of 20 to 25 open clusters older than 0.5 Gyr. This sample will be used to study in detail the formation and evolution of the Galactic disc using open clusters as tracers.Comment: 6 pages, 1 figure, Highlights of Spanish Astrophysics VIII, Proceedings of the XI Scientific Meeting of the Spanish Astronomical Society held on September 8 - 12, 2014, in Teruel, Spain. A. J. Cenarro, F. Figueras, C. Hern\'andez-Monteagudo, J. Trujillo, and L. Valdivielso (eds.

A spectroscopic survey of thick disc stars outside the solar neighbourhood

We performed a spectroscopic survey of nearly 700 stars probing the galactic thick disc far from the solar neighbourhood towards the galactic coordinates (l~277, b~47). The derived effective temperatures, surface gravities and overall metallicities were then combined with stellar evolution isochrones, radial velocities and proper motions to derive the distances, kinematics and orbital parameters of the sample stars. The targets belonging to each galactic component (thin disc, thick disc, halo) were selected either on their kinematics or according to their position above the galactic plane, and the vertical gradients were also estimated. We present here atmospheric parameters, distances and kinematics for this sample, and a comparison of our kinematic and metallicity distributions with the Besancon model of the Milky Way. The thick disc far from the solar neighbourhood is found to differ only slightly from the thick disc properties as derived in the solar vicinity. For regions where the thick disc dominates, we measured vertical velocity and metallicity trends of d(V_phi)/dZ = 19 +/- 8 km/s/kpc and d[M/H]/dZ = -0.14 +/- 0.05 dex/kpc, respectively. These trends can be explained as a smooth transition between the different galactic components, although intrinsic gradients could not be excluded. In addition, a correlation d(V_phi)/d[M/H] = -45 +/- 12 km/s/dex between the orbital velocity and the metallicity of the thick disc is detected. This gradient is inconsistent with the SDSS photometric survey analysis, which did not detect any such trend, and challenges radial migration models of thick disc formation. Estimations of the scale heights and scale lengths for different metallicity bins of the thick disc result in consistent values, with hR~3.4 \pm 0.7 kpc, and hZ~694 \pm 45 pc, showing no evidence of relics of destroyed massive satellites.Comment: 19 pages, 15 figures, accepted for publication in A&

Stellar atmosphere parameters with MAx, a MAssive compression of x^2 for spectral fitting

MAx is a new tool to estimate parameters from stellar spectra. It is based on the maximum likelihood method, with the likelihood compressed in a way that the information stored in the spectral fluxes is conserved. The compressed data are given by the size of the number of parameters, rather than by the number of flux points. The optimum speed-up reached by the compression is the ratio of the data set to the number of parameters. The method has been tested on a sample of low-resolution spectra from the Sloan Extension for Galactic Understanding and Exploration (SEGUE) survey for the estimate of metallicity, effective temperature and surface gravity, with accuracies of 0.24 dex, 130K and 0.5 dex, respectively. Our stellar parameters and those recovered by the SEGUE Stellar Parameter Pipeline agree reasonably well. A small sample of high-resolution VLT-UVES spectra were also used to test the method and the results have been compared to a more classical approach. The speed and multi-resolution capability of MAx combined with its performance compared with other methods indicates that it will be a useful tool for the analysis of upcoming spectral surveys.Comment: 17 pages, 10 figures, minor changes after the chief language editor. A&A, in pres

Quantifying landscape-level methane fluxes in subarctic Finland using a multiscale approach

Journal ArticleQuantifying landscape-scale methane (CH4) fluxes from boreal and arctic regions, and determining how they are controlled, is critical for predicting the magnitude of any CH4 emission feedback to climate change. Furthermore, there remains uncertainty regarding the relative importance of small areas of strong methanogenic activity, vs. larger areas with net CH4 uptake, in controlling landscape-level fluxes. We measured CH4 fluxes from multiple microtopographical subunits (sedge-dominated lawns, interhummocks and hummocks) within an aapa mire in subarctic Finland, as well as in drier ecosystems present in the wider landscape, lichen heath and mountain birch forest. An intercomparison was carried out between fluxes measured using static chambers, up-scaled using a high-resolution landcover map derived from aerial photography and eddy covariance. Strong agreement was observed between the two methodologies, with emission rates greatest in lawns. CH4 fluxes from lawns were strongly related to seasonal fluctuations in temperature, but their floating nature meant that water-table depth was not a key factor in controlling CH4 release. In contrast, chamber measurements identified net CH4 uptake in birch forest soils. An intercomparison between the aerial photography and satellite remote sensing demonstrated that quantifying the distribution of the key CH4 emitting and consuming plant communities was possible from satellite, allowing fluxes to be scaled up to a 100 km2 area. For the full growing season (May to October), ~ 1.1-1.4 g CH4 m-2 was released across the 100 km2 area. This was based on up-scaled lawn emissions of 1.2-1.5 g CH4 m-2, vs. an up-scaled uptake of 0.07-0.15 g CH4 m-2 by the wider landscape. Given the strong temperature sensitivity of the dominant lawn fluxes, and the fact that lawns are unlikely to dry out, climate warming may substantially increase CH4 emissions in northern Finland, and in aapa mire regions in general.This work was carried out within the Natural Environment Research Council (NERC) funded Arctic Biosphere Atmosphere Coupling at Multiple Scales (ABACUS) project (a contribution to International Polar Year 2007_2008) plus NERC small grant NE/F010222/1 awarded to RB and BH. We are grateful for the support of the staff at the Kevo Subarctic Research Institute, to David Sayer for operation and maintenance of the eddy covariance apparatus, and to Lorna English for helping with the analysis of the CH4 samples. We also thank the NERC Field Spectroscopy Facility for support in ground data collection for the remote sensing analysis. Finally, we wish to express our gratitude to two anonymous reviewers whose comments and suggestions substantially improved the manuscript

Living at the top. Connectivity limitations and summit depth drive fish diversity patterns in an isolated seamount

The fish assemblages of the Galicia Bank and the closest continental slope (northwest of Spain) were analysed using otter trawls to improve our understanding of how environmental drivers structure seamount fish communities in the deep sea. The effect of environmental drivers on these assemblages was studied using multivariate techniques together with the variation in α and β diversity across assemblages. Fish fauna in the study area was distributed in 5 different assemblages generated by the action of 3 main drivers: depth, distance to the coast and presence of cold-water corals. The observed differences in species composition among assemblages were mostly explained by species turnover across a depth gradient. The seamount summit and the continental slope showed important differences despite sharing similar depths, mainly because several species requiring shallow juvenile habitats were absent from the summit. These absences were observed in both summit assemblages inside and outside the cold-water coral reef. Our results show that in isolated seamounts with relatively deep summits, the lack of connectivity with shallower areas limits the presence of certain species, probably due to the impossibility for these species to migrate directly from shallow to deeper seabed areas. These species are replaced by species with preferences for deeper habitats, providing the fish assemblages located at the top of the summit with a deeper profile than observed in fish assemblages of the continental slope.En prensa2,48