Self-assembled biotransesterified cyclodextrins as potential Artemisinin nanocarriers. II: In vitro behavior toward the immune system and in vivo biodistribution assessment of unloaded nanoparticles.

In a previous study, we reported on the formulation of Artemisinin-loaded surface-decorated nanoparticles (nanospheres and nanoreservoirs) by co-nanoprecipitation of PEG derivatives (PEG1500 and PEG4000-stearate, polysorbate 80) and biosynthesized γ-CD fatty esters. In the present study, the co-nanoprecipitation was extended to the use of a PEGylated phospholipid, namely DMPE-PEG2000. As our goal was to prepare long-circulating nanocarriers for further systemic delivery of Artemisinin (ART), here, we have investigated, on the one hand, the in vitro behavior of these surface-modified γ-CD-C10 particles toward the immune system (complement activation and macrophage uptake assays) and, on the other hand, their biodistribution features in mice. These experiments showed that the in vitro plasma protein adsorption and phagocytosis by macrophage cells triggered by γ-CD-C10 nanoparticles were significantly reduced when their surface was decorated with amphiphilic PEGylated molecules, in particular PEG1500-stearate, DMPE-mPEG2000 or polysorbate 80. The prolonged blood circulation time assessed by fluorescence imaging was demonstrated for unloaded γ-CD-C10-based nanospheres and nanoreservoir particles containing DMPE-PEG2000 and polysorbate80, respectively. These nanoparticles also proved to be non-hemolytic at the concentration range used in vivo. Within the limits of the conducted experiments, the co-nanoprecipitation technique may be considered as an alternative for surface modification of amphiphilic CD-based drug delivery systems and may be applied to the systemic delivery of ART

MeMoVolc report on classification and dynamics of volcanic explosive eruptions

Classifications of volcanic eruptions were first introduced in the early twentieth century mostly based on qualitative observations of eruptive activity, and over time, they have gradually been developed to incorporate more quantitative descriptions of the eruptive products from both deposits and observations of active volcanoes. Progress in physical volcanology, and increased capability in monitoring, measuring and modelling of explosive eruptions, has highlighted shortcomings in the way we classify eruptions and triggered a debate around the need for eruption classification and the advantages and disadvantages of existing classification schemes. Here, we (i) review and assess existing classification schemes, focussing on subaerial eruptions; (ii) summarize the fundamental processes that drive and parameters that characterize explosive volcanism; (iii) identify and prioritize the main research that will improve the understanding, characterization and classification of volcanic eruptions and (iv) provide a roadmap for producing a rational and comprehensive classification scheme. In particular, classification schemes need to be objective-driven and simple enough to permit scientific exchange and promote transfer of knowledge beyond the scientific community. Schemes should be comprehensive and encompass a variety of products, eruptive styles and processes, including for example, lava flows, pyroclastic density currents, gas emissions and cinder cone or caldera formation. Open questions, processes and parameters that need to be addressed and better characterized in order to develop more comprehensive classification schemes and to advance our understanding of volcanic eruptions include conduit processes and dynamics, abrupt transitions in eruption regime, unsteadiness, eruption energy and energy balance

Bioesterified polysubstituted-cyclodextrin/surfactant nanoparticles obtained by multilevel self-assembly

The purpose of this work is to investigate the inclusion complexation between a novel amphiphilic biotransesterified cyclodextrin (CD), incorporated in nanostructured environment, and a model drug compound. A water-insoluble γ-cyclodextrin derivative (γ-CD-C10), polysubstituted with multiple (n=7-8) decanoyl chains (C10) on the secondary face, is produced by enzymatically-assisted esterification. The γ-CD-C10 derivative is embedded in amphiphilic nanoenvironment created by self-assembly with the lipophilic dye Nile red (NR) and the non-ionic surfactant polysorbate 80 (P80). The inclusion complexation and the environmental effects upon the γ-CD-C10/NR/P80 nanoparticle (NP) formation, in a multilevel self-assembly approach, are investigated by means of steady-state fluorescence and Förster resonance energy transfer (FRET) techniques. Quasi-elastic light scattering (QELS) is used to control the NP size distribution during the sequential steps of the assembling process

Jurassic amber outcrops from Lebanon

International audienc

SI Datasets - Strullu-Derrien et al - An expanded diversity of oomycetes in Carboniferous forests: Reinterpretation of Oochytrium lepidodendri (Renault 1894) from the Esnost chert, Massif Central, France

SI dataset related to the 3D reconstructions presented in: An expanded diversity of oomycetes in Carboniferous forests: Reinterpretation of Oochytrium lepidodendri (Renault 1894) from the Esnost chert, Massif Central, France Two .zip archive are provided, these form the basis for the published three-dimentional reconstruction SI videos and figures. The folder struture in each zip is as follows: airyscan_raw_data - Raw data from the Airyscan confocal microscope (see published paper for full details). This is in its native .czi format. dragonfly - Dragonfly (https://www.theobjects.com/dragonfly/) session data. Contains the segmentation data. model_stls - Exported stl format meshes from Dragonfly, used for imprtortation into Blender to create the published videos. videos - Videos related to this data. Either .mp4 or .avi format. z-stack_bmp - Tomogrpahic dataset of slice images extracted from raw data in .bmp format. z-stack_tiffs - Tomogrpahic dataset of slice images extracted from raw data in .tiff format

Révision de la "Falaise de Blanche" (Crétacé inférieur) au Liban et définition de l'Étage Régional Jezzinien

International audienceThe "Falaise de Blanche" is a prominent cliff, consisting mostly of Lower Cretaceous limestones that extends as linear outcrops over most of the Lebanese territory and provides geologists a remarkable reference for stratigraphic studies. However, until now, this unit was lacking a clear definition. We introduce herein the Jezzinian Regional Stage, the type-locality of which is at Jezzine. It equates as an unconformity-bounded unit and, per definition, it is framed by two discontinuities. Because we identified an additional, median sequence-boundary, poorly-expressed in the type-section but better at Aazour, only 4.5 km westward of Jezzine, the new regional stage implicitly spans two sequences. The lithostratigraphic framework being properly redefined, we were able to investigate time-constrained micropaleontological assemblages, consisting mostly of benthic foraminifers and calcareous algae. Typically Southern Tethysian, these assemblages contribute to high-resolution, holostratigraphic correlations with the Persian Gulf area, on the eastern part of the Arabian Plate. The Jezzinian interval correlates with the upper part of the Kharaibian Regional Stage (also known as "Thamama II" reservoir unit in the oil industry). In turn, the Jezzinian is indirectly correlated with the Northern Tethysian Urgonian stratigraphic units where it corresponds to a rather short interval encompassing the standard Barremian - Bedoulian stage boundary. Locally the upper discontinuity is associated to a significant intra-Bedoulian hiatus. The macrofossil assemblages found in the Jezzinian (echinids) and above it (ammonites) support, or at least do not contradict, our micropaleontological dating.Les calcaires du Crétacé inférieur de la "Falaise de Blanche" affleurent sur une grande partie du territoire libanais. Ils apparaissent dans le paysage sous forme d'escarpements linéaires saillants constituant autant de points d'ancrage remarquables pour tout recalage stratigraphique. Toutefois, jusqu'à très récemment, cette unité était piètrement caractérisée : il lui manquait notamment une définition rigoureuse. Nous introduisons ici l'Étage Régional Jezzinien, dont la localité-type est sise à Jezzine. Il s'agit d'une unité stratigraphique particulière, aussi appelée U.B.U. (pour "unconformity-bounded unit"), une unité qui, par définition, est encadrée par deux discontinuités. Parce que nous avons identifié une limite de séquence supplémentaire, en position médiane, peu exprimée dans la section-type, mais beaucoup mieux à Aazour, à 4,5 km à peine à l'ouest de Jezzine, le nouvel étage régional devrait implicitement couvrir deux séquences. Le canevas lithostratigraphique étant clairement redéfini, nous avons pu étudier les associations micropaléontologiques, constituées essentiellement de foraminifères benthiques et d'algues calcaires, associations dorénavant relativement bien contraintes du point de vue de leur âge. Typiquement sud-téthysiennes, elles facilitent les corrélations holostratigraphiques à haute résolution avec la région du Golfe persique, sur le côté oriental de la Plaque arabique. L'intervalle Jezzinien correspond ainsi à la partie supérieure de l'Étage Régional Kharaibien (aussi connu comme unité réservoir "Thamama II" dans l'industrie pétrolière). À son tour, le Jezzinien est indirectement corrélé avec les unités stratigraphiques urgoniennes nord-téthysiennes où il correspond à un intervalle relativement court comprenant la limite des étages standards (internationaux) Barrémien et Bédoulien. Localement la discontinuité sommitale est associée à un hiatus intra-Bédoulien significatif. Les associations macropaléontologiques reconnues dans le Jezzinien (échinides) et au-dessus de cette unité (ammonites) viennent à l'appui de notre datation micropaléontologique ou tout au moins ne la contredisent pas

The acridone derivative MBLI-87 sensitizes breast cancer resistance protein-expressing xenografts to irinotecan.

International audienceThe breast cancer resistance protein ABCG2 confers cellular resistance to irinotecan (CPT-11) and its active metabolite SN-38. We utilised ABCG2-expressing xenografts as a model to evaluate the ability of a non-toxic ABCG2 inhibitor to increase intracellular drug accumulation. We assessed the activity of irinotecan in vivo in SCID mice: irinotecan completely inhibited the development of control pcDNA3.1 xenografts, whilst only delaying the growth of ABCG2-expressing xenografts. Addition of MBLI-87, an acridone derivative inhibitor, significantly increased the irinotecan effect against the growth of ABCG2-expressing xenografts. In vitro, MBLI-87 was as potent as GF120918 against ABCG2-mediated irinotecan efflux, and additionally was specific for ABCG2. A significant sensitisation to irinotecan was achieved despite the fact that doses remained well below the maximum tolerated dose (due to the rather limited solubility of MBLI-87). This suggested that MBLI-87 is an excellent candidate to prevent drug efflux by ABCG2, without altering plasma concentrations of irinotecan and SN-38 after IP (intra-peritoneal) injections. This could constitute a useful strategy to improve drug pharmacology, to facilitate drug penetration into normal tissue compartments protected by ABCG2, and potentially to reverse drug resistance in cancer cells