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

Lysosomes, a key target of hydrophobic photosensitizers proposed for photochemotherapeutic applications

Despite their important biological activity, lysosomes have been generally neglected as important primary targets of photosensitizers, because they are not easily accessible for experiments. This paper reviews factors favoring the localization of photosensitizers in lysosomes and the various experimental approaches which have been used so far for the characterization of the lysosomal staining by various photosensitizing dyes, including porphyrins, chlorins and phenoxazines. The experimental difficulties observed in combining several in vitro techniques for the unambiguous demonstration of lysosomal targeting are examined. New data on tetraphenylporphine derivatives and a pyropheophorbide, as well as previous data on photofrin II, are presented to illustrate the advantages and possibilities of microspectrofluorometry in the study of photosensitizer localization in single living cells. Both spectral and topographic information available from areas smaller than 1 μm2 make it possible to characterize fairly specific sites of localization through the use of specific and vital fluorescent probes of lysosomes, such as Lucifer Yellow. It is also shown by microspectrofluorometry on single living cells that the chronology of the photosensitized reactions induced by specific or unspecific lysosomal photosensitizers can be easily followed. The photosensitized lipofuscin formation observed at the plasma membrane level with the lysosomotropic tetraphenylporphine supports the contention that it is very rare to find a truly specific lysosomal photosensitizer. © 1993

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

On the external forcing of global eruptive activity in the past 300 years

International audienceThe decryption of the temporal sequence of volcanic eruptions is a key step in better anticipating future events. Volcanic activity is the result of a complex interaction between internal and external processes, with time scales spanning multiple orders of magnitude. We review periodicities that have been detected or correlated with volcanic eruptions/phenomena and interpreted as resulting from external forces. Taking a global perspective and longer time scales than a few years, we approach this interaction by analyzing three time series using singular spectral analysis: the global number of volcanic eruptions (NVE) between 1700 and 2022, the number of sunspots (ISSN), a proxy for solar activity, the polar motion (PM) and length of day (lod), two proxies for gravitational force. Several pseudo-periodicities are common to NVE and ISSN, in addition to the 11-year Schwabe cycle that has been reported in previous work, but NVE shares even more periodicities with PM. These quasi-periodic components range from ~5 to ~130 years. We interpret our analytical results in light of the Laplace's paradigm and propose that, similarly to the movement of Earth's rotation axis, global eruptive activity is modulated by commensurable orbital moments of the Jovian planets, whose influence is also detected in solar activity

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