Formulation and in vitro evaluation of pellets containing sulfasalazine and caffeine to verify ileo-colonic drug delivery

The ColoPulse coating is a pH-dependent coating that can be used to target drug release to the ileo-colonic region. ColoPulse coated tablets and capsules have demonstrated their targeting capabilities in vivo in more than 100 volunteers and patients. However, so far the ColoPulse coating has not been used for multi-particulate pellet formulations. The sulfasalazine–caffeine method can be used to confirm ileo-colonic drug delivery in vivo. Caffeine serves as a release marker in this method, while sulfasalazine serves as a marker for colonic arrival. In this study, extrusion–spheronization was used to produce microcrystalline cellulose based pellets containing both caffeine and sulfasalazine. Dissolution tests revealed that a superdisintegrant, i.e., croscarmellose sodium or sodium starch glycolate, should be incorporated in the formulation to achieve acceptable release profiles for both sulfasalazine and caffeine. However, acceptable release profiles were only obtained when the pelletizing liquid consisted of ethanol/water 1/1 (v/v) but not with pure water. This phenomenon was ascribed to the differences in the degree of swelling of the superdisintegrant in the pelletizing liquid during the granulation process. The pellets were coated with the ColoPulse coating and showed the desired pH-dependent pulsatile release profile in vitro. In future clinical studies, ileo-colonic targeting should be verified

Študija o Solčavskem 1932-2007: Poročilo o skupnem terenskem delu Univerze v Ljubljani in Univerze v Londonu 1932-2007

This is a report – in Slovene, but with summaries in German and English – of research carried out in Solčavsko, a 'remote' region in northern Slovenia, between 2004-2007. The impetus for the study was a joint UK-Slovene field study conducted in September 2004 by postgraduate students on the Birkbeck MSc in Countryside and Protected Area Management and the University of Ljubljana MSc in Natural Heritage Protection, part of a 'twinning' of the two institutions between 1997 and 2007. During our preparation of the field course, a report was discovered in the archives of the Royal Geographical Society of an earlier study of the area in 1932, led by Sir Dudley Stamp, possibly the foremost British geographer of his generation, when he was a young academic at the London School of Economics. This was the first 'expedition' of the newly formed Le Play Society - a body set up by Sir Halford Mackinder under the influence of Sir Patrick Geddes at a time when geography was beginning to emerge from its 19th century imperial tradition (of collecting, cataloguing and ranking), to focus on the interactions between people and nature under the slogan 'Place, Work, and Folk' – an early concern with sustainability. This 1932 study,conducted at a time when Slovenia was part of the Kingdom of Yugoslavia, plus a report of subsequent visits to Solčavsko by the Brathay Exploration Society in 1971 and 1972 (under socialist Yugoslavia, provided a 'time slice' through the area facilitating our own 2004 understanding of the changes in and prospects for the region within an independant Slovenia which had just become part of the European Union. Subsequent to the joint London-Ljubljana field study, a small travelling grant was secured from the Sir Frederick Soddy Trust which enabled us to carry out additional research and to write up the results as 'Študija o Solčavskem' – 'Solčavsko Studies' – 75 years after Stamp

PlatoSim: an end-to-end PLATO camera simulator for modelling high-precision space-based photometry

Context. PLAnetary Transits and Oscillations of stars (PLATO) is the ESA M3 space mission dedicated to detect and characterise transiting exoplanets including information from the asteroseismic properties of their stellar hosts. The uninterrupted and high-precision photometry provided by space-borne instruments such as PLATO require long preparatory phases. An exhaustive list of tests are paramount to design a mission that meets the performance requirements and as such simulations are an indispensable tool in the mission preparation. Aims. To accommodate PLATOs need of versatile simulations prior to mission launch that at the same time describe innovative yet complex multi-telescope design accurately, in this work we present the end-to-end PLATO simulator specifically developed for that purpose, namely PlatoSim. We show, step-by-step, the algorithms embedded into the software architecture of PlatoSim that allow the user to simulate photometric time series of charge-coupled device (CCD) images and light curves in accordance to the expected observations of PLATO. Methods. In the context of the PLATO payload, a general formalism of modelling, end-to-end, incoming photons from the sky to the final measurement in digital units is discussed. According to the light path through the instrument, we present an overview of the stellar field and sky background, the short- and long-term barycentric pixel displacement of the stellar sources, the cameras and their optics, the modelling of the CCDs and their electronics, and all main random and systematic noise sources. Results. We show the strong predictive power of PlatoSim through its diverse applicability and contribution to numerous working groups within the PLATO mission consortium. This involves the ongoing mechanical integration and alignment, performance studies of the payload, the pipeline development, and assessments of the scientific goals. Conclusions. PlatoSim is a state-of-the-art simulator that is able to produce the expected photometric observations of PLATO to a high level of accuracy. We demonstrate that PlatoSim is a key software tool for the PLATO mission in the preparatory phases until mission launch and prospectively beyond

The non-coding transcriptome as a dynamic regulator of cancer metastasis.

Since the discovery of microRNAs, non-coding RNAs (NC-RNAs) have increasingly attracted the attention of cancer investigators. Two classes of NC-RNAs are emerging as putative metastasis-related genes: long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs). LncRNAs orchestrate metastatic progression through several mechanisms, including the interaction with epigenetic effectors, splicing control and generation of microRNA-like molecules. In contrast, snoRNAs have been long considered "housekeeping" genes with no relevant function in cancer. However, recent evidence challenges this assumption, indicating that some snoRNAs are deregulated in cancer cells and may play a specific role in metastasis. Interestingly, snoRNAs and lncRNAs share several mechanisms of action, and might synergize with protein-coding genes to generate a specific cellular phenotype. This evidence suggests that the current paradigm of metastatic progression is incomplete. We propose that NC-RNAs are organized in complex interactive networks which orchestrate cellular phenotypic plasticity. Since plasticity is critical for cancer cell metastasis, we suggest that a molecular interactome composed by both NC-RNAs and proteins orchestrates cancer metastasis. Interestingly, expression of lncRNAs and snoRNAs can be detected in biological fluids, making them potentially useful biomarkers. NC-RNA expression profiles in human neoplasms have been associated with patients' prognosis. SnoRNA and lncRNA silencing in pre-clinical models leads to cancer cell death and/or metastasis prevention, suggesting they can be investigated as novel therapeutic targets. Based on the literature to date, we critically discuss how the NC-RNA interactome can be explored and manipulated to generate more effective diagnostic, prognostic, and therapeutic strategies for metastatic neoplasms

Finally! Insights into the ARCHES Lunar Planetary Exploration Analogue Campaign on Etna in summer 2022

This paper summarises the first outcomes of the space demonstration mission of the ARCHES project which could have been performed this year from 13 june until 10 july on Italy’s Mt. Etna in Sicily. After the second postponement related to COVID from the initially for 2020 planed campaign, we are now very happy to report, that the whole campaign with more than 65 participants for four weeks has been successfully conduced. In this short overview paper, we will refer to all other publication here on IAC22. This paper includes an overview of the performed 4-week campaign and the achieved mission goals and first results but also share our findings on the organisational and planning aspects

Heterologous microProtein expression identifies LITTLE NINJA, a dominant regulator of jasmonic acid signaling

MicroProteins are small, often single-domain proteins that are sequence-related to larger, often multidomain proteins. Here, we used a combination of comparative genomics and heterologous synthetic misexpression to isolate functional cereal microProtein regulators. Our approach identified LITTLE NINJA (LNJ), a microProtein that acts as a modulator of jasmonic acid (JA) signaling. Ectopic expression of LNJ in Arabidopsis resulted in stunted plants that resembled the decuple JAZ (jazD) mutant. In fact, comparing the transcriptomes of transgenic LNJ overexpressor plants and jazD revealed a large overlap of deregulated genes, suggesting that ectopic LNJ expression altered JA signaling. Transgenic Brachypodium plants with elevated LNJ expression levels showed deregulation of JA signaling as well and displayed reduced growth and enhanced production of side shoots (tiller). This tillering effect was transferable between grass species, and overexpression of LNJ in barley and rice caused similar traits. We used a clustered regularly interspaced short palindromic repeats (CRISPR) approach and created a LNJ-like protein in Arabidopsis by deleting parts of the coding sentence of the AFP2 gene that encodes a NINJA-domain protein. These afp2-crispr mutants were also stunted in size and resembled jazD Thus, similar genome-engineering approaches can be exploited as a future tool to create LNJ proteins and produce cereals with altered architectures.Work in the laboratory was funded by the European Research Council (ERC-StG miPDesign, 336295), the Independent Research Fund Denmark (DFF-FNU, Adaptogenomics), the NovoNordisk Foundation (NNF18OC0034226), and start-up funding of Copenhagen Plant Science Centre through the University of Copenhagen. We thank the anonymous reviewers from a previous submission, Hans Thordal-Christensen, Gregg Howe, and Michael Broberg Palmgren for critically reading and improving our manuscript

Predicted asteroseismic detection yield for solar-like oscillating stars with PLATO

Aims. In this work, we determine the expected yield of detections of solar-like oscillations for the targets of the foreseen PLATO ESA mission. Our estimates are based on a study of the detection probability, which takes into account the properties of the target stars, using the information available in the PIC 1.1.0, including the current best estimate of the signal-to-noise ratio (S/N). The stellar samples, as defined for this mission, include those with the lowest noise level (P1 and P2 samples) and the P5 sample, which has a higher noise level. For the P1 and P2 samples, the S/N is high enough (by construction) that we can assume that the individual mode frequencies can be measured. For these stars, we estimate the expected uncertainties in mass, radius, and age due to statistical errors induced by uncertainties from the observations only. Methods. We used a formulation from the literature to calculate the detection probability. We validated this formulation and the underlying assumptions with Kepler data. Once validated, we applied this approach to the PLATO samples. Using again Kepler data as a calibration set, we also derived relations to estimate the uncertainties of seismically inferred stellar mass, radius, and age. We then applied those relations to the main sequence stars with masses equal to or below 1.2 MSun belonging to the PLATO P1 and P2 samples and for which we predict a positive seismic detection. Results. We found that we can expect positive detections of solar-like oscillations for more than 15 000 FGK stars in one single field after a two-year observation run. Among them, 1131 main sequence stars with masses of <=1.2 MSun satisfy the PLATO requirements for the uncertainties of the seismically inferred stellar masses, radii, and ages. The baseline observation programme of PLATO consists of observing two fields of similar size (one in the southern hemisphere and one in the northern hemisphere) for two years apiece. Accordingly, the expected seismic yields of the mission amount to over 30 000 FGK dwarfs and subgiants, with positive detections of solar-like oscillations. This sample of expected solar-like oscillating stars is large enough to enable the PLATO mission's stellar objectives to be amply satisfied. Conclusions. The PLATO mission is expected to produce a catalog sample of extremely well seismically characterized stars of a quality that is equivalent to the Kepler Legacy sample, but containing a number that is about 80 times greater, when observing two PLATO fields for two years apiece. These stars are a gold mine that will make it possible to make significant advances in stellar modelling