Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms.

The aim of the present study was to develop novel daptomycin-loaded poly-epsilon-caprolactone (PCL) microparticles with enhanced antibiofilm activity against mature biofilms of clinically relevant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and polysaccharide intercellular adhesin-positive Staphylococcus epidermidis. Daptomycin was encapsulated into PCL microparticles by a double emulsion-solvent evaporation method. For comparison purposes, formulations containing vancomycin were also prepared. Particle morphology, size distribution, encapsulation efficiency, surface charge, thermal behavior, and in vitro release were assessed. All formulations exhibited a spherical morphology, micrometer size, and negative surface charge. From a very early time stage, the released concentrations of daptomycin and vancomycin were higher than the minimal inhibitory concentration and continued so up to 72 hours. Daptomycin presented a sustained release profile with increasing concentrations of the drug being released up to 72 hours, whereas the release of vancomycin stabilized at 24 hours. The antibacterial activity of the microparticles was assessed by isothermal microcalorimetry against planktonic and sessile MRSA and S. epidermidis. Regarding planktonic bacteria, daptomycin-loaded PCL microparticles presented the highest antibacterial activity against both strains. Isothermal microcalorimetry also revealed that lower concentrations of daptomycin-loaded microparticles were required to completely inhibit the recovery of mature MRSA and S. epidermidis biofilms. Further characterization of the effect of daptomycin-loaded PCL microparticles on mature biofilms was performed by fluorescence in situ hybridization. Fluorescence in situ hybridization showed an important reduction in MRSA biofilm, whereas S. epidermidis biofilms, although inhibited, were not eradicated. In addition, an important attachment of the microparticles to MRSA and S. epidermidis biofilms was observed. Finally, all formulations proved to be biocompatible with both ISO compliant L929 fibroblasts and human MG63 osteoblast-like cells

Kepler-93: a benchmark target for accurate asteroseismic characterization in preparation for the plato era

peer reviewedThe advent of space-based photometry missions, such as CoRoT, Kepler and TESS, has favoured a rapid development of asteroseismology and its synergies with exoplanetology. Such multidisciplinary studies will further develop in the future with the PLATO mission

Thorough characterisation of the 16 Cygni system

Context. The advent of space-based photometry observations provided high-quality asteroseismic data for a large number of stars. These observations enabled the adaptation of advanced analyses techniques, until then restricted to the field of helioseismology, to study the best asteroseismic targets. Amongst these, the 16Cyg binary system holds a special place, as they are the brightest solar twins observed by the Kepler mission. For this specific system, modellers have access to high-quality asteroseismic, spectroscopic and interferometric data, making it the perfect testbed for the limitations of stellar models. Aims. We aim to further constrain the internal structure and fundamental parameters of 16CygA&B using linear seismic inversion techniques of both global indicators and localised corrections of the hydrostatic structure. Methods. We start from the models defined by detailed asteroseismic modelling in our previous paper and extend our analysis by applying variational inversions to our evolutionary models. We carried out inversions of so-called seismic indicators and attempted to provide local corrections of the internal structure of the two stars. Results. Our results indicate that linear seismic inversions alone are not able to discriminate between standard and non-standard models for 16CygA&B. We confirm the results of our previous studies that used linear inversion techniques, but consider that the observed differences could be linked to small fundamental parameters variations rather than to a missing process in the models. Conclusions. We confirm the robustness and reliability of the results of the modelling we performed in our previous paper. We conclude that non-linear inversions are likely required to further investigate the properties of 16CygA&B from a seismic point of view, but that these inversions have to be coupled to analyses of the depletion of light elements such as lithium and beryllium to constrain the macroscopic transport of chemicals in these stars and also to constrain potential non-standard evolutionary paths

Hybridization as a threat in climate relict Nuphar pumila (Nymphaeaceae)

Field studies and conceptual work on hybridization-mediated extinction risk in climate relicts are extremely rare. Nuphar pumila (Nymphaeaceae) is one of the most emblematic climate relicts in Europe with few isolated populations in the Alpine arc. The extent of introgression with related lowland and generalist species Nupharlutea has never been studied using molecular methods. All biogeographical regions where N.pumila naturally occurs in the neighbourhood of the Alpine arc were sampled and studied using nuclear microsatellite markers. Furthermore, we used forward-in-time simulations and Approximate Bayesian Computation to check whether an introgression scenario fits with the observed admixture patterns and estimated the demographic parameters associated with this process. Our study confirms ongoing hybridization between N.pumila and N.lutea and validates it by the use of population models. More than 40 % of investigated N.pumila individuals were admixed and hybrids were found in over 60 % of studied populations. The introgression is bidirectional and is most likely a result of very recent gene flow. Our work provides strong evidence for rapid extinction risk and demographic swamping between specialized climatic relicts and closely related generalists. The remaining pure populations of N.pumila are rare in the Alpine arc and deserve high conservation priority

Activities of fosfomycin and rifampin on planktonic and adherent Enterococcus faecalis strains in an experimental foreign-body infection model.

Enterococcal implant-associated infections are difficult to treat because antibiotics generally lack activity against enterococcal biofilms. We investigated fosfomycin, rifampin, and their combinations against planktonic and adherent Enterococcus faecalis (ATCC 19433) in vitro and in a foreign-body infection model. The MIC/MBClog values were 32/>512 μg/ml for fosfomycin, 4/>64 μg/ml for rifampin, 1/2 μg/ml for ampicillin, 2/>256 μg/ml for linezolid, 16/32 μg/ml for gentamicin, 1/>64 μg/ml for vancomycin, and 1/5 μg/ml for daptomycin. In time-kill studies, fosfomycin was bactericidal at 8× and 16× MIC, but regrowth of resistant strains occurred after 24 h. With the exception of gentamicin, no complete inhibition of growth-related heat production was observed with other antimicrobials on early (3 h) or mature (24 h) biofilms. In the animal model, fosfomycin alone or in combination with daptomycin reduced planktonic counts by ≈4 log10 CFU/ml below the levels before treatment. Fosfomycin cleared planktonic bacteria from 74% of cage fluids (i.e., no growth in aspirated fluid) and eradicated biofilm bacteria from 43% of cages (i.e., no growth from removed cages). In combination with gentamicin, fosfomycin cleared 77% and cured 58% of cages; in combination with vancomycin, fosfomycin cleared 33% and cured 18% of cages; in combination with daptomycin, fosfomycin cleared 75% and cured 17% of cages. Rifampin showed no activity on planktonic or adherent E. faecalis, whereas in combination with daptomycin it cured 17% and with fosfomycin it cured 25% of cages. Emergence of fosfomycin resistance was not observed in vivo. In conclusion, fosfomycin showed activity against planktonic and adherent E. faecalis. Its role against enterococcal biofilms should be further investigated, especially in combination with rifampin and/or daptomycin treatment

Activity of bone cement loaded with daptomycin alone or in combination with gentamicin or PEG600 against Staphylococcus epidermidis biofilms.

Daptomycin is a promising candidate for local treatment of bone infection due to its activity against multi-resistant staphylococci. We investigated the activity of antibiotic-loaded PMMA against Staphylococcus epidermidis biofilms using an ultra-sensitive method bacterial heat detection method (microcalorimetry). PMMA cylinders loaded with daptomycin alone or in combination with gentamicin or PEG600, vancomycin and gentamicin were incubated with S. epidermidis-RP62A in tryptic soy broth (TSB) for 72h. Cylinders were thereafter washed and transferred in microcalorimetry ampoules pre-filled with TSB. Bacterial heat production, proportional to the quantity of biofilm on the PMMA, was measured by isothermal microcalorimetry at 37°C. Heat detection time was considered time to reach 20μW. Experiments were performed in duplicate. The heat detection time was 5.7-7.0h for PMMA without antibiotics. When loaded with 5% of daptomycin, vancomycin or gentamicin, detection times were 5.6-16.4h, 16.8-35.7h and 4.7-6.2h, respectively. No heat was detected when 5% gentamicin or 0.5% PEG600 was added to the daptomycin-loaded PMMA. The study showed that vancomycin was superior to daptomycin and gentamicin in inhbiting staphylococcal adherence in vitro. However, PMMA loaded with daptomycin combined with gentamicin or PEG600 completely inhibited S. epidermidis-biofilm formation. PMMA loaded with these combinations may represent effective strategies for local treatment in the presence of multi-resistant staphylococci

Mapping habitats sensitive to overgrazing in the Swiss Northern Alps using ecological niche modeling

The Swiss Northern Alps are rich in biodiversity, including some subalpine and alpine natural herbaceous communities of high biogeographic and conservation value. At the northwestern edge of the Alps, such habitats are refugia for slow-growing, locally rare, and cold-adapted species, which are sensitive to sheep overgrazing. However, at a regional scale, no map of these sensitive habitats exists that the authorities could refer to for regulating grazing. We therefore studied the possibility of using ecological niche modeling (ENM) to map five habitats that are potentially threatened by overgrazing in the Northern Alps of the Swiss canton of Fribourg. For each habitat, we defined a group of characteristic species and gathered their occurrences from national data centers. These occurrences were pooled within each group and used as presences to calibrate the ENM. High-resolution predictors (10 m) were used to achieve fine-scale modeling. The models predicted accurate and ecologically relevant distributions for three of the habitats: alpine swards and heaths on exposed ridges and peaks, unstable calcareous screes and vegetated snow patches. These results show that habitats that are topographically and environmentally well-defined can be finely predicted by ENM using distributions of characteristic species for use in spatial conservation planning. In the context of summer pasture management, this helped us to translate the Swiss legal basis onto maps of authorized grazing pressur

Kepler-93:a testbed for detailed seismic modelling and orbital evolution of super-earths around solar-like stars

The advent of space-based photometry missions such as CoRoT, Kepler and TESS has sparkled the development of asteroseismology and exoplanetology. The advent of PLATO will further strengthen such multi-disciplinary studies. Testing asteroseismic modelling and its importance for our understanding of planetary systems is crucial. We carried out a detailed modelling of Kepler-93, an exoplanet host star observed by Kepler. This star is particularly interesting as it is very similar to the PLATO benchmark target (G spectral type, ~ 6000K, ~ 1 Msun and ~ 1 Rsun) and provides a real-life testbed for potential procedures to be used for PLATO. We use global and local minimization techniques for the seismic modelling of Kepler-93, varying the ingredients of our stellar models. We compute seismic inversions of the mean density. We use these revised stellar parameters to provide new planetary parameters and simulate the orbital evolution of the system under the effects of tides and atmospheric evaporation. Our fundamental parameters for Kepler-93: mean density = 1.654 +/- 0.004 g/cm3, M = 0.907 +/- 0.023 Msun , R = 0.918 +/- 0.008 Rsun and Age = 6.78 +/- 0.32 Gyr. The uncertainties we report for this benchmark are within the requirements of PLATO. For the exoplanet Kepler-93b, we find Mp = 4.01 +/- 0.67 Mearth, Rp = 1.478 +/- 0.014 Rearth and semi-major axis a = 0.0533 +/- 0.0005 AU. According to our simulations, it seems unlikely that Kepler-93b formed with a mass large enough to be impacted by stellar tides. For the benchmark of PLATO, detailed asteroseismic modelling procedures will be able to provide fundamental stellar parameters within the requirements. We illustrate what synergies can be achieved regarding the orbital evolution and atmospheric evaporation of exoplanets. We note the importance of the high-quality radial velocity follow-up to constrain the formation scenarii of exoplanets.Comment: Accepted for publication in Astronomy and Astrophysic

Imprint of the magnetic activity cycle on solar asteroseismic characterisation based on 26 years of GOLF and BiSON data

Context. Asteroseismic modelling will play a key role in future space-based missions, such as PLATO, CubeSpec, and Roman. Despite remarkable achievements, asteroseismology has revealed significant discrepancies between observations and theoretical predictions of the physics used in stellar models, which have the potential to bias stellar characterisation at the precision level demanded by PLATO. The current modelling strategies largely overlook magnetic activity, assuming that its effects are masked within the parametrisation of the so-called ‘surface effects’. Given the presence of activity cycles in multiple solar-like oscillators and activity variations in a significant fraction of Kepler observations of main-sequence stars, it is therefore relevant to investigate systematic errors in asteroseismic characterisations caused by our incomplete understanding of magnetic activity. Aims. Based on 26.5 years of GOLF and BiSON observations, we measured the impact of magnetic activity on the asteroseismic characterisation of the Sun as a star, a reference target for assessing the PLATO mission requirements. Methods. The GOLF and BiSON observations, which fully cover solar cycles 23 and 24, were divided into yearly overlapping snapshots, each delayed by a quarter of a year. For each snapshot, an advanced asteroseismic characterisation, similar to that to be adopted by the PLATO pipeline, was performed with standard prescriptions for the parametrisation of the surface effects. This allowed us to monitor the apparent temporal evolution of fundamental solar parameters such as mass, radius, and age. The correlation of these parameters with the 10.7 cm radio emission flux, a proxy of the solar activity cycle, was then measured. Results. The effects of magnetic activity are partially absorbed into the parametrisation of the surface effects when suitable prescriptions are used, and they do not significantly affect the measured solar mass or radius. However, contrary to literature expectations, we find a significant imprint on the age determination, with variations of up to 6.5% between solar minima and maxima. This imprint persists across both BiSON and GOLF datasets. Conclusions. Considering that the Sun exhibits low levels of activity, our study highlights the looming challenge posed by magnetic activity for future photometry missions, and it prompts a potential reevaluation of the asteroseismic characterisation of the most active Kepler targets