Bioinspired Liposomes for Oral Delivery of Colistin to Combat Intracellular Infections by Salmonella enterica.

Bacterial invasion into eukaryotic cells and the establishment of intracellular infection has proven to be an effective means of resisting antibiotic action, as anti-infective agents commonly exhibit a poor permeability across the host cell membrane. Encapsulation of anti-infectives into nanoscaled delivery systems, such as liposomes, is shown to result in an enhancement of intracellular delivery. The aim of the current work is, therefore, to formulate colistin, a poorly permeable anti-infective, into liposomes suitable for oral delivery, and to functionalize these carriers with a bacteria-derived invasive moiety to enhance their intracellular delivery. Different combinations of phospholipids and cholesterol are explored to optimize liposomal drug encapsulation and stability in biorelevant media. These liposomes are then surface-functionalized with extracellular adherence protein (Eap), derived from Staphylococcus aureus. Treatment of HEp-2 and Caco-2 cells infected with Salmonella enterica using colistin-containing, Eap-functionalized liposomes resulted in a significant reduction of intracellular bacteria, in comparison to treatment with nonfunctionalized liposomes as well as colistin alone. This indicates that such bio-invasive carriers are able to facilitate intracellular delivery of colistin, as necessary for intracellular anti-infective activity. The developed Eap-functionalized liposomes, therefore, present a promising strategy for improving the therapy of intracellular infections

Largest recent impact craters on Mars: Orbital imaging and surface seismic co-investigation.

Two >130-meter-diameter impact craters formed on Mars during the later half of 2021. These are the two largest fresh impact craters discovered by the Mars Reconnaissance Orbiter since operations started 16 years ago. The impacts created two of the largest seismic events (magnitudes greater than 4) recorded by InSight during its 3-year mission. The combination of orbital imagery and seismic ground motion enables the investigation of subsurface and atmospheric energy partitioning of the impact process on a planet with a thin atmosphere and the first direct test of martian deep-interior seismic models with known event distances. The impact at 35°N excavated blocks of water ice, which is the lowest latitude at which ice has been directly observed on Mars

Constraints on the shallow elastic and anelastic structure of Mars from InSight seismic data

Mars’s seismic activity and noise have been monitored since January 2019 by the seismometer of the InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) lander. At night, Mars is extremely quiet; seismic noise is about 500 times lower than Earth’s microseismic noise at periods between 4 s and 30 s. The recorded seismic noise increases during the day due to ground deformations induced by convective atmospheric vortices and ground-transferred wind-generated lander noise. Here we constrain properties of the crust beneath InSight, using signals from atmospheric vortices and from the hammering of InSight’s Heat Flow and Physical Properties (HP3) instrument, as well as the three largest Marsquakes detected as of September 2019. From receiver function analysis, we infer that the uppermost 8–11 km of the crust is highly altered and/ or fractured. We measure the crustal diffusivity and intrinsic attenuation using multiscattering analysis and find that seismic attenuation is about three times larger than on the Moon, which suggests that the crust contains small amounts of volatiles

Bioinspired Liposomes for Oral Delivery of Colistin to Combat Intracellular Infections by Salmonella enterica

Bacterial invasion into eukaryotic cells and the establishment of intracellular infection has proven to be an effective means of resisting antibiotic action, as anti-infective agents commonly exhibit a poor permeability across the host cell membrane. Encapsulation of anti-infectives into nanoscaled delivery systems, such as liposomes, is shown to result in an enhancement of intracellular delivery. The aim of the current work is, therefore, to formulate colistin, a poorly permeable anti-infective, into liposomes suitable for oral delivery, and to functionalize these carriers with a bacteria-derived invasive moiety to enhance their intracellular delivery. Different combinations of phospholipids and cholesterol are explored to optimize liposomal drug encapsulation and stability in biorelevant media. These liposomes are then surface-functionalized with extracellular adherence protein (Eap), derived from Staphylococcus aureus. Treatment of HEp-2 and Caco-2 cells infected with Salmonella enterica using colistin-containing, Eap-functionalized liposomes resulted in a significant reduction of intracellular bacteria, in comparison to treatment with nonfunctionalized liposomes as well as colistin alone. This indicates that such bio-invasive carriers are able to facilitate intracellular delivery of colistin, as necessary for intracellular anti-infective activity. The developed Eap-functionalized liposomes, therefore, present a promising strategy for improving the therapy of intracellular infections. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Stratification of Heterogeneity in the Lithosphere of Mars From Envelope Modeling of Event S1222a and Near Impacts: Interpretation and Implications for Very-High-Frequency Events

International audienceWe have modeled the high-frequency seismogram envelopes of the large event S1222a and four recently identified near impacts recorded by the InSight mission by introducing a stratification of velocity and attenuation into a multiple-scattering approach. We show that a simple conceptual model composed of a strongly diffusive, weakly attenuating layer overlying a transparent medium captures the essential features of the observed envelopes. The attenuation profiles reveal that the minimal extension of heterogeneities at depth is of the order of 20 km in the vicinity of InSight and 60 km on the path to S1222a. We interpret this result as an indication that the Martian crust as a whole is at the origin of the strong scattering. Our heterogeneity model suggests that the sources of a number of distant Very-high-Frequency seismic events are shallow and located to the south or in close vicinity of the Martian dichotomy

Mars Structure Service: Single-Station and Single-Event Marsquake Inversion for Structure Using Synthetic Martian Waveforms

The 50th Lunar and Planetary Science Conference in The Woodlands, Texas, March 18–22, 2019.Introduction: The InSight lander successfully delivered a geophysical instrument package on the Martian surface on November 26th, 2018, including a broadband and a short-period seismometer (Seismic Experiment for Interior Structure, SEIS). The seismic instrument package is specifically designed to record marsquakes and meteoritic impacts in Martian conditions [1]. Routine operations are split into two services: the Mars Structure Service (MSS) and the Marsquake Service (MQS that are responsible for defining structure models and seismicity catalogs, respectively [2, 3]. The first ¿deliverable¿ of the MSS will be a model based on the events detected during the first 3 months of seismic monitoring of the mission, for which only a few quakes might be expected based on current estimates of Mars seismic activity. To test our approach of determining the interior model of Mars and to prepare the InSight science team for data return, we made use of a ¿blind test¿ time series for which the Marsquake parameters (location, depth, origin time, and moment tensor) and interior model were unknown to the group at large

Mars Structure Service: Single-station and single-event marsquake inversion for structure using synthetic Martian waveforms

EGU General Assembly in Viena, Austria,7–12 April 201926th, 2018, including a broadband and a short-period seismometer (Seismic Experiment for Interior Structure, SEIS). The seismic instrument package is specifically designed to record marsquakes and meteoritic impacts in Martian conditions. Routine operations are split into two services: the Mars Structure Service (MSS) and the Marsquake Service (MQS), which are responsible for defining structure models and seismicity catalogs, respectively. The first “deliverable” of the MSS will be a model based on the events detected during the first 3 months of seismic monitoring of the mission, for which only a few quakes might be expected based on current estimates of Mars seismic activity. To test our approach of determining the interior model of Mars and to prepare the InSight science team for data return, we made use of a “blind test” time series for which the Marsquake parameters (location, depth, origin time, and moment tensor) and interior model were unknown to the group at large. In preparation for the mission, the goal was to develop mature algorithms to handle the data as efficiency as possible. Synthetic seismic waveforms were computed in a 1D mantle model with a 3D crust on top using AxiSEM and Salvus. The time series were created by adding seismic noise that relies on pre-landing estimates of noise generated by the sensors, electronic system, environment, and nearby lander. To characterize what we could learn about Mars interior structure with only one station and with the first seismic event, we performed inversions of a synthetic data following a blind test process, where the interior model was unknown to all team members carrying out data analysis and inversion. We detail and compare the results of this “blind test” using different methods including inversion of surface wave dispersion data, body waves travel times, and the waveforms themselves.We have used mainly Bayesian techniques to obtain robust probability density functions of interior structure parameters. The effects on the retrieved model distributions of fixing mars quake location and origin time are investigated, as is the effect of using fixed Vs flexible parameterizations. To allow for tighter constraints, we also test the use of priors based on thermodynamicallyconstrained models together with seismic observations, as well as seismic confirmation/rejection of models purely based on thermodynamical modelling. These techniques considered here form a large part of the planned modeling of the MSS that will be ultimately employed with the first recording of a seismic event by InSight

The Mars Structure Service for InSight:Single-Station Marsquake Inversions for Structure

AGU Fall Meeting in San Francisco, 9-13 December 2019The SEIS seismometer package was successfully deployed on Mars by February 2019. Routine operations are split into two services: the Mars Structure Service (MSS) and the Marsquake Service (MQS), which are responsible for defining interior structure models and seismicity catalogs, respectively. Initial model delivery from MSS is based on a limited dataset of two Marsquakes with a clear P and S arrivals. Different inversion algorithms were developed by the MSS team in order to retrieve the first 1D averaged model of Mars. Two complementary approaches are considered. One set of models (called M1) is parameterized in seismic velocity and density as a function of depth. A second set of models (called M2) is obtained by parameterizing with geodynamical constraints like temperature and composition. We use Bayesian inversion techniques to obtain robust probability density functions of seismic velocity profiles. Different types of data are considered for these inversions including body waves, surface waves and receiver functions. To characterize what we could learn about Mars¿ interior structure with only one station and with the first seismic event, we performed inversions of synthetic data following a blind test process, where the interior model and the Marsquake parameters (location, depth, origin time, and moment tensor) were unknown to all team members carrying out data analysis and inversion. In this presentation we will discuss the results of this blind test in terms of structure and compare different methods developed by the MSS. We will then show results from investigations of the first, real seismic data due to quakes on Mars recorded by SEIS in terms of the structure and quake locations. We will especially focus our investigation on joint inversions made not only with the arrival time, but also with secondary seismic data extracted from the detected events, including apparent attenuation rate and with receiver functions. Of course, much more detailed analysis will be made if Mars seismicity provide us in the near future larger quakes with body wave phases and first orbit surface wave dispersion, and/or one event large enough to record multiple orbit surface waves, and will augment future interiors models of Mars