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Tumor-derived exosomes can modulate the cancer microenvironment and induce metastatic spread. Exosomes may carry enzymes for leukotriene (LT) biosynthesis, but the role of exosomal LTs has not been studied in cancer. We isolated exosomes and malignant cells from pleura exudates from 14 patients with non-small cell lung cancer. Lipidomic profiles, migration and apoptosis were determined. Both exosomes and primary cancer cells contained γ-glutamyl transpeptidase 1 (GGT-1) and avidly transformed exogenous LTC4 to pro-tumorigenic LTD4, for the cells to levels 100-fold above their endogenous CysLT production. This suggests that cancer cells promote their own survival via LTD4 if supplied with LTC4, which in the exudates was produced by monocytic cells. Furthermore, exosomes promoted migration of cancer cells, which was counteracted by the CysLT1 antagonist montelukast. Montelukast also induced apoptosis of cancer cells, and this was partially inhibited by exosomes. Our results demonstrate how cancer cells and exosomes, together with monocytic cells in lung cancer tissue, can produce high amounts of LTD4, to stimulate cancer cell migration and survival. This suggests that part of the pro-metastatic effect of exosomes is mediated by the leukotriene machinery, further supporting the use of CysLT1 antagonists for lung cancer therapy.

Pulmonary sarcoidosis has unknown etiology, a difficult diagnostic procedure and no curative treatment. Extracellular vesicles including exosomes are nano-sized entities released from all cell types. Previous studies of exosomes from bronchoalveolar lavage fluid (BALF) of sarcoidosis patients have revealed pro-inflammatory components and abilities, but cell sources and mechanisms have not been identified. In the current study, we found that BALF exosomes from sarcoidosis patients, but not from healthy individuals, induced a dose-dependent elevation of intracellular IL-1β in monocytes. Analyses of supernatants showed that patient exosomes also induced release of IL-1β, IL-6 and TNF from both PBMCs and enriched monocytes, suggesting that the observed effect is direct on monocytes. The potently chemotactic chemokine CCL2 was induced by exosomes from a subgroup of patients, and in a blocking assay the exosome-induced CCL2 was reduced for 13 out of 19 patients by the asthma drug Montelukast, a cysteinyl leukotriene receptor antagonist. Further, reactive oxygen species generation by PBMCs was induced to a higher degree by patient exosomes compared to healthy exosomes. These findings add to an emerging picture of exosomes as mediators and disseminators of inflammation, and open for further investigations of the link between CCL2 and exosomal leukotrienes in sarcoidosis.

Using a particle-in-cell electrostatic simulation, we examine the conditions that allow low energy ions, like those produced in the Enceladus plume, to be attracted and trapped within the sheaths of negatively-charged dust grains. The conventional wisdom is that all new ions produced in the Enceladus plume are free to get picked up (i.e., accelerated by the local E-field to then undergo vB acceleration). However, we suggest herein that the presence of submicron charged dust in the plume impedes this pickup process since the local grain electric field greatly exceeds the co-rotation E-fields. The simulations demonstrate that cold ions will tend to accelerate toward the negatively charged grains and become part of the ion plasma sheath. These trapped ions will move with the grains, exiting the plume region at the dust speed. We suggest that Cassini’s Langmuir probe is measuring the entire ion population (free and trapped ions), while the Cassini magnetometer detects the magnetic perturbations associated with pickup currents from the smaller population of free ions, with this distinction possibly reconciling the ongoing debate in the literature on the ion density in the plume.

We present a semianalytical photochemical model of Saturn’s near-equatorial ionosphere and adapt it to two regions (∼2200 and ∼1700 km above the 1 bar level) probed during the inbound portion of Cassini’s orbit 292 (2017 September 9). The model uses as input the measured concentrations of molecular hydrogen, hydrogen ion species, and free electrons, as well as the measured electron temperature. The output includes upper limits, or constraints, on the mixing ratios of two families of molecules, on ion concentrations, and on the attachment rates of electrons and ions onto dust grains. The model suggests mixing ratios of the two molecular families that, particularly near ∼1700 km, differ notably from what independent measurements by the Ion Neutral Mass Spectrometer suggest. Possibly connected to this, the model suggests an electron-depleted plasma with a level of electron depletion of around 50%. This is in qualitative agreement with interpretations of Radio Plasma Wave Science/Langmuir Probe measurements, but an additional conundrum arises in the fact that a coherent photochemical equilibrium scenario then relies on a dust component with typical grain radii smaller than 3 Å.

Cassini’s Grand Finale orbits provided for the first time in-situ measurements of Saturn’s topside ionosphere. We present the Pedersen and Hall conductivities of the top near-equatorial dayside ionosphere, derived from the in-situ measurements by the Cassini Radio and Wave Plasma Science Langmuir Probe, the Ion and Neutral Mass Spectrometer and the fluxgate magnetometer. The Pedersen and Hall conductivities are constrained to at least 10−5–10−4 S/m at (or close to) the ionospheric peak, a factor 10–100 higher than estimated previously. We show that this is due to the presence of dusty plasma in the near-equatorial ionosphere. We also show the conductive ionospheric region to be extensive, with thickness of 300–800 km. Furthermore, our results suggest a temporal variation (decrease) of the plasma densities, mean ion masses and consequently the conductivities from orbit 288 to 292.

Short dipole or monopole radio antennas are defined as being small in length relative to the wavelength of the frequency of operation. The reception properties of short linear antennas can be described by the so-called effective length vector which is pointing along the direction of minimum gain in the toroidal radiation pattern. We deal here with such antennas, and additionally the word ”short” also means a small antenna with respect to a large spacecraft body. Using numerical computer simulations we calculate the reception properties of an antenna system consisting of three short monopoles positioned on a large spacecraft body in the frequency range of several hundred kHz. It turns out that such a configuration has the major disadvantage that the angular separation between its three effective length vectors is quite small, which would lead to large errors in polarization and direction–finding measurements. We will show ways how to overcome this problem by changing the configuration to an antenna triad consisting of three short dipoles mounted on a boom. The calculations were employed to find a good configuration of the radio antennas for ESA’s future JUICE (Jupiter Icy Moons Explorer) mission.

Cells of the airways are constantly exposed to environmental hazards including cigarette smoke, irritants, pathogens, and mechanical insults. Maintaining barrier integrity is vital, and mounting responses to threats depends on intercellular communication. Extracellular vesicles (EVs), including exosomes and microvesicles, are major signal mediators between cells, shuttling cargo in health and disease. Depending on the state of the originating cells, EVs are capable of inducing proinflammatory effects including antigen presentation, cellular migration, apoptosis induction, and inflammatory cytokine release. Cells of the airways release EVs, which can be found in bronchoalveolar lavage fluid. EVs of the airways can support inflammation in the lung, but may also exit into the circulation and carry a cocktail of pro-inflammatory molecules to recipient cells in distant organs. In this review, we discuss the possibility that EVs originating from the airways contribute to dissemination of inflammation in both lung disorders and systemic inflammatory conditions.

The Cassini mission has provided much information about the Titan environment, with numerous low altitude encounters with the moon being always inside the magnetosphere. The only encounter taking place outside the magnetopause, in the magnetosheath, occurred the 13 June 2007 (T32 flyby). This paper is dedicated to the analysis of the Radio and Plasma Wave investigation data during this specific encounter, in particular with the Langmuir probe, providing a detailed picture of the cold plasma environment and of Titan's ionosphere with these unique plasma conditions. The various pressure terms were also calculated during the flyby. The comparison with the T30 flyby, whose geometry was very similar to the T32 encounter but where Titan was immersed in the kronian magnetosphere, reveals that the evolution of the incident plasma has a significant influence on the structure of the ionosphere, with in particular a change of the exo-ionospheric shape. The electrical conductivities are given along the trajectory of the spacecraft and the discovery of a polar plasma cavity is reported.

We have investigated statistically the electron density below 5 cm−3 in the magnetosphere of Saturn (7–80 RS, Saturn radii) using 44 orbits of the floating potential data from the RPWS Langmuir probe (LP) onboard Cassini. The density distribution shows a clear dependence on the distance from the Saturnian rotation axis (√X2+Y2) as well as on the distance from the equatorial plane (|Z|), indicating a disc-like structure. From the characteristics of the density distribution, we have identified three regions: the extension of the plasma disc, the magnetodisc region, and the lobe regions. The plasma disc region is at LL is the radial distance to the equatorial crossing of the dipole magnetic field line, and confined to |Z|RS. The magnetodisc is located beyond L=15, and its density has a large variability. The variability has quasi-periodic characteristics with a periodicity corresponding to the planetary rotation. For Z>15 RS, the magnetospheric density distribution becomes constant in Z. However, the density still varies quasi-periodically with the planetary rotation also in this region. In fact, the quasi-periodic variation has been observed all over the magnetosphere beyond L=15. The region above Z=15 RS is identified as the lobe region. We also found that the magnetosphere can occasionally move latitudinally under the control of the density in the magnetosphere and the solar wind. From the empirical distributions of the electron densities obtained in this study, we have constructed an electron density model of the Saturnian nightside magnetosphere beyond 7 RS. The obtained model can well reproduce the observed density distribution, and can thus be useful for magnetospheric modelling studies.

Extracellular vesicles (EV), including exosomes and microvesicles (MV), represent a rapidly expanding field of research with diagnostic and therapeutic applications. Although many aspects of EV function remain to be revealed and broad investigations are warranted, most published findings focus on only one vesicle category or a non-separated mix of EVs. In this paper, we investigated both MVs and exosomes from Ovalbumin (OVA)-pulsed dendritic cells for their immunostimulatory potential side-by-side in vivo. Only exosomes induced antigen-specific CD8+ T-cells, and were more efficient than MVs in eliciting antigen-specific IgG production. Further, mainly exosome-primed mouse splenocytes showed significant ex vivo interferon gamma production in response to antigen restimulation. Exosomes carried high levels of OVA, while OVA in MVs was barely detectable, which could explain the more potent antigen-specific response induced by exosomes. Moreover, exosomes induced increased germinal center B cell proportions, whereas MVs had no such effect. Immunisation with both vesicle types combined showed neither inhibitory nor synergistic effects. We conclude that DC-derived MVs and exosomes differ in their capacity to incorporate antigen and induce immune responses. The results are of importance for understanding the role of EVs in vivo, and for future design of vesicle-based immunotherapies and vaccines.

Dispersive Alfvén wave activity is identified in four dayside auroral oval events measured by the Freja satellite. The events are characterized by ion injection, bursty electron precipitation below about 1 keV, transverse ion heating and broadband extremely low frequency (ELF) emissions below the lower hybrid cutoff frequency (a few kHz). Large-scale density depletions/cavities, as determined by the Langmuir probe measurements, and strong electrostatic emissions are often observed simultaneously. A correlation study has been carried out between the E and B field fluctuations below 64 Hz and 10 Hz, respectively, (the DC instruments upper threshold) and the characteristics of the precipitating electrons. This study revealed that the energisation of electrons is indeed related to the broadband ELF emissions and that the electrostatic component plays a predominant role during very active magnetospheric conditions. Furthermore, the effect of the ELF electromagnetic emissions on the larger scale field-aligned current systems has been investigated, and it is found that such an effect cannot be detected. Instead, the Alfvénic activity creates a local region of field-aligned currents. It is suggested that dispersive Alfvén waves set up these local field-aligned current regions and, in turn, trigger more electrostatic emissions during certain conditions. In these regions, ions are transversely heated, and large-scale density depletions/cavities may be created during especially active periods.Key words. Ionosphere (particle acceleraton; wave-particle interactions) Magnetospheric physics (auroral phenomena)