Microglia/macrophage derived human CCL18 promotes glioma progression via CCR8-ACP5 axis analyzed in humanized slice model

Factors released from glioma-associated microglia/macrophages (GAMs) play a crucial role in glioblastoma multiforme (GBM) progression. Here, we study the importance of CCL18, a cytokine expressed in human but not in rodent GAMs, as a modulator of glioma growth. Since CCL18 signaling could not be studied in classical mouse glioma models, we developed an approach by transplanting induced pluripotent stem cell-derived human microglia and human glioma cells into mouse brain slices depleted of their intrinsic microglia. We observe that CCL18 promotes glioma cell growth and invasion. Chemokine (C-C motif) receptor 8 (CCR8) is identified as a functional receptor for CCL18 on glioma cells, and ACP5 (acid phosphatase 5) is revealed as an important part of the downstream signaling cascade for mediating glioma growth. We conclude, based on the results from an in vitro, ex vivo humanized glioma model and an in vivo GBM model that microglia/macrophage-derived CCL18 promotes glioma growth

Neurofibromatosis 1 (NF1) mutation results in impaired function of human induced pluripotent stem cell-derived microglia

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by germline mutations in the NF1 gene. Children with NF1 are prone to the development of multiple nervous system abnormalities, including autism and brain tumors, which could reflect the effect of NF1 mutation on microglia function. Using heterozygous Nf1-mutant mice, we previously demonstrated that impaired purinergic signaling underlies deficits in microglia process extension and phagocytosis in situ. To determine whether these abnormalities are also observed in human microglia in the setting of NF1, we leveraged an engineered isogenic series of human induced pluripotent stem cells to generate human microglia-like (hiMGL) cells heterozygous for three different NF1 patient-derived NF1 gene mutations. While all NF1-mutant and isogenic control hiMGL cells expressed classical microglia markers and exhibited similar transcriptomes and cytokine/chemokine release profiles, only NF1-mutant hiMGL cells had defects in P2X receptor activation, phagocytosis and motility. Taken together, heterozygous NF1 mutation impairs a subset of human microglia functional properties, which could contribute to the neurological abnormalities seen in children with NF1

On deviations from free-radial outflow in the inner coma of comet 67P/Churyumov–Gerasimenko

The Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) onboard the European Space Agency's Rosetta spacecraft acquired images of comet 67P/Churyumov–Gerasimenko (67P) and its surrounding dust coma starting from May 2014 until September 2016. In this paper we present methods and results from analysis of OSIRIS images regarding the dust outflow in the innermost coma of 67P. The aim is to determine the global dust outflow behaviour and place constraints on physical processes affecting particles in the inner coma. We study the coma region right above the nucleus surface, spanning from the nucleus centre out to a distance of about 50 km comet centric distance (approximately 25 average comet radii). We primarily adopt an approach used by Thomas and Keller (1990) to study the dust outflow. We present the effects on azimuthally-averaged values of the dust reflectance of non-radial flow and non-point-source geometry, acceleration of dust particles, sublimation of icy dust particles after ejection from the surface, dust particle fragmentation, optical depth effects and the influence of gravitationally bound particles. All of these physical processes could modify the observed distribution of light scattered by the dust coma. In the image analysis, profiles of azimuthally averaged dust brightness as a function of impact parameter b (azimuthal average, “Ā-curve”) were fitted with a simple function that best fits the shape of our profile curves (f(b;u,v,w,z)=u/bv+wb+z). The analytical fit parameters (u, v, w, z), which hold the key information about the dust outflow behaviour, were saved in a comprehensive database. Through statistical analysis of these information, we show that the spatial distribution of dust follows free-radial outflow behaviour (i.e. force-free radial outflow with constant velocity) beyond distances larger than ∼11.9 km from the comet centre, which corresponds to a relative distance of about 6 average comet radii from the comet centre. Hence, we conclude that beyond this distance, and on average, fragmentation and gravitationally bound particles are negligible processes in determining the optically scattered light distribution in the innermost coma. Closer to the nucleus we observe dust outflow behaviour that deviates from free-radial outflow. A comparison of our result profiles with numerical models using a Direct Simulation Monte Carlo (DSMC) approach with dust particle distributions calculated using a test particle approach has been used to demonstrate the influence of a complex shape and particle acceleration on the azimuthal average profiles. We demonstrate that, while other effects such as fragmentation or sublimation of dust particles cannot be ruled out, acceleration of the dust particles and effects arising from the shape of the irregular nucleus (non-point source geometry) are sufficient to explain the observed dust outflow behaviour from image data analysis. As a by-product of this work, we have calculated “Afρ” values for the 1/r regime. We found a peak in the coma activity in terms of Afρ (normalised to a phase angle of 90°) of ∼210 cm 20 days after perihelion. Furthermore, based on simplified models of particle motion within bound orbits, it is shown that limits on the total cross-sectional area of bound particles might be derived through further analysis. An example is given

Exposed bright features on the comet 67P/Churyumov-Gerasimenko: Distribution and evolution

Context. Since its arrival at the comet 67P/Churyumov-Gerasimenko in August 2014, the Rosetta spacecraft followed the comet as it went past the perihelion and beyond until September 2016. During this time there were many scientific instruments operating on board Rosetta to study the comet and its evolution in unprecedented detail. In this context, our study focusses on the distribution and evolution of exposed bright features that have been observed by OSIRIS, which is the scientific imaging instrument aboard Rosetta. Aims. We envisage investigating various morphologies of exposed bright features and the mechanisms that triggered their appearance. Methods. We co-registered multi-filter observations of OSIRIS images that are available in reflectance. The Lommel-Seeliger disk function was used to correct for the illumination conditions and the resulting colour cubes were used to perform spectrophotometric analyses on regions of interest. Results. We present a catalogue of 57 exposed bright features observed on the nucleus of the comet, all of which are attributed to the presence of H2O ice on the comet. Furthermore, we categorise these patches under four different morphologies and present geometric albedos for each category. Conclusions. Although the nucleus of 67P/Churyumov-Gerasimenko appears to be dark in general, there are localised H2O ice sources on the comet. Cometary activity escalates towards the perihelion passage and reveals such volatile ices. We propose that isolated H2O ice patches found in smooth terrains in regions, such as Imhotep, Bes, and Hapi, result from frost as an aftermath of the cessation of the diurnal water cycle on the comet as it recedes from perihelion. Upon the comet's return to perihelion, such patches are revealed when sublimation-driven erosion removes the thin dust layers that got deposited earlier. More powerful activity sources such as cometary outbursts are capable of revealing much fresher, less contaminated H2O ice that is preserved with consolidated cometary material, as observed on exposed patches resting on boulders. This is corroborated by our albedo calculations that attribute higher albedos for bright features with formations related to outbursts

The rotation state of 67P/Churyumov-Gerasimenko from approach observations with the OSIRIS cameras on Rosetta

Aims. Approach observations with the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) experiment onboard Rosetta are used to determine the rotation period, the direction of the spin axis, and the state of rotation of comet 67P's nucleus. Methods. Photometric time series of 67P have been acquired by OSIRIS since the post wake-up commissioning of the payload in March 2014. Fourier analysis and convex shape inversion methods have been applied to the Rosetta data as well to the available ground-based observations. Results. Evidence is found that the rotation rate of 67P has significantly changed near the time of its 2009 perihelion passage, probably due to sublimation-induced torque. We find that the sidereal rotation periods P1 = 12.76129 ± 0.00005 h and P2 = 12.4043 ± 0.0007 h for the apparitions before and after the 2009 perihelion, respectively, provide the best fit to the observations. No signs of multiple periodicity are found in the light curves down to the noise level, which implies that the comet is presently in a simple rotation state around its axis of largest moment of inertia. We derive a prograde rotation model with spin vector J2000 ecliptic coordinates λ = 65° ± 15°, β = + 59° ± 15°, corresponding to equatorial coordinates RA = 22°, Dec = + 76°. However, we find that the mirror solution, also prograde, at λ = 275° ± 15°, β = + 50° ± 15° (or RA = 274°, Dec = + 27°), is also possible at the same confidence level, due to the intrinsic ambiguity of the photometric problem for observations performed close to the ecliptic plane

Opposition effect on comet 67P/Churyumov-Gerasimenko using Rosetta-OSIRIS images

Aims. We aim to explore the behavior of the opposition effect as an important tool in optical remote sensing on the nucleus of comet 67P/Churyumov-Gerasimenko (67P), using Rosetta-OSIRIS images acquired in different filters during the approach phase, July-August 2014 and the close flyby images on 14 of February 2015, which contain the spacecraft shadow. Methods. We based our investigation on the global and local brightness from the surface of 67P with respect to the phase angle, also known as phase curve. The local phase curve corresponds to a region that is located at the Imhotep-Ash boundary of 67P. Assuming that the region at the Imhotep-Ash boundary and the entire nucleus have similar albedo, we combined the global and local phase curves to study the opposition-surge morphology and constrain the structure and properties of 67P. The model parameters were furthermore compared with other bodies in the solar system and existing laboratory study. Results. We found that the morphological parameters of the opposition surge decrease monotonically with wavelength, whereas in the case of coherent backscattering this behavior should be the reverse. The results from comparative analysis place 67P in the same category as the two Mars satellites, Phobos and Deimos, which are notably different from all airless bodies in the solar system. The similarity between the surface phase function of 67P and a carbon soot sample at extremely small angles is identified, introducing regolith at the boundary of the Imhotep-Ash region of 67P as a very dark and fluffy layer

Gas outflow and dust transport of comet 67P/Churyumov-Gerasimenko

Because of the diurnal thermal cycle and the irregular shape of the nucleus, gas outflow of comet 67P/Churyumov-Gerasimenko could be highly anisotropic as indicated by the colliminated dust jet structures on the sunlit side. Based on the OSIRIS imaging observations of the outgassing effect, a simple model of surface sublimation can be constructed by taking into account the dependence on the solar insolation. With preliminary information on the time variability of the global gas production rate, a sequence of gas coma models can be generated at different epochs before and after perihelion. We also investigate different patterns of dust particle dynamics under the influences of nuclear rotation and gas drag. From these considerations, a consistent picture of the spatial distribution of dusty materials across the surface of comet 67P as it moves around the perihelion can be developed. It is found that because of the redeposition of the ejected dust from the Southern hemisphere to the Northern hemisphere during the southern summer season the Hapi region could gain up to 0.4 m while the Wosret region would lose up to 1.8 m of dust mantle per orbit

Characterization of OSIRIS NAC filters for the interpretation of multispectral data of comet 67P/Churyumov-Gerasimenko

We interpret multicolor data from OSIRISNAC for the remote-sensing exploration of comet 67P/Churyumov-Gerasimenko. We determine the most meaningful definition of color maps for the characterization of surface variegation with filters available on OSIRIS NAC. Methods. We analyzed laboratory spectra of selected minerals and olivine-pyroxene mixtures seen through OSIRIS NAC filters, with spectral methods existing in the literature: reflectance ratios, minimum band wavelength, spectral slopes, band tilt, band curvature, and visible tilt. Results. We emphasize the importance of reflectance ratios and particularly the relation of visible tilt vs. band tilt. This technique provides a reliable diagnostic of the presence of silicates. Color maps constructed by red-green-blue colors defined with the green, orange, red, IR, and Fe2O3 filters let us define regions that may significantly differ in composition

Distance determination method of dust particles using Rosetta OSIRIS NAC and WAC data

The ESA Rosetta spacecraft has been tracking its target, the Jupiter-family comet 67P/Churyumov-Gerasimenko, in close vicinity for over two years. It hosts the OSIRIS instruments: the Optical, Spectroscopic, and Infrared Remote Imaging System composed of two cameras, see e.g. Keller et al. (2007). In some imaging sequences dedicated to observe dust particles in the comet's coma, the two cameras took images at the same time. The aim of this work is to use these simultaneous double camera observations to calculate the dust particles’ distance to the spacecraft. As the two cameras are mounted on the spacecraft with an offset of 70 cm, the distance of particles observed by both cameras can be determined by a shift of the particles’ apparent trails on the images. This paper presents first results of the ongoing work, introducing the distance determination method for the OSIRIS instrument and the analysis of an example particle. We note that this method works for particles in the range of about 500–6000 m from the spacecraft

Gravitational slopes, geomorphology, and material strengths of the nucleus of comet 67P/Churyumov-Gerasimenko from OSIRIS observations

We study the link between gravitational slopes and the surface morphology on the nucleus of comet 67P/Churyumov-Gerasimenko and provide constraints on the mechanical properties of the cometary material (tensile, shear, and compressive strengths). Methods. We computed the gravitational slopes for five regions on the nucleus that are representative of the different morphologies observed on the surface (Imhotep, Ash, Seth, Hathor, and Agilkia), using two shape models computed from OSIRIS images by the stereo-photoclinometry (SPC) and stereo-photogrammetry (SPG) techniques. We estimated the tensile, shear, and compressive strengths using different surface morphologies (overhangs, collapsed structures, boulders, cliffs, and Philae's footprint) and mechanical considerations. Results. The different regions show a similar general pattern in terms of the relation between gravitational slopes and terrain morphology: i) low-slope terrains (0-20°) are covered by a fine material and contain a few large (>10 m) and isolated boulders; ii) intermediate-slope terrains (20-45°) are mainly fallen consolidated materials and debris fields, with numerous intermediate-size boulders from <1 m to 10 m for the majority of them; and iii) high-slope terrains (45-90°) are cliffs that expose a consolidated material and do not show boulders or fine materials. The best range for the tensile strength of overhangs is 3-15 Pa (upper limit of 150 Pa), 4-30 Pa for the shear strength of fine surface materials and boulders, and 30-150 Pa for the compressive strength of overhangs (upper limit of 1500 Pa). The strength-to-gravity ratio is similar for 67P and weak rocks on Earth. As a result of the low compressive strength, the interior of the nucleus may have been compressed sufficiently to initiate diagenesis, which could have contributed to the formation of layers. Our value for the tensile strength is comparable to that of dust aggregates formed by gravitational instability and tends to favor a formation of comets by the accrection of pebbles at low velocities