| 1. |
- Marconi, A., et al.
(author)
-
ANDES, the high resolution spectrograph for the ELT : science case, baseline design and path to construction
- 2022
-
In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
-
Conference paper (peer-reviewed)abstract
- The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs (UBV, RIZ, YJH) providing a spectral resolution of similar to 100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 mu m with the goal of extending it to 0.35-2.4 mu m with the addition of a K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Its modularity will ensure that ANDES can be placed entirely on the ELT Nasmyth platform, if enough mass and volume is available, or partly in the Coude room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of more than 200 scientists and engineers which represent the majority of the scientific and technical expertise in the field among ESO member states.
|
|
| 2. |
- Leleu, A., et al.
(author)
-
Six transiting planets and a chain of Laplace resonances in TOI-178
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
-
Journal article (peer-reviewed)abstract
- Determining the architecture of multi-planetary systems is one of the cornerstones of understanding planet formation and evolution. Resonant systems are especially important as the fragility of their orbital configuration ensures that no significant scattering or collisional event has taken place since the earliest formation phase when the parent protoplanetary disc was still present. In this context, TOI-178 has been the subject of particular attention since the first TESS observations hinted at the possible presence of a near 2:3:3 resonant chain. Here we report the results of observations from CHEOPS, ESPRESSO, NGTS, and SPECULOOS with the aim of deciphering the peculiar orbital architecture of the system. We show that TOI-178 harbours at least six planets in the super-Earth to mini-Neptune regimes, with radii ranging from 1.152 to 2.87 Earth radii and periods of 1.91, 3.24, 6.56, 9.96, 15.23, and 20.71 days. All planets but the innermost one form a 2:4:6:9:12 chain of Laplace resonances, and the planetary densities show important variations from planet to planet, jumping from 1.02 to 0.177 times the Earth's density between planets c and d. Using Bayesian interior structure retrieval models, we show that the amount of gas in the planets does not vary in a monotonous way, contrary to what one would expect from simple formation and evolution models and unlike other known systems in a chain of Laplace resonances. The brightness of TOI-178 (H = 8.76 mag, J = 9.37 mag, V = 11.95 mag) allows for a precise characterisation of its orbital architecture as well as of the physical nature of the six presently known transiting planets it harbours. The peculiar orbital configuration and the diversity in average density among the planets in the system will enable the study of interior planetary structures and atmospheric evolution, providing important clues on the formation of super-Earths and mini-Neptunes. -0.070 -0.13 -0.23 -0.061 +0.073 +0.14 +0.28 +0.055
|
|
| 3. |
- Mallorquin, M., et al.
(author)
-
TOI-1801 b: A temperate mini-Neptune around a young M0.5 dwarf
- 2023
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 680
-
Journal article (peer-reviewed)abstract
- We report the discovery, mass, and radius determination of TOI-1801 b, a temperate mini-Neptune around a young M dwarf. TOI-1801 b was observed in TESS sectors 22 and 49, and the alert that this was a TESS planet candidate with a period of 21.3 days went out in April 2020. However, ground-based follow-up observations, including seeing-limited photometry in and outside transit together with precise radial velocity (RV) measurements with CARMENES and HIRES revealed that the true period of the planet is 10.6 days. These observations also allowed us to retrieve a mass of 5.74 +/- 1.46 M-circle plus, which together with a radius of 2.08 +/- 0.12 R-circle plus, means that TOI-1801 b is most probably composed of water and rock, with an upper limit of 2% by mass of H-2 in its atmosphere. The stellar rotation period of 16 days is readily detectable in our RV time series and in the ground-based photometry. We derived a likely age of 600-800 Myr for the parent star TOI-1801, which means that TOI-1801 b is the least massive young mini-Neptune with precise mass and radius determinations. Our results suggest that if TOI-1801 b had a larger atmosphere in the past, it must have been removed by some evolutionary mechanism on timescales shorter than 1 Gyr.
|
|
| 4. |
- Bluhm, P., et al.
(author)
-
Precise mass and radius of a transiting super-Earth planet orbiting the M dwarf TOI-1235: a planet in the radius gap?
- 2020
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 639
-
Journal article (peer-reviewed)abstract
- We report the confirmation of a transiting planet around the bright weakly active M0.5 V star TOI-1235 (TYC 4384-1735-1, V ≈ 11.5 mag), whose transit signal was detected in the photometric time series of sectors 14, 20, and 21 of the TESS space mission. We confirm the planetary nature of the transit signal, which has a period of 3.44 d, by using precise RV measurements with the CARMENES, HARPS-N, and iSHELL spectrographs, supplemented by high-resolution imaging and ground-based photometry. A comparison of the properties derived for TOI-1235 b with theoretical models reveals that the planet has a rocky composition, with a bulk density slightly higher than that of Earth. In particular, we measure a mass of Mp = 5.9 ± 0.6 M⊕ and a radius of Rp = 1.69 ± 0.08 R⊕, which together result in a density of ρp = 6.7- 1.1+ 1.3 g cm-3. When compared with other well-characterized exoplanetary systems, the particular combination of planetary radius and mass places our discovery in the radius gap, which is a transition region between rocky planets and planets with significant atmospheric envelopes. A few examples of planets occupying the radius gap are known to date. While the exact location of the radius gap for M dwarfs is still a matter of debate, our results constrain it to be located at around 1.7 R⊕ or larger at the insolation levels received by TOI-1235 b (~60 S⊕). This makes it an extremely interesting object for further studies of planet formation and atmospheric evolution.
|
|
| 5. |
- Marconi, Alessandro, et al.
(author)
-
ELT-HIRES, the high resolution spectrograph for the ELT : Phase A study and path to construction
- 2020
-
In: Ground-based and Airborne Instrumentation for Astronomy VIII. - : SPIE - International Society for Optical Engineering. - 9781510636828 - 9781510636811
-
Conference paper (peer-reviewed)abstract
- HIRES is the high-resolution spectrograph of the European Extremely Large Telescope at optical and near-infrared wavelengths. It consists of three fibre-fed spectrographs providing a wavelength coverage of 0.4-1.8 µm (goal 0.35-2.4 µm) at a spectral resolution of 100,000. The fibre-feeding allows HIRES to have several, interchangeable observing modes including a SCAO module and a small diffraction-limited IFU in the NIR. Therefore, it will be able to operate both in seeing- and diffraction-limited modes. Its modularity will ensure that HIRES can be placed entirely on the Nasmyth platform, if enough mass and volume is available, or part on the Nasmyth and part in the Coud`e room. ELT-HIRES has a wide range of science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars (PopIII), tests on the stability of Nature’s fundamental couplings, and the direct detection of the cosmic acceleration. The HIRES consortium is composed of more than 30 institutes from 14 countries, forming a team of more than 200 scientists and engineers.
|
|
| 6. |
- Fukui, A., et al.
(author)
-
TOI-1749: an M dwarf with a Trio of Planets including a Near-resonant Pair
- 2021
-
In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 162:4
-
Journal article (peer-reviewed)abstract
- We report the discovery of one super-Earth- (TOI-1749b) and two sub-Neptune-sized planets (TOI-1749c and TOI-1749d) transiting an early M dwarf at a distance of 100 pc, which were first identified as planetary candidates using data from the TESS photometric survey. We have followed up this system from the ground by means of multiband transit photometry, adaptive optics imaging, and low-resolution spectroscopy, from which we have validated the planetary nature of the candidates. We find that TOI-1749b, c, and d have orbital periods of 2.39, 4.49, and 9.05 days, and radii of 1.4, 2.1, and 2.5 R (circle plus), respectively. We also place 95% confidence upper limits on the masses of 57, 14, and 15 M (circle plus) for TOI-1749b, c, and d, respectively, from transit timing variations. The periods, sizes, and tentative masses of these planets are in line with a scenario in which all three planets initially had a hydrogen envelope on top of a rocky core, and only the envelope of the innermost planet has been stripped away by photoevaporation and/or core-powered mass-loss mechanisms. These planets are similar to other planetary trios found around M dwarfs, such as TOI-175b,c,d and TOI-270b,c,d, in the sense that the outer pair has a period ratio within 1% of 2. Such a characteristic orbital configuration, in which an additional planet is located interior to a near 2:1 period-ratio pair, is relatively rare around FGK dwarfs.
|
|
| 7. |
- Van Eylen, Vincent, et al.
(author)
-
Masses and compositions of three small planets orbiting the nearby M dwarf L231-32 (TOI-270) and the M dwarf radius valley
- 2021
-
In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 507:2, s. 2154-2173
-
Journal article (peer-reviewed)abstract
- We report on precise Doppler measurements of L231-32 (TOI-270), a nearby M dwarf (d = 22 pc, M = 0.39 M, R = 0.38 R), which hosts three transiting planets that were recently discovered using data from the Transiting Exoplanet Survey Satellite (TESS). The three planets are 1.2, 2.4, and 2.1 times the size of Earth and have orbital periods of 3.4, 5.7, and 11.4 d. We obtained 29 high-resolution optical spectra with the newly commissioned Echelle Spectrograph for Rocky Exoplanet and Stable Spectroscopic Observations (ESPRESSO) and 58 spectra using the High Accuracy Radial velocity Planet Searcher (HARPS). From these observations, we find the masses of the planets to be 1.58 ± 0.26, 6.15 ± 0.37, and 4.78 ± 0.43 M, respectively. The combination of radius and mass measurements suggests that the innermost planet has a rocky composition similar to that of Earth, while the outer two planets have lower densities. Thus, the inner planet and the outer planets are on opposite sides of the 'radius valley'-a region in the radius-period diagram with relatively few members-which has been interpreted as a consequence of atmospheric photoevaporation. We place these findings into the context of other small close-in planets orbiting M dwarf stars, and use support vector machines to determine the location and slope of the M dwarf (Teff < 4000 K) radius valley as a function of orbital period. We compare the location of the M dwarf radius valley to the radius valley observed for FGK stars, and find that its location is a good match to photoevaporation and core-powered mass-loss models. Finally, we show that planets below the M dwarf radius valley have compositions consistent with stripped rocky cores, whereas most planets above have a lower density consistent with the presence of a H-He atmosphere.
|
|
| 8. |
- Seidel, J. V., et al.
(author)
-
Into the storm : Diving into the winds of the ultra-hot Jupiter WASP-76 b with HARPS and ESPRESSO
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
-
Journal article (peer-reviewed)abstract
- Context. Despite swift progress in the characterisation of exoplanet atmospheres in composition and structure, the study of atmospheric dynamics has not progressed at the same speed. While theoretical models have been developed to describe the lower layers of the atmosphere, and independently, the exosphere, little is known about the intermediate layers up to the thermosphere. Aims. We aim to provide a clearer picture of atmospheric dynamics for the class of ultra-hot Jupiters, which are highly irradiated gas giants, based on the example of WASP-76 b. Methods. We jointly analysed two datasets that were obtained with the HARPS and ESPRESSO spectrographs to interpret the resolved planetary sodium doublet. We then applied the MERC code, which retrieves wind patterns, speeds, and temperature profiles on the line shape of the sodium doublet. An updated version of MERC, with added planetary rotation, also provides the possibility of modelling the latitude dependence of the wind patterns. Results. We retrieve the highest Bayesian evidence for an isothermal atmosphere, interpreted as a mean temperature of 3389 ± 227 K, a uniform day- to nightside wind of 5.5-2.0+1.4 km s-1 in the lower atmosphere with a vertical wind in the upper atmosphere of 22.7-4.1+4.9 km s-1, switching atmospheric wind patterns at 10-3 bar above the reference surface pressure (10 bar). Conclusions. Our results for WASP-76 b are compatible with previous studies of the lower atmospheric dynamics of WASP-76 b and other ultra-hot Jupiters. They highlight the need for vertical winds in the intermediate atmosphere above the layers probed by global circulation model studies to explain the line broadening of the sodium doublet in this planet. This work demonstrates the capability of exploiting the resolved spectral line shapes to observationally constrain possible wind patterns in exoplanet atmospheres. This is an invaluable input to more sophisticated 3D atmospheric models in the future.
|
|
| 9. |
- Esparza-Borges, E., et al.
(author)
-
A hot sub-Neptune in the desert and a temperate super-Earth around faint M dwarfs Color validation of TOI-4479b and TOI-2081b
- 2022
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
-
Journal article (peer-reviewed)abstract
- Aims. We report the discovery and validation of two TESS exoplanets orbiting faint M dwarfs: TOI-4479b and TOI-2081b. Methods. We jointly analyzed space (TESS mission) and ground-based (MuSCAT2, MuSCAT3 and SINISTRO instruments) light curves using our multicolor photometry transit analysis pipeline. This allowed us to compute contamination limits for both candidates and validate them as planet-sized companions. Results. We found TOI-4479b to be a sub-Neptune-sized planet (R-p = 2.82(-0.63)(+0.65) R-circle plus) and TOI-2081b to be a super-Earth-sized planet (R-p = 2.04(-0.54)(+0.50) R-circle plus). Furthermore, we obtained that TOI-4479b, with a short orbital period of 1.15890(-0.00001)(+0.00002) days, lies within the Neptune desert and is in fact the largest nearly ultra-short period planet around an M dwarf known to date. Conclusions. These results make TOI-4479b rare among the currently known exoplanet population of M dwarf stars and an especially interesting target for spectroscopic follow-up and future studies of planet formation and evolution.
|
|
| 10. |
- Luque, R., et al.
(author)
-
Precise mass determination for the keystone sub-Neptune planet transiting the mid-type M dwarf G 9-40
- 2022
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
-
Journal article (peer-reviewed)abstract
- Context. Despite being a prominent subset of the exoplanet population discovered in the past three decades, the nature and provenance of sub-Neptune-sized planets is still one of the open questions in exoplanet science. Aims. For planets orbiting bright stars, precisely measuring the orbital and planet parameters of the system is the best approach to distinguish between competing theories regarding their formation and evolution. Methods. We obtained 69 new radial velocity observations of the mid-M dwarf G 9-40 with the CARMENES instrument to measure for the first time the mass of its transiting sub-Neptune planet, G 9-40 b, discovered in data from the K2 mission. Results. Combined with new observations from the TESS mission during Sectors 44, 45, and 46, we are able to measure the radius of the planet to an uncertainty of 3.4% (R-b = 1.900 +/- 0.065 R-circle plus) and determine its mass with a precision of 16% (M-b = 4.00 +/- 0.63 M-circle plus). The resulting bulk density of the planet is inconsistent with a terrestrial composition and suggests the presence of either a water-rich core or a significant hydrogen-rich envelope. Conclusions. G 9-40 b is referred to as a keystone planet due to its location in period-radius space within the radius valley. Several theories offer explanations for the origin and properties of this population and this planet is a valuable target for testing the dependence of those models on stellar host mass. By virtue of its brightness and small size of the host, it joins L 98-59 d as one of the two best warm (T-eq similar to 400 K) sub-Neptunes for atmospheric characterization with JWST, which will probe cloud formation in sub-Neptune-sized planets and break the degeneracies of internal composition models.
|
|
| 11. |
- Orell-Miquel, J., et al.
(author)
-
Confirmation of an He I evaporating atmosphere around the 650-Myr-old sub-Neptune HD 235088 b (TOI-1430 b) with CARMENES
- 2023
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 677
-
Journal article (peer-reviewed)abstract
- HD 235088 (TOI-1430) is a young star known to host a sub-Neptune-sized planet candidate. We validated the planetary nature of HD 235088 b with multiband photometry, refined its planetary parameters, and obtained a new age estimate of the host star, placing it at 600- 800 Myr. Previous spectroscopic observations of a single transit detected an excess absorption of He I coincident in time with the planet candidate transit. Here, we confirm the presence of He I in the atmosphere of HD 235088 b with one transit observed with CARMENES. We also detected hints of variability in the strength of the helium signal, with an absorption of -0.91 ± 0.11%, which is slightly deeper (2γ) than the previous measurement. Furthermore, we simulated the He I signal with a spherically symmetric 1D hydrodynamic model, finding that the upper atmosphere of HD 235088 b escapes hydrodynamically with a significant mass loss rate of (1.5-5) × 1010 g s-1 in a relatively cold outflow, with T = 3125 ±375 K, in the photon-limited escape regime. HD 235088 b (Rp = 2.045 ± 0.075 R⊕) is the smallest planet found to date with a solid atmospheric detection - not just of He I but any other atom or molecule. This positions it a benchmark planet for further analyses of evolving young sub-Neptune atmospheres.
|
|
| 12. |
- Parviainen, H., et al.
(author)
-
TOI-2266 b: A keystone super-Earth at the edge of the M dwarf radius valley
- 2024
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
-
Journal article (peer-reviewed)abstract
- We validate the Transiting Exoplanet Survey Satellite (TESS) object of interest TOI-2266.01 (TIC 8348911) as a small transiting planet (most likely a super-Earth) orbiting a faint M5 dwarf (V = 16.54) on a 2.33 d orbit. The validation is based on an approach where multicolour transit light curves are used to robustly estimate the upper limit of the transiting object's radius. Our analysis uses SPOC-pipeline TESS light curves from Sectors 24, 25, 51, and 52, simultaneous multicolour transit photometry observed with MuSCAT2, MuSCAT3' and HiPERCAM, and additional transit photometry observed with the LCOGT telescopes. TOI-2266 b is found to be a planet with a radius of 1.54 ± 0.09 R, which locates it at the edge of the transition zone between rocky planets, water-rich planets, and sub-Neptunes (the so-called M dwarf radius valley). The planet is amenable to ground-based radial velocity mass measurement with red-sensitive spectrographs installed in large telescopes, such as MAROON-X and Keck Planet Finder (KPF), which makes it a valuable addition to a relatively small population of planets that can be used to probe the physics of the transition zone. Further, the planet's orbital period of 2.33 days places it inside a 'keystone planet'wedge in the period-radius plane where competing planet formation scenarios make conflicting predictions on how the radius valley depends on the orbital period. This makes the planet also a welcome addition to the small population of planets that can be used to test small-planet formation scenarios around M dwarfs.
|
|
| 13. |
- Haid, Sibylle, et al.
(author)
-
Repurposing screen identifies novel candidates for broad-spectrum coronavirus antivirals and druggable host targets
- 2024
-
In: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 68:3
-
Journal article (peer-reviewed)abstract
- Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiological processes in humans, providing unique opportunities for the discovery of host-targeting antivirals. We screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) repurposing library with approximately 12,000 molecules for broad-spectrum coronavirus antivirals and discovered 134 compounds inhibiting an alphacoronavirus and mapping to 58 molecular target categories. Dominant targets included the 5-hydroxytryptamine receptor, the dopamine receptor, and cyclin-dependent kinases. Gene knock-out of the drugs’ host targets including cathepsin B and L (CTSB/L; VBY-825), the aryl hydrocarbon receptor (AHR; Phortress), the farnesyl-diphosphate farnesyltransferase 1 (FDFT1; P-3622), and the kelch-like ECH-associated protein 1 (KEAP1; Omaveloxolone), significantly modulated HCoV-229E infection, providing evidence that these compounds inhibited the virus through acting on their respective host targets. Counter-screening of all 134 primary compound candidates with SARS-CoV-2 and validation in primary cells identified Phortress, an AHR activating ligand, P-3622-targeting FDFT1, and Omaveloxolone, which activates the NFE2-like bZIP transcription factor 2 (NFE2L2) by liberating it from its endogenous inhibitor KEAP1, as antiviral candidates for both an Alpha- and a Betacoronavirus. This study provides an overview of HCoV-229E repurposing candidates and reveals novel potentially druggable viral host dependency factors hijacked by diverse coronaviruses.
|
|
| 14. |
- Palle, E., et al.
(author)
-
ESPRESSO mass determination of TOI-263b : An extreme inhabitant of the brown dwarf desert
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 650
-
Journal article (peer-reviewed)abstract
- The TESS mission has reported a wealth of new planetary systems around bright and nearby stars amenable for detailed characterizations of planet properties and atmospheres. However, not all interesting TESS planets orbit around bright host stars. TOI-263 b is a validated ultra-short-period substellar object in a 0.56-day orbit around a faint (V = 18.97) M 3.5 dwarf star. The substellar nature of TOI-263 b was explored using multicolor photometry: a true radius of 0.87 ± 0.21 RJ was determined, establishing TOI-263 b 's nature as somewhere between an inflated Neptune and a brown dwarf. The orbital period-radius parameter space occupied by TOI-263 b is quite unique, which prompted a further characterization of its true nature. Here, we report radial velocity measurements of TOI-263 obtained with three VLT units and the ESPRESSO spectrograph to retrieve the mass of TOI-263 b. We find that TOI-263 b is a brown dwarf with a mass of 61.6 ± 4.0 MJup. Additionally, the orbital period of the brown dwarf is found to be synchronized with the rotation period of the host star, and the system is found to be relatively active, possibly revealing a star-brown dwarf interaction. All these findings suggest that the system's formation history might be explained via disk fragmentation and a later migration to close-in orbits. If the system is found to be unstable, TOI-263 will be an excellent target to test the migration mechanisms before the brown dwarf becomes "engulfed"by its parent star.
|
|
| 15. |
- Ricke-Hoch, Melanie, et al.
(author)
-
Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease
- 2021
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:8
-
Journal article (peer-reviewed)abstract
- The SARS-CoV-2 coronavirus has led to a pandemic with millions of people affected. The present study finds that risk-factors for severe COVID-19 disease courses, i.e. male sex, older age and sedentary life style are associated with higher prostaglandin E2 (PGE2) serum levels in blood samples from unaffected subjects. In COVID-19 patients, PGE2 blood levels are markedly elevated and correlate positively with disease severity. SARS-CoV-2 induces PGE2 generation and secretion in infected lung epithelial cells by upregulating cyclo-oxygenase (COX)-2 and reducing the PG-degrading enzyme 15-hydroxyprostaglan-din-dehydrogenase. Also living human precision cut lung slices (PCLS) infected with SARS-CoV-2 display upregulated COX-2. Regular exercise in aged individuals lowers PGE2 serum levels, which leads to increased Paired-Box-Protein-Pax-5 (PAX5) expression, a master regulator of B-cell survival, proliferation and differentiation also towards long lived memory B-cells, in human pre-B-cell lines. Moreover, PGE2 levels in serum of COVID-19 patients lowers the expression of PAX5 in human pre-B-cell lines. The PGE2 inhibitor Taxifolin reduces SARS-CoV-2-induced PGE2 production. In conclusion, SARS-CoV-2, male sex, old age, and sedentary life style increase PGE2 levels, which may reduce the early anti-viral defense as well as the development of immunity promoting severe disease courses and multiple infections. Regular exercise and Taxifolin treatment may reduce these risks and prevent severe disease courses.
|
|
| 16. |
- Carriquí-Madroñal, Belén, et al.
(author)
-
The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity
- 2023
-
In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 19:11
-
Journal article (peer-reviewed)abstract
- Hepatitis C virus (HCV) exploits the four entry factors CD81, scavenger receptor class B type I (SR-BI, also known as SCARB1), occludin, and claudin-1 as well as the co-factor epidermal growth factor receptor (EGFR) to infect human hepatocytes. Here, we report that the disintegrin and matrix metalloproteinase 10 (ADAM10) associates with CD81, SR-BI, and EGFR and acts as HCV host factor. Pharmacological inhibition, siRNA-mediated silencing and genetic ablation of ADAM10 reduced HCV infection. ADAM10 was dispensable for HCV replication but supported HCV entry and cell-to-cell spread. Substrates of the ADAM10 sheddase including epidermal growth factor (EGF) and E-cadherin, which activate EGFR family members, rescued HCV infection of ADAM10 knockout cells. ADAM10 did not influence infection with other enveloped RNA viruses such as alphaviruses and a common cold coronavirus. Collectively, our study reveals a critical role for the sheddase ADAM10 as a HCV host factor, contributing to EGFR family member transactivation and as a consequence to HCV uptake.
|
|
| 17. |
- Damasso, M., et al.
(author)
-
Photometric follow-up of the 20 Myr old multi-planet host star V1298 Tau with CHEOPS and ground-based telescopes
- 2023
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 680
-
Journal article (peer-reviewed)abstract
- Context. The 20 Myr old star V1298 Tau hosts at least four planets. Since its discovery, this system has been a target of intensive photometric and spectroscopic monitoring. To date, the characterisation of its architecture and planets’ fundamental properties has been very challenging.Aims. The determination of the orbital ephemeris of the outermost planet V1298 Tau e remains an open question. Only two transits have been detected so far by Kepler/K2 and TESS, allowing for a grid of reference periods to be tested with new observations, without excluding the possibility of transit timing variations. Observing a third transit would allow for better constraints to be set on the orbital period and would also help in determining an accurate radius for V1298 Tau e because the previous transits showed different depths.Methods. We observed V1298 Tau with the CHaracterising ExOPlanet Satellite (CHEOPS) to search for a third transit of planet e within observing windows selected to test three of the shortest predicted orbital periods. We also collected ground-based observations to verify the result found with CHEOPS. We reanalysed Kepler/K2 and TESS light curves to test how the results derived from these data are affected by alternative photometric extraction and detrending methods.Results. We report the CHEOPS detection of a transit-like signal that could be attributed to V1298 Tau e. If so, that result would imply that the orbital period calculated from fitting a linear ephemeris to the three available transits is close to ~45 days. Results from the ground-based follow-up marginally support this possibility. We found that i) the transit observed by CHEOPS has a longer duration compared to that of the transits observed by Kepler/K2 and TESS; and ii) the transit observed by TESS is >30% deeper than that of Kepler/K2 and CHEOPS, and it is also deeper than the measurement previously reported in the literature, according to our reanalysis.Conclusions. If the new transit detected by CHEOPS is found to be due to V1298 Tau e, this would imply that the planet experiences TTVs of a few hours, as deduced from three transits, as well as orbital precession, which would explain the longer duration of the transit compared to the Kepler/K2 and TESS signals. Another and a priori less likely possibility is that the newly detected transit belongs to a fifth planet with a longer orbital period than that of V1298 Tau e. Planning further photometric follow-up to search for additional transits is indeed necessary to solve the conundrum, as well as to pin down the radius of V1298 Tau e.
|
|
| 18. |
- Lasswitz, Lisa, et al.
(author)
-
The tetraspanin CD81 is a host factor for Chikungunya virus replication
- 2022
-
In: mBio. - : ASM International. - 2161-2129 .- 2150-7511. ; 13:3
-
Journal article (peer-reviewed)abstract
- Chikungunya virus (CHIKV) is an arthritogenic reemerging virus replicating in plasma membrane-derived compartments termed "spherules." Here, we identify the human transmembrane protein CD81 as host factor required for CHIKV replication. Ablation of CD81 results in decreased CHIKV permissiveness, while overexpression enhances infection. CD81 is dispensable for virus uptake but critically required for viral genome replication. Likewise, murine CD81 is crucial for CHIKV permissiveness and is expressed in target cells such as dermal fibroblasts, muscle and liver cells. Whereas related alphaviruses, including Ross River virus (RRV), Semliki Forest virus (SFV), Sindbis virus (SINV) and Venezuelan equine encephalitis virus (VEEV), also depend on CD81 for infection, RNA viruses from other families, such as coronaviruses, replicate independently of CD81. Strikingly, the replication-enhancing function of CD81 is linked to cholesterol binding. These results define a mechanism exploited by alphaviruses to hijack the membrane microdomain-modeling protein CD81 for virus replication through interaction with cholesterol.IMPORTANCE: In this study, we discover the tetraspanin CD81 as a host factor for the globally emerging chikungunya virus and related alphaviruses. We show that CD81 promotes replication of viral genomes in human and mouse cells, while virus entry into cells is independent of CD81. This provides novel insights into how alphaviruses hijack host proteins to complete their life cycle. Alphaviruses replicate at distinct sites of the plasma membrane, which are enriched in cholesterol. We found that the cholesterol-binding ability of CD81 is important for its function as an alphavirus host factor. This discovery thus broadens our understanding of the alphavirus replication process and the use of host factors to reprogram cells into virus replication factories.
|
|
| 19. |
- Mhlekude, Baxolele, et al.
(author)
-
Pharmacological inhibition of bromodomain and extra-terminal proteins induces an NRF-2-mediated antiviral state that is subverted by SARS-CoV-2 infection
- 2023
-
In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 19:9
-
Journal article (peer-reviewed)abstract
- Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential prophylactics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-mediated antiviral activity and its susceptibility to viral subversion remain incompletely understood. Pretreatment of cells with iBETs inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. The antiviral activity manifested itself by reduced reporter expression of recombinant viruses, and reduced viral RNA quantities and infectious titers in the culture supernatant. While we confirmed JQ-1-mediated downregulation of expression of angiotensin-converting enzyme 2 (ACE2) and interferon-stimulated genes (ISGs), multi-omics analysis addressing the chromatin accessibility, transcriptome and proteome uncovered induction of an antiviral nuclear factor erythroid 2-related factor 2 (NRF-2)-mediated cytoprotective response as an additional mechanism through which JQ-1 inhibits SARS-CoV-2 replication. Pharmacological inhibition of NRF-2, and knockdown of NRF-2 and its target genes reduced JQ-1-mediated inhibition of SARS-CoV-2 replication. Serial passaging of SARS-CoV-2 in the presence of JQ-1 resulted in predominance of ORF6-deficient variant, which exhibited resistance to JQ-1 and increased sensitivity to exogenously administered type I interferon (IFN-I), suggesting a minimised need for SARS-CoV-2 ORF6-mediated repression of IFN signalling in the presence of JQ-1. Importantly, JQ-1 exhibited a transient antiviral activity when administered prophylactically in human airway bronchial epithelial cells (hBAECs), which was gradually subverted by SARS-CoV-2, and no antiviral activity when administered therapeutically following an established infection. We propose that JQ-1 exerts pleiotropic effects that collectively induce an antiviral state in the host, which is ultimately nullified by SARS-CoV-2 infection, raising questions about the clinical suitability of the iBETs in the context of COVID-19.
|
|
| 20. |
- Passos, Vania, et al.
(author)
-
Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons
- 2024
-
In: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 96:2
-
Journal article (peer-reviewed)abstract
- Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes neurological disease in the peripheral and central nervous system (PNS and CNS, respectively) of some patients. It is not clear whether SARS-CoV-2 infection or the subsequent immune response are the key factors that cause neurological disease. Here, we addressed this question by infecting human induced pluripotent stem cell-derived CNS and PNS neurons with SARS-CoV-2. SARS-CoV-2 infected a low number of CNS neurons and did not elicit a robust innate immune response. On the contrary, SARS-CoV-2 infected a higher number of PNS neurons. This resulted in expression of interferon (IFN) λ1, several IFN-stimulated genes and proinflammatory cytokines. The PNS neurons also displayed alterations characteristic of neuronal damage, as increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein, and lower levels of cytoskeletal proteins. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neuronal damage, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. Our results provide a basis to study coronavirus disease 2019 (COVID-19) related neuronal pathology and to test future preventive or therapeutic strategies.
|
|
| 21. |
- Zapatero-Belinchón, Francisco J., et al.
(author)
-
Fluvastatin mitigates SARS-CoV-2 infection in human lung cells
- 2021
-
In: iScience. - : Elsevier. - 2589-0042. ; 24:12
-
Journal article (peer-reviewed)abstract
- Clinical data of patients suffering from COVID-19 indicates that statin therapy, used to treat hypercholesterolemia, is associated with a better disease outcome. Whether statins directly affect virus replication or influence the clinical outcome through modulation of immune responses is unknown. We therefore investigated the effect of statins on SARS-CoV-2 infection in human lung cells and found that only fluvastatin inhibited low and high pathogenic coronaviruses in vitro and ex vivo in a dose-dependent manner. Quantitative proteomics revealed that fluvastatin and other tested statins modulated the cholesterol synthesis pathway without altering innate antiviral immune responses in infected lung epithelial cells. However, fluvastatin treatment specifically downregulated proteins that modulate protein translation and viral replication. Collectively, these results support the notion that statin therapy poses no additional risk to individuals exposed to SARS-CoV-2 and that fluvastatin has a moderate beneficial effect on SARS-CoV-2 infection of human lung cells.
|
|
| 22. |
- Zapatero-Belinchón, Francisco J., et al.
(author)
-
Interdependent Impact of Lipoprotein Receptors and Lipid-Lowering Drugs on HCV Infectivity
- 2021
-
In: Cells. - : MDPI. - 2073-4409. ; 10:7
-
Journal article (peer-reviewed)abstract
- The HCV replication cycle is tightly associated with host lipid metabolism: Lipoprotein receptors SR-B1 and LDLr promote entry of HCV, replication is associated with the formation of lipid-rich membranous organelles and infectious particle assembly highjacks the very‑low-density lipoprotein (VLDL) secretory pathway. Hence, medications that interfere with the lipid metabolism of the cell, such as statins, may affect HCV infection. Here, we study the interplay between lipoprotein receptors, lipid homeostasis, and HCV infection by genetic and pharmacological interventions. We found that individual ablation of the lipoprotein receptors SR‑B1 and LDLr did not drastically affect HCV entry, replication, or infection, but double lipoprotein receptor knock-outs significantly reduced HCV infection. Furthermore, we could show that this effect was neither due to altered expression of additional HCV entry factors nor caused by changes in cellular cholesterol content. Strikingly, whereas lipid‑lowering drugs such as simvastatin or fenofibrate did not affect HCV entry or infection of immortalized hepatoma cells expressing SR-B1 and/or LDLr or primary human hepatocytes, ablation of these receptors rendered cells more susceptible to these drugs. Finally, we observed no significant differences between statin users and control groups with regards to HCV viral load in a cohort of HCV infected patients before and during HCV antiviral treatment. Interestingly, statin treatment, which blocks the mevalonate pathway leading to decreased cholesterol levels, was associated with mild but appreciable lower levels of liver damage markers before HCV therapy. Overall, our findings confirm the role of lipid homeostasis in HCV infection and highlight the importance of the mevalonate pathway in the HCV replication cycle.
|
|
