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  • Huhn, Stefanie, et al. (författare)
  • Coding variants in NOD-like receptors : An association study on risk and survival of colorectal cancer
  • 2018
  • Ingår i: PLoS ONE. - : Public Library of Science. - 1932-6203. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.
  • Jung, Martin, et al. (författare)
  • Compensatory water effects link yearly global land CO 2 sink changes to temperature
  • 2017
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836. ; 541:7638, s. 516-520
  • Tidskriftsartikel (refereegranskat)abstract
    • Large interannual variations in the measured growth rate of atmospheric carbon dioxide (CO 2) originate primarily from fluctuations in carbon uptake by land ecosystems. It remains uncertain, however, to what extent temperature and water availability control the carbon balance of land ecosystems across spatial and temporal scales. Here we use empirical models based on eddy covariance data and process-based models to investigate the effect of changes in temperature and water availability on gross primary productivity (GPP), terrestrial ecosystem respiration (TER) and net ecosystem exchange (NEE) at local and global scales. We find that water availability is the dominant driver of the local interannual variability in GPP and TER. To a lesser extent this is true also for NEE at the local scale, but when integrated globally, temporal NEE variability is mostly driven by temperature fluctuations. We suggest that this apparent paradox can be explained by two compensatory water effects. Temporal water-driven GPP and TER variations compensate locally, dampening water-driven NEE variability. Spatial water availability anomalies also compensate, leaving a dominant temperature signal in the year-to-year fluctuations of the land carbon sink. These findings help to reconcile seemingly contradictory reports regarding the importance of temperature and water in controlling the interannual variability of the terrestrial carbon balance. Our study indicates that spatial climate covariation drives the global carbon cycle response.
  • Keppler, M., et al. (författare)
  • Discovery of a planetary-mass companion within the gap of the transition disk around PDS 70
  • 2018
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 617
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Young circumstellar disks are the birthplaces of planets. Their study is of prime interest to understand the physical and chemical conditions under which planet formation takes place. Only very few detections of planet candidates within these disks exist, and most of them are currently suspected to be disk features.Aims. In this context, the transition disk around the young star PDS 70 is of particular interest, due to its large gap identified in previous observations, indicative of ongoing planet formation. We aim to search for the presence of an embedded young planet and search for disk structures that may be the result of disk-planet interactions and other evolutionary processes.Methods. We analyse new and archival near-infrared images of the transition disk PDS 70 obtained with the VLT/SPHERE, VLT/NaCo, and Gemini/NICI instruments in polarimetric differential imaging and angular differential imaging modes.Results. We detect a point source within the gap of the disk at about 195 mas (similar to 22 au) projected separation. The detection is confirmed at five different epochs, in three filter bands and using different instruments. The astrometry results in an object of bound nature, with high significance. The comparison of the measured magnitudes and colours to evolutionary tracks suggests that the detection is a companion of planetary mass. The luminosity of the detected object is consistent with that of an L-type dwarf, but its IR colours are redder, possibly indicating the presence of warm surrounding material. Further, we confirm the detection of a large gap of similar to 54 au in size within the disk in our scattered light images, and detect a signal from an inner disk component. We find that its spatial extent is very likely smaller than similar to 17 au in radius, and its position angle is consistent with that of the outer disk. The images of the outer disk show evidence of a complex azimuthal brightness distribution which is different at different wavelengths and may in part be explained by Rayleigh scattering from very small grains.Conclusions. The detection of a young protoplanet within the gap of the transition disk around PDS 70 opens the door to a so far observationally unexplored parameter space of planetary formation and evolution. Future observations of this system at different wavelengths and continuing astrometry will allow us to test theoretical predictions regarding planet-disk interactions, planetary atmospheres, and evolutionary models.
  • Keskin, Isil, et al. (författare)
  • Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients
  • 2016
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations in superoxide dismutase-1 (SOD1) are a common known cause of amyotrophic lateral sclerosis (ALS). The neurotoxicity of mutant SOD1s is most likely caused by misfolded molecular species, but disease pathogenesis is still not understood. Proposed mechanisms include impaired mitochondrial function, induction of endoplasmic reticulum stress, reduction in the activities of the proteasome and autophagy, and the formation of neurotoxic aggregates. Here we examined whether perturbations in these cellular pathways in turn influence levels of misfolded SOD1 species, potentially amplifying neurotoxicity. For the study we used fibroblasts, which express SOD1 at physiological levels under regulation of the native promoter. The cells were derived from ALS patients expressing 9 different SOD1 mutants of widely variable molecular characteristics, as well as from patients carrying the GGGGCC-repeat-expansion in C9orf72 and from non-disease controls. A specific ELISA was used to quantify soluble, misfolded SOD1, and aggregated SOD1 was analysed by western blotting. Misfolded SOD1 was detected in all lines. Levels were found to be much lower in non-disease control and the non-SOD1 C9orf72 ALS lines. This enabled us to validate patient fibroblasts for use in subsequent perturbation studies. Mitochondrial inhibition, endoplasmic reticulum stress or autophagy inhibition did not affect soluble misfolded SOD1 and in most cases, detergent-resistant SOD1 aggregates were not detected. However, proteasome inhibition led to uniformly large increases in misfolded SOD1 levels in all cell lines and an increase in SOD1 aggregation in some. Thus the ubiquitin-proteasome pathway is a principal determinant of misfolded SOD1 levels in cells derived both from patients and controls and a decline in activity with aging could be one of the factors behind the mid-to late-life onset of inherited ALS.
  • Klimek, Ludger, et al. (författare)
  • In-vivo diagnostic test allergens in Europe : A call to action and proposal for recovery plan-An EAACI position paper
  • 2020
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 75:9, s. 2161-2169
  • Tidskriftsartikel (refereegranskat)abstract
    • Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high‐quality diagnostic allergens for in vivo diagnosis of IgE‐mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies.With the need to ensure the availability of high‐quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens.Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.
  • Lagrange, A. -M., et al. (författare)
  • A narrow, edge-on disk resolved around HD 106906 with SPHERE
  • 2016
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 586
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. HD 106906AB is the only young binary system so far around which a planet has been imaged and a debris disk has been shown to exist, thanks to a strong IR excess. As such, it represents a unique opportunity for studying the dynamics of young planetary systems. Aims. We aim at further investigating the close (tens of au scales) environment of the HD 106906AB system. Methods. We used the extreme adaptive-optics-fed, high-contrast imager SPHERE that has recently been installed on the VLT to observe HD 106906. Both the IRDIS imager and the Integral Field Spectrometer were used. Results. We discovered a highly inclined, ring-like disk at a distance of 65 au from the star. The disk shows a strong brightness asymmetry with respect to its semi-major axis. It shows a smooth outer edge, compatible with ejection of small grains by the stellar radiation pressure. We show furthermore that the planet's projected position is significantly above the PA of the disk. Given the determined disk inclination, it is not excluded, however, that the planet could still orbit within the disk plane if at a large separation (2000 3000 au). We identified several additional point sources in the SPHERE /IRDIS field of view that appear to be background objects. We compare this system with other debris disks sharing similarities, and we briefly discuss the present results in the framework of dynamical evolution.
  • Langlois, M., et al. (författare)
  • First scattered light detection of a nearly edge-on transition disk around the T Tauri star RY Lupi
  • 2018
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 614
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Transition disks are considered sites of ongoing planet formation, and their dust and gas distributions could be signposts of embedded planets. The transition disk around the T Tauri star RY Lup has an inner dust cavity and displays a strong silicate emission feature. Aims. Using high-resolution imaging we study the disk geometry, including non-axisymmetric features, and its surface dust grain, to gain a better understanding of the disk evolutionary process. Moreover, we search for companion candidates, possibly connected to the disk. Methods. We obtained high-contrast and high angular resolution data in the near-infrared with the VLT/SPHERE extreme adaptive optics instrument whose goal is to study the planet formation by detecting and characterizing these planets and their formation environments through direct imaging. We performed polarimetric imaging of the RY Lup disk with IRDIS (at 1.6 mu m), and obtained intensity images with the IRDIS dual-band imaging camera simultaneously with the IFS spectro-imager (0.9-1.3 mu m). Results. We resolved for the first time the scattered light from the nearly edge-on circumstellar disk around RY Lup, at projected separations in the 100 au range. The shape of the disk and its sharp features are clearly detectable at wavelengths ranging from 0.9 to 1.6 mu m. We show that the observed morphology can be interpreted as spiral arms in the disk. This interpretation is supported by in-depth numerical simulations. We also demonstrate that these features can be produced by one planet interacting with the disk. We also detect several point sources which are classified as probable background objects.
  • Ligi, R., et al. (författare)
  • Investigation of the inner structures around HD 169142 with VLT/SPHERE
  • 2018
  • Ingår i: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 473:2, s. 1774-1783
  • Tidskriftsartikel (refereegranskat)abstract
    • We present observations of the Herbig Ae star HD 169142 with the VLT/SPHERE instruments InfraRed Dual-band Imager and Spectrograph (IRDIS) (K1K2 and H2H3 bands) and the Integral Field Spectrograph (IFS) (Y, J and H bands). We detect several bright blobs at similar to 180 mas separation from the star, and a faint arc-like structure in the IFS data. Our reference differential imaging (RDI) data analysis also finds a bright ring at the same separation. We show, using a simulation based on polarized light data, that these blobs are actually part of the ring at 180 mas. These results demonstrate that the earlier detections of blobs in the H and K-S bands at these separations in Biller et al. as potential planet/substellar companions are actually tracing a bright ring with a Keplerian motion. Moreover, we detect in the images an additional bright structure at similar to 93 mas separation and position angle of 355 degrees, at a location very close to previous detections. It appears point-like in the YJ and K bands but is more extended in the H band. We also marginally detect an inner ring in the RDI data at similar to 100 mas. Follow-up observations are necessary to confirm the detection and the nature of this source and structure.
  • Maire, A-L, et al. (författare)
  • Hint of curvature in the orbital motion of the exoplanet 51 Eridani b using 3 yr of VLT/SPHERE monitoring
  • 2019
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 624
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The 51 Eridani system harbors a complex architecture with its primary star forming a hierarchical system with the binary GJ 3305AB at a projected separation of 2000 au, a giant planet orbiting the primary star at 13 au, and a low-mass debris disk around the primary star with possible cold and warm components inferred from the spectral energy distribution. Aims. We aim to better constrain the orbital parameters of the known giant planet. Methods. We monitored the system over three years from 2015 to 2018 with the Spectro-Polarimetric High-contrast Exoplanet REsearch (SPHERE) instrument at the Very Large Telescope (VET). Results. We measure an orbital motion for the planet of similar to 130 mas with a slightly decreasing separation (similar to 10 mas) and find a hint of curvature. This potential curvature is further supported at 3 sigma significance when including literature Gemini Planet Imager (GPI) astrometry corrected for calibration systematics. Fits of the SPHERE and GPI data using three complementary approaches provide broadly similar results. The data suggest an orbital period of 32(-9)(+17) yr (i.e., 12(-2)(+4), au in semi-major axis), an inclination of 133(-7)(+1)(4) deg, an eccentricity of 0.45(-0.15)(+0.10), and an argument of periastron passage of 87(-30)(+34) deg [mod 180 degrees]. The time at periastron passage and the longitude of node exhibit bimodal distributions because we do not yet detect whether the planet is accelerating or decelerating along its orbit. Given the inclinations of the orbit and of the stellar rotation axis (134-144 degrees), we infer alignment or misalignment within 18 degrees for the star-planet spin-orbit. Further astrometric monitoring in the next 3-4 yr is required to confirm at a higher significance the curvature in the motion of the planet, determine if the planet is accelerating or decelerating on its orbit, and further constrain its orbital parameters and the star-planet spin-orbit.
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