| 1. |
- Barrado, David, et al.
(författare)
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15NH3 in the atmosphere of a cool brown dwarf
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 624:7991, s. 263-266
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Tidskriftsartikel (refereegranskat)abstract
- Brown dwarfs serve as ideal laboratories for studying the atmospheres of giant exoplanets on wide orbits, as the governing physical and chemical processes within them are nearly identical. Understanding the formation of gas-giant planets is challenging, often involving the endeavour to link atmospheric abundance ratios, such as the carbon-to-oxygen (C/O) ratio, to formation scenarios. However, the complexity of planet formation requires further tracers, as the unambiguous interpretation of the measured C/O ratio is fraught with complexity. Isotope ratios, such as deuterium to hydrogen and 14N/15N, offer a promising avenue to gain further insight into this formation process, mirroring their use within the Solar System. For exoplanets, only a handful of constraints on 12C/13C exist, pointing to the accretion of 13C-rich ice from beyond the CO iceline of the disks. Here we report on the mid-infrared detection of the 14NH3 and 15NH3 isotopologues in the atmosphere of a cool brown dwarf with an effective temperature of 380 K in a spectrum taken with the Mid-Infrared Instrument (MIRI) of JWST. As expected, our results reveal a 14N/15N value consistent with star-like formation by gravitational collapse, demonstrating that this ratio can be accurately constrained. Because young stars and their planets should be more strongly enriched in the 15N isotope, we expect that 15NH3 will be detectable in several cold, wide-separation exoplanets.
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| 2. |
- Dyrek, Achrène, et al.
(författare)
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SO2, silicate clouds, but no CH4 detected in a warm Neptune
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 51-54
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Tidskriftsartikel (refereegranskat)abstract
- WASP-107b is a warm (approximately 740 K) transiting planet with a Neptune-like mass of roughly 30.5 M⊕ and Jupiter-like radius of about 0.94 RJ (refs. 1,2), whose extended atmosphere is eroding3. Previous observations showed evidence for water vapour and a thick, high-altitude condensate layer in the atmosphere of WASP-107b (refs. 4,5). Recently, photochemically produced sulfur dioxide (SO2) was detected in the atmosphere of a hot (about 1,200 K) Saturn-mass planet from transmission spectroscopy near 4.05 μm (refs. 6,7), but for temperatures below about 1,000 K, sulfur is predicted to preferably form sulfur allotropes instead of SO2 (refs. 8,9,10). Here we report the 9σ detection of two fundamental vibration bands of SO2, at 7.35 μm and 8.69 μm, in the transmission spectrum of WASP-107b using the Mid-Infrared Instrument (MIRI) of JWST. This discovery establishes WASP-107b as the second irradiated exoplanet with confirmed photochemistry, extending the temperature range of exoplanets exhibiting detected photochemistry from about 1,200 K down to about 740 K. Furthermore, our spectral analysis reveals the presence of silicate clouds, which are strongly favoured (around 7σ) over simpler cloud set-ups. Furthermore, water is detected (around 12σ) but methane is not. These findings provide evidence of disequilibrium chemistry and indicate a dynamically active atmosphere with a super-solar metallicity.
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| 3. |
- Foley, Daniel J., et al.
(författare)
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Phenotyping Reveals Targets of a Pseudo-Natural-Product Autophagy Inhibitor
- 2020
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Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 59:30
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Tidskriftsartikel (refereegranskat)abstract
- Pseudo-natural-product (NP) design combines natural product fragments to provide unprecedented NP-inspired compounds not accessible by biosynthesis, but endowed with biological relevance. Since the bioactivity of pseudo-NPs may be unprecedented or unexpected, they are best evaluated in target agnostic cell-based assays monitoring entire cellular programs or complex phenotypes. Here, the Cinchona alkaloid scaffold was merged with the indole ring system to synthesize indocinchona alkaloids by Pd-catalyzed annulation. Exploration of indocinchona alkaloid bioactivities in phenotypic assays revealed a novel class of azaindole-containing autophagy inhibitors, the azaquindoles. Subsequent characterization of the most potent compound, azaquindole-1, in the morphological cell painting assay, guided target identification efforts. In contrast to the parent Cinchona alkaloids, azaquindoles selectively inhibit starvation- and rapamycin-induced autophagy by targeting the lipid kinase VPS34.
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| 4. |
- Grinberg, Marianna, et al.
(författare)
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Toxicogenomics directory of chemically exposed human hepatocytes
- 2014
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 1432-0738 .- 0340-5761. ; 88:12, s. 2261-2287
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Tidskriftsartikel (refereegranskat)abstract
- A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. However, a systematic directory summarizing key features of chemically influenced genes in human hepatocytes is not yet available. To bridge this gap, we used the Open TG-GATES database with Affymetrix files of cultivated human hepatocytes incubated with chemicals, further sets of gene array data with hepatocytes from human donors generated in this study, and publicly available genome-wide datasets of human liver tissue from patients with non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular cancer (HCC). After a curation procedure, expression data of 143 chemicals were included into a comprehensive biostatistical analysis. The results are summarized in the publicly available toxicotranscriptomics directory (http://wiki.toxbank.net/toxicogenomics-map/) which provides information for all genes whether they are up- or downregulated by chemicals and, if yes, by which compounds. The directory also informs about the following key features of chemically influenced genes: (1) Stereotypical stress response. When chemicals induce strong expression alterations, this usually includes a complex but highly reproducible pattern named 'stereotypical response.' On the other hand, more specific expression responses exist that are induced only by individual compounds or small numbers of compounds. The directory differentiates if the gene is part of the stereotypical stress response or if it represents a more specific reaction. (2) Liver disease-associated genes. Approximately 20 % of the genes influenced by chemicals are up- or downregulated, also in liver disease. Liver disease genes deregulated in cirrhosis, HCC, and NASH that overlap with genes of the aforementioned stereotypical chemical stress response include CYP3A7, normally expressed in fetal liver; the phase II metabolizing enzyme SULT1C2; ALDH8A1, known to generate the ligand of RXR, one of the master regulators of gene expression in the liver; and several genes involved in normal liver functions: CPS1, PCK1, SLC2A2, CYP8B1, CYP4A11, ABCA8, and ADH4. (3) Unstable baseline genes. The process of isolating and the cultivation of hepatocytes was sufficient to induce some stress leading to alterations in the expression of genes, the so-called unstable baseline genes. (4) Biological function. Although more than 2,000 genes are transcriptionally influenced by chemicals, they can be assigned to a relatively small group of biological functions, including energy and lipid metabolism, inflammation and immune response, protein modification, endogenous and xenobiotic metabolism, cytoskeletal organization, stress response, and DNA repair. In conclusion, the introduced toxicotranscriptomics directory offers a basis for a rationale choice of candidate genes for biomarker evaluation studies and represents an easy to use source of background information on chemically influenced genes.
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| 5. |
- Habicher, Judith, et al.
(författare)
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Chondroitin/dermatan sulfate glycosyltransferase genes are essential for craniofacial development
- 2022
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 18:2
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Tidskriftsartikel (refereegranskat)abstract
- Chondroitin/dermatan sulfate (CS/DS) proteoglycans are indispensable for animal development and homeostasis but the large number of enzymes involved in their biosynthesis have made CS/DS function a challenging problem to study genetically. In our study, we generated loss-of-function alleles in zebrafish genes encoding CS/DS biosynthetic enzymes and characterized the effect on development in single and double mutants. Homozygous mutants in chsy1, csgalnact1a, csgalnat2, chpfa, ust and chst7, respectively, develop to adults. However, csgalnact1a-/- fish develop distinct craniofacial defects while the chsy1-/- skeletal phenotype is milder and the remaining mutants display no gross morphological abnormalities. These results suggest a high redundancy for the CS/DS biosynthetic enzymes and to further reduce CS/DS biosynthesis we combined mutant alleles. The craniofacial phenotype is further enhanced in csgalnact1a-/-;chsy1-/- adults and csgalnact1a-/-;csgalnact2-/- larvae. While csgalnact1a-/-;csgalnact2-/- was the most affected allele combination in our study, CS/DS is still not completely abolished. Transcriptome analysis of chsy1-/-, csgalnact1a-/- and csgalnact1a-/-;csgalnact2-/- larvae revealed that the expression had changed in a similar way in the three mutant lines but no differential expression was found in any of fifty GAG biosynthesis enzymes identified. Thus, zebrafish larvae do not increase transcription of GAG biosynthesis genes as a consequence of decreased CS/DS biosynthesis. The new zebrafish lines develop phenotypes similar to clinical characteristics of several human congenital disorders making the mutants potentially useful to study disease mechanisms and treatment.
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| 6. |
- Hertel, Stefan, et al.
(författare)
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Tailoring the graphene/silicon carbide interface for monolithic wafer-scale electronics
- 2012
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Graphene is an outstanding electronic material, predicted to have a role in post-silicon electronics. However, owing to the absence of an electronic bandgap, graphene switching devices with high on/off ratio are still lacking. Here in the search for a comprehensive concept for wafer-scale graphene electronics, we present a monolithic transistor that uses the entire material system epitaxial graphene on silicon carbide (0001). This system consists of the graphene layer with its vanishing energy gap, the underlying semiconductor and their common interface. The graphene/semiconductor interfaces are tailor-made for ohmic as well as for Schottky contacts side-by-side on the same chip. We demonstrate normally on and normally off operation of a single transistor with on/off ratios exceeding 10 4 and no damping at megahertz frequencies. In its simplest realization, the fabrication process requires only one lithography step to build transistors, diodes, resistors and eventually integrated circuits without the need of metallic interconnects.
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| 7. |
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HumaNetten Nr 48, våren 2022 : Educational Linguistics
- 2022
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- Under pågående pandemi och uppseendeväckande världshändelser fortsätter HumaNetten sin mission som spridare av humaniora i ordets bredare bemärkelse. Linnéuniversitetet har turen att ha en kader av driftiga språkforskare som tagit initiativet till flera artiklar och temanummer genom åren. I detta vårnummer har vi glädjen att se Daniel Ocic Ihrmark, Sergej Ivanov och Christian Waldmann som gästredaktörer för ett tema om Educational Linguistics, vilket kan översättas som utbildningsinriktad språkvetenskap. Det handlar om relationen mellan språk, tanke, kommunikation och kunskapsutveckling inom olika skol- och utbildnings-nivåer. Det är med andra ord en högst samhällsrelevant inriktning som förstärker bilden av humanioras roll i det moderna samhället. Den forskningsmiljö som utvecklats vid Linnéuniversitetet sammanför språkvetare och språkdidaktiker inom de olika språk som undervisas om vid universitetet. I det här temanumret presenteras tio studier med nya perspektiv på Educational Linguistics. Vi ska inte ge en detaljerad översikt över innehållet på denna plats eftersom gästredaktörerna ger en närmare presentation av temat i sin separata introduktion. Utanför huvudtemat publicerar Sara Snoder, doktorand i språkdidaktik, sin studie ”Utrymmen för flerspråkighet – funktionella aspekter av flerspråkiga låg- och mellanstadie-lärares språkliga praktiker”, där hon med en etnografisk ansats söker vinna ny kunskap om flerspråkig användning i skolundervisning.För redaktionens räkningHans Hägerdal
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| 8. |
- Krebs, Alice, et al.
(författare)
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Template for the Description of Cell-Based Toxicological Test Methods to Allow Evaluation and Regulatory Use of the Data
- 2019
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Ingår i: Altex. - : ALTEX Edition. - 1868-596X .- 1868-8551. ; 36:4, s. 682-699
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Only few cell-based test methods are described by Organisation for Economic Co-operation and Development (OECD) test guidelines or other regulatory references (e.g., the European Pharmacopoeia). The majority of toxicity tests still falls into the category of non-guideline methods. Data from these tests may nevertheless be used to support regulatory decisions or to guide strategies to assess compounds (e.g., drugs, agrochemicals) during research and development if they fulfill basic requirements concerning their relevance, reproducibility and predictivity. Only a method description of sufficient clarity and detail allows interpretation and use of the data. To guide regulators faced with increasing amounts of data from non-guideline studies, the OECD formulated Guidance Document 211 (GD211) on method documentation for the purpose of safety assessment. As GD211 is targeted mainly at regulators, it leaves scientists less familiar with regulation uncertain as to what level of detail is required and how individual questions should be answered. Moreover, little attention was given to the description of the test system (i.e., cell culture) and the steps leading to it being established in the guidance. To address these issues, an annotated toxicity test method template (ToxTemp) was developed (i) to fulfill all requirements of GD211, (ii) to guide the user concerning the types of answers and detail of information required, (iii) to include acceptance criteria for test elements, and (iv) to define the cells sufficiently and transparently. The fully annotated ToxTemp is provided here, together with reference to a database containing exemplary descriptions of more than 20 cell-based tests.
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| 9. |
- Laraia, Luca, et al.
(författare)
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Image-Based Morphological Profiling Identifies a Lysosomotropic, Iron-Sequestering Autophagy Inhibitor
- 2020
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Ingår i: Angewandte Chemie International Edition. - : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 59, s. 5721-5729
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Tidskriftsartikel (refereegranskat)abstract
- Chemical proteomics is widely applied in small-molecule target identification. However, in general it does not identify non-protein small-molecule targets, and thus, alternative methods for target identification are in high demand. We report the discovery of the autophagy inhibitor autoquin and the identification of its molecular mode of action using image-based morphological profiling in the cell painting assay. A compound-induced fingerprint representing changes in 579 cellular parameters revealed that autoquin accumulates in lysosomes and inhibits their fusion with autophagosomes. In addition, autoquin sequesters Fe2+ in lysosomes, resulting in an increase of lysosomal reactive oxygen species and ultimately cell death. Such a mechanism of action would have been challenging to unravel by current methods. This work demonstrates the potential of the cell painting assay to deconvolute modes of action of small molecules, warranting wider application in chemical biology.
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| 10. |
- Mocsar, Gabor, et al.
(författare)
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MHC I Expression Regulates Co-clustering and Mobility of Interleukin-2 and-15 Receptors in T Cells
- 2016
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Ingår i: Biophysical Journal. - : Cell Press. - 0006-3495 .- 1542-0086. ; 111:1, s. 100-112
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Tidskriftsartikel (refereegranskat)abstract
- MHC glycoproteins form supramolecular clusters with interleukin-2 and -15 receptors in lipid rafts of T cells. The role of highly expressed MHC I in maintaining these clusters is unknown. We knocked down MHC I in FT7.10 human T cells, and studied protein clustering at two hierarchic levels: molecular aggregations and mobility by Forster resonance energy transfer and fluorescence correlation spectroscopy; and segregation into larger domains or superclusters by superresolution stimulated emission depletion microscopy. Fluorescence correlation spectroscopy-based molecular brightness analysis revealed that the studied molecules diffused as tight aggregates of several proteins of a kind. Knockdown reduced the number of MHC I containing molecular aggregates and their average MHC I content, and decreased the heteroassociation of MHC I with IL-2R alpha/IL-15R alpha. The mobility of not only MHC I but also that of IL-2R alpha/IL-15R alpha increased, corroborating the general size decrease of tight aggregates. A multifaceted analysis of stimulated emission depletion images revealed that the diameter of MHC I superclusters diminished from 400-600 to 200-300 nm, whereas those of IL-2R alpha/IL-15R alpha hardly changed. MHC I and IL-2R alpha/IL-15R alpha colocalized with GM1 ganglioside-rich lipid rafts, but MHC I clusters retracted to smaller subsets of GM1-and IL-2R alpha/IL-15R alpha-rich areas upon knockdown. Our results prove that changes in expression level may significantly alter the organization and mobility of interacting membrane proteins.
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