| 1. |
- d'Alessandro, Elisa, et al.
(författare)
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Thrombo-Inflammation in Cardiovascular Disease : An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis
- 2020
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 538-564
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Tidskriftsartikel (refereegranskat)abstract
- Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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| 2. |
- Bley, Hanna, et al.
(författare)
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Proximity labeling of host factor ANXA3 in HCV infection reveals a novel LARP1 function in viral entry
- 2024
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Ingår i: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 300:5
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis C virus (HCV) infection is tightly connected to the lipid metabolism with lipid droplets (LDs) serving as assembly sites for progeny virions. A previous LD proteome analysis identified annexin A3 (ANXA3) as an important HCV host factor that is enriched at LDs in infected cells and required for HCV morphogenesis. To further characterize ANXA3 function in HCV, we performed proximity labeling using ANXA3-BioID2 as bait in HCV-infected cells. Two of the top proteins identified proximal to ANXA3 during HCV infection were the La-related protein 1 (LARP1) and the ADP ribosylation factor-like protein 8B (ARL8B), both of which have been previously described to act in HCV particle production. In follow-up experiments, ARL8B functioned as a pro-viral HCV host factor without localizing to LDs and thus likely independent of ANXA3. In contrast, LARP1 interacts with HCV core protein in an RNA-dependent manner and is translocated to LDs by core protein. Knockdown of LARP1 decreased HCV spreading without altering HCV RNA replication or viral titers. Unexpectedly, entry of HCV particles and E1/E2-pseudotyped lentiviral particles was reduced by LARP1 depletion, whereas particle production was not altered. Using a recombinant vesicular stomatitis virus (VSV)ΔG entry assay, we showed that LARP1 depletion also decreased entry of VSV with VSV, MERS, and CHIKV glycoproteins. Therefore, our data expand the role of LARP1 as an HCV host factor that is most prominently involved in the early steps of infection, likely contributing to endocytosis of viral particles through the pleiotropic effect LARP1 has on the cellular translatome.
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| 3. |
- Bülck, Cynthia, et al.
(författare)
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Proteolytic processing of galectin-3 by meprin metalloproteases is crucial for host-microbiome homeostasis
- 2023
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 9:13
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Tidskriftsartikel (refereegranskat)abstract
- The metalloproteases meprin α and meprin β are highly expressed in the healthy gut but significantly decreased in inflammatory bowel disease, implicating a protective role in mucosal homeostasis. In the colon, meprin α and meprin β form covalently linked heterodimers tethering meprin α to the plasma membrane, therefore presenting dual proteolytic activity in a unique enzyme complex. To unravel its function, we applied N-terminomics and identified galectin-3 as the major intestinal substrate for meprin α/β heterodimers. Galectin-3-deficient and meprin α/β double knockout mice show similar alterations in their microbiome in comparison to wild-type mice. We further demonstrate that meprin α/β heterodimers differentially process galectin-3 upon bacterial infection, in germ-free, conventionally housed (specific pathogen-free), or wildling mice, which in turn regulates the bacterial agglutination properties of galectin-3. Thus, the constitutive cleavage of galectin-3 by meprin α/β heterodimers may play a key role in colon host-microbiome homeostasis.
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| 4. |
- Guedes Salgado, Marco, et al.
(författare)
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Legume NCRs and nodule-specific defensins of actinorhizal plants-Do they share a common origin?
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- The actinorhizal plant Datisca glomerata (Datiscaceae, Cucurbitales) establishes a root nodule symbiosis with actinobacteria from the earliest branching symbiotic Frankia clade. A subfamily of a gene family encoding nodule-specific defensin-like cysteine-rich peptides is highly expressed in D. glomerata nodules. Phylogenetic analysis of the defensin domain showed that these defensin-like peptides share a common evolutionary origin with nodulespecific defensins from actinorhizal Fagales and with nodule-specific cysteine-rich peptides (NCRs) from legumes. In this study, the family member with the highest expression levels, DgDef1, was characterized. Promoter-GUS studies on transgenic hairy roots showed expression in the early stage of differentiation of infected cells, and transient expression in the nodule apex. DgDef1 contains an N-terminal signal peptide and a C-terminal acidic domain which are likely involved in subcellular targeting and do not affect peptide activity. In vitro studies with E. coli and Sinorhizobium meliloti 1021 showed that the defensin domain of DgDef1 has a cytotoxic effect, leading to membrane disruption with 50% lethality for S. meliloti 1021 at 20.8 μM. Analysis of the S. meliloti 1021 transcriptome showed that, at sublethal concentrations, DgDef1 induced the expression of terminal quinol oxidases, which are associated with the oxidative stress response and are also expressed during symbiosis. Overall, the changes induced by DgDef1 are reminiscent of those of some legume NCRs, suggesting that nodule-specific defensin-like peptides were part of the original root nodule toolkit and were subsequently lost in most symbiotic legumes, while being maintained in the actinorhizal lineages.
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| 5. |
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| 6. |
- Kienzle, J., et al.
(författare)
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Toward model-driven sustainability evaluation
- 2020
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Ingår i: Communications of the ACM. - : Association for Computing Machinery (ACM). - 0001-0782 .- 1557-7317. ; 63:3, s. 80-91
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Forskningsöversikt (refereegranskat)abstract
- Exploring the vision of a model-based framework that may enable broader engagement with and informed decision making about sustainability issues.
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| 7. |
- Kraxberger, Florian, et al.
(författare)
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On the Alignment of Acoustic and Coupled Mechanic-Acoustic Eigenmodes in Phonation by Supraglottal Duct Variations
- 2023
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Ingår i: Bioengineering. - : MDPI AG. - 2306-5354. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Sound generation in human phonation and the underlying fluid–structure–acoustic interaction that describes the sound production mechanism are not fully understood. A previous experimental study, with a silicone made vocal fold model connected to a straight vocal tract pipe of fixed length, showed that vibroacoustic coupling can cause a deviation in the vocal fold vibration frequency. This occurred when the fundamental frequency of the vocal fold motion was close to the lowest acoustic resonance frequency of the pipe. What is not fully understood is how the vibroacoustic coupling is influenced by a varying vocal tract length. Presuming that this effect is a pure coupling of the acoustical effects, a numerical simulation model is established based on the computation of the mechanical-acoustic eigenvalue. With varying pipe lengths, the lowest acoustic resonance frequency was adjusted in the experiments and so in the simulation setup. In doing so, the evolution of the vocal folds’ coupled eigenvalues and eigenmodes is investigated, which confirms the experimental findings. Finally, it was shown that for normal phonation conditions, the mechanical mode is the most efficient vibration pattern whenever the acoustic resonance of the pipe (lowest formant) is far away from the vocal folds’ vibration frequency. Whenever the lowest formant is slightly lower than the mechanical vocal fold eigenfrequency, the coupled vocal fold motion pattern at the formant frequency dominates.
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| 8. |
- Kreisz, Philipp, et al.
(författare)
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S1 basic leucine zipper transcription factors shape plant architecture by controlling C/N partitioning to apical and lateral organs
- 2024
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 121:7
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Tidskriftsartikel (refereegranskat)abstract
- Plants tightly control growth of their lateral organs, which led to the concept of apical dominance. However, outgrowth of the dormant lateral primordia is sensitive to the plant's nutritional status, resulting in an immense plasticity in plant architecture. While the impact of hormonal regulation on apical dominance is well characterized, the prime importance of sugar signaling to unleash lateral organ formation has just recently emerged. Here, we aimed to identify transcriptional regulators, which control the trade-off between growth of apical versus lateral organs. Making use of locally inducible gain-of-function as well as single and higher-order loss-of-function approaches of the sugar-responsive S1-basic-leucine-zipper (S1-bZIP) transcription factors, we disclosed their largely redundant function in establishing apical growth dominance. Consistently, comprehensive phenotypical and analytical studies of S1-bZIP mutants show a clear shift of sugar and organic nitrogen (N) allocation from apical to lateral organs, coinciding with strong lateral organ outgrowth. Tissue-specific transcriptomics reveal specific clade III SWEET sugar transporters, crucial for long-distance sugar transport to apical sinks and the glutaminase GLUTAMINE AMIDO-TRANSFERASE 1_2.1, involved in N homeostasis, as direct S1-bZIP targets, linking the architectural and metabolic mutant phenotypes to downstream gene regulation. Based on these results, we propose that S1-bZIPs control carbohydrate (C) partitioning from source leaves to apical organs and tune systemic N supply to restrict lateral organ formation by C/N depletion. Knowledge of the underlying mechanisms controlling plant C/N partitioning is of pivotal importance for breeding strategies to generate plants with desired architectural and nutritional characteristics.
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| 9. |
- Kristan, Matej, et al.
(författare)
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The first visual object tracking segmentation VOTS2023 challenge results
- 2023
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Ingår i: 2023 IEEE/CVF International conference on computer vision workshops (ICCVW). - : Institute of Electrical and Electronics Engineers Inc.. - 9798350307443 - 9798350307450 ; , s. 1788-1810
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking Segmentation VOTS2023 challenge is the eleventh annual tracker benchmarking activity of the VOT initiative. This challenge is the first to merge short-term and long-term as well as single-target and multiple-target tracking with segmentation masks as the only target location specification. A new dataset was created; the ground truth has been withheld to prevent overfitting. New performance measures and evaluation protocols have been created along with a new toolkit and an evaluation server. Results of the presented 47 trackers indicate that modern tracking frameworks are well-suited to deal with convergence of short-term and long-term tracking and that multiple and single target tracking can be considered a single problem. A leaderboard, with participating trackers details, the source code, the datasets, and the evaluation kit are publicly available at the challenge website1
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| 10. |
- McGrath, Matthew J., et al.
(författare)
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The consolidated European synthesis of CO2 emissions and removals for the European Union and United Kingdom : 1990-2020
- 2023
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Ingår i: Earth System Science Data. - 1866-3508. ; 15:10, s. 4295-4370
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Tidskriftsartikel (refereegranskat)abstract
- Quantification of land surface-atmosphere fluxes of carbon dioxide (CO2) and their trends and uncertainties is essential for monitoring progress of the EU27+UK bloc as it strives to meet ambitious targets determined by both international agreements and internal regulation. This study provides a consolidated synthesis of fossil sources (CO2 fossil) and natural (including formally managed ecosystems) sources and sinks over land (CO2 land) using bottom-up (BU) and top-down (TD) approaches for the European Union and United Kingdom (EU27+UK), updating earlier syntheses (Petrescu et al., 2020, 2021). Given the wide scope of the work and the variety of approaches involved, this study aims to answer essential questions identified in the previous syntheses and understand the differences between datasets, particularly for poorly characterized fluxes from managed and unmanaged ecosystems. The work integrates updated emission inventory data, process-based model results, data-driven categorical model results, and inverse modeling estimates, extending the previous period 1990-2018 to the year 2020 to the extent possible. BU and TD products are compared with the European national greenhouse gas inventory (NGHGI) reported by parties including the year 2019 under the United Nations Framework Convention on Climate Change (UNFCCC). The uncertainties of the EU27+UK NGHGI were evaluated using the standard deviation reported by the EU member states following the guidelines of the Intergovernmental Panel on Climate Change (IPCC) and harmonized by gap-filling procedures. Variation in estimates produced with other methods, such as atmospheric inversion models (TD) or spatially disaggregated inventory datasets (BU), originate from within-model uncertainty related to parameterization as well as structural differences between models. By comparing the NGHGI with other approaches, key sources of differences between estimates arise primarily in activities. System boundaries and emission categories create differences in CO2 fossil datasets, while different land use definitions for reporting emissions from land use, land use change, and forestry (LULUCF) activities result in differences for CO2 land. The latter has important consequences for atmospheric inversions, leading to inversions reporting stronger sinks in vegetation and soils than are reported by the NGHGI. For CO2 fossil emissions, after harmonizing estimates based on common activities and selecting the most recent year available for all datasets, the UNFCCC NGHGI for the EU27+UK accounts for 926g±g13gTggCgyr-1, while eight other BU sources report a mean value of 948 [937,961]gTggCgyr-1 (25th, 75th percentiles). The sole top-down inversion of fossil emissions currently available accounts for 875gTggC in this same year, a value outside the uncertainty of both the NGHGI and bottom-up ensemble estimates and for which uncertainty estimates are not currently available. For the net CO2 land fluxes, during the most recent 5-year period including the NGHGI estimates, the NGHGI accounted for -91g±g32gTggCgyr-1, while six other BU approaches reported a mean sink of -62 [-117,-49]gTggCgyr-1, and a 15-member ensemble of dynamic global vegetation models (DGVMs) reported -69 [-152,-5]gTggCgyr-1. The 5-year mean of three TD regional ensembles combined with one non-ensemble inversion of -73gTggCgyr-1 has a slightly smaller spread (0th-100th percentiles of [-135,+45]gTggCgyr-1), and it was calculated after removing net land-atmosphere CO2 fluxes caused by lateral transport of carbon (crop trade, wood trade, river transport, and net uptake from inland water bodies), resulting in increased agreement with the NGHGI and bottom-up approaches. Results at the category level (Forest Land, Cropland, Grassland) generally show good agreement between the NGHGI and category-specific models, but results for DGVMs are mixed. Overall, for both CO2 fossil and net CO2 land fluxes, we find that current independent approaches are consistent with the NGHGI at the scale of the EU27+UK. We conclude that CO2 emissions from fossil sources have decreased over the past 30 years in the EU27+UK, while land fluxes are relatively stable: positive or negative trends larger (smaller) than 0.07 (-0.61)gTggCgyr-2 can be ruled out for the NGHGI. In addition, a gap on the order of 1000gTggCgyr-1 between CO2 fossil emissions and net CO2 uptake by the land exists regardless of the type of approach (NGHGI, TD, BU), falling well outside all available estimates of uncertainties. However, uncertainties in top-down approaches to estimate CO2 fossil emissions remain uncharacterized and are likely substantial, in addition to known uncertainties in top-down estimates of the land fluxes. The data used to plot the figures are available at 10.5281/zenodo.8148461 (McGrath et al., 2023).
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