1. |
- Rajewsky, N., et al.
(author)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Journal article (peer-reviewed)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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2. |
- van Bragt, JJMH, et al.
(author)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Journal article (peer-reviewed)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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3. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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4. |
- Willemse, Jorke, et al.
(author)
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Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids
- 2022
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In: Biomaterials. - : Elsevier BV. - 0142-9612. ; 284
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Journal article (peer-reviewed)abstract
- Human cholangiocyte organoids are promising for regenerative medicine applications, such as repair of damaged bile ducts. However, organoids are typically cultured in mouse tumor-derived basement membrane extracts (BME), which is poorly defined, highly variable and limits the direct clinical applications of organoids in patients. Extracellular matrix (ECM)-derived hydrogels prepared from decellularized human or porcine livers are attractive alternative culture substrates. Here, the culture and expansion of human cholangiocyte organoids in liver ECM(LECM)-derived hydrogels is described. These hydrogels support proliferation of cholangiocyte organoids and maintain the cholangiocyte-like phenotype. The use of LECM hydrogels does not significantly alter the expression of selected genes or proteins, such as the cholangiocyte marker cytokeratin-7, and no species-specific effect is found between human or porcine LECM hydrogels. Proliferation rates of organoids cultured in LECM hydrogels are lower, but the differentiation capacity of the cholangiocyte organoids towards hepatocyte-like cells is not altered by the presence of tissue-specific ECM components. Moreover, human LECM extracts support the expansion of ICO in a dynamic culture set up without the need for laborious static culture of organoids in hydrogel domes. Liver ECM hydrogels can successfully replace tumor-derived BME and can potentially unlock the full clinical potential of human cholangiocyte organoids.
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5. |
- de Fouw, Jimmy, et al.
(author)
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A facultative mutualism facilitates European seagrass meadows
- 2023
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In: Ecography. - 0906-7590 .- 1600-0587. ; 2023:5
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Journal article (peer-reviewed)abstract
- Coastal ecosystem functioning often hinges on habitat-forming foundation species that engage in positive interactions (e.g. facilitation and mutualism) to reduce environmental stress. Seagrasses are important foundation species in coastal zones but are rapidly declining with losses typically linked to intensifying global change-related environmental stress. There is growing evidence that loss or disruption of positive interactions can amplify coastal ecosystem degradation as it compromises its stress mitigating capacity. Multiple recent studies highlight that seagrass can engage in a facultative mutualistic relationship with lucinid bivalves that alleviate sulphide toxicity. So far, however, the generality of this mutualism, and how its strength and relative importance depend on environmental conditions, remains to be investigated. Here we study the importance of the seagrass-lucinid mutualistic interaction on a continental-scale using a field survey across Europe. We found that the lucinid bivalve Loripes orbiculatus is associated with the seagrasses Zostera noltii and Zostera marina across a large latitudinal range. At locations where the average minimum temperature was above 1 °C, L. orbiculatus was present in 79% of the Zostera meadows; whereas, it was absent below this temperature. At locations above this minimum temperature threshold, mud content was the second most important determinant explaining the presence or absence of L. orbiculatus. Further analyses suggest that the presence of the lucinids have a positive effect on seagrass biomass by mitigating sulphide stress. Finally, results of a structural equation model (SEM) support the existence of a mutualistic feedback between L. orbiculatus and Z. noltii. We argue that this seagrass-lucinid mutualism should be more solidly integrated into management practices to improve seagrass ecosystem resilience to global change as well as the success of restoration efforts.
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6. |
- Alfaro-Cuello, M., et al.
(author)
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A Deep View into the Nucleus of the Sagittarius Dwarf Spheroidal Galaxy with MUSE. II. Kinematic Characterization of the Stellar Populations
- 2020
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 892:1
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Journal article (peer-reviewed)abstract
- The Sagittarius dwarf spheroidal galaxy is in an advanced stage of disruption but still hosts its nuclear star cluster (NSC), M54, at its center. In this paper, we present a detailed kinematic characterization of the three stellar populations present in M54: Young metal-rich (YMR); intermediate-age metal-rich (IMR); and old metal-poor (OMP), based on the spectra of 6500 individual M54 member stars extracted from a large Multi-Unit Spectroscopic Explorer (MUSE)/Very Large Telescope data set. We find that the OMP population is slightly flattened with a low amount of rotation (0.8 km s-1) and with a velocity dispersion that follows a Plummer profile. The YMR population displays a high amount of rotation (5 km s-1) and a high degree of flattening, with a lower and flat velocity dispersion profile. The IMR population shows a high but flat velocity dispersion profile, with some degree of rotation (2 km s-1). We complement our MUSE data with information from Gaia DR2 and confirm that the stars from the OMP and YMR populations are comoving in 3D space, suggesting that they are dynamically bound. While dynamical evolutionary effects (e.g., energy equipartition) are able to explain the differences in velocity dispersion between the stellar populations, the strong differences in rotation indicate different formation paths for the populations, as supported by an N-body simulation tailored to emulate the YMR-OMP system. This study provides additional evidence for the M54 formation scenario proposed in our previous work, where this NSC formed via GC accretion (OMP) and in situ formation from gas accretion in a rotationally supported disk (YMR).
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