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- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)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. |
- Sungnak, W., et al.
(författare)
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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
- 2020
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Ingår i: Nature Medicine. - : Nature Research. - 1078-8956 .- 1546-170X. ; 26:5, s. 681-687
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Tidskriftsartikel (refereegranskat)abstract
- We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
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| 3. |
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| 4. |
- Sikkema, Lisa, et al.
(författare)
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An integrated cell atlas of the lung in health and disease
- 2023
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Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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| 5. |
- Diwekar, U., et al.
(författare)
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A perspective on the role of uncertainty in sustainability science and engineering
- 2021
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Ingår i: Resources, Conservation and Recycling. - : Elsevier BV. - 0921-3449 .- 1879-0658. ; 164
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Trans-Atlantic Research and Development Interchange on Sustainability Workshop (TARDIS) is a meeting on scientific topics related to sustainability. The 2019 workshop theme was "On the Role of Uncertainty in Managing the Earth for Global Sustainability." This paper presents the perspectives on this topic derived from talks and discussions at the 2019 TARDIS workshop. There are four kinds of uncertainties encountered in sustainability ranging from clear enough futures to true surprises. The current state-of-the-art in assessing and mitigating these uncertainties is discussed.
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| 8. |
- Weyhenmeyer, Gesa A., Professor, et al.
(författare)
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Global Lake Health in the Anthropocene : Societal Implications and Treatment Strategies
- 2024
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Ingår i: Earth's Future. - : American Geophysical Union (AGU). - 2328-4277. ; 12:4
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Forskningsöversikt (refereegranskat)abstract
- The world's 1.4 million lakes (>= 10 ha) provide many ecosystem services that are essential for human well-being; however, only if their health status is good. Here, we reviewed common lake health issues and classified them using a simple human health-based approach to outline that lakes are living systems that are in need of oxygen, clean water and a balanced energy and nutrient supply. The main reason for adopting some of the human health terminology for the lake health classification is to increase the awareness and understanding of global lake health issues. We show that lakes are exposed to various anthropogenic stressors which can result in many lake health issues, ranging from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning. Of particular concern for human well-being is the widespread lake drying, which is a severe circulatory issue with many cascading effects on lake health. We estimated that similar to 115,000 lakes evaporate twice as much water as they gain from direct precipitation, making them vulnerable to potential drying if inflowing waters follow the drying trend, putting more than 153 million people at risk who live in close vicinity to those lakes. Where lake health issues remain untreated, essential ecosystem services will decline or even vanish, posing a threat to the well-being of millions of people. We recommend coordinated multisectoral and multidisciplinary prevention and treatment strategies, which need to include a follow-up of the progress and an assessment of the resilience of lakes to intensifying threats. Priority should be given to implementing sewage water treatment, mitigating climate change, counteracting introductions of non-native species to lakes and decreasing uncontrolled anthropogenic releases of chemicals into the hydro-, bio-, and atmosphere. Lakes around the world come in an array of sizes, shapes and colors, each telling a unique story of geological history and environmental importance. When lakes are healthy they contribute to the achievement of the global sustainable development goals by providing many important ecosystem services. Lakes are, however, not always healthy. Here, it is shown that lakes can suffer from a large variety of health issues, ranging from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning. Without improved treatment strategies, many of the health issues may become chronic, affecting millions of people who are dependent on the ecosystem services from the lakes. To prevent and cure lakes from critical health conditions, strategies that are similar to those used in human healthcare should be applied: intervention and preventative actions before health problems occur, regular screening and early identification of lake health issues, and remediation and mitigation efforts at an appropriate scale, spanning from local to global. Anthropogenic stressors can cause lake health issues that range from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning Lake health varies geographically, with the highest risk of critical conditions occurring in densely populated low-income countries There is an urgent need to follow-up the progress of treatments and to make adjustments whenever needed
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| 9. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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