| 1. |
- Wilkinson, John L., et al.
(författare)
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Pharmaceutical pollution of the world's rivers
- 2022
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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. - 0027-8424 .- 1091-6490. ; 119:8
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Tidskriftsartikel (refereegranskat)abstract
- Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.
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| 2. |
- Pan, W. H., et al.
(författare)
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Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development
- 2018
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The interplay of epigenetic processes and the intestinal microbiota may play an important role in intestinal development and homeostasis. Previous studies have established that the microbiota regulates a large proportion of the intestinal epithelial transcriptome in the adult host, but microbial effects on DNA methylation and gene expression during early postnatal development are still poorly understood. Here, we sought to investigate the microbial effects on DNA methylation and the transcriptome of intestinal epithelial cells (IECs) during postnatal development. Methods: We collected IECs from the small intestine of each of five 1-, 4-and 12 to 16-week-old mice representing the infant, juvenile, and adult states, raised either in the presence or absence of a microbiota. The DNA methylation profile was determined using reduced representation bisulfite sequencing (RRBS) and the epithelial transcriptome by RNA sequencing using paired samples from each individual mouse to analyze the link between microbiota, gene expression, and DNA methylation. Results: We found that microbiota-dependent and -independent processes act together to shape the postnatal development of the transcriptome and DNA methylation signatures of IECs. The bacterial effect on the transcriptome increased over time, whereas most microbiota-dependent DNA methylation differences were detected already early after birth. Microbiota-responsive transcripts could be attributed to stage-specific cellular programs during postnatal development and regulated gene sets involved primarily immune pathways and metabolic processes. Integrated analysis of the methylome and transcriptome data identified 126 genomic loci at which coupled differential DNA methylation and RNA transcription were associated with the presence of intestinal microbiota. We validated a subset of differentially expressed and methylated genes in an independent mouse cohort, indicating the existence of microbiota-dependent " functional" methylation sites which may impact on long-term gene expression signatures in IECs. Conclusions: Our study represents the first genome-wide analysis of microbiota-mediated effects on maturation of DNA methylation signatures and the transcriptional program of IECs after birth. It indicates that the gut microbiota dynamically modulates large portions of the epithelial transcriptome during postnatal development, but targets only a subset of microbially responsive genes through their DNA methylation status.
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| 3. |
- Zimmer, S, et al.
(författare)
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Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming
- 2016
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Ingår i: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 8:333, s. 333ra50-
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Tidskriftsartikel (refereegranskat)abstract
- The cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin facilitates atheroprotective mechanisms through oxysterol-mediated reprogramming of macrophages.
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| 4. |
- Kübler, André, et al.
(författare)
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Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterial proliferation.
- 2015
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 235:3, s. 431-444
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Tidskriftsartikel (refereegranskat)abstract
- Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP-1 are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model results in consistent progression of consolidation to human-like cavities (100% by day 28) with resultant bacillary burdens (>10(7) CFU/g) far greater than those found in matched granulomatous tissue (10(5) CFU/g). Using a novel, breath-hold computerized tomography scanning and image analysis protocol. We show that cavities develop rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue as estimated by changes in lung density during controlled pulmonary expansion (R(2) =0.6356, p < 0.0001). We demonstrated that the expression of interstitial collagenase (MMP-1) is specifically greater in cavitary compared to granulomatous lesions (p < 0.01), and that TIMP-3 significantly decreases at the cavity surface. Our findings demonstrate that an MMP-1/TIMP imbalance, is associated with the progression of consolidated regions to cavities containing very high bacterial burdens. Our model provided mechanistic insight, correlating with human disease at the pathological, microbiological and molecular levels,. It also provides a strategy to investigate therapeutics in the context of complex TB pathology. We used these findings to predict a MMP/TIMP balance in active TB; and confirmed this in human plasma, revealing the potential of MMP/TIMP levels as key components of a diagnostic matrix aimed at distinguishing active from latent TB (PPV=92.9%; 95%CI 66.1-99.8%, NPV=85.6%; 95%CI 77.0-91.9%).
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| 5. |
- Oestreich, M., et al.
(författare)
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hCoCena : horizontal integration and analysis of transcriptomics datasets
- 2022
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Ingår i: Bioinformatics. - : NLM (Medline). - 1367-4803 .- 1367-4811. ; 38:20, s. 4727-4734
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Tidskriftsartikel (refereegranskat)abstract
- MOTIVATION: Transcriptome-based gene co-expression analysis has become a standard procedure for structured and contextualized understanding and comparison of different conditions and phenotypes. Since large study designs with a broad variety of conditions are costly and laborious, extensive comparisons are hindered when utilizing only a single dataset. Thus, there is an increased need for tools that allow the integration of multiple transcriptomic datasets with subsequent joint analysis, which can provide a more systematic understanding of gene co-expression and co-functionality within and across conditions. To make such an integrative analysis accessible to a wide spectrum of users with differing levels of programming expertise it is essential to provide user-friendliness and customizability as well as thorough documentation. RESULTS: This article introduces horizontal CoCena (hCoCena: horizontal construction of co-expression networks and analysis), an R-package for network-based co-expression analysis that allows the analysis of a single transcriptomic dataset as well as the joint analysis of multiple datasets. With hCoCena, we provide a freely available, user-friendly and adaptable tool for integrative multi-study or single-study transcriptomics analyses alongside extensive comparisons to other existing tools. AVAILABILITY AND IMPLEMENTATION: The hCoCena R-package is provided together with R Markdowns that implement an exemplary analysis workflow including extensive documentation and detailed descriptions of data structures and objects. Such efforts not only make the tool easy to use but also enable the seamless integration of user-written scripts and functions into the workflow, creating a tool that provides a clear design while remaining flexible and highly customizable. The package and additional information including an extensive Wiki are freely available on GitHub: https://github.com/MarieOestreich/hCoCena. The version at the time of writing has been added to Zenodo under the following link: https://doi.org/10.5281/zenodo.6911782. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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| 6. |
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| 7. |
- von Salzen, Knut, et al.
(författare)
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Clean air policies are key for successfully mitigating Arctic warming
- 2022
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Ingår i: Communications Earth & Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- A tighter integration of modeling frameworks for climate and air quality is urgently needed to assess the impacts of clean air policies on future Arctic and global climate. We combined a new model emulator and comprehensive emissions scenarios for air pollutants and greenhouse gases to assess climate and human health co-benefits of emissions reductions. Fossil fuel use is projected to rapidly decline in an increasingly sustainable world, resulting in far-reaching air quality benefits. Despite human health benefits, reductions in sulfur emissions in a more sustainable world could enhance Arctic warming by 0.8 °C in 2050 relative to the 1995–2014, thereby offsetting climate benefits of greenhouse gas reductions. Targeted and technically feasible emissions reduction opportunities exist for achieving simultaneous climate and human health co-benefits. It would be particularly beneficial to unlock a newly identified mitigation potential for carbon particulate matter, yielding Arctic climate benefits equivalent to those from carbon dioxide reductions by 2050.
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