| 1. |
- Lundquist, Patrik, et al.
(författare)
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Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat
- 2022
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:9, s. 14210-14229
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Tidskriftsartikel (refereegranskat)abstract
- Peptide drugs and biologics provide opportunities for treatments of many diseases. However, due to their poor stability and permeability in the gastrointestinal tract, the oral bioavailability of peptide drugs is negligible. Nanoparticle formulations have been proposed to circumvent these hurdles, but systemic exposure of orally administered peptide drugs has remained elusive. In this study, we investigated the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles displaying differing composition and surface characteristics, developed within the pan-European consortium TRANS-INT. The transport mechanisms and major barriers to nanoparticle permeability were investigated in freshly isolated human jejunal tissue. Cytokine release profiles and standard toxicity markers indicated that the nanoparticles were nontoxic. Three out of four nanoparticles displayed pronounced binding to the mucus layer and did not reach the epithelium. One nanoparticle composed of a mucus inert shell and cell-penetrating octarginine (ENCP), showed significant uptake by the intestinal epithelium corresponding to 28 ± 9% of the administered nanoparticle dose, as determined by super-resolution microscopy. Only a small fraction of nanoparticles taken up by epithelia went on to be transcytosed via a dynamin-dependent process. In situ studies in intact rat jejunal loops confirmed the results from human tissue regarding mucus binding, epithelial uptake, and negligible insulin bioavailability. In conclusion, while none of the four arginine-rich nanoparticles supported systemic insulin delivery, ENCP displayed a consistently high uptake along the intestinal villi. It is proposed that ENCP should be further investigated for local delivery of therapeutics to the intestinal mucosa.
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| 2. |
- Artursson, Per, et al.
(författare)
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A new opening for orally taken peptide drugs
- 2020
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Ingår i: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 4:1, s. 12-13
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Negatively charged nanoparticles of about 50 nm in size permit the oral delivery of insulin and other peptide drugs by temporally enhancing the permeability of the intestinal wall.
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| 3. |
- Chapman, Elizabeth A., et al.
(författare)
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Perennials as Future Grain Crops : Opportunities and Challenges
- 2022
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Perennial grain crops could make a valuable addition to sustainable agriculture, potentially even as an alternative to their annual counterparts. The ability of perennials to grow year after year significantly reduces the number of agricultural inputs required, in terms of both planting and weed control, while reduced tillage improves soil health and on-farm biodiversity. Presently, perennial grain crops are not grown at large scale, mainly due to their early stages of domestication and current low yields. Narrowing the yield gap between perennial and annual grain crops will depend on characterizing differences in their life cycles, resource allocation, and reproductive strategies and understanding the trade-offs between annualism, perennialism, and yield. The genetic and biochemical pathways controlling plant growth, physiology, and senescence should be analyzed in perennial crop plants. This information could then be used to facilitate tailored genetic improvement of selected perennial grain crops to improve agronomic traits and enhance yield, while maintaining the benefits associated with perennialism.
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| 4. |
- Lundquist, Per-Olof, et al.
(författare)
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Discussion: Prioritize perennial grain development for sustainable food production and environmental benefits
- 2023
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Ingår i: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 895
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Tidskriftsartikel (refereegranskat)abstract
- Perennial grains have potential to contribute to ecological intensification of food production by enabling the direct har-vest of human-edible crops without requiring annual cycles of disturbance and replanting. Studies of prototype peren-nial grains and other herbaceous perennials point to the ability of agroecosystems including these crops to protect water quality, enhance wildlife habitat, build soil quality, and sequester soil carbon. However, genetic improvement of perennial grain candidates has been hindered by limited investment due to uncertainty about whether the approach is viable. As efforts to develop perennial grain crops have expanded in past decades, critiques of the approach have arisen. With a recent report of perennial rice producing yields equivalent to those of annual rice over eight consecutive harvests, many theoretical concerns have been alleviated. Some valid questions remain over the timeline for new crop development, but we argue these may be mitigated by implementation of recent technological advances in crop breed-ing and genetics such as low-cost genotyping, genomic selection, and genome editing. With aggressive research invest-ment in the development of new perennial grain crops, they can be developed and deployed to provide atmospheric greenhouse gas reductions.
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| 5. |
- Meirose, Bernhard, et al.
(författare)
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Real-time accelerator diagnostic tools for the max iv storage rings
- 2020
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Ingår i: Instruments. - : MDPI AG. - 2410-390X. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, beam diagnostic and monitoring tools developed by the MAX IV Operations Group are discussed. In particular, beam position monitoring and accelerator tunes visualization software tools, as well as tools that directly influence the beam quality and stability, are introduced. An availability and downtime monitoring application is also presented.
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| 6. |
- Moreno, Silvana, et al.
(författare)
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Response to Waterlogging Stress in Wild and Domesticated Accessions of Timothy (Phleum pratense) and Its Relatives P. alpinum and P. nodosum
- 2023
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Ingår i: Plants. - 2223-7747. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Timothy (Phleum pratense) is a cool-season perennial forage grass widely grown for silage and hay production in northern regions. Climate change scenarios predict an increase in extreme weather events with fluctuating periods of high rainfall, requiring new varieties adapted to waterlogging (WL). Wild accessions could serve as germplasm for breeding, and we evaluated the responses of 11 wild and 8 domesticated accessions of timothy, P. nodosum and P. alpinum from different locations in northern Europe. Young plants at tillering stage were exposed to WL for 21 days in a greenhouse, and responses in growth allocation and root anatomy were studied. All accessions produced adventitious roots and changed allocation of growth between shoot and root as a response to WL, but the magnitude of these responses varied among species and among accessions. P. pratense responded less in these traits in response to WL than the other two species. The ability to form aerenchyma in the root cortex in response to WL was found for all species and also varied among species and among accessions, with the highest induction in P. pratense. Interestingly, some accessions were able to maintain and even increase root growth, producing more leaves and tillers, while others showed a reduction in the root system. Shoot dry weight (SDW) was not significantly affected by WL, but some accessions showed different and significant responses in the rate of production of leaves and tillers. Overall correlations between SDW and aerenchyma and between SDW and adventitious root formation were found. This study identified two wild timothy accessions and one wild P. nodosum accession based on shoot and root system growth, aerenchyma formation and having a root anatomy considered to be favorable for WL tolerance. These accessions are interesting genetic resources and candidates for development of climate-resilient timothy varieties.
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| 7. |
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| 8. |
- Wegler, Christine, et al.
(författare)
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Global variability analysis of mRNA and protein concentrations across and within human tissues
- 2020
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Ingår i: NAR Genomics and Bioinformatics. - : Oxford University Press (OUP). - 2631-9268. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Genes and proteins show variable expression patterns throughout the human body. However, it is not clear whether relative differences in mRNA concentrations are retained on the protein level. Furthermore, inter-individual protein concentration variability within single tissue types has not been comprehensively explored. Here, we used the Gini index for in-depth concentration variability analysis of publicly available transcriptomics and proteomics data, and of an in-house proteomics dataset of human liver and jejunum from 38 donors. We found that the transfer of concentration variability from mRNA to protein is limited, that established ‘reference genes’ for data normalization vary markedly at the protein level, that protein concentrations cover a wide variability spectrum within single tissue types, and that concentration variability analysis can be a convenient starting point for identifying disease-associated proteins and novel biomarkers. Our results emphasize the importance of considering individual concentration levels, as opposed to population averages, for personalized systems biology analysis.
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