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| 2. |
- Conlan, J. Wayne, et al.
(författare)
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Modern Development and Production of a New Live Attenuated Bacterial Vaccine, SCHU S4 Delta clpB, to Prevent Tularemia
- 2021
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Ingår i: Pathogens. - : MDPI. - 2076-0817. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Inhalation of small numbers of Francisella tularensis subspecies tularensis (Ftt) in the form of small particle aerosols causes severe morbidity and mortality in people and many animal species. For this reason, Ftt was developed into a bona fide biological weapon by the USA, by the former USSR, and their respective allies during the previous century. Although such weapons were never deployed, the 9/11 attack quickly followed by the Amerithrax attack led the U.S. government to seek novel countermeasures against a select group of pathogens, including Ftt. Between 2005-2009, we pursued a novel live vaccine against Ftt by deleting putative virulence genes from a fully virulent strain of the pathogen, SCHU S4. These mutants were screened in a mouse model, in which the vaccine candidates were first administered intradermally (ID) to determine their degree of attenuation. Subsequently, mice that survived a high dose ID inoculation were challenged by aerosol or intranasally (IN) with virulent strains of Ftt. We used the current unlicensed live vaccine strain (LVS), first discovered over 70 years ago, as a comparator in the same model. After screening 60 mutants, we found only one, SCHU S4 Delta clpB, that outperformed LVS in the mouse ID vaccination-respiratory-challenge model. Currently, SCHU S4 Delta clpB has been manufactured under current good manufacturing practice conditions, and tested for safety and efficacy in mice, rats, and macaques. The steps necessary for advancing SCHU S4 Delta clpB to this late stage of development are detailed herein. These include developing a body of data supporting the attenuation of SCHU S4 Delta clpB to a degree sufficient for removal from the U.S. Select Agent list and for human use; optimizing SCHU S4 Delta clpB vaccine production, scale up, and long-term storage; and developing appropriate quality control testing approaches.
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| 3. |
- Evengård, Birgitta, 1952-, et al.
(författare)
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Healthy ecosystems for human and animal health : Science diplomacy for responsible development in the Arctic
- 2021
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Ingår i: Polar Record. - : Cambridges Institutes Press. - 0032-2474 .- 1475-3057. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- Climate warming is occurring most rapidly in the Arctic, which is both a sentinel and a driver of further global change. Ecosystems and human societies are already affected by warming. Permafrost thaws and species are on the move, bringing pathogens and vectors to virgin areas. During a five-year project, the CLINF - a Nordic Center of Excellence, funded by the Nordic Council of Ministers, has worked with the One Health concept, integrating environmental data with human and animal disease data in predictive models and creating maps of dynamic processes affecting the spread of infectious diseases. It is shown that tularemia outbreaks can be predicted even at a regional level with a manageable level of uncertainty. To decrease uncertainty, rapid development of new and harmonised technologies and databases is needed from currently highly heterogeneous data sources. A major source of uncertainty for the future of contaminants and infectious diseases in the Arctic, however, is associated with which paths the majority of the globe chooses to follow in the future. Diplomacy is one of the most powerful tools Arctic nations have to influence these choices of other nations, supported by Arctic science and One Health approaches that recognise the interconnection between people, animals, plants and their shared environment at the local, regional, national and global levels as essential for achieving a sustainable development for both the Arctic and the globe.
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| 4. |
- Grapotte, M, et al.
(författare)
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Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3297-
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Tidskriftsartikel (refereegranskat)abstract
- Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
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| 5. |
- Sjöstedt, Johanna, et al.
(författare)
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Substrate diversity affects carbon utilization rate and threshold concentration for uptake by natural bacterioplankton communities
- 2022
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Ingår i: Aquatic Microbial Ecology. - 0948-3055. ; 88, s. 95-108
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Tidskriftsartikel (refereegranskat)abstract
- Persistence of dissolved organic matter (DOM) in aquatic environments may in part be explained by high diversity and low concentrations of carbon substrates. However, changes in dissolved substrate quality can modify aquatic bacterial community composition and rate of carbon uptake. The aim of this study was to test if the presence of multiple simple substrates affects the turnover of organic carbon. Natural bacterial communities were grown in continuous cultures supplied with either individual carbon substrates-salicylic acid (SA), tryptophan (Trp) or tyrosine (Tyr)-or a combination of the 3 substrates. Concentrations were tracked using fluorescence spectroscopy, and steady-state concentrations of a few nanomolar were reached. Bacterial growth efficiency was dependent on which carbon sources were present and reached an intermediate level in the combined treatment. The bacterial community maintained steady-state concentrations of Trp that were lower in the combined treatment than in the individual substrate treatment. In addition, steady-state concentrations were reached faster during growth on combined carbon substrates, although the maximum utilization rate of each individual compound was lower. However, the steady-state concentration of total carbon (sum of carbon content of SA, Trp and Tyr) was higher in the combined culture than in the individual substrate treatments, and seemed to be determined by the carbon substate for which the bacteria had the lowest affinity. The results from this study indicate that persistence of dissolved organic carbon can in part be explained by vast substrate diversity, which raises the threshold concentration for utilization by natural bacterial communities.
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| 6. |
- Sjöstedt, Johanna, 1982-, et al.
(författare)
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Substrate diversity affects carbon utilization rate and threshold concentration for uptake by natural bacterioplankton communities
- 2022
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Ingår i: Aquatic Microbial Ecology. - : Inter-Research Science Center. - 0948-3055 .- 1616-1564. ; 88
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Tidskriftsartikel (refereegranskat)abstract
- Persistence of dissolved organic matter (DOM) in aquatic environments may in part be explained by high diversity and low concentrations of carbon substrates. However, changes in dissolved substrate quality can modify aquatic bacterial community composition and rate of carbon uptake. The aim of this study was to test if the presence of multiple simple substrates affects the turnover of organic carbon. Natural bacterial communities were grown in continuous cultures supplied with either individual carbon substrates—salicylic acid (SA), tryptophan (Trp) or tyrosine (Tyr)—or a combination of the 3 substrates. Concentrations were tracked using fluorescence spectroscopy, and steady-state concentrations of a few nanomolar were reached. Bacterial growth efficiency was dependent on which carbon sources were present and reached an intermediate level in the combined treatment. The bacterial community maintained steady-state concentrations of Trp that were lower in the combined treatment than in the individual substrate treatment. In addition, steady-state concentrations were reached faster during growth on combined carbon substrates, although the maximum utilization rate of each individual compound was lower. However, the steady-state concentration of total carbon (sum of carbon content of SA, Trp and Tyr) was higher in the combined culture than in the individual substrate treatments, and seemed to be determined by the carbon substate for which the bacteria had the lowest affinity. The results from this study indicate that persistence of dissolved organic carbon can in part be explained by vast substrate diversity, which raises the threshold concentration for utilization by natural bacterial communities.
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| 7. |
- Sjöstedt, Lovisa M., et al.
(författare)
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CFD Modelling as a Tool to Better Understand Fish Behavior
- 2023
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Ingår i: Proceedings of the 40th IAHR World Congress - 2023. - : International Association for Hydro-Environment Engineering and Research (IAHR). ; , s. 2665-2672
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Konferensbidrag (refereegranskat)
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