| 1. |
- Borgos, S., et al.
(författare)
-
Mapping global effects of the anti-sigma factor MucA in Pseudomonas fluorescens SBW25 through genome-scale metabolic modeling
- 2013
-
Ingår i: BMC Systems Biology. - : Springer Science and Business Media LLC. - 1752-0509. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlginate is an industrially important polysaccharide, currently produced commercially by harvesting of marine brown sea-weeds. The polymer is also synthesized as an exo-polysaccharide by bacteria belonging to the genera Pseudomonas and Azotobacter, and these organisms may represent an alternative alginate source in the future. The current work describes an attempt to rationally develop a biological system tuned for very high levels of alginate production, based on a fundamental understanding of the system through metabolic modeling supported by transcriptomics studies and carefully controlled fermentations.ResultsAlginate biosynthesis in Pseudomonas fluorescens was studied in a genomics perspective, using an alginate over-producing strain carrying a mutation in the anti-sigma factor gene mucA. Cells were cultivated in chemostats under nitrogen limitation on fructose or glycerol as carbon sources, and cell mass, growth rate, sugar uptake, alginate and CO2 production were monitored. In addition a genome scale metabolic model was constructed and samples were collected for transcriptome analyses. The analyses show that polymer production operates in a close to optimal way with respect to stoichiometric utilization of the carbon source and that the cells increase the uptake of carbon source to compensate for the additional needs following from alginate synthesis. The transcriptome studies show that in the presence of the mucA mutation, the alg operon is upregulated together with genes involved in energy generation, genes on both sides of the succinate node of the TCA cycle and genes encoding ribosomal and other translation-related proteins. Strains expressing a functional MucA protein (no alginate production) synthesize cellular biomass in an inefficient way, apparently due to a cycle that involves oxidation of NADPH without ATP production. The results of this study indicate that the most efficient way of using a mucA mutant as a cell factory for alginate production would be to use non-growing conditions and nitrogen deprivation.ConclusionsThe insights gained in this study should be very useful for a future efficient production of microbial alginates.
|
|
| 2. |
- Dussex, Nicolas, et al.
(författare)
-
Adaptation to the High-Arctic island environment despite long-term reduced genetic variation in Svalbard reindeer
- 2023
-
Ingår i: iScience. - 2589-0042. ; 26:10
-
Tidskriftsartikel (refereegranskat)abstract
- Typically much smaller in number than their mainland counterparts, island populations are ideal systems to investigate genetic threats to small populations. The Svalbard reindeer (Rangifer tarandus platyrhynchus) is an endemic subspecies that colonized the Svalbard archipelago ca. 6,000–8,000 years ago and now shows numerous physiological and morphological adaptations to its arctic habitat. Here, we report a de-novo chromosome-level assembly for Svalbard reindeer and analyze 133 reindeer genomes spanning Svalbard and most of the species’ Holarctic range, to examine the genomic consequences of long-term isolation and small population size in this insular subspecies. Empirical data, demographic reconstructions, and forward simulations show that long-term isolation and high inbreeding levels may have facilitated the reduction of highly deleterious—and to a lesser extent, moderately deleterious—variation. Our study indicates that long-term reduced genetic diversity did not preclude local adaptation to the High Arctic, suggesting that even severely bottlenecked populations can retain evolutionary potential.
|
|
| 3. |
|
|
| 4. |
- Lützhøft, Ditte Olsen, et al.
(författare)
-
Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model
- 2022
-
Ingår i: BMC Microbiology. - : BioMed Central (BMC). - 1471-2180. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH.RESULTS: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.CONCLUSIONS: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.
|
|
| 5. |
- Temmesfeld, M. J., et al.
(författare)
-
Surgical helmets can be converted into efficient disinfectable powered air-purifying respirators
- 2022
-
Ingår i: American Journal of Infection Control. - : Elsevier BV. - 0196-6553. ; 50:6, s. 624-630
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Filtering facepiece respirators often fail to provide sufficient protection due to a poor fit. Powered air-purifying respirators (PAPRs) are not designed for healthcare personnel, and are challenging to disinfect. Surgical helmets (SH) are available in many United States hospitals but do not provide respiratory protection. Several modifications to SH have been suggested, but none are sufficiently compliant with safety and efficiency standards. The purpose of this investigation was the development of a filter adaptor, which converts SHs into efficient, safe, and disinfectable PAPRs. Methods: Four critical features were investigated close to regulatory requirements: total inward leakage of particles, CO2 concentrations, intra-helmet differential pressure, and automated disinfection. Results: The average total inward leakage in the 2 independent tests were 0.005% and 0.01%. CO2 concentrations were lower than in the original SH. The modification generates a positive differential pressure. The filter's performance was not compromised after 50 cycles in a sterilization machine. Discussion: The modified SH provides several hundred times better protection than FFP-3 masks. Conclusions: Surgical helmets can be modified into safe, efficient, and disinfectable PAPRs, suitable for HCP and the operating room in particular. They can play a role in the preparedness for upcoming events requiring efficient respiratory protection.
|
|
