| 1. |
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| 2. |
- Ahlinder, Jon, et al.
(författare)
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Upstream land use with microbial downstream consequences : iron and humic substances link to Legionella spp
- 2024
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Ingår i: Water Research. - : Elsevier. - 0043-1354 .- 1879-2448. ; 256
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Tidskriftsartikel (refereegranskat)abstract
- Intensified land use can disturb water quality, potentially increasing the abundance of bacterial pathogens, threatening public access to clean water. This threat involves both direct contamination of faecal bacteria as well as indirect factors, such as disturbed water chemistry and microbiota, which can lead to contamination. While direct contamination has been well described, the impact of indirect factors is less explored, despite the potential of severe downstream consequences on water supply. To assess direct and indirect downstream effects of buildings, farms, pastures and fields on potential water sources, we studied five Swedish lakes and their inflows. We analysed a total of 160 samples in a gradient of anthropogenic activity spanning four time points, including faecal and water-quality indicators. Through species distribution modelling, Random Forest and network analysis using 16S rRNA amplicon sequencing data, our findings highlight that land use indirectly impacts lakes via inflows. Land use impacted approximately one third of inflow microbiota taxa, in turn impacting ∌20–50 % of lake taxa. Indirect effects via inflows were also suggested by causal links between e.g. water colour and lake bacterial taxa, where this influenced the abundance of several freshwater bacteria, such as Polynucleobacter and Limnohabitans. However, it was not possible to identify direct effects on the lakes based on analysis of physiochemical- or microbial parameters. To avoid potential downstream consequences on water supply, it is thus important to consider possible indirect effects from upstream land use and inflows, even when no direct effects can be observed on lakes. Legionella (a genus containing bacterial pathogens) illustrated potential consequences, since the genus was particularly abundant in inflows and was shown to increase by the presence of pastures, fields, and farms. The approach presented here could be used to assess the suitability of lakes as alternative raw water sources or help to mitigate contaminations in important water catchments. Continued broad investigations of stressors on the microbial network can identify indirect effects, avoid enrichment of pathogens, and help secure water accessibility.
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| 3. |
- Bonaglia, Stefano, et al.
(författare)
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Activated carbon stimulates microbial diversity and PAH biodegradation under anaerobic conditions in oil-polluted sediments
- 2020
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 248
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Tidskriftsartikel (refereegranskat)abstract
- Biodegradation by microorganisms is a useful tool that helps alleviating hydrocarbon pollution in nature. Microbes are more efficient in degradation under aerobic than anaerobic conditions, but the majority of sediment by volume is generally anoxic. Incubation experiments were conducted to study the biodegradation potential of naphthalene-a common polycyclic aromatic hydrocarbon (PAH)-and the diversity of microbial communities in presence/absence of activated carbon (AC) under aerobic/anaerobic conditions. Radio-respirometry experiments with endogenous microorganisms indicated that degradation of naphthalene was strongly stimulated (96%) by the AC addition under anaerobic conditions. In aerobic conditions, however, AC had no effects on naphthalene biodegradation. Bioaugmentation tests with cultured microbial populations grown on naphthalene showed that AC further stimulated (92%) naphthalene degradation in anoxia. Analysis of the 16S rRNA gene sequences implied that sediment amendment with AC increased microbial community diversity and changed community structure. Moreover, the relative abundance of Geobacter, Thiobacillus, Sulfuricurvum, and methanogenic archaea increased sharply after amendment with AC under anaerobic conditions. These results may be explained by the fact that AC particles promoted direct interspecies electron transfer (DIET) between microorganisms involved in PAH degradation pathways. We suggest that important ecosystem functions mediated by microbes-such as hydrocarbon degradation-can be induced and that AC enrichment strategies can be exploited for facilitating bioremediation of anoxic oil-contaminated sediments and soils.
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| 4. |
- Brindefalk, Björn, et al.
(författare)
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A Phylometagenomic Exploration of Oceanic Alphaproteobacteria Reveals Mitochondrial Relatives Unrelated to the SAR11 Clade
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:9, s. e24457-
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Tidskriftsartikel (refereegranskat)abstract
- Background: According to the endosymbiont hypothesis, the mitochondrial system for aerobic respiration was derived from an ancestral Alphaproteobacterium. Phylogenetic studies indicate that the mitochondrial ancestor is most closely related to the Rickettsiales. Recently, it was suggested that Candidatus Pelagibacter ubique, a member of the SAR11 clade that is highly abundant in the oceans, is a sister taxon to the mitochondrial-Rickettsiales clade. The availability of ocean metagenome data substantially increases the sampling of Alphaproteobacteria inhabiting the oxygen-containing waters of the oceans that likely resemble the originating environment of mitochondria. Methodology/Principal Findings: We present a phylogenetic study of the origin of mitochondria that incorporates metagenome data from the Global Ocean Sampling (GOS) expedition. We identify mitochondrially related sequences in the GOS dataset that represent a rare group of Alphaproteobacteria, designated OMAC (Oceanic Mitochondria Affiliated Clade) as the closest free-living relatives to mitochondria in the oceans. In addition, our analyses reject the hypothesis that the mitochondrial system for aerobic respiration is affiliated with that of the SAR11 clade. Conclusions/Significance: Our results allude to the existence of an alphaproteobacterial clade in the oxygen-rich surface waters of the oceans that represents the closest free-living relative to mitochondria identified thus far. In addition, our findings underscore the importance of expanding the taxonomic diversity in phylogenetic analyses beyond that represented by cultivated bacteria to study the origin of mitochondria.
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| 5. |
- Brindefalk, Björn, et al.
(författare)
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Distribution and expression of microbial rhodopsins in the Baltic Sea and adjacent waters
- 2016
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Ingår i: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 18:12, s. 4442-4455
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Tidskriftsartikel (refereegranskat)abstract
- Rhodopsins are light-driven ion-pumping membrane proteins found in many organisms and are proposed to be of global importance for oceanic microbial energy generation. Several studies have focused on marine environments, with less exploration of rhodopsins in brackish waters. We investigated microbial rhodopsins in the Baltic Sea using size-fractionated metagenomic and metatranscriptomic datasets collected along a salinity gradient spanning from similar to 0 to 35 PSU. The normalised genomic abundance of rhodopsins in Bacteria, as well as rhodopsin gene expression, was highest in the smallest size fraction (0.1-0.8 mu m), relative to the medium (0.8-3.0 mu m) and large (> 3.0 mu m) size fractions. The abundance of rhodopsins in the two smaller size fractions displayed a positive correlation with salinity. Proteobacteria and Bacteroidetes rhodopsins were the most abundant while Actinobacteria rhodopsins, or actinorhodopsins, were common at lower salinities. Phylogenetic analysis indicated that rhodopsins have adapted independently to the marine-brackish transition on multiple occasions, giving rise to green light-adapted variants from ancestral blue light-adapted ones. A notable diversity of viral-like rhodopsins was also detected in the dataset and potentially linked with eukaryotic phytoplankton blooms. Finally, a new clade of likely proton-pumping rhodopsin with non-canonical amino acids in the spectral tuning and proton accepting site was identified.
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| 6. |
- Brindefalk, Björn, et al.
(författare)
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Evolutionary history of the TBP-domain superfamily
- 2013
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 41:5, s. 2832-2845
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Tidskriftsartikel (refereegranskat)abstract
- The TATA binding protein (TBP) is an essential transcription initiation factor in Archaea and Eucarya. Bacteria lack TBP, and instead use sigma factors for transcription initiation. TBP has a symmetric structure comprising two repeated TBP domains. Using sequence, structural and phylogenetic analyses, we examine the distribution and evolutionary history of the TBP domain, a member of the helix-grip fold family. Our analyses reveal a broader distribution than for TBP, with TBP-domains being present across all three domains of life. In contrast to TBP, all other characterized examples of the TBP domain are present as single copies, primarily within multidomain proteins. The presence of the TBP domain in the ubiquitous DNA glycosylases suggests that this fold traces back to the ancestor of all three domains of life. The TBP domain is also found in RNase HIII, and phylogenetic analyses show that RNase HIII has evolved from bacterial RNase HII via TBP-domain fusion. Finally, our comparative genomic screens confirm and extend earlier reports of proteins consisting of a single TBP domain among some Archaea. These monopartite TBP-domain proteins suggest that this domain is functional in its own right, and that the TBP domain could have first evolved as an independent protein, which was later recruited in different contexts.
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| 7. |
- Brindefalk, Björn, 1977-, et al.
(författare)
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Loss of Mitochondrial tRNA Genes Correlates with Loss of Genes for Aminoacyl-tRNA Synthetases
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Most mitochondrial genomes encode their own tRNAs, whereas the mitochondrial aminoacyl-tRNA synthetases (aaRS) are encoded by the nuclear genome. It has been suggested that the loss of mitochondrial tRNA genes from the mitocchondrial genome correlates with the sequence similarity between bacterial and eukaryotic aaRSs, in that aaRSs that are similar across the two domains can easily shift between charging mitochondrial and cytosolic tRNAs (Schneider 2001). However, recent work has shown that mitochondrial and cytosolic aaRSs have complex evolutionary histories and are not always of bacterial and eukaryotic origin, respectively (Brindefalk et al. 2007). We repeated the analysis performed by Schneider using all available mitochondrial genomes as of December 2006 and found that the loss of mitochondrial tRNA genes correlates with replacements of the genes for the corresponding aaRS. Our observations provide new insights into the co-evolution of mitochondrial tRNAs and their charging enzymes.
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| 8. |
- Brindefalk, Björn, 1977-, et al.
(författare)
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Lost and Found at Sea: a Phylomentagenomic Exploration of Mitochondrial Affiliations with Oceanic Bacteria.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background According to the endosymbiont hypothesis, the mitochondrial system for aerobic respiration was derived from a free-living bacterium related to present-day alpha-proteobacteria. Recent studies have identified two lineages as the closest mitochondrial relatives among bacteria with sequenced genomes; the Rickettsiales, a lineage comprising obligate intracellular pathogens, and Pelagibacter ubique, a member of the SAR11 clade that is highly abundant in the upper surface waters of the global oceans. Principal Findings Here, we present a phylogenetic study incorporating metagenomic data of mitochondrial genes for aerobic respiration that includes sequence data from the Global Ocean Sampling (GOS) Expedition, thereby increasing the sampling of alpha-proteobacterial sequences available for analysis greatly. Phylogenetic analysis of these expanded datasets including oceanic sequences that had been pruned down in numbers but still maintained the full genetic diversity present failed to show an increased support for a specific mitochondrial affiliation to any alpha-proteobacterial group, although concatenated datasets of different genes gave good support for conflicting mitochondrial placement. We utilized a jack-knifing method to randomly sample sequences from the GOS dataset and examined how the inclusion of such sequences influenced the support for mitochondrial affiliation in trees inferred from proteins in aerobic respiration. No evidence of an increased support for a specific mitochondrial placement in the alpha-proteobacterial tree in the jack-knifing analysis was obtained. A systematic search for sequences affiliated with mitochondria in the GOS dataset suggests the existence of previously unidentified clades of deeply diverging alpha-proteobacteria, with an unclear affiliation. Conclusions/Significance Our findings have several important implications. First, they support an early divergence of the mitochondrial ancestor from the alpha-proteobacterial lineage, possibly pre-dating the radiation of alpha-proteobacterial species with sequenced genomes. Second, they reject the hypothesis that the system for aerobic respiration in mitochondria is affiliated with the SAR11 clade. Third, they indicate horizontal transfer of genes for respiratory chain proteins in bacteria adapted to the upper surface waters of the oceans. Fourth, they show the presence of oceanic sequences for respiratory chain proteins that diverge as deeply as mitochondria in the alpha-proteobacterial phylogeny, possibly indicating a previously unidentified alpha-proteobacterial group at a basal position of the alpha-proteobacterial tree, underscoring the importance of expanding studies on mitochondrial origins beyond those of cultivated and intracellular bacteria. Finally, our study outlines a new methodology, phylometagenomics, which provides guidance on how to incorporate metagenome data into a phylogenetic framework for inferences of early evolutionary events.
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| 9. |
- Brindefalk, Björn, 1977-, et al.
(författare)
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Mitochondrial and alpha-proteobacterial time of divergence - a question of antecedence
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Mitochondria are believed to have originated by the incorporation of an alpha-proteobacterium into an un-defined "proto-eukaryote", although the exact nature of the two participants in this endo-symbiotic event is not known. Attempts to place the endo-symbiont with a specific group of extant alpha-proteobacteria has in most cases identified the Rickettsiales as the sister-group to mitochondria, although recent work has shown that this could be due to methodological artefacts and that the mitochondria should instead be considered a sister-clade to alphaproteobacteria. Equally uncertain is the time at which this endo-symbiotic event took place, and if it coincides with the event that gave rise to the eukaryotes themselves. In this work we attempt to use molecular dating methods to compare the time-point of mitochondrial divergence to the time-point of divergence of the alpha-proteobacteria, under the two hypothetical topologies mentioned. We show that if mitochondria are considered as a sister-clade to the alpha-proteobacteria, mitochondria likely diverged prior to the radiation of extant alpha-proteobacteria, and that the alpha-proteobacterial clade itself might be significantly younger than shown in previous analyses.
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| 10. |
- Brindefalk, Björn, 1977-
(författare)
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Mitochondrial and Eukaryotic Origins : A Phylogenetic Perspective
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mitochondria are eukaryotic cellular organelles responsible for power-generation, believed to have come into existence by an endo-symbiontic event where a bacterial cell was incorporated by an un-specified "proto-eukaryote". Phylogenetic analysis have shown that the mitochondrial ancestor was most related to present-day alpha-proteobacteria, although the exact nature of the mitochondrial progenitor remains disputed. In this work, I have used phylogenetic and other methods to investigate the identity of the organism giving rise to mitochondria, by analysing the evolutionary history of select proteins, the events where they have been transfered to the eukaryotic nucleus, and the time-point of mitochondrial establishment. In addition, a search for mitochondrially related organisms in the ocean metagenome was performed, in the hope that something more related to the mitochondrial progenitor than anything previously identified could be found. Previous analysis have shown that a large fraction of mitochondrial proteins does indeed trace their descent to the alpha-proteobacteria, but I found that the amino-acyl tRNA-synthetases display more general bacterial descent, making it likely that these proteins are of a different origin from the mitochondria themselves. While the synthetases are encoded on the nuclear genome, most mitochondria still posses most of the tRNA on their own genomes. In the cases where the tRNA has been lost from the mitochondrial genome, I found that the probability of loss correspond to the evolutionary history of their synthetase. The ocean metagenome represents an order of magnitude more data than previously available, making it suitable for improving the analyses dealing with mitochondrial placement. This large of amount of data was utilised to improve the phylogenetic analyses, showing that previous works might have suffered from artefacts inflating the support for placement of mitochondria with a specific alpha-proteobacterial group. Eukaryotic/mitochondrial radiation was shown to be as old, or older, than radiation of extant alpha-proteobacteria, casting doubt on previous analysis identifying a specific alpha-proteobacterial group as the mitochondrial ancestor.
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| 11. |
- Brindefalk, Björn, et al.
(författare)
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Origin and evolution of the mitochondrial aminoacyl-tRNA synthetases
- 2007
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 24:3, s. 743-756
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Tidskriftsartikel (refereegranskat)abstract
- Many theories favor a fusion of 2 prokaryotic genomes for the origin of the Eukaryotes, but there are disagreements on the origin, timing, and cellular structures of the cells involved. Equally controversial is the source of the nuclear genes for mitochondrial proteins, although the α-proteobacterial contribution to the mitochondrial genome is well established. Phylogenetic inferences show that the nuclearly encoded mitochondrial aminoacyl-tRNA synthetases (aaRSs) occupy a position in the tree that is not close to any of the currently sequenced α-proteobacterial genomes, despite cohesive and remarkably well-resolved α-proteobacterial clades in 12 of the 20 trees. Two or more α-proteobacterial clusters were observed in 8 cases, indicative of differential loss of paralogous genes or horizontal gene transfer. Replacement and retargeting events within the nuclear genomes of the Eukaryotes was indicated in 10 trees, 4 of which also show split α-proteobacterial groups. A majority of the mitochondrial aaRSs originate from within the bacterial domain, but none specifically from the α-Proteobacteria. For some aaRS, the endosymbiotic origin may have been erased by ongoing gene replacements on the bacterial as well as the eukaryotic side. For others that accurately resolve the α-proteobacterial divergence patterns, the lack of affiliation with mitochondria is more surprising. We hypothesize that the ancestral eukaryotic gene pool hosted primordial "bacterial-like" genes, to which a limited set of α-proteobacterial genes, mostly coding for components of the respiratory chain complexes, were added and selectively maintained.
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| 12. |
- Dupont, Chris L., et al.
(författare)
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Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e89549-
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.
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| 13. |
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| 14. |
- Motiei, Asa, et al.
(författare)
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Disparate effects of antibiotic-induced microbiome change and enhanced fitness in Daphnia magna
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- It is a common view that an organism's microbiota has a profound influence on host fitness; however, supporting evidence is lacking in many organisms. We manipulated the gut microbiome of Daphnia magna by chronic exposure to different concentrations of the antibiotic Ciprofloxacin (0.01-1 mg L-1), and evaluated whether this affected the animals fitness and antioxidant capacity. In line with our expectations, antibiotic exposure altered the microbiome in a concentration-dependent manner. However, contrary to these expectations, the reduced diversity of gut bacteria was not associated with any fitness detriment. Moreover, the growth-related parameters correlated negatively with microbial diversity; and, in the daphnids exposed to the lowest Ciprofloxacin concentrations, the antioxidant capacity, growth, and fecundity were even higher than in control animals. These findings suggest that Ciprofloxacin exerts direct stimulatory effects on growth and reproduction in the host, while microbiome- mediated effects are of lesser importance. Thus, although microbiome profiling of Daphnia may be a sensitive tool to identify early effects of antibiotic exposure, disentangling direct and microbiome-mediated effects on the host fitness is not straightforward.
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| 15. |
- Persad, Emma, et al.
(författare)
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Blood pressure trends following birth in infants born under 25 weeks' gestational age : a retrospective cohort study
- 2024
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Ingår i: BMJ Paediatrics Open. - 2399-9772. ; 8:1, s. e002438-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of our study was to describe postnatal blood pressure (BP) trends and evaluate relevant dynamics and outcomes for a subgroup of extremely preterm (EPT) infants. Design: Retrospective observational cohort study. Setting: Patients admitted to Karolinska University Hospital Stockholm. Patients EPT infants born between 22+0 and 24+6 weeks’ gestational age (GA) undergoing invasive, continuous BP monitoring through an umbilical arterial catheter. Main outcome measures Physiological BP trends, the influence of cardiovascular active interventions and fluid boluses on BP, and relevant adverse outcomes, including intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC) and death, were mapped over the first week of life. Results: We included 125 infants between January 2009 and November 2021. Mean BP values were 31 mm Hg, 32 mm Hg and 35 mm Hg, at 3 hours, 24 hours and 48 hours, respectively. A pronounced BP dip and nadir were observed around 20 hours, with a mean BP value of 32 mm Hg. 84% received fluid boluses within the first week of life; however, we could not observe any noteworthy change in BP following administration. Only 8% of patients received cardiovascular active drugs, which were too few to infer drug-specific effects. Overall, 48% developed IVH, 15% developed NEC and 25% died. Conclusions: Approximating clinically acceptable mean BP values using GA gives underestimations in these infants. The postnatal BP dip should be regarded as a physiological phenomenon and not automatic grounds for interventions which may momentarily stabilise BP but have no appreciable short-term or long-term effects. Further studies are warranted for improved understanding of clinically relevant trends and outcomes.
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| 16. |
- Rossell, Joana, et al.
(författare)
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Diet change affects intestinal microbiota restoration and improves vertical sleeve gastrectomy outcome in diet-induced obese rats
- 2020
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 59, s. 3555-3564
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Obesity, a worldwide health problem, is linked to an abnormal gut microbiota and is currently most effectively treated by bariatric surgery. Our aim was to characterize the microbiota of high-fat fed Sprague-Dawley rats when subjected to bariatric surgery (i.e., vertical sleeve gastrectomy) and posterior refeeding with either a high-fat or control diet. We hypothesized that bariatric surgery followed by the control diet was more effective in reverting the microbiota modifications caused by the high-fat diet when compared to either of the two factors alone. Methods Using next-generation sequencing of ribosomal RNA amplicons, we analyzed and compared the composition of the cecal microbiota after vertical sleeve gastrectomy with control groups representing non-operated rats, control fed, high-fat fed, and post-operative diet-switched animals. Rats were fed either a high-fat or control low-fat diet and were separated into three comparison groups after eight weeks comprising no surgery, sham surgery, and vertical sleeve gastrectomy. Half of the rats were then moved from the HFD to the control diet. Using next-generation sequencing of ribosomal RNA amplicons, we analyzed the composition of the cecal microbiota of rats allocated to the vertical sleeve gastrectomy group and compared it to that of the non-surgical, control fed, high-fat fed, and post-operative diet-switched groups. Additionally, we correlated different biological parameters with the genera exhibiting the highest variation in abundance between the groups. Results The high-fat diet was the strongest driver of altered taxonomic composition, relative microbial abundance, and diversity in the cecum. These effects were partially reversed in the diet-switched cohort, especially when combined with sleeve gastrectomy, resulting in increased diversity and shifting relative abundances. Several highly-affected genera were correlated with obesity-related parameters. Conclusions The dysbiotic state caused by high-fat diet was improved by the change to the lower fat, higher fiber control diet. Bariatric surgery contributed significantly and additively to the diet in restoring microbiome diversity and complexity. These results highlight the importance of dietary intervention following bariatric surgery for improved restoration of cecal diversity, as neither surgery nor change of diet alone had the same effects as when combined.
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| 17. |
- Silao, Fitz Gerald S., et al.
(författare)
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Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans
- 2019
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Amino acids are among the earliest identified inducers of yeast-to-hyphal transitions in Candida albicans, an opportunistic fungal pathogen of humans. Here, we show that the morphogenic amino acids arginine, ornithine and proline are internalized and metabolized in mitochondria via a PUT1- and PUT2-dependent pathway that results in enhanced ATP production. Elevated ATP levels correlate with Ras1/cAMP/PKA pathway activation and Efg1-induced gene expression. The magnitude of amino acid-induced filamentation is linked to glucose availability; high levels of glucose repress mitochondrial function thereby dampening filamentation. Furthermore, arginine-induced morphogenesis occurs more rapidly and independently of Dur1,2-catalyzed urea degradation, indicating that mitochondrial-generated ATP, not CO2, is the primary morphogenic signal derived from arginine metabolism. The important role of the SPS-sensor of extracellular amino acids in morphogenesis is the consequence of induced amino acid permease gene expression, i.e., SPS-sensor activation enhances the capacity of cells to take up morphogenic amino acids, a requisite for their catabolism. C. albicans cells engulfed by murine macrophages filament, resulting in macrophage lysis. Phagocytosed put1-/- and put2-/- cells do not filament and exhibit reduced viability, consistent with a critical role of mitochondrial proline metabolism in virulence. Author summary Candida albicans is an opportunistic fungal pathogen that exists as a benign member of the human microbiome. Immunosuppression, or microbial dysbiosis, can predispose an individual to infection, enabling this fungus to evade innate immune cells and initiate a spectrum of pathologies, including superficial mucocutaneous or even life-threatening invasive infections. Infectious growth is attributed to an array of virulence characteristics, a major one being the ability to switch morphologies from round yeast-like to elongated hyphal cells. Here we report that mitochondrial proline catabolism is required to induce hyphal growth of C. albicans cells in phagosomes of engulfing macrophages, which is key to evade killing by macrophages. The finding that proline catabolism, also required for the utilization of arginine and ornithine, is required to sustain the energy demands of hyphal growth underscores the central role of mitochondria in fungal virulence. In contrast to existing dogma, we show that in C. albicans, mitochondrial function is subject to glucose repression, amino acid-induced signals are strictly dependent on Ras1 and the SPS-sensor is the primary sensor of extracellular amino acids. The results provide a clear example of how C. albicans cells sense and respond to host nutrients to ensure proper nutrient uptake and survival.
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| 18. |
- Sundell, David, et al.
(författare)
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FlexTaxD : flexible modification of taxonomy databases for improved sequence classification
- 2021
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Ingår i: Bioinformatics. - : Oxford University Press. - 1367-4803 .- 1367-4811 .- 1460-2059. ; 37:21, s. 3932-3933
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Tidskriftsartikel (refereegranskat)abstract
- The Flexible Taxonomy Database framework provides a method for modification and merging official and custom taxonomic databases to create improved databases. Using such databases will increase accuracy and precision of existing methods to classify sequence reads.
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| 19. |
- Öhrman, Caroline, et al.
(författare)
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Reorganized Genomic Taxonomy of Francisellaceae Enables Design of Robust Environmental PCR Assays for Detection of Francisella tularensis
- 2021
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, an increasing diversity of species has been recognized within the family Francisellaceae. Unfortunately, novel isolates are sometimes misnamed in initial publications or multiple sources propose different nomenclature for genetically highly similar isolates. Thus, unstructured and occasionally incorrect information can lead to confusion in the scientific community. Historically, detection of Francisella tularensis in environmental samples has been challenging due to the considerable and unknown genetic diversity within the family, which can result in false positive results. We have assembled a comprehensive collection of genome sequences representing most known Francisellaceae species/strains and restructured them according to a taxonomy that is based on phylogenetic structure. From this structured dataset, we identified a small number of genomic regions unique to F. tularensis that are putatively suitable for specific detection of this pathogen in environmental samples. We designed and validated specific PCR assays based on these genetic regions that can be used for the detection of F. tularensis in environmental samples, such as water and air filters.
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