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- Berglund, Eva C., et al.
(författare)
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Genome dynamics of Bartonella grahamii in micro-populations of woodland rodents
- 2010
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11, s. 152-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rodents represent a high-risk reservoir for the emergence of new human pathogens. The recent completion of the 2.3 Mb genome of Bartonella grahamii, one of the most prevalent blood-borne bacteria in wild rodents, revealed a higher abundance of genes for host-cell interaction systems than in the genomes of closely related human pathogens. The sequence variability within the global B. grahamii population was recently investigated by multi locus sequence typing, but no study on the variability of putative host-cell interaction systems has been performed. Results: To study the population dynamics of B. grahamii, we analyzed the genomic diversity on a whole-genome scale of 27 B. grahamii strains isolated from four different species of wild rodents in three geographic locations separated by less than 30 km. Even using highly variable spacer regions, only 3 sequence types were identified. This low sequence diversity contrasted with a high variability in genome content. Microarray comparative genome hybridizations identified genes for outer surface proteins, including a repeated region containing the fha gene for filamentous hemaggluttinin and a plasmid that encodes a type IV secretion system, as the most variable. The estimated generation times in liquid culture medium for a subset of strains ranged from 5 to 22 hours, but did not correlate with sequence type or presence/absence patterns of the fha gene or the plasmid. Conclusion: Our study has revealed a geographic microstructure of B. grahamii in wild rodents. Despite near-identity in nucleotide sequence, major differences were observed in gene presence/absence patterns that did not segregate with host species. This suggests that genetically similar strains can infect a range of different hosts.
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- Ellegaard, Kirsten Maren, et al.
(författare)
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Comparative Genomics of Wolbachia and the Bacterial Species Concept
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:4, s. e1003381-
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Tidskriftsartikel (refereegranskat)abstract
- The importance of host-specialization to speciation processes in obligate host-associated bacteria is well known, as is also the ability of recombination to generate cohesion in bacterial populations. However, whether divergent strains of highly recombining intracellular bacteria, such as Wolbachia, can maintain their genetic distinctness when infecting the same host is not known. We first developed a protocol for the genome sequencing of uncultivable endosymbionts. Using this method, we have sequenced the complete genomes of the Wolbachia strains wHa and wNo, which occur as natural double infections in Drosophila simulans populations on the Seychelles and in New Caledonia. Taxonomically, wHa belong to supergroup A and wNo to supergroup B. A comparative genomics study including additional strains supported the supergroup classification scheme and revealed 24 and 33 group-specific genes, putatively involved in host-adaptation processes. Recombination frequencies were high for strains of the same supergroup despite different host-preference patterns, leading to genomic cohesion. The inferred recombination fragments for strains of different supergroups were of short sizes, and the genomes of the co-infecting Wolbachia strains wHa and wNo were not more similar to each other and did not share more genes than other A- and B-group strains that infect different hosts. We conclude that Wolbachia strains of supergroup A and B represent genetically distinct clades, and that strains of different supergroups can co-exist in the same arthropod host without converging into the same species. This suggests that the supergroups are irreversibly separated and that barriers other than host-specialization are able to maintain distinct clades in recombining endosymbiont populations. Acquiring a good knowledge of the barriers to genetic exchange in Wolbachia will advance our understanding of how endosymbiont communities are constructed from vertically and horizontally transmitted genes.
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- Falkén, Y., et al.
(författare)
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Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans
- 2010
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:6, s. e192-e200
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Tidskriftsartikel (refereegranskat)abstract
- Background Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6-h infusion in humans. Methods Ghrelin (15 pmol kg−1 min−1) or saline was infused intravenously for 360 min after intake of radio-opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon-like peptide-1 (GLP-1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed. Key Results The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half-emptying time (50.3 ± 3.9 vs 59.9 ± 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP-1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin. Conclusions & Inferences The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders.
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- Falkén, Y., et al.
(författare)
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Changes in Glucose Homeostasis after Roux-en-Y Gastric Bypass Surgery for Obesity at Day Three, Two Months, and One Year after Surgery : Role of Gut Peptides
- 2011
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 96:7, s. 2227-2235
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Tidskriftsartikel (refereegranskat)abstract
- Context: Endocrine effects of gastric bypass (GBP) surgery for obesity on glucose homeostasis are not fully understood. Main Objective: The main objective of the study was to assess the changes in plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), leptin, somatostatin, glucose-dependent insulinotropic peptide, enteroglucagon, and glucagon early after GBP. Method: Twelve obese subjects (body mass index 45.3 ± 1.9 kg/m2) were subjected to a liquid meal without lipids before and 3 d, 2 months, and 1 yr after GBP. Plasma concentrations of glucose, insulin, leptin, and gut peptide hormones were assessed before and for 180 min after the meal. Satiety was measured with visual analog scales. The absorption rate of acetaminophen added to the liquid meal was measured. Insulin resistance was measured by the homeostasis model assessment of insulin resistance. Results: All subjects lost weight (body mass index 30.3 ± 1.8 kg/m2 at 1 yr). Fasting glucose was significantly lower on d 3 (P < 0.05). There was a progressive decrease in the homeostasis model assessment of insulin resistance after 2 months postoperatively. Postprandially, there was a progressive rise of GLP-1 and enteroglucagon and a transient increase in pancreatic glucagon release over the study period. There was a leftward shift of the time course of plasma glucose and insulin. Somatostatin release was lower on d 3 (P < 0.05) but then unchanged. The absorption rate of acetaminophen was twice as fast after GBP compared with before surgery and did not change over time. Satiety scores increased markedly postoperatively. Conclusion: Both enhanced insulin sensitivity and incretin hormones, such as GLP-1, contribute to the early control of glucose homeostasis. Progressively increasing postprandial levels of enteroglucagon (oxyntomodulin) and GLP-1 facilitate weight loss and enhance insulin effectiveness.
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- Guy, Lionel, et al.
(författare)
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A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen Bartonella
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:3, s. e1003393-
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Tidskriftsartikel (refereegranskat)abstract
- Gene transfer agents (GTAs) randomly transfer short fragments of a bacterial genome. A novel putative GTA was recently discovered in the mouse-infecting bacterium Bartonella grahamii. Although GTAs are widespread in phylogenetically diverse bacteria, their role in evolution is largely unknown. Here, we present a comparative analysis of 16 Bartonella genomes ranging from 1.4 to 2.6 Mb in size, including six novel genomes from Bartonella isolated from a cow, two moose, two dogs, and a kangaroo. A phylogenetic tree inferred from 428 orthologous core genes indicates that the deadly human pathogen B. bacilliformis is related to the ruminant-adapted clade, rather than being the earliest diverging species in the genus as previously thought. A gene flux analysis identified 12 genes for a GTA and a phage-derived origin of replication as the most conserved innovations. These are located in a region of a few hundred kb that also contains 8 insertions of gene clusters for type III, IV, and V secretion systems, and genes for putatively secreted molecules such as cholera-like toxins. The phylogenies indicate a recent transfer of seven genes in the virB gene cluster for a type IV secretion system from a catadapted B. henselae to a dog-adapted B. vinsonii strain. We show that the B. henselae GTA is functional and can transfer genes in vitro. We suggest that the maintenance of the GTA is driven by selection to increase the likelihood of horizontal gene transfer and argue that this process is beneficial at the population level, by facilitating adaptive evolution of the host-adaptation systems and thereby expansion of the host range size. The process counters gene loss and forces all cells to contribute to the production of the GTA and the secreted molecules. The results advance our understanding of the role that GTAs play for the evolution of bacterial genomes.
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| 10. |
- Guy, Lionel, et al.
(författare)
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A genome-wide study of recombination rate variation in Bartonella henselae
- 2012
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 12, s. 65-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rates of recombination vary by three orders of magnitude in bacteria but the reasons for this variation is unclear. We performed a genome-wide study of recombination rate variation among genes in the intracellular bacterium Bartonella henselae, which has among the lowest estimated ratio of recombination relative to mutation in prokaryotes. Results: The 1.9 Mb genomes of B. henselae strains IC11, UGA10 and Houston-1 genomes showed only minor gene content variation. Nucleotide sequence divergence levels were less than 1% and the relative rate of recombination to mutation was estimated to 1.1 for the genome overall. Four to eight segments per genome presented significantly enhanced divergences, the most pronounced of which were the virB and trw gene clusters for type IV secretion systems that play essential roles in the infection process. Consistently, multiple recombination events were identified inside these gene clusters. High recombination frequencies were also observed for a gene putatively involved in iron metabolism. A phylogenetic study of this gene in 80 strains of Bartonella quintana, B. henselae and B. grahamii indicated different population structures for each species and revealed horizontal gene transfers across Bartonella species with different host preferences. Conclusions: Our analysis has shown little novel gene acquisition in B. henselae, indicative of a closed pan-genome, but higher recombination frequencies within the population than previously estimated. We propose that the dramatically increased fixation rate for recombination events at gene clusters for type IV secretion systems is driven by selection for sequence variability.
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| 11. |
- Janek Strååt, Sara, et al.
(författare)
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Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy
- 2013
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Ingår i: Physics in Medicine and Biology. - : Institute of Physics (IOP). - 0031-9155 .- 1361-6560. ; 58:16, s. 5541-5553
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for 30 min, starting 7 min after the end of the treatment. The CT volume from the PET/CT and the treatment planning CT were coregistered by matching anatomical reference points in the patient. The treatment delivery was imaged in vivo based on the distribution of the induced positron emitters produced by photonuclear reactions in tissue mapped on to the associated dose distribution of the treatment plan. The results showed that spatial distribution of induced activity in both patients agreed well with the delivered beam portals of the treatment plans in the entrance subcutaneous fat regions but less so in blood and oxygen rich soft tissues. For the preoperative rectal cancer patient however, a 2 +/- (0.5) cm misalignment was observed in the cranial-caudal direction of the patient between the induced activity distribution and treatment plan, indicating a beam patient setup error. No misalignment of this kind was seen in the prostate cancer patient. However, due to a fast patient setup error in the PET/CT scanner a slight mis-position of the patient in the PET/CT was observed in all three planes, resulting in a deformed activity distribution compared to the treatment plan. The present study indicates that the induced positron emitters by high energy photon beams can be measured quite accurately using PET imaging of subcutaneous fat to allow portal verification of the delivered treatment beams. Measurement of the induced activity in the patient 7 min after receiving 5 Gy involved count rates which were about 20 times lower than that of a patient undergoing standard F-18-FDG treatment. When using a combination of short lived nuclides such as O-15 (half-life: 2 min) and C-11 (half-life: 20 min) with low activity it is not optimal to use clinical reconstruction protocols. Thus, it might be desirable to further optimize reconstruction parameters as well as to address hardware improvements in realizing in vivo treatment verification with PET/CT in the future. A significant improvement with regard to O-15 imaging could also be expected by having the PET/CT unit located close to the radiation treatment room.
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| 12. |
- Näslund, Joacim, 1985, et al.
(författare)
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Hatchery tank enrichment affects cortisol levels and shelter-seeking in Atlantic salmon (Salmo salar)
- 2013
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Ingår i: Canadian Journal of Fisheries and Aquatic Sciences. - : Canadian Science Publishing. - 0706-652X .- 1205-7533. ; 70:4, s. 585-590
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Tidskriftsartikel (refereegranskat)abstract
- Stocking programs using hatchery-reared salmon are often implemented for augmenting natural populations. However, survival of these fish is often low compared with wild conspecifics, possibly because of genetic, physiological, and behavioural deficiencies. Here, we compared presmolt Atlantic salmon (Salmo salar) from three different environmental treatments (barren environment, plastic tube enrichment, and plastic shredding enrichment) with regard to plasma cortisol levels, shelter-seeking behaviour, and fin deterioration. Basal plasma cortisol levels were higher in barren-reared fish, indicating higher stress levels, while no differences were found in acute cortisol response after a 30 min confinement test. Shelter-seeking was higher in salmon reared in enriched tanks when tested alone, but not when tested in small groups. Barren-reared fish had higher levels of fin deterioration over winter, potentially owing to higher aggression levels. These results suggest that enrichment can reduce the impact of stressors experienced in the hatchery and thus increase fish welfare. Tank enrichment may also be used to produce salmon better adapted for the more complex environment encountered after release.
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