| 1. |
- Alalam, Hanna, et al.
(författare)
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A High-Throughput Method for Screening for Genes Controlling Bacterial Conjugation of Antibiotic Resistance.
- 2020
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Ingår i: mSystems. - 2379-5077. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- The rapid horizontal transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high-throughput. We then mix the resistance plasmid-carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals, and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within Escherichia coli populations, by screening the Keio deletion collection in high replication. We recover all seven known chromosomal gene mutants affecting conjugation as donors and identify many novel mutants, all of which diminish antibiotic resistance transmission. We validate nine of the novel genes' effects in liquid mating assays and complement one of the novel genes' effect on conjugation (rseA). The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improve the longevity of current and future antibiotics. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.IMPORTANCE The rapid transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within E. coli populations. We recover all previously known and many novel chromosomal gene mutants that affect conjugation efficiency. The new framework holds great potential for rapid screening of compounds that decrease transmission. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.
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| 2. |
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| 3. |
- Alalam, Hanna, et al.
(författare)
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Conjugation factors controlling F-plasmid antibiotic resistance transmission
- 2018
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Ingår i: BioRxiv. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The rapid horizontal transmission of many antibiotic resistance genes between bacterial host cells on conjugative plasmids is a major cause of the accelerating antibiotic resistance crisis. Preventing understanding and targeting conjugation, there currently are no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation. We introduce a novel experimental framework to screen for conjugation based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high throughput. We then mix the resistance plasmid carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explored chromosomal genes controlling F plasmid donation within E. coli populations, by screening the Keio deletion collection at high replication. We recover all six known chromosomal gene mutants affecting conjugation and identify >50 novel factors, all of which diminish antibiotic resistance transmission. We verify 10 of the novel genes' effects in a liquid mating assay. The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improves the longevity of current and future antibiotics.
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| 4. |
- Augustsson, Evelina, et al.
(författare)
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Density-dependent dinner: Wild boar overuse agricultural land at high densities
- 2024
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Ingår i: European Journal of Wildlife Research. - 1612-4642 .- 1439-0574. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish wild boar (Sus scrofa) population has increased rapidly over the last decades, resulting in conflicts with human activities. Particularly, the increase has been challenging for agriculture as wild boar cause damage on crops and grasslands. To predict under what conditions to expect damage and where to prioritize management actions, basic knowledge about wild boar habitat and space use is needed. In this study, we used data from 99 wild boar equipped with GPS-collars, collected over a large temporal scale and throughout their distributional range in southern Sweden. We investigated wild boar home range size and habitat use across gradients of habitat availability and population density. Functional response in habitat use was assessed by estimating the use and availability of agricultural land on individual level and then, on population-level evaluating how use changed with changing availability. Finally, a potential response in habitat use was evaluated in relation to population density, i.e., the interaction between availability and population density. Home range size was negatively related to population density for both male and female wild boar. Wild boar used agricultural land more intensively with increasing population density and when other habitat types were less available. Our findings show that wild boar spatial behavior is highly context dependent and may vary considerably due to landscape characteristics and local conditions. Wild boars tend to overuse agricultural land at high densities which has strong implications for wildlife management. It is therefore important to consider local conditions when predicting space and habitat use by wild boar. Overall, this study provided a better understanding of the drivers of wild boar distribution and space use in agro-forested mosaic landscapes and how this knowledge can improve management practices.
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| 6. |
- den Hollander, J, et al.
(författare)
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Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:9, s. 1498-1505
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Tidskriftsartikel (refereegranskat)abstract
- Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans. The induction of Aurka by Myc is transcriptional and is directly mediated via E-boxes, whereas Aurkb is regulated indirectly. Blocking Aurka/b kinase activity with a selective Aurora kinase inhibitor triggers transient mitotic arrest, polyploidization, and apoptosis of Myc-induced lymphomas. These phenotypes are selectively bypassed by a kinase inhibitor-resistant-Aurkb mutant, demonstrating that Aurkb is the primary therapeutic target in the context of Myc. Importantly, apoptosis provoked by Aurk inhibition was p53 independent, suggesting that Aurka/Aurkb inhibitors will show efficacy in treating primary or relapsed malignancies having Myc involvement and/or loss of p53 function. (Blood. 2010;116(9):1498-1505)
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| 7. |
- Ericsson, Elisabeth, 1959-, et al.
(författare)
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Child Behavior and Quality of Life Before and After Tonsillotomy versus Tonsillectomy
- 2008
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Ingår i: Swedish Sleep Medicine Congress.
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Konferensbidrag (refereegranskat)abstract
- Objective: to compare two techniques for tonsil surgery with respect to postoperative pain and morbidity and changes in sleep, behavior, health related quality of life (HRQL) and benefit due to surgery. Methods: 67 pre-school children with tonsillar hypertrophy were randomized to regular tonsillectomy (TE) or tonsillotomy (TT) with Radiofrequency surgical technique. The parents completed a validated quality of life survey, Obstructive Sleep Apnea-18 (OSA18) , assessed the children’s behavior with the Child Behavior Checklist (CBCL) before and six month after surgery and evaluated the post-operative health related benefits using the Glasgow Children’s Benefit Inventory (GCBI). Results: TT-children recorded less pain from the first day, and were pain-free 3 days earlier than TE-children. Six months post-surgery, there was no difference between TT and TE with regard to snoring and ENT-infections. The total scores in all the individual domains between the initial OSA-18 and post-surgery scores differed (p<0.0001). Improvement in CBCL score was also significant (p<0.01) . There were no differences between TT- and TE-children. GCBI indicated a significant health benefit of both methods. Conclusions: Tonsillar hypertrophy shows impact on HRQL and behavior. After tonsillar operation, improvements occur as much after TT as after TE. TT should be first choice for treatment.
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| 8. |
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| 9. |
- Ericsson, Elisabeth, 1959-, et al.
(författare)
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Child behavior and quality of life before and after tonsillotomy versus tonsillectomy
- 2008
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Ingår i: International conference in pediatric otorhinolaryngology, 2008. ; , s. 40-40
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The objective of the present investigation was to compare two techniques for pediatric tonsil surgery with respect to postoperative pain and morbidity and changes in sleep behavior, health related quality of life (HRQL) and benefit due to surgery. Methods: 67 children (4,5-5,5 years) with tonsillar hypertrophy and obstructive sleep related distress with or without recurrent tonsillitis were randomized to either regular tonsillectomy (TE)(n=32) or intracapsular tonsillectomy/tonsillotomy (TT) (n=35) with Radiofrequency surgical technique (Ellman Int) Before TT/TE, the parents completed a validated Quality of Life survey of pediatric obstructive sleep apnea, the OSA18 (Obstructive Sleep Apnea-18) and a standardized assessment of their children-s behavior with the Child Behavior Checklist (CBCL). Six months after surgery, the parents repeated these measurements, and assessed the health related benefits of the surgery using the Glasgow Children´s Benefit Inventory (GCBI). Results: In the TT group, the children recorded less pain from the first day after surgery onwards, used fewer doses of painkillers and were pain-free 3 days earlier than the children in the TE group. Six months after surgery, there was no significant difference between TT and TE with regard to snoring and ENT-infections. The differences were all significant in the total scores and in all the individual domains between the initial OSA-18 and post-surgery scores (p<0.0001). The improvement in the total problem score measured with CBCL was also significant (p<0.01) and there were no differences between the TT and TE children. The improvements in all sub scores of the GCBI indicated a significant health benefit of both TT and TE. Conclusions: TT with RF-surgery is a safe method, which causes less pain and postoperative morbidity than regular TE and has a similar effect on snoring and recurrent infections. Young children with tonsillar hypertrophy and different degrees of obstructive sleep related distress all show an impact on HRQL and behavior. All improve dramatically after a tonsillar operation-improving just as much after TT as after TE. Based on these results, TT should be the first choice for treatment of these small children. Support: Financial support from the Research Council of South East Sweden (FORSS).
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| 10. |
- Ericsson, Elisabeth, 1959-, et al.
(författare)
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Intracapsular tonsillectomy with RF-surgery : Effects on snoring one-year results
- 2004
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Ingår i: 17th congress of the European Sleep research Sociaty, Prag, Tjeckien 5-9 okt, 2004.
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Konferensbidrag (refereegranskat)abstract
- Objektive: To compare two techniques for pediatric tonsil surgery with respect to postoperative pain and the long-term effects (one year) on snoring. Methods: 92 children with a history of snoring and few to several tonsillitis, were randomized to either regular tonsillectomy (T)(n=43) or intracapsular tonsillectomy (TT) with RF surgical technique, where only the obstructive parts of the tonsils were removed. Results: In the TT group, the children recorded less pain from the second hour after surgery onwards, and were back in school and pain-free 3 days earlier than the children in the T group. The TT children used fewer doses of painkillers and did not lose weight postoperatively compared to the T-children, who lost a mean of 660g in 10 days. Effect on snoring was the same in both groups. One year after surgery, some children in both groups still had slight snoring, but no apneás. Both groups were satisfied and in good health. The T-children remembered their pain more than TT-children. A surgical technique, which results in less suffering and a shorter time the child and a parent have to stay at home postoperatively, is a health- and socioeconomic gain. Is it defendable to continue performing traditional tonsillectomy? Intracapsular tonsillectomy with RF-surgery is a safe method, which causes less pain and morbidity than regular tonsillectomy and has the same effect on snoring.
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