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| 2. |
- Ahlstrand, Tuuli, et al.
(författare)
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A novel intrinsically disordered outer membrane lipoprotein of Aggregatibacter actinomycetemcomitans binds various cytokines and plays a role in biofilm response to interleukin-1β and interleukin-8
- 2017
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Ingår i: Virulence. - : Informa UK Limited. - 2150-5594 .- 2150-5608. ; 8:2, s. 115-134
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Tidskriftsartikel (refereegranskat)abstract
- Intrinsically disordered proteins (IDPs) do not have a well-defined and stable 3-dimensional fold. Some IDPs can function as either transient or permanent binders of other proteins and may interact with an array of ligands by adopting different conformations. A novel outer membrane lipoprotein, bacterial interleukin receptor I (BilRI) of the opportunistic oral pathogen Aggregatibacter actinomycetemcomitans binds a key gatekeeper proinflammatory cytokine interleukin (IL)-1β. Because the amino acid sequence of the novel lipoprotein resembles that of fibrinogen binder A of Haemophilus ducreyi, BilRI could have the potential to bind other proteins, such as host matrix proteins. However, from the tested host matrix proteins, BilRI interacted with neither collagen nor fibrinogen. Instead, the recombinant non-lipidated BilRI, which was intrinsically disordered, bound various pro/anti-inflammatory cytokines, such as IL-8, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-10. Moreover, BilRI played a role in the in vitro sensing of IL-1β and IL-8 because low concentrations of cytokines did not decrease the amount of extracellular DNA in the matrix of bilRI− mutant biofilm as they did in the matrix of wild-type biofilm when the biofilms were exposed to recombinant cytokines for 22 hours. BilRI played a role in the internalization of IL-1β in the gingival model system but did not affect either IL-8 or IL-6 uptake. However, bilRI deletion did not entirely prevent IL-1β internalization, and the binding of cytokines to BilRI was relatively weak. Thus, BilRI might sequester cytokines on the surface of A. actinomycetemcomitans to facilitate the internalization process in low local cytokine concentrations.
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| 3. |
- Ahlstrand, Tuuli, et al.
(författare)
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Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake
- 2018
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Ingår i: Virulence. - : Informa UK Limited. - 2150-5594 .- 2150-5608. ; 9:1, s. 1205-1223
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Tidskriftsartikel (refereegranskat)abstract
- Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43nM in static settings and 2.4M in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested -lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.
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| 4. |
- Ammar, Yosr, et al.
(författare)
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Exploring future ecosystem novelty and resilience using the adaptive cycle
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Marine ecosystems worldwide are under unprecedented pressure from the impacts of climate change and human activities. Such pressure increased novelty in species assemblages, i.e., assemblages increasingly outside their historical range of variation. It may further rise in the future, and whether it will unfold and influence resilience remains unclear. Using the adaptive cycle, we explore the relationship between resilience and novelty under the compound effect of climate, nutrient load, and fishing management scenarios in the Finnish Archipelago Sea (FAS) future food web model. Novelty was measured as the minimum dissimilarity over time relative to a specific baseline. Ecological Network Analysis indices associated to the model: ascendancy, capacity, and overhead flow, were used as indicators of connectedness, potential, and resilience axes of the adaptive cycle. A model-based clustering method distinguished four regimes determined by the impact of the nutrient load and climate on the bottom-up dynamic of the FAS food web. Resilience decreased in regimes where higher and faster novelty emerged in response to warmer climate pathways. The number of reorganization phases of the adaptive cycle, characterized by the generation of novelty, was greater in regimes under low nutrient load management scenarios. We highlight the importance of understanding ecosystem reorganization and resilience in a growing Anthropogenic novelty to inform future management.
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| 6. |
- Blanchet, F. Guillaume, et al.
(författare)
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Related herbivore species show similar temporal dynamics
- 2018
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Ingår i: Journal of Animal Ecology. - : Wiley. - 0021-8790 .- 1365-2656. ; 87:3, s. 801-812
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Tidskriftsartikel (refereegranskat)abstract
- 1. Within natural communities, different taxa display different dynamics in time. Why this is the case we do not fully know. This thwarts our ability to predict changes in community structure, which is important for both the conservation of rare species in natural communities and for the prediction of pest outbreaks in agriculture. 2. Species sharing phylogeny, natural enemies and/or life-history traits have been hypothesized to share similar temporal dynamics. We operationalized these concepts into testing whether feeding guild, voltinism, similarity in parasitoid community and/or phylogenetic relatedness explained similarities in temporal dynamics among herbivorous community members. 3. Focusing on two similar datasets from different geographical regions (Finland and Japan), we used asymmetric eigenvector maps as temporal variables to characterize species-and community-level dynamics of specialist insect herbivores on oak (Quercus). We then assessed whether feeding guild, voltinism, similarity in parasitoid community and/or phylogenetic relatedness explained similarities in temporal dynamics among taxa. 4. Species-specific temporal dynamics varied widely, ranging from directional decline or increase to more complex patterns. Phylogeny was a clear predictor of similarity in temporal dynamics at the Finnish site, whereas for the Japanese site, the data were uninformative regarding a phylogenetic imprint. Voltinism, feeding guild and parasitoid overlap explained little variation at either location. Despite the rapid temporal dynamics observed at the level of individual species, these changes did not translate into any consistent temporal changes at the community level in either Finland or Japan. 5. Overall, our findings offer no direct support for the notion that species sharing natural enemies and/or life-history traits would be characterized by similar temporal dynamics, but reveal a strong imprint of phylogenetic relatedness. As this phylogenetic signal cannot be attributed to guild, voltinism or parasitoids, it will likely derive from shared microhabitat, microclimate, anatomy, physiology or behaviour. This has important implications for predicting insect outbreaks and for informing insect conservation. We hope that future studies will assess the generality of our findings across plant-feeding insect communities and beyond, and establish the more precise mechanism(s) underlying the phylogenetic imprint.
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| 7. |
- Eskelund, Christian W., et al.
(författare)
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15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2) : prolonged remissions without survival plateau
- 2016
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 175:3, s. 410-418
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Tidskriftsartikel (refereegranskat)abstract
- In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
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| 8. |
- Hellevuo, Heidi, et al.
(författare)
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Deeper chest compression - More complications for cardiac arrest patients?
- 2013
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 84:6, s. 760-765
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Tidskriftsartikel (refereegranskat)abstract
- Aim of the study: Sternal and rib fractures are frequent complications caused by chest compressions during cardiopulmonary resuscitation (CPR). This study aimed to investigate the potential association of CPR-related thoracic and abdominal injuries and compression depth measured with an accelerometer. Methods: We analysed the autopsy records, CT scans or chest radiographs of 170 adult patients, suffering in-hospital cardiac arrest at the Tampere University Hospital during the period 2009-2011 to investigate possible association of chest compressions and iatrogenic injuries. The quality of manual compressions during CPR was recorded on a Philips, HeartStart MRx Q-CPR (TM)-defibrillator. Results: Patients were 110 males and 60 females. Injuries were found in 36% of male and 23% of female patients. Among male patients CPR-related injuries were associated with deeper mean - and peak compression depths (p < 0.05). No such association was observed in women. The frequency of injuries in mean compression depth categories <5, 5-6 and >6 cm, was 28%, 27% and 49% (p = 0.06). Of all patients 27% sustained rib fractures, 11% sternal fracture and eight patients had haematomas/ruptures in the myocardium. In addition, we observed one laceration of the stomach without bleeding, one ruptured spleen, one mediastinal haemorrhage and two pneumothoraxes. Conclusion: The number of iatrogenic injuries in male patients was associated with chest compressions during cardiopulmonary resuscitation increased as the measured compression depth exceeded 6 cm. While there is an increased risk of complications with deeper compressions it is important to realize that the injuries were by and large not fatal.
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| 9. |
- Husby, Simon, et al.
(författare)
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miR-18b overexpression identifies mantle cell lymphoma patients with poor outcome and improves the MIPI-B prognosticator
- 2015
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 125:17, s. 2669-2677
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies show that mantle cell lymphoma (MCL) express aberrant microRNA (miRNA) profiles; however, the clinical effect of miRNA expression has not previously been examined and validated in large prospective homogenously treated cohorts. We performed genome-wide miRNA microarray profiling of 74 diagnostic MCL samples from the Nordic MCL2trial (screening cohort). Prognosticmi RNAs were validated in diagnostic MCL samples from 94 patients of the independent Nordic MCL3 trial (validation cohort). Three miRNAs (miR-18b, miR-92a, and miR-378d) were significantly differentially expressed in patients who died of MCL in both cohorts. MiR-18b was superior to miR-92a and miR-378d in predicting high risk. Thus, we generated a new biological MCL International Prognostic Index (MIPI-B)-miR prognosticator, combining expression levels of miR-18b with MIPI-B data. Compared to the MIPI-B, this prognosticator improved identification of high-risk patients with regard to cause-specific, overall, and progression free survival. Transfection of 2 MCL cell lines with miR-18b decreased their proliferation rate without inducing apoptosis, suggesting that miR-18b may render MCL cells resistant to chemotherapy by decelerating cell proliferation. We conclude that overexpression of miR-18b identifies patients with poor prognosis in 2 large prospective MCL cohorts and adds prognostic information to the MIPI-B. MiR-18b may reduce the proliferation rate of MCL cells as a mechanism of chemoresistance.
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