| 1. |
- Ahonen, Hanna
(författare)
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The multifaceted concept of oral health : Studies on a Swedish general population and perspectives of persons with experience of long-term CPAP-treated obstructive sleep apnea
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Oral health is a multifaceted and changeable part of our overall health and well-being as it contributes to important everyday functions such as eating, talking, and conveying feelings. Our oral health can be affected by a range of determinants, one of which is obstructive sleep apnea [OSA] treated with continuous positive airway pressure [CPAP]. Even though xerostomia has been frequently reported upon, the possible relationship between oral health and CPAP-treated OSA is not clearly understood. The World Dental Federation [FDI] recently proposed a definition and theoretical framework of oral health, intended to be globally applicable and to move dentistry toward a more promotive approach. By using the FDI’s framework as a basis for exploration, studies in a general population can increase the understanding of different aspects of oral health and set the frame of reference for whether and how CPAP-treated OSA can be experienced to affect a person’s oral health.The overall aim of this thesis was to gain a deeper understanding of how the FDI’s theoretical framework of oral health can be applied in a general population and how oral health is experienced in a specific population of persons with increased risk for adverse oral health.The FDI’s framework was explored with empirical data from a general population (N=630) and a population of persons with experience of CPAP-treated OSA (N=18). In papers I and II, the FDI framework was tested and evaluated with quantitative methods (principal component analysis and structural equation modeling), using cross-sectional data from the Jönköping studies. In papers III and IV, qualitative methods (directed content analysis and critical incident technique) were used where personal views and experiences were explored using individual semi-structured interviews.The findings in paper I showed that factors such as dental caries, periodontal disease, experience of xerostomia, and aesthetic satisfaction can be included in the FDI’s component the core elements of oral health. In paper II, driving determinants and moderating factors were found to have direct effects on all core elements of oral health except aesthetic satisfaction. Three of the core elements of oral health (oral health-related quality of life, aesthetic satisfaction, and xerostomia) had direct effects on the latent variable overall health and well-being. Driving determinants and moderating factors had no direct effect on overall health and well-being, and no indirect effects were found. In paper III, the study participants’ views on oral health determinants were described and could be categorized into all the FDI framework dimensions. The component driving determinants could include a range of determinants affecting a person’s oral health such as CPAP treatment, age, the influence of family and social surroundings, interdental cleaning, willingness to change when needed, and relationship with oral healthcare professionals. In paper IV, the study participants described both negative and positive experiences occurring with or without their CPAP. The negative experiences included increased xerostomia, pain or discomfort, tooth wear, and negative feelings. The positive experiences included decreased xerostomia and improved oral health habits due to improved sleep. Many of the difficulties could be managed by easily accessible facilitators. The experiences the study participants described could be included in all the FDI framework components.In conclusion, the FDI’s framework can be applied in a general population to describe different components of oral health, and is also useful to describe a person’s views and experiences of oral health in a specific population. CPAP treatment could be considered an oral health determinant as it can affect a person’s oral health. Both positive and negative experiences can contribute to CPAP adherence as negative experiences often can be successfully managed.
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| 2. |
- Cheng, Fang, et al.
(författare)
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Complex modulation of cytokine-induced α-synuclein aggregation by glypican-1-derived heparan sulfate in neural cells
- 2022
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 32:4, s. 333-342
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Tidskriftsartikel (refereegranskat)abstract
- In Parkinson's disease (PD), there is accumulation of α-synuclein (SYN) aggregates in neurons, which is promoted by neuroinflammation. The cytokines TNF-α, IL-1β and IL-6 induce accumulation of degradation products of the amyloid precursor protein (APP) combined with heparan sulfate (HS) chains released from glypican-1 (Gpc-1) by NO-dependent cleavage. We have investigated the effects of the cytokines and HS on SYN aggregation and secretion in dividing human neuroblastoma (SH-SY5Y) and inducible neural progenitor cells (NPC) by using immunofluorescence microscopy, vesicle isolation and slot blotting with antibodies recognizing SYN monomers and aggregates, Gpc-1, the released HS, endosomes, and autophagosomes. In SH-SY5Y cells, the capacity to release HS was fully utilized, while NPC displayed dormant capacity. TNF-α induced increased formation of SYN aggregates and clustering of HS in SH-SY5Y cells. When the supply of NO was simultaneously increased, SYN and HS accumulation disappeared. When NO formation was inhibited, SYN and HS aggregation also disappeared, but there was now a 4-fold increase in SYN secretion. In NPC, IL-6 induced increased aggregation of SYN and stimulated HS release from Gpc-1. Both SYN and HS co-localized with autophagosome marker. When HS-deficient Gpc-1 was simultaneously generated, by using a cyanobacterial neurotoxin, accumulation diminished and there was massive secretion of SYN. We suggest that the cytokines increase APP processing, which initiates NO-dependent release of HS from Gpc-1. The APP degradation products also trigger SYN aggregation. As HS can inhibit APP processing, HS-or NO-deficiency may result in autophagosomal dysfunction and both APP degradation products and SYN are secreted.
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| 3. |
- Cheng, Fang, et al.
(författare)
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Interplay between APP and glypican-1 processing and α-synuclein aggregation in undifferentiated and differentiated human neural progenitor cells
- 2023
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 33:4, s. 325-341
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Tidskriftsartikel (refereegranskat)abstract
- In Parkinson’s disease, there is an accumulation of α-synuclein (SYN) aggregates in neurons, which is promoted by neuroinflammation. In neural cells, cytokine-induced SYN aggregation is modulated by heparan sulfate (HS) derived from glypican-1 (GPC1) by amyloid precursor protein (APP) and nitric oxide (NO)-dependent cleavage. We have explored possible interplay between APP, GPC1, and SYN in undifferentiated and differentiated neural progenitor cells (NPCs) by modulating APP and GPC1 processing. Effects were monitored by immunofluorescence microscopy and slot immunoblotting using antibodies recognizing APP degradation products, HS released from GPC1, and SYN aggregates (filamentous SYN [SYNfil]). Suppression of HS release from GPC1 by inhibition of β-secretase or by NO deprivation resulted in no or slight increase in SYNfil aggregation. Stimulation of HS release by ascorbate did not further increase SYNfil staining. Interleukin-6 (IL-6) induced increased APP and GPC1 processing and SYNfil formation, which was reduced when βsecretase was inhibited and when HS release was impeded by NO deprivation. Ascorbate restored APP and GPC1 processing but did not affect SYNfil formation. Ascorbate-dependent differentiation of NPC resulted in the expression of tyrosine hydroxylase (TH) which colocalized with SYNfil. Suppression of APP processing by inhibition of β-secretase greatly disturbed the differentiation process. IL-6 induced coclustering of APP-degradation products, TH, HS, and SYNfil, which could be reversed by stimulation of HS release from GPC1 by excess ascorbate. We suggest that continuous release of HS from GPC1 moderates SYN aggregation and supports differentiation of NPC to dopaminergic neurons.
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| 4. |
- Cheng, Fang, et al.
(författare)
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Proinflammatory cytokines induce accumulation of glypican-1-derived heparan sulfate and the C-terminal fragment of β-cleaved APP in autophagosomes of dividing neuronal cells
- 2020
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 30:8, s. 539-549
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Tidskriftsartikel (refereegranskat)abstract
- Proinflammatory cytokines stimulate expression of β-secretase, which increases processing of amyloid precursor protein (APP), ultimately leading to the deposition of amyloid beta (Aβ). The N-terminal domain of β-cleaved APP supports Cu/NO-dependent release of heparan sulfate (HS) from the glypican-1 (Gpc-1) proteoglycan. HS is an inhibitor of β-secretase, thereby constituting a regulatory, negative feedback loop. Here, we have investigated the effect of the proinflammatory cytokines TNF-α, IL-1β and IL-6 on the interplay between APP processing and release of HS from Gpc-1 in neuronal cells. We have used deconvolution immunofluorescence microscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and a panel of monoclonal/polyclonal antibodies recognizing the released HS, the N-terminus of Aβ, Aβ, the C-terminus of APP and the autophagosome marker LC3 as well as the chemical lysosome marker LysoTrackerRed (LTR). We repeatedly found that N2a neuroblastoma cells and human neural stem cells grown in the presence of the cytokines developed large cytoplasmic clusters, which stained positive for HS, the N-terminus of Aβ, Aβ, the C-terminus of APP, LC3 and LTR, indicating accumulation of HS and APP/APP degradation products in enlarged autophagosomes/lysosomes. The SDS-PAGE of immunoisolates obtained from TNF-α-treated N2a cells by using anti-C-terminus of APP revealed the presence of SDS-stable complexes between HS and the C-terminal fragment of β-cleaved APP (βCTF) migrating in the range 10-18 kDa. Clustered accumulation of βCTF disappeared when HS release was prevented and slightly enhanced when HS release was increased. Hence, when proinflammatory cytokines induce increased processing of APP, inhibition of β-secretase by HS is insufficient, which may lead to the impaired autophagosomal degradation.
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| 5. |
- Cheng, Fang, et al.
(författare)
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Reversal of apolipoprotein E4-dependent or chemical-induced accumulation of APP degradation products by vitamin C-induced release of heparan sulfate from glypican-1
- 2021
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 31:7, s. 800-811
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Tidskriftsartikel (refereegranskat)abstract
- The Apolipoprotein E4 (ApoE4) genotype is the most influential risk factor for sporadic Alzheimer's disease. It appears to be associated with retarded endosome-to-autophagosome trafficking. The amyloid precursor protein (APP) and the heparan sulfate (HS)-containing proteoglycan glypican-1 (Gpc-1) are both processed in endosomes, and mutually regulated by the APP degradation products and the released HS. We have investigated APP and Gpc-1 processing in ApoE3 and ApoE4 expressing human fibroblasts, in human neural stem cells (NSC) exposed to the cholesterol transport inhibitor U18666A and in induced neurons obtained by reprogramming of ApoE fibroblasts (ApoE-iN). We have used immunofluorescence microscopy, flow cytometry, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis western blotting with antibodies recognizing the released HS, APP, amyloid β(Aβ), late endosomes (Rab7), autophagosomes (LC3) and neurons (Tuj1). We found that the capacity to release HS was not fully utilized in ApoE4 expressing fibroblasts and that HS-Aβ complexes accumulated in the nuclei. In ApoE3 fibroblasts, the β-cleaved APP C-terminal fragment (β-CTF) and Aβ were primarily present in late endosomes and autophagosomes. When HS release from Gpc-1 was enhanced by ascorbate in ApoE4/4 fibroblasts, there was efficient transfer of Aβ and HS from the nuclei to autophagosomes. In U18666A-treated NSC as well as in ApoE4/4-iN we repeatedly found accumulation of APP degradation products (β-CTF/Aβ). This was reversed by subsequent exposure to ascorbate or dehydroascorbic acid.
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| 6. |
- Fransson, Peter, 1988-, et al.
(författare)
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A simulation-based approach to a near optimal thinning strategy : allowing for individual harvesting times for individual trees
- 2020
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Ingår i: Canadian Journal of Forest Research. - : Canadian Science Publishing. - 0045-5067 .- 1208-6037. ; 50:3, s. 320-331
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Tidskriftsartikel (refereegranskat)abstract
- As various methods for precision inventories, such as LiDAR, are becoming increasingly common in forestry, individual-tree level planning is becoming more viable. Here, we present a method for finding the optimal thinning times for individual trees from an economic perspective. The method utilizes an individual tree-based forest growth model that has been fitted to Norway spruce (Picea abies (L.) Karst.) stands in northern Sweden. We find that the optimal management strategy is to thin from above, i.e. harvesting trees that are larger than average. We compare our optimal strategy with a conventional management strategy and find that it results in approximately 20% higher land expectation value. Furthermore, we find that increasing the discount rate will, for the optimal strategy, reduce the final harvest age and increase the basal area reduction. Decreasing the cost to initiate a thinning (e.g., machinery-related transportation costs) increases the number of thinnings and delays the first thinning.
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| 7. |
- Fransson, Peter, 1988-, et al.
(författare)
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A tree’s quest for light : optimal height and diameter growth under a shading canopy
- 2021
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Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 0829-318X .- 1758-4469. ; 41:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- For trees in forests, striving for light is matter of life and death, either by growing taller toward brighter conditions or by expanding the crown to capture more of the available light. Here, we present a mechanistic model for the development path of stem height and crown size, accounting for light capture and growth, as well as mortality risk. We determine the optimal growth path among all possible trajectories using dynamic programming. The optimal growth path follows a sequence of distinct phases: (i) initial crown size expansion, (ii) stem height growth toward the canopy, (iii) final expansion of the crown in the canopy and (iv) seed production without further increase in size. The transition points between these phases can be optimized by maximizing fitness, defined as expected lifetime reproductive production. The results imply that to reach the canopy in an optimal way, trees must consider the full profile of expected increasing light levels toward the canopy. A shortsighted maximization of growth based on initial light conditions can result in arrested height growth, preventing the tree from reaching the canopy. The previous result can explain canopy stratification, and why canopy species often get stuck at a certain size under a shading canopy. The model explains why trees with lower wood density have a larger diameter at a given tree height and grow taller than trees with higher wood density. The model can be used to implement plasticity in height versus diameter growth in individual-based vegetation and forestry models.
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| 8. |
- Hoffman, Tove, et al.
(författare)
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A divergent Anaplasma phagocytophilum variant in an Ixodes tick from a migratory bird; Mediterranean basin
- 2020
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Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686 .- 2000-8686. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Anaplasma phagocytophilum (AP) has vast geographical and host ranges and causes disease in humans and domesticated animals. We investigated the role of northward migratory birds in the dispersal of tick-borne AP in the African-Western Palearctic.Ticks were collected from northward migratory birds trapped during spring migration of 2010 at two localities in the central Mediterranean Sea. AP DNA was detected by PCR (gltA and 16S rRNA) and variant determination was performed using ankA sequences.In total, 358 ticks were collected. One of 19 ticks determined as Ixodes was confirmed positive for AP DNA. The tick was collected from a woodchat shrike (Lanius senator senator) trapped in Greece, and molecularly determined to belong to the I. ricinus complex and sharing highest (95%) 16S RNA sequence identity to I. gibbosus. The ankA AP sequence exhibited highest similarity to sequences from rodents and shrews (82%) and ruminants (80%). Phylogenetic analyses placed it convincingly outside other clades, suggesting that it represents a novel AP variant.The divergent Ixodes species harboring a novel AP variant could either indicate an enzootic cycle involving co-evolution with birds, or dissemination from other regions by avian migration. None of the 331 Hyalomma marginatum sensu lato ticks, all immature stages, were positive for AP DNA, lending no evidence for the involvement of Hyalomma ticks transported by birds in the ecology of AP.
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| 9. |
- Hoffman, Tove, et al.
(författare)
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Association between guilds of birds in the African-Western Palaearctic region and the tick species Hyalomma rufipes, one of the main vectors of Crimean-Congo hemorrhagic fever virus
- 2021
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Ingår i: One Health. - : Elsevier. - 2352-7714. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe ecology of the vertebrate host contributes to the geographical range expansion of ticks. In this study, we investigated which tick taxa that infest and are dispersed by birds along African-Western Palaearctic flyways during northward migration, and whether bird ecology was associated with tick taxa.Materials and methodsTicks were collected from birds trapped at bird observatories in Spain, Italy, Greece, and Israel during the spring migration of 2014 and 2015, using mist nets. The tick-infested bird species were classified into guilds, using different combinations of the variables: migration distance, wintering region, foraging behaviour, and winter habitat. Ticks were molecularly determined to genus and species level by sequencing fragments of the 12S ribosomal DNA (rDNA) gene and by phylogenetic inference, using the Maximum Likelihood algorithm. Data were analysed using descriptive measures, graphs, Chi2 tests, the Tukey-Kramer test, and a parametric linear model (generalized linear model) in order to analyse and adjust for characteristics in the bird guilds and their relationship to collected tick taxa.ResultsMost (84.2%) of the 10,209 trapped birds were long-distance migrants, of which 2.4% were infested by ticks. The most common tick species was Hyalomma rufipes (77.7%; 447/575), a known vector and reservoir of Crimean-Congo hemorrhagic fever virus. Bird guilds containing only long-distance migrants with wintering areas in Africa were associated with the tick species H. rufipes (p < 0.0001). Furthermore, bird winter habitat was associated with H. rufipes (p = 0.003); with bird species overwintering in open habitat (p = 0.014) and wetlands (p = 0.046) having significantly more H. rufipes as compared to birds with a winter habitat comprising forest and shrubs (p = 0.82).ConclusionsWith climate change, the likelihood of establishment of permanent Hyalomma populations in central and northern Europe is increasing. Thus, surveillance programs for monitoring the risk of introduction and establishment of H. rufipes in the Western-Palaearctic should be established. Our study suggests that migratory bird species wintering in African open habitats and wetlands are good candidates for monitoring potential introduction.
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| 10. |
- Hoffman, Tove, et al.
(författare)
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Association between guilds of birds in the African-Western Palaearctic region and the tick species Hyalomma rufipes, one of the main vectors of Crimean-Congo hemorrhagic fever virus.
- 2022
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Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The migratory behavior of wild birds contributes to the geographical spread of ticks and their microorganisms. In this study, we aimed to investigate the dispersal and co-occurrence of Francisella and spotted fever group Rickettsia (SFGR) in ticks infesting birds migrating northward in the African-Western Palaearctic region (AWPR). Birds were trapped with mist nests across the Mediterranean basin during the 2014 and 2015 spring migration. In total, 575 ticks were collected from 244 birds. We screened the ticks for the species Francisella tularensis, the genus Francisella, and SFGR by microfluidic real-time PCR. Confirmatory analyses and metagenomic sequencing were performed on tick samples that putatively tested positive for F. tularensis during initial screenings. Hyalomma rufipes was the most common tick species and had a high prevalence of Francisella, including co-occurrence of Francisella and SFGR. Metagenomic analysis of total DNA extracted from two H. rufipes confirmed the presence of Francisella, Rickettsia, and Midichloria. Average nucleotide identity and phylogenetic inference indicated the highest identity of the metagenome-assembled genomes to a Francisella-like endosymbiont (FLE), Rickettsia aeschlimannii, and Midichloria mitochondrii. The results of this study suggest that (i) FLE- and SFGR-containing ticks are dispersed by northbound migratory birds in the AWPR, (ii) H. rufipes likely is not involved in transmission of F. tularensis in the AWPR, and (iii) a dual endosymbiosis of FLEs and Midichloria may support some of the nutritional requirements of H. rufipes.
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