| 1. |
- Jönsson, Mats, et al.
(författare)
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Initiation of the decorin glycosaminoglycan chain in the endoplasmic reticulum-Golgi intermediate compartment
- 2003
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 278:24, s. 21415-21420
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Tidskriftsartikel (refereegranskat)abstract
- We have transiently expressed decorin with a C- terminal KDEL endoplasmic reticulum retention signal peptide in COS- 7 cells to study initiation of galactosaminoglycan synthesis in the endoplasmic reticulum- Golgi intermediate compartment. All decorin- KDEL molecules were substituted with N- linked oligosaccharides sensitive to endoglycosidase H, indicating that the core protein was located proximal to the medial- Golgi. O-Linked glycosylation was only initiated in a minor fraction of the molecules. The O- linked saccharides were characterized by gel filtration after stepwise degradations using chondroitin ABC/ AC-I lyases, beta1 - 3- glycuronidase, beta-galactosidase, and alkaline phosphatase. The major O- linked saccharide was the linkage region pentasaccharide GalNAcbeta1-4GlcUAbeta1-3Galbeta1-3Galbeta1-4-Xyl- 2- phosphate, demonstrating initiation of chondroitin synthesis in the endoplasmic reticulum- Golgi intermediate compartment. In the presence of brefeldin A, partial elongation of a chondroitin chain took place, indicating retrieval of polymerases but not of sulfotransferases.
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| 2. |
- Wallensten, Anders, et al.
(författare)
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Surveillance of influenza A virus in migratory waterfowl in northern Europe
- 2007
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Ingår i: Emerging Infectious Diseases. - 1080-6040 .- 1080-6059. - 1080-6040 ; 13:3, s. 404-411
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Tidskriftsartikel (refereegranskat)abstract
- We conducted large-scale, systematic sampling of influenza type A virus in migratory waterfowl (mostly mallards [Anas platyrhynchos]) at Ottenby Bird Observatory, southeast Sweden. As with previous studies, we found a higher prevalence in fall than spring, and among juveniles compared with adults. However, in contrast to other studies, we found that prevalence in spring was sometimes high (mean 4.0%, highest 9.5%). This finding raises the possibility that ducks are capable of perpetuating influenza A virus of different subtypes and subtype combinations throughout the year and from 1 year to the next. Isolation of the H5 and H7 subtypes was common, which suggests risk for transmission to sensitive domestic animals such as poultry. We argue that wild bird screening can function as a sentinel system, and we give an example of how it could have been used to forecast a remote and deadly outbreak of influenza A in poultry.
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| 3. |
- 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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| 4. |
- Aili, Ulrika, et al.
(författare)
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Attenuation of tumor growth by formation of antiproliferative glycosaminoglycans correlates with low acetylation of histone H3.
- 2010
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Ingår i: Cancer Research. - 1538-7445. ; 70:9, s. 3771-3779
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Tidskriftsartikel (refereegranskat)abstract
- Glycosaminoglycan (GAG) chains anchored to core proteins form proteoglycans, widely distributed cell-surface macromolecules with multiple functions, such as regulation of growth factor and cytokine signaling, cell-cell interactions, and uptake of biomolecules. The biosynthesis of GAG can be manipulated by xylosides attached to various hydrophobic groups, and we have earlier reported that a naphthoxyloside, 2-(6-hydroxynaphthyl) beta-D-xylopyranoside (XylNapOH), which serves as a primer for GAG synthesis, reduces tumor load up to 97% in vivo, despite lower efficiency in vitro. Here we show, using radiolabeled xylosides and coculture experiments, that XylNapOH-treated bladder and breast carcinoma cells secrete antiproliferative GAG chains that are taken up by both normal and cancer cells and transported to the cell nuclei where they induce an antiproliferative effect, accompanied by apoptosis. We also show that XylNapOH treatment lowers the level of histone H3 acetylation selectively in bladder and breast carcinoma cells without affecting expression of histone H3. However, XylNapOH-primed GAG chains from normal cells are not internalized and do not cause growth retardation. Using in vitro and in vivo C6 glioma cell and tumor models, we show that XylNapOH is much more effective in vivo than in vitro. We propose that, in vivo, the antiproliferative XylNapOH-primed GAG chains produced by tumor cells inhibit tumor growth in an autocrine fashion by formation of antiproliferative GAG chains on the xyloside prodrug, whereas no antiproliferative GAG chains are produced by surrounding normal cells. This is a novel mechanism for targeting tumor cells, making these xylosides promising drug candidates for antitumor therapy.
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| 5. |
- Belting, Mattias, et al.
(författare)
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Glypican-1 is a vehicle for polyamine uptake in mammalian cells. A pivotal role for nitrosothiol-derived nitric oxide.
- 2003
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 278:47, s. 47181-47189
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Tidskriftsartikel (refereegranskat)abstract
- Polyamines (putrescine, spermidine, and spermine) are essential for growth and survival of all cells. When polyamine biosynthesis is inhibited, there is up-regulation of import. The mammalian polyamine transport system is unknown. We have previously shown that the heparan sulfate (HS) side chains of recycling glypican-1 (Gpc-1) can sequester spermine, that intracellular polyamine depletion increases the number of NO-sensitive N-unsubstituted glucosamines in HS, and that NO-dependent cleavage of HS at these sites is required for spermine uptake. The NO is derived from S-nitroso groups in the Gpc-1 protein. Using RNA interference technology as well as biochemical and microscopic techniques applied to both normal and uptake-deficient cells, we demonstrate that inhibition of Gpc-1 expression abrogates spermine uptake and intracellular delivery. In unperturbed cells, spermine and recycling Gpc-1 carrying HS chains rich in N-unsubstituted glucosamines were co-localized. By exposing cells to ascorbate, we induced release of NO from the S-nitroso groups, resulting in HS degradation and unloading of the sequestered polyamines as well as nuclear targeting of the deglycanated Gpc-1 protein. Polyamine uptake-deficient cells appear to have a defect in the NO release mechanism. We have managed to restore spermine uptake partially in these cells by providing spermine NONOate and ascorbate. The former bound to the HS chains of recycling Gpc-1 and S-nitrosylated the core protein. Ascorbate released NO, which degraded HS and liberated the bound spermine. Recycling HS proteoglycans of the glypican-type may be plasma membrane carriers for cargo taken up by caveolar endocytosis.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Belting, Mattias, et al.
(författare)
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Tumor attenuation by combined heparan sulfate and polyamine depletion.
- 2002
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Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 99:1, s. 371-376
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Tidskriftsartikel (refereegranskat)abstract
- Cells depend on polyamines for growth and their depletion represents a strategy for the treatment of cancer. Polyamines assemble de novo through a pathway sensitive to the inhibitor, alpha-difluoromethylornithine (DFMO). However, the presence of cell-surface heparan sulfate proteoglycans may provide a salvage pathway for uptake of circulating polyamines, thereby sparing cells from the cytostatic effect of DFMO. Here we show that genetic or pharmacologic manipulation of proteoglycan synthesis in the presence of DFMO inhibits cell proliferation in vitro and in vivo. In cell culture, mutant cells lacking heparan sulfate were more sensitive to the growth inhibitory effects of DFMO than wild-type cells or mutant cells transfected with the cDNA for the missing biosynthetic enzyme. Moreover, extracellular polyamines did not restore growth of mutant cells, but completely reversed the inhibitory effect of DFMO in wild-type cells. In a mouse model of experimental metastasis, DFMO provided in the water supply also dramatically diminished seeding and growth of tumor foci in the lungs by heparan sulfate-deficient mutant cells compared with the controls. Wild-type cells also formed tumors less efficiently in mice fed both DFMO and a xylose-based inhibitor of heparan sulfate proteoglycan assembly. The effect seemed to be specific for heparan sulfate, because a different xyloside known to affect only chondroitin sulfate did not inhibit tumor growth. Hence, combined inhibition of heparan sulfate assembly and polyamine synthesis may represent an additional strategy for cancer therapy.
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| 10. |
- Bhattacharyya, Anirban, et al.
(författare)
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ESS RF Source and Spoke Cavity Test Plan
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report describes the test plan for the first high power RF source, ESS prototype double spoke cavity and ESS prototype cryomodule at the FREIA Laboratory.
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