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| 2. |
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| 3. |
- Strömbeck, Anna, et al.
(författare)
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Allergic disease in 8-year old children is preceded by delayed B-cell maturation.
- 2017
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Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 47:7, s. 918-928
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that exposure to a farming environment is allergy-protective, while high proportions of neonatal immature/naïve CD5(+) B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age.To examine if B- and T-cell maturation are associated with allergic disease and farming environment over the first 8 years in life.In the prospective FARMFLORA study, including both farming and non-farming families, 48 out of 65 children took part in the 8-year follow-up study. Various B- and T-cell maturation variables were examined in blood samples obtained at several occasions from birth to 8 years of age and related to doctors' diagnosed allergic disease and sensitization, and to farming environment.We found that the incidence of allergic disease was lower among farmers' compared to non-farmers' children during the 8-years follow-up period, and that farmers' children had higher proportions of memory B cells at 8 years of age. Moreover, a high proportion of neonatal CD5(+) B cells was a risk factor for and may predict development of allergic disease at 8 years of age. A high proportion of Tregs was not protective against development of these conditions.High proportions of neonatal naïve B cells remained as a risk factor for allergic disease in school-aged children. Thus, the accelerated B-cell maturation observed among farmers' children may be crucial for the allergy-protective effect of a farming environment. This article is protected by copyright. All rights reserved.
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| 4. |
- Aldridge, Jonathan, et al.
(författare)
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Sex-based differences in association between circulating T cell subsets and disease activity in untreated early rheumatoid arthritis patients
- 2018
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is not known if sex-based disparities in immunological factors contribute to the disease process in rheumatoid arthritis (RA). Hence, we examined whether circulating T cell subset proportions and their association with disease activity differed in male and female patients with untreated early rheumatoid arthritis (ueRA). Methods: Proportions of T cell subsets were analyzed in peripheral blood from 72 ueRA DMARD-and corticosteroid-naive patients (50 females and 22 males) and in 31 healthy age-and sex-matched controls. Broad analysis of helper and regulatory CD4(+) T cell subsets was done using flow cytometry. Disease activity in patients was assessed using DAS28, CDAI, swollen joint counts, tender joint counts, CRP, and ESR. Results: Multivariate factor analyses showed that male and female ueRA patients display distinct profiles of association between disease activity and circulating T cell subset proportions. In male, but not female, ueRA patients Th2 cells showed a positive association with disease activity and correlated significantly with DAS28-ESR, CDAI, and swollen and tender joint counts. Likewise, proportions of non-regulatory CTLA-4(+) T cells associated positively with disease activity in male patients only, and correlated with DAS28-ESR. In contrast, there was a negative relation between Th1Th17 subset proportions and disease activity in males only. The proportions of Th17 cells correlated positively with DAS28-ESR in males only, while proportions of Th1 cells showed no relation to disease activity in either sex. There were no significant differences in proportions of T cell subsets between the sexes in patients with ueRA. Conclusions: Our findings show sex-based differences in the association between T cell subsets and disease activity in ueRA patients, and that Th2 helper T cells may have a role in regulating disease activity in male patients.
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| 5. |
- Andersson, Britt-Inger
(författare)
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Förstudie Del A Underlag till en FoU-strategi : inspel till myndighetens strategiska plan 2021-2023
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med förstudien är att ta fram ett underlag till en FoU-strategi för myndigheten. Den ska användas som inspel till myndighetens kommande strategiska plan 2021– 2023. Myndigheten saknar en FoU-strategi som omfattar hela verksamheten. Idag utförs en liten del egen forskningsverksamhet främst runforskning och en större del annan FoU-verksamhet. I stort sett all FoU utförs i samarbete och/eller samverkan med externa parter exempelvis museer, universitet och högskolor. I rapporten har sex kategorier av FoU-verksamhet identifierats. De flesta avdelningar utför FoU-verksamhet främst Kulturvårdsavdelningen, men även Arkiv och bibliotek samt Informationsavdelningen. Kulturmiljöavdelningen arbetar främst operativt med FoU-anslaget och det tillhörande externa FoU-programmet. Staben arbetar strategiskt med FoU-frågor i Sverige och inom EU samt ansvarar strategiskt för det externa FoU-programmet.
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| 6. |
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| 7. |
- Andersson, Emil, et al.
(författare)
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Low pericyte coverage of endometrial microvessels in heavy menstrual bleeding correlates with the microvessel expression of VEGF-A.
- 2015
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1791-244X .- 1107-3756. ; 35:2, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- A prospective clinical study was carried out to investigate whether endometrial microvessels in patients with idiopathic heavy menstrual bleeding (HMB) of endometrial origin (HMB-E) are fragile due to low pericyte coverage. Idiopathic HMB-E is characterized by large endothelial cell gaps related to the microvascular overexpression of vascular endothelial growth factor (VEGF)-A and VEGF receptors 1-3. A total of 10 women with a normal menstrual cycle and a history of HMB of <5 years, and 17 healthy women with a normal menstrual cycle were recruited from the Karolinska University Hospital. Blood samples were obtained for hormone analysis and coagulation tests. Endometrial biopsies were collected in the proliferative or in the secretory phase. Pericyte coverage was assessed using immunohistochemical staining for smooth muscle actin-α (SMAα) and by image analysis (microvascular density) of endometrial biopsies from 10 patients with HMB-E and 17 healthy ovulating women (control subjects). Previously published data on endothelial cell gap size and the expression of VEGF receptors were used. Although microvascular density did not differ between the patients with HMB-E and the control subjects, the number of SMAα-positive microvessels in the proliferative phase was significantly (P=0.005) lower in the patients with HMB-E than in the control subjects. Moreover, the number of SMAα-positive microvessels in the control subjects was significantly fewer in the secretory (P=0.04) than in the proliferative phase, whereas this number did not differ among the patients with HMB-E regardless of phase. A significant negative correlation was observed between the number of VEGF-A-positive microvessels and microvessels with pericyte coverage (r=0.8; P=0.04). Finally, the endothelial cell layer was significantly thicker in the patients with HMB-E than in the control subjects. Thus, the upregulation of VEGF-A in idiopathic HMB-E is associated with a low pericyte coverage during the proliferative phase of intense angiogenesis, which may confer vessel fragility, possibly leading to excessive blood loss.
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| 8. |
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| 9. |
- Andersson Marchesoni, Maria, et al.
(författare)
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Technologies in older people's care : Values related to a caring rationality
- 2017
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Ingår i: Nursing Ethics. - : Sage Publications. - 0969-7330 .- 1477-0989. ; 24:2, s. 125-137
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDThe tension between care-based and technology-based rationalities motivates studies concerning how technology can be used in the care sector to support the relational foundation of care.OBJECTIVESThis study interprets values related to care and technologies connected to the practice of good care.RESEARCH DESIGNThis research study was part of a development project aimed at developing innovative work practices through information and communication technology. Participants and research context: All staff (n = 18) working at two wards in a care facility for older people were asked to participate in interviews, and 12 accepted. We analysed the data using latent content analysis in combination with normative analysis. Ethical considerations: The caregivers were informed that participation was voluntary and that they could drop out at any time without providing any explanation.FINDINGSFour values were identified: 'presence', 'appreciation', 'competence' and 'trust'. Caregivers wanted to focus on care receivers as unique persons, a view that they thought was compromised by time-consuming and beeping electronic devices. Appraising from next-of-kin and been seen as someone who can contribute together with knowledge to handle different situations were other desires. The caregivers also desired positive feedback from next-of-kin, as they wanted to be seen as professionals who have the knowledge and skills to handle difficult situations. In addition, the caregivers wanted their employer to trust them, and they wanted to work in a calm environment.DISCUSSIONCaregivers' desire for disturbance-free interactions, being valued for their skills and working in a trustful working environment were interpreted as their base for providing good care. The caregivers' arguments are based on caring rationality, and sometimes they felt the technological rationality interfered with their main mission, providing quality care.CONCLUSIONIntroducing new technology in caring should support the caring relationship. Although society's overall technology-based approach may have gained popularity as a problem solver, technology-based rationality may compromise a care-based rationality. A shift in attitudes towards care as a concept on all societal levels is needed.
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| 10. |
- Andersson, Roger, 1952-, et al.
(författare)
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Natives' opinions on ethnic residential segregation and neighbourhood diversity in Helsinki, Oslo and Stockholm
- 2017
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Ingår i: Housing Studies. - : Informa UK Limited. - 0267-3037 .- 1466-1810. ; 32:4, s. 491-516
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Tidskriftsartikel (refereegranskat)abstract
- Nordic countries rank high on measures indicating tolerant views on immigrants. Yet, ethnic residential segregation is stated as being a major social problem in these countries. Neighbourhood flight and avoidance behaviour among the native born could be a sign of less tolerant views on minorities, but could of course be restricted to native-born residents in areas of high-ethnic concentration. So far, no research in these countries has explicitly focused on the majority population’s view on segregation, and we know little about how native-born residents in different neighbourhood contexts view ethnic segregation or how own residential experience shapes decisions on staying or leaving; this paper aims to help fill this research lacuna. In a survey targeting 9000 native-born residents in three Nordic capital cities—stratified into neighbourhood movers and stayers and into neighbourhoods having different proportions of non-Nordic-born residents—we answer three questions: do native-born respondents prefer a neighbourhood ethnic mix? Do they see ethnic segregation as a problem? Do they prefer lower, current or higher shares of ethnic minorities in their own neighbourhoods?
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| 11. |
- Andersson, Sofia E M, 1979, et al.
(författare)
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Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis
- 2016
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance. Methods: To generate expression of the CII-peptide specifically on B-cell major histocompatibility complex type II, lentiviral-based gene therapy including a B-cell-specific Igk promoter was used. Results: Presentation of the CII-peptide on B cells significantly reduced the frequency and severity of arthritis as well as the serum levels of CII -specific IgG antibodies. Further, both frequency and suppressive function of regulatory T cells were increased in tolerized mice. Adoptive transfer of regulatory T cells from tolerized mice to naive mice ameliorated the development of CII-induced arthritis. Conclusion: Our data suggest that endogenous presentation of the CII-peptide on B cells is one of the key contributors to arthritis tolerance induction and maintenance.
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| 12. |
- Ansari, Daniel, et al.
(författare)
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Hemorrhage after Major Pancreatic Resection: Incidence, Risk Factors, Management, and Outcome.
- 2017
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Ingår i: Scandinavian Journal of Surgery. - : SAGE Publications. - 1799-7267 .- 1457-4969. ; 106:1, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- Hemorrhage is a rare but dreaded complication after pancreatic surgery. The aim of this study was to examine the incidence, risk factors, management, and outcome of postpancreatectomy hemorrhage in a tertiary care center. A retrospective observational study was conducted on 500 consecutive patients undergoing major pancreatic resections at our institution. Postpancrea-tectomy hemorrhage was defined according to the International Study Group of Pancreatic Surgery criteria. RESULTS: A total of 68 patients (13.6%) developed postpancreatectomy hemorrhage. Thirty-four patients (6.8%) had a type A, 15 patients (3.0%) had a type B, and the remaining 19 patients (3.8%) had a type C bleed. Postoperative pancreatic fistula Grades B and C and bile leakage were significantly associated with severe postpancreatectomy hemorrhage on multivariable logistic regression. For patients with postpancreatectomy hemorrhage Grade C, the onset of bleeding was in median 13 days after the index operation, ranging from 1 to 85 days. Twelve patients (63.2%) had sentinel bleeds. Surgery lead to definitive hemostatic control in six of eight patients (75.0%). Angiography was able to localize the bleeding source in 8/10 (80.0%) cases. The success rate of angiographic hemostasis was 8/8. (100.0%). The mortality rate among patients with postpancreatectomy hemorrhage Grade C was 2/19 (10.5%), and both fatalities occurred late as a consequence of eroded vessels in association with pancreaticogastrostomy. CONCLUSION: Delayed hemorrhage is a serious complication after major pancreatic surgery.Sentinel bleed is an early warning sign. Postoperative pancreatic fistula and bile leakage are important risk factors for severe postpancreatectomy hemorrhage.
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| 13. |
- Bergquist, Maria, et al.
(författare)
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Increased RANKL/OPG ratio and sclerostin in patients with septic shock
- 2017
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Ingår i: Clinical Microbiology and Infectious Diseases. - 2398-8096. ; 2:1, s. 1-3
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Tidskriftsartikel (refereegranskat)abstract
- We report an increased RANKL/OPG ratio and increased sclerostin levels in patients with septic shock one day after admission compared to healthy subjects,indicating an increased risk for bone loss in survivors of septic shock. No increase in RANKL/OPG ratio was observed in patients treated with hydrocortisone during septic shock.
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| 14. |
- Bielecki, Johan, 1982, et al.
(författare)
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Electrospray sample injection for single-particle imaging with x-ray lasers
- 2019
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution.
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| 15. |
- Bremer, Hanna, et al.
(författare)
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ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Dogs can spontaneously develop complex systemic autoimmune disorders, with similarities to human autoimmune disease. Autoantibodies directed at self-antigens are a key feature of these autoimmune diseases. Here we report the identification of interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) as autoantigens in canine immune-mediated rheumatic disease. The ILF2 autoantibodies were discovered in a small, selected canine cohort through the use of human protein arrays; a method not previously described in dogs. Subsequently, ILF3 autoantibodies were also identified in the same cohort. The results were validated with an independent method in a larger cohort of dogs. ILF2 and ILF3 autoantibodies were found exclusively, and at a high frequency, in dogs that showed a speckled pattern of antinuclear antibodies on immunofluorescence. ILF2 and ILF3 autoantibodies were also found at low frequency in human patients with SLE and Sjogren's syndrome. These autoantibodies have the potential to be used as diagnostic biomarkers for canine, and possibly also human, autoimmune disease.
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| 16. |
- Carlsson, Gunilla H., et al.
(författare)
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The elusive ligand complexes of the DWARF14 strigolactone receptor
- 2018
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Ingår i: Journal of Experimental Botany. - : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 69:9, s. 2345-2354
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Tidskriftsartikel (refereegranskat)abstract
- Strigolactones, a group of terpenoid lactones, control many aspects of plant growth and development, but the active forms of these plant hormones and their mode of action at the molecular level are still unknown. The strigolactone protein receptor is unusual because it has been shown to cleave the hormone and supposedly forms a covalent bond with the cleaved hormone fragment. This interaction is suggested to induce a conformational change in the receptor that primes it for subsequent interaction with partners in the signalling pathway. Substantial efforts have been invested into describing the interaction of synthetic strigolactone analogues with the receptor, resulting in a number of crystal structures. This investigation combines a re-evaluation of models in the Protein Data Bank with a search for new conditions that may permit the capture of a receptor-ligand complex. While weak difference density is frequently observed in the binding cavity, possibly due to a low-occupancy compound, the models often contain features not supported by the X-ray data. Thus, at this stage, we do not believe that any detailed deductions about the nature, conformation, or binding mode of the ligand can be made with any confidence.
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| 17. |
- Chang, Ya-Ting, et al.
(författare)
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Versican accumulates in vascular lesions in pulmonary arterial hypertension
- 2016
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Ingår i: PULMONARY CIRCULATION. - : Wiley. - 2045-8932 .- 2045-8940. ; 6:3, s. 347-359
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [S-35] sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH.
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| 18. |
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| 19. |
- Daurer, Benedikt J., et al.
(författare)
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Experimental strategies for imaging bioparticles with femtosecond hard X-ray pulses
- 2017
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Ingår i: IUCrJ. - : INT UNION CRYSTALLOGRAPHY. - 2052-2525. ; 4, s. 251-262
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Tidskriftsartikel (refereegranskat)abstract
- This study explores the capabilities of the Coherent X-ray Imaging Instrument at the Linac Coherent Light Source to image small biological samples. The weak signal from small samples puts a significant demand on the experiment. Aerosolized Omono River virus particles of similar to 40 nm in diameter were injected into the submicrometre X-ray focus at a reduced pressure. Diffraction patterns were recorded on two area detectors. The statistical nature of the measurements from many individual particles provided information about the intensity profile of the X-ray beam, phase variations in the wavefront and the size distribution of the injected particles. The results point to a wider than expected size distribution (from similar to 35 to similar to 300 nm in diameter). This is likely to be owing to nonvolatile contaminants from larger droplets during aerosolization and droplet evaporation. The results suggest that the concentration of nonvolatile contaminants and the ratio between the volumes of the initial droplet and the sample particles is critical in such studies. The maximum beam intensity in the focus was found to be 1.9 * 10(12) photons per mu m(2) per pulse. The full-width of the focus at half-maximum was estimated to be 500 nm (assuming 20% beamline transmission), and this width is larger than expected. Under these conditions, the diffraction signal from a sample-sized particle remained above the average background to a resolution of 4.25 nm. The results suggest that reducing the size of the initial droplets during aerosolization is necessary to bring small particles into the scope of detailed structural studies with X-ray lasers.
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| 20. |
- Ekeberg, Tomas, et al.
(författare)
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Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser
- 2016
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms.
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| 21. |
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| 22. |
- Granfors, Michaela, et al.
(författare)
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Iodine deficiency in a study population of pregnant women in Sweden
- 2015
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:11, s. 1168-1174
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionIodine deficiency in utero may impair neurological development of the fetus. In Sweden, iodine nutrition is considered to be adequate in the general population. The aim of this study was to evaluate iodine nutrition during pregnancy in Sweden. Material and methodsIn this cross-sectional study, the total study population (n=459) consisted of two cohorts (Varmland County, n=273, and Uppsala County, n=186) of pregnant non-smoking women without pre-gestational diabetes mellitus or known thyroid disease before or during pregnancy. Spot urine samples were collected in the third trimester of pregnancy for median urinary iodine concentration (UIC) analysis. ResultsThe median UIC in the total study population was 98g/L (interquartile range 57-148g/L). ConclusionsAccording to WHO/UNICEF/IGN criteria, population-based median UIC during pregnancy should be 150-249g/L. Thus, our results indicate insufficient iodine status in the pregnant population of Sweden. There is an urgent need for further assessments in order to optimize iodine nutrition during pregnancy.
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| 23. |
- Grimsholm, Ola, 1979, et al.
(författare)
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Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding V(H)81X-expressing B cells
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Random recombination of antibody heavy- and light-chain genes results in a diverse B-cell receptor (BCR) repertoire including self-reactive BCRs. However, tolerance mechanisms that prevent the development of self-reactive B cells remain incompletely understood. The absence of the surrogate light chain, which assembles with antibody heavy chain forming a pre-BCR, leads to production of antinuclear antibodies (ANAs). Here we show that the naive follicular B-cell pool is enriched for cells expressing prototypic ANA heavy chains in these mice in a non-autoimmune background with a broad antibody repertoire. This results in the spontaneous formation of T-cell-dependent germinal centres that are enriched with B cells expressing prototypic ANA heavy chains. However, peripheral tolerance appears maintained by selection thresholds on cells entering the memory B-cell and plasma cell pools, as exemplified by the exclusion of cells expressing the intrinsically self-reactive V(H)81X from both pools.
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| 24. |
- Gunn, Laura, 1986-, et al.
(författare)
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A unique structural domain in Methanococcoides burtonii ribulose-1,5-bisphosphatecarboxylase/oxygenase (Rubisco) acts as a small subunit mimic
- 2017
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 292:16, s. 6838-6850
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Tidskriftsartikel (refereegranskat)abstract
- The catalytic inefficiencies of the CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) often limit plant productivity. Strategies to engineer more efficient plant Rubiscos have been hampered by evolutionary constraints, prompting interest in Rubisco isoforms from non-photosynthetic organisms. The methanogenic archaeon Methanococcoides burtonii contains a Rubisco isoform that functions to scavenge the ribulose-1,5-bisphosphate (RuBP) byproduct of purine/pyrimidine metabolism. The crystal structure of M. burtonii Rubisco (MbR) presented here at 2.6 Å resolution is composed of catalytic large subunits (LSu) assembled into pentamers of dimers, (L2)5 and differs from Rubiscos from higher plants where LSus are glued together by small subunits (SSu) into hexadecameric L8S8 enzymes. MbR contains a unique 29-amino-acid insertion near the C-terminus, which folds as a separate domain in the structure. This domain, which is visualized for the first time in this study, is located in a similar position to SSus in L8S8 enzymes between LSus of adjacent L2 dimers, where negatively charged residues co-ordinate around a Mg2+ ion in a fashion that suggests this domain may be important for the assembly process. The Rubisco assembly domain is thus an inbuilt SSu mimic that concentrates L2 dimers. MbR assembly is ligand-stimulated and we show that only 6-carbon molecules with a particular stereochemistry at the C3 carbon can induce oligomerization. Based on MbR structure, subunit arrangement, sequence, phylogenetic distribution and function, MbR and a subset of Rubiscos from the Methanosarcinales order are proposed to belong to a new Rubisco sub-group, named form IIIB.
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| 25. |
- Hantke, Max F., et al.
(författare)
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A data set from flash X-ray imaging of carboxysomes
- 2016
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Ultra-intense femtosecond X-ray pulses from X-ray lasers permit structural studies on single particles and biomolecules without crystals. We present a large data set on inherently heterogeneous, polyhedral carboxysome particles. Carboxysomes are cell organelles that vary in size and facilitate up to 40% of Earth’s carbon fixation by cyanobacteria and certain proteobacteria. Variation in size hinders crystallization. Carboxysomes appear icosahedral in the electron microscope. A protein shell encapsulates a large number of Rubisco molecules in paracrystalline arrays inside the organelle. We used carboxysomes with a mean diameter of 115±26 nm from Halothiobacillus neapolitanus. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min. Every diffraction pattern is a unique structure measurement and high-throughput imaging allows sampling the space of structural variability. The different structures can be separated and phased directly from the diffraction data and open a way for accurate, high-throughput studies on structures and structural heterogeneity in biology and elsewhere.
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| 26. |
- Hasse, Dirk, et al.
(författare)
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Structure and mechanism of piperideine-6-carboxylate dehydrogenase from Streptomyces clavuligerus
- 2019
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Ingår i: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 75, s. 1107-1118
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Tidskriftsartikel (refereegranskat)abstract
- The core of beta-lactam antibiotics originates from amino acids of primary metabolism in certain microorganisms. beta-Lactam-producing bacteria, including Streptomyces clavuligerus, synthesize the precursor of the amino acid alpha-aminoadipic acid by the catabolism of lysine in two steps. The second reaction, the oxidation of piperideine-6-carboxylate (or its open-chain form alpha-aminoadipate semialdehyde) to alpha-aminoadipic acid, is catalysed by the NAD(+)-dependent enzyme piperideine-6-carboxylate dehydrogenase (P6CDH). This structural study, focused on ligand binding and catalysis, presents structures of P6CDH from S. clavuligerus in its apo form and in complexes with the cofactor NAD(+), the product alpha-aminoadipic acid and a substrate analogue, picolinic acid. P6CDH adopts the common aldehyde dehydrogenase fold, consisting of NAD-binding, catalytic and oligomerization domains. The product binds in the oxyanion hole, close to the catalytic residue Cys299. Clear density is observed for the entire cofactor, including the nicotinamide riboside, in the binary complex. NAD(+) binds in an extended conformation with its nicotinamide ring overlapping with the binding site of the carboxylate group of the product, implying that the conformation of the cofactor may change during catalysis. The binding site of the substrate analogue overlaps with that of the product, suggesting that the cyclic form of the substrate, piperideine-6-carboxylate, may be accepted as a substrate by the enzyme. The catalytic mechanism and the roles of individual residues are discussed in light of these results.
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| 27. |
- Hasse, Dirk, et al.
(författare)
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Structure of Arabidopsis thaliana Rubisco activase
- 2015
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Ingår i: Acta Crystallographica Section D. - 0907-4449 .- 1399-0047. ; 71:Pt 4, s. 800-808
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Tidskriftsartikel (refereegranskat)abstract
- The CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is inactivated by the formation of dead-end complexes with inhibitory sugar phosphates. In plants and green algae, the ATP-dependent motor protein Rubisco activase restores catalytic competence by facilitating conformational changes in Rubisco that promote the release of the inhibitory compounds from the active site. Here, the crystal structure of Rubisco activase from Arabidopsis thaliana is presented at 2.9 Å resolution. The structure reveals an AAA+ two-domain structure. More than 100 residues in the protein were not visible in the electron-density map owing to conformational disorder, but were verified to be present in the crystal by mass spectrometry. Two sulfate ions were found in the structure. One was bound in the loop formed by the Walker A motif at the interface of the domains. A second sulfate ion was bound at the N-terminal end of the first helix of the C-terminal domain. The protein packs in a helical fashion in the crystal, as observed previously for Rubisco activase, but differences in the helical pitch indicate flexibility in the packing of the protein.
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| 28. |
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| 29. |
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| 30. |
- Hultman, Oscar, et al.
(författare)
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The Danish Rural Eye Study : prevalence of strabismus among 3785 Danish adults - a population-based cross-sectional study
- 2019
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Ingår i: Acta Ophthalmologica. - : John Wiley & Sons. - 1755-375X .- 1755-3768. ; 97:8, s. 784-792
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine the prevalence of strabismus among Danish adults and to find the frequency of history of strabismus and strabismus surgery. Furthermore, to evaluate the prevalence of strabismus-associated amblyopia among participants with strabismus and to relate the results to the current national vision screening programme.METHODS: In total, 3785 adults in the Danish Rural Eye Study underwent an interview regarding eye health, visual acuity measurement, Hirschberg test and retinal photography. Participants were categorized into groups based on their birth date in relation to the introduction of the national vision screening programme.RESULTS: In total, the prevalence of strabismus was 1.1% (41/3785; 95% CI: 0.8-1.5); no differences were found in relation to gender or screening status. The prevalence of exotropia (XT) was 0.3% (12/3785; 95% CI: 0.2-0.6) and of esotropia (ET) 0.8% (29/3785; 95% CI: 0.5-1.1), resulting in an XT:ET ratio of 1:2.7. A history of strabismus was present in 4.6% (174/3785; 95% CI: 4.0-5.3), and a history of strabismus surgery was present in 0.8% (32/3785; 95% CI: 0.6-1.2) of the participants. Among participants with manifest strabismus, 24% had strabismus-associated amblyopia.CONCLUSION: In this first European population-based study of strabismus prevalence in adults, the prevalence was similar to three out of five previous studies using cover test. The use of Hirschberg test may have led to an underestimation of the true prevalence. The prevalence was neither related to screening status nor gender. Our results are the first to display a predominance of ET among Caucasian Scandinavian adults.
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| 31. |
- Johansson, Inger, 1953, et al.
(författare)
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Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients
- 2015
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Ingår i: Bmc Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. Methods: A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 +/- 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. Results: Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0-7.4) compared with CMV disease (4.2 years; CI, 3.2-5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3-6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant. Conclusions: CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.
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| 32. |
- Karlsson Videhult, Frida, et al.
(författare)
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Impact of probiotics during weaning on the metabolic and inflammatory profile : follow-up at school age
- 2015
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Ingår i: International Journal of Food Sciences and Nutrition. - : Taylor & Francis Group. - 0963-7486 .- 1465-3478. ; 66:6, s. 686-691
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesised that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) (dep. nr LMG P-17806) during weaning would program the metabolic and inflammatory profile and studied its association with previously assessed body composition. In a double-blind, placebo-controlled trial, 179 infants were randomised to daily feeding of cereals with or without LF19 10 8 CFU from 4 to 13 months of age. At age 8-9 years, 120 children were reassessed. Using high-sensitivity multiplex immunoassay technology and ELISA, we found that overweight/obese children had increased plasma C-peptide, plasminogen activator inhibitor-1, leptin and serum high-sensitivity C-reactive protein (hsCRP) after overnight fasting compared with normal weight children, independently of LF19. After excluding the obese, leptin and hsCRP were still increased, revealing an aberrant metabolic and inflammatory state already in overweight, pre-pubertal children. Higher body mass index z-score, sagittal abdominal diameter, truncal and total body fat % were associated with an aberrant metabolic and inflammatory profile, emphasising the need for early prevention strategies although no programming effect of LF19 was observed.
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| 33. |
- Larsson, Anna M., et al.
(författare)
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Crystal structures of β-carboxysome shell protein CcmP : ligand binding correlates with the closed or open central pore
- 2017
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Ingår i: Journal of Experimental Botany. - : OXFORD UNIV PRESS. - 0022-0957 .- 1460-2431. ; 68:14, s. 3857-3867
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Tidskriftsartikel (refereegranskat)abstract
- Cyanobacterial CO2 fixation is promoted by encapsulating and co-localizing the CO2-fixing enzymes within a protein shell, the carboxysome. A key feature of the carboxysome is its ability to control selectively the flux of metabolites in and out of the shell. The beta-carboxysome shell protein CcmP has been shown to form a double layer of pseudohexamers with a relatively large central pore (similar to 13 angstrom diameter), which may allow passage of larger metabolites such as the substrate for CO2 fixation, ribulose 1,5-bisphosphate, through the shell. Here we describe two crystal structures, at 1.45 angstrom and 1.65 angstrom resolution, of CcmP from Synechococcus elongatus PCC7942 (SeCcmP). The central pore of CcmP is open or closed at its ends, depending on the conformation of two conserved residues, Glu69 and Arg70. The presence of glycerol resulted in a pore that is open at one end and closed at the opposite end. When glycerol was omitted, both ends of the barrel became closed. A binding pocket at the interior of the barrel featured residual density with distinct differences in size and shape depending on the conformation, open or closed, of the central pore of SeCcmP, suggestive of a metabolite-driven mechanism for the gating of the pore.
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| 34. |
- Lexomboon, Duangjai, et al.
(författare)
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Incidence and causes of dental trauma in children living in the county of Varmland, Sweden
- 2016
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Ingår i: Dental Traumatology. - : Wiley. - 1600-4469 .- 1600-9657. ; 32:1, s. 58-64
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Tidskriftsartikel (refereegranskat)abstract
- AimThe aims of this study were to determine the incidence of injuries to permanent incisors in 2011-2013 in children aged 8-10years living in the county of Varmland, Sweden, and to compare it with the incidence rates in 1989/1990 in the county of Vastmanland, as well as to determine the cause of dental trauma in relation to time and place. MethodThe study analysed the patient records from dental visits (2011-2013) of trauma to the permanent incisors in children aged 8-10years. The incidence rates were the incidence per 1000 children at risk. Standardized incidence rates were calculated for the comparison between different years. Information about month, location where the trauma occurred as well as cause of trauma was recorded. ResultsA total of 2.2% of 21721 children aged 8-10years had experienced at least one trauma. The incidence rate in Varmland increased from 18.9 in 2011 to 21.3 in 2012 to 28.5 in 2013. The standardized incidence rate in Varmland in 2011 and 2012 was not significantly different than in Vastmanland in 1989/1990 (P>0.05), but the standardized rates in 2013 were significantly higher than in 1989/90 (P<0.001). Dental trauma occurred most often outdoors, followed by sports arenas/sports fields, and more often at school than at home. Falling and slipping was the most common cause of trauma, followed by accidents during leisure activities, playing and sports. ConclusionThe incidence rate for dental trauma has not decreased in the past 20years, and there is an indication that parents and teachers should be more aware of the risks of dental trauma at leisure times and at school as well as during sports and exercise.
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| 35. |
- Lindqvist, Helen, 1977, et al.
(författare)
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Influence of blue mussel (Mytilus edulis) intake on fatty acid composition in erythrocytes and plasma phospholipids and serum metabolites in women with rheumatoid arthritis
- 2019
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Ingår i: Prostaglandins Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 0952-3278. ; 150, s. 7-15
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Tidskriftsartikel (refereegranskat)abstract
- Intake of blue mussels decreased disease activity in women with rheumatoid arthritis (RA) in the randomized cross-over MIRA (Mussels, inflammation and RA) trial. This study investigates potential causes of the decreased disease activity by analysing fatty acid composition in erythrocytes and plasma phospholipids and serum metabolites in samples from the participants of the MIRA trial. Twenty-three women completed the randomized 2 × 11-week cross-over dietary intervention, exchanging one cooked meal per day, 5 days a week, with a meal including 75 g blue mussels or 75 g meat. Fatty acid composition in erythrocytes and plasma and 1H Nuclear Magnetic Resonance (1H NMR) metabolomics data were analysed with multivariate data analysis. Orthogonal Projections to Latent Structures with Discriminant Analysis (OPLS-DA) and OPLS with effect projections (OPLS-EP) were performed to compare the two diets. The fatty acid profile in erythrocytes was different after intake of blue mussels compared to the control diet, and all samples were correctly classified to either the blue mussel diet or control diet. Changes following blue mussel intake included significant increases in omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at the group level but not for all individuals. The fatty acid profile in plasma phospholipids and 1H NMR serum metabolites did not differ significantly between the diets. To conclude, modelling fatty acids in erythrocytes may be a better biomarker for seafood intake than only EPA and DHA content. The change in fatty acid pattern in erythrocytes could be related to reduction in disease activity, although it cannot be excluded that other factors than omega-3 fatty acids potentiate the effect. © 2019 Elsevier Ltd
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| 36. |
- Locmelis, Roland, 1984-
(författare)
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Structural biology studies of thylakoid lumen proteins required for photosystem II assembly and function
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Little is known about the structures and functions of thylakoid lumen proteins. However, some of these proteins have an essential role in photosynthesis. Photosystem II (PSII) complexes are embedded in the thylakoid membrane of oxygenic photosynthetic organisms and one of the central subunits, the D1 protein, is damaged by light during the light driven water – splitting reaction and must be replaced frequently. One of the thylakoid lumen proteins that is essential for assembly and renewal of PSII complexes is the High Chlorophyll Fluorescence 136 (HCF136) protein. Another important protein for the PSII complex assembly is the Low PSII Accumulation Protein 19 (LPA19). Both proteins, HCF136 and LPA19, were shown to bind to the core subunits of the PSII complex from the lumenal side and LPA19 has been shown to explicitly interact with the soluble C-terminus of the D1 protein, one of the core PSII complex proteins. Prior to the replacement of the damaged D1 protein, the PSII complex needs to be disassembled, which is done with the help of the Maintenance of Photosystem II under High light 2 (MPH2) protein. MPH2, also called TL16, is required during the repair cycle of the PSII complex particularly under increased and fluctuating light conditions.In this work I have determined the three-dimensional X-ray structures of the HCF136 protein at 1.6 Å resolution and the LPA19 protein at 1.2 Å resolution and have also biochemically analyzed possible interactions of HCF136 with the C-termini of D1 protein. In addition, we have determined the NMR structure of the MPH2 protein.The protein structures of HCF136, LPA19, and MPH2 determined from A. thaliana provide us with a starting point for further studies to improve our understanding of their functional roles in the assembly, maintenance, disassembly and renewal of the PSII complex. The structures are revealing the molecular details that are particularly important during the design of mutations to study protein-protein interactions and the binding of co-factors.Furthermore, I have contributed to the characterization of AnPrx6, the 1-Cyx peroxiredoxin from Anabaena sp. 7120. Peroxiredoxins are important caretakers of reactive oxygen species and a homolog PrxQ in A.thaliana is found in the thylakoid lumen. The dimeric AnPrx6 protein revealed different active site residues conformations in each of the dimers, which is probably coupled to its enzymatic activity. Unexpectedly, the protein acted also as a chaperone and showed chaperone activity in its dimeric state, which is a novelty for Prx proteins.
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| 37. |
- Lundell, Anna-Carin, 1976, et al.
(författare)
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Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5+ B cells in boys.
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Boys present with higher proportions of immature/naïve CD5+ B cells than girls up to 3 years of age. Boys also have higher fractions of regulatory T cells (Tregs) in early infancy, but the mechanisms for these sex-related differences are unknown. In the prospective FARMFLORA follow-up study of 23 boys and 25 girls, we investigated if these immunological differences remained at 8 years of age. We also examined if testosterone or dihydrotestosterone (DHT) levels at birth and at 8 years of age were associated with immune maturation. Immunological variables and androgen levels were examined and measured in blood samples obtained at birth, 3-5 days and at 8 years of age. Boys had higher proportions of CD5+ and immature/transitional CD24hiCD38hi B cells, whereas girls had higher fractions of B cells with a memory phenotype at 8 years of age. School-aged boys also presented with higher frequencies of Tregs, and a greater capacity to produce T-cell-associated cytokines. Among boys, higher cord blood DHT levels were associated with higher proportions of CD5+ B cells in early infancy and at 8 years of life. These results suggest that DHT actions in utero might be involved in the mechanism for delayed peripheral B-cell maturation in boys.
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| 38. |
- Lundell, Anna-Carin, 1976, et al.
(författare)
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IFN type I and II induce BAFF secretion from human decidual stromal cells
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- B cell activating factor (BAFF) is a critical cytokine for maturation of immature B cells. In murine lymph nodes, BAFF is mainly produced by podoplanin-expressing stromal cells. We have previously shown that circulating BAFF levels are maximal at birth, and that farmers' children exhibit higher BAFF levels in cord blood than non-farmers' children. Here, we sought to investigate whether maternal-derived decidual stromal cells from placenta secrete BAFF and examine what factors could stimulate this production. We found that podoplanin is expressed in decidua basalis and in the underlying villous tissue as well as on isolated maternal-derived decidual stromal cells. Decidual stromal cells produced BAFF when stimulated with IFN-gamma and IFN-alpha, and NK cells and NK-T-like cells competent of IFN-gamma production were isolated from the decidua. Finally, B cells at different maturational stages are present in decidua and all expressed BAFF-R, while stromal cells did not. These findings suggest that decidual stromal cells are a cellular source of BAFF for B cells present in decidua during pregnancy.
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| 39. |
- Marchesoni, Maria Andersson, et al.
(författare)
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Going from “paper and pen” to ICT systems : Perspectives on managing the change process
- 2017
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Ingår i: Informatics for Health and Social Care. - : Taylor & Francis. - 1753-8157 .- 1753-8165. ; 42:2, s. 109-121
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lack of participation from staff when developing information and communication technologies (ICT) has been shown to lead to negative consequences and might be one explanation for failure. Management during development processes has rarely been empirically studied, especially when introducing ICT systems in a municipality context. Objective: To describe and interpret experiences of the management during change processes where ICT was introduced among staff and managers in elderly care. Design: A qualitative interpretive method was chosen for this study and content analysis for analyzing the interviews. Results: “Clear focus–unclear process” demonstrated that focus on ICT solutions was clear but the process of introducing the ICT was not. “First-line managers receiving a system of support” gave a picture of the first-line manager as not playing an active part in the projects. First-line managers and staff described “Low power to influence” when realizing that for some reasons, they had not contributed in the change projects. “Low confirmation” represented the previous and present feelings of staff not being listened to. Lastly, “Reciprocal understanding” pictures how first-line managers and staff, although having some expectations on each other, understood each other’s positions. Conclusions: Empowerment could be useful in creating an organization where critical awareness and reflection over daily practice becomes a routine.
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| 40. |
- Munke, Anna, et al.
(författare)
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Coherent diffraction of single Rice Dwarf Virus particles using soft X-rays at the Linac Coherent Light Source
- 2018
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Ingår i: Nature Scientific Data.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Single particle imaging using X-ray Free Electron Lasers has recently made major advancements that have facilitated experiments on smaller samples compared to the earliest reported works on giant viruses and cells. Here, the technique was used to image the 70 nm Rice dwarf virus, for which the generated dataset is described here. The virus particles were aerosolized and injected into the X-ray beam of the Linac Coherent Light Source. A total number of 36534 diffraction patterns were recorded, of which approximately 10 % were classified as ‘single hits’ by the RedFlamingo software. With the anticipation to advance method development, the dataset along with usage instructions are deposited in the Coherent X-ray imaging data bank, free to access and analyze.
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| 41. |
- Munke, Anna
(författare)
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Structural studies of small viruses using an X-ray Free Electron Laser
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- X-ray crystallography has since its introduction been the most successful technique for solving protein structures. Viruses however, often possess structural components such as fibrils, tails and envelopes that make them difficult or impossible to crystallize. To explore virus structures and the structural changes they undergo during host entry and infection, instrumental developments are required. X-ray Free Electron Lasers posses some advantages compared to conventional synchrotron sources, which enable experiments that previously were impossible. The femtosecond pulses and peak brilliance that exceeds synchrotrons by 109 facilitate recording of diffraction from nano/microcrystals and single particles before radiation damage takes place. The challenges for XFELs to reach its true potential in structural biology are nevertheless still many. During the technical and computational developments, using well-characterized reference samples is advantageous. In this thesis, the Rice Dwarf virus and MS2 bacteriophage have been used for single particle imaging and crystallography experiments using XFELs. These viruses are two of the smallest biological samples so far studied as single particles using this technique and the crystallography data of MS2 presented might serve as basis for solving the first high-resolution genome structure.Nanodiamonds, having a similar elemental composition as biological samples, could potentially serve as reference samples in XFEL studies. However, the biomedical field also has an interest in nanodiamonds, for drug delivery and as implant coating for example. Toxicity and biocompatibility is therefore a legitimate concern. Here, results from toxicity experiments of nanodiamonds on bacterial and zebrafish model organisms are presented.
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| 42. |
- Nicolia, Alessandro, et al.
(författare)
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Targeted gene mutation in tetraploid potato through transient TALEN expression in protoplasts
- 2015
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 204, s. 17-24
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Tidskriftsartikel (refereegranskat)abstract
- Potato is the third largest food crop in the world, however, the high degree of heterozygosity, the tetrasomic inheritance and severe inbreeding depression are major difficulties for conventional potato breeding. The rapid development of modern breeding methods offers new possibilities to enhance breeding efficiency and precise improvement of desirable traits. New site-directed mutagenesis techniques that can directly edit the target genes without any integration of recombinant DNA are especially favorable. Here we present a successful pipeline for site-directed mutagenesis in tetraploid potato through transient TALEN expression in protoplasts. The transfection efficiency of protoplasts was 38-39% and the site-directed mutation frequency was 7-8% with a few base deletions as the predominant type of mutation. Among the protoplast-derived calli, 11-13% showed mutations and a similar frequency (10%) was observed in the regenerated shoots. Our results indicate that the site-directed mutagenesis technology could be used as a new breeding method in potato as well as for functional analysis of important genes to promote sustainable potato production. (C) 2015 Elsevier B.V. All rights reserved.
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| 43. |
- Nilsson, Kerstin, et al.
(författare)
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54 forskare: Inte alla klarar höjd pensions-ålder
- 2017
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Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet, så att fler klarar att arbeta i högre ålder. Att enbart genom ekonomiska åtgärder höja pensionsåldern är inte långsiktigt hållbart, skriver 54 forskare.DEBATT | PENSIONForskning visar att cirka var fjärde har en diagnos eller skada orsakad av sitt arbete. Detta gör arbetsorsakad sjukdom och skada till ett betydelsefullt folkhälsoproblem. Att då enbart genom ekonomiska åtgärder höja pensionsåldern för samtliga (yrkes)grupper utifrån deras kronologiska ålder är inte långsiktigt hållbart när individers biologiska ålder är så olika bland annat till följd av arbetslivet. Detta är en demokratifråga. Forskning om äldre i arbetslivet och hållbart arbete visar att man då främst flyttar individer från pensionssystemet till sjukförsäkringssystemet och ökar klyftorna i samhället.Debatt Det här är en argumenterande text med syfte att påverka. Åsikterna som uttrycks är skribentens egna.Vi är 54 forskare som nu gemensamt har skrivit denna debattartikel. Anledningen är att vi är oroade över att cirka var fjärde blir sjuk av sitt arbete samtidigt som man i det förslag som ligger om att senarelägga ålderspensionen i princip utgår ifrån att arbetskraftsdeltagande enbart styrs av ekonomin. Vi vill trycka på betydelsen av åtgärder i arbetslivet för att komma tillrätta med ohälsan, det vill säga inte enbart ekonomiska restriktioner som tvingar folk som inte kan, vill och orkar att stanna kvar i arbetslivet till en högre kronologisk ålder.Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att förtjäna möjligheter till pension. Vi bör dock inte enbart utgå ifrån antalet år sedan en person föddes, då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Den svenska sjukförsäkringsreformen 2008 avsåg att få tillbaka människor i arbete. Men studien fann att den faktiskt bidrog till att fler gick i tidig ålderspension av dem som var i åldern 55–64 år. Ökningen var störst bland korttidsutbildade. Mer än 5 procent fler gick i tidig ålderspension då det blev svårare att få sjukpenning och sjukersättning. Vi kan notera att det är vanligare att manliga chefer tar ut tidig ålderspension, jämfört med kvinnliga maskinskötare inom tillverkningsindustrin. I vissa yrken är det dessutom vanligare att människor, trots pension, både orkar och faktiskt ges möjlighet att arbeta vidare om de har en specialkompetens som efterfrågas. Om vi endast kombinerar ekonomiska morötter med piskor finns en stor risk att vi ökar klyftan mellan grupper som både kan och vill fortsätta att yrkesarbeta och personer som av olika skäl inte längre kan eller orkar.Ta nytta av den forskning som vi har tagit fram. Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas och våra attityder som är kopplade till ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.”Morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi.Forskning visar att pedagogik som bygger på ”morötter” oftast är betydligt bättre än ”piskor” för att nå framgångsrika och långsiktiga mål. ”Morötter” i samhället, för organisationer, företag och individer är därför viktiga för god arbetshälsa och fortsatt produktivitet och kan bidra till ett längre arbetsliv även för grupper som tidigare inte ens klarat av att arbeta fram till pensionsåldern. Genom forskning inom området har bland annat swage-modellen utarbetats. Detta är ett verktyg som visar på komplexiteten i ett hållbart arbetsliv och tillsammans med systematiskt arbetsmiljöarbete, handlingsplaner och åtgärder syftar till ett mer hållbart arbetsliv. Morötter är enligt forskningen i detta sammanhang åtgärder för en god fysisk och mental arbetsmiljö, avpassad arbetsbelastning, stödjande teknik, att man kan anpassa arbetstakten, alternativa arbetstidsmodeller vid behov. Det är viktigt att man känner sig trygg och förväntas och tillåts vara delaktig, att man blir sedd av chefen och arbetskamraterna. Att de egna arbetsuppgifterna upplevs som meningsfulla och behövda av andra skapar självförverkligande och tillfredsställelse i arbetet. Att man känner att ens arbetsuppgifter och man själv är viktig för organisationen och företaget. Att man trots högre ålder inkluderas i olika nysatsningar och får tillgång till kompetensutveckling och inte blir åsidosatt eller åldersdiskriminerad. Utvärderingar visar att de äldre medarbetarna som fick några av dessa anpassningar och möjligheter var mer effektiva, utvilade, stimulerade när de var på arbetet samtidigt som sjukfrånvaron minskade. Vilket i sin tur bidrar till ett längre arbetsliv för grupper som tidigare inte klarat av att arbeta fram till pensionsåldern. I organisationer som bygger på en deltagar- och lärandekultur rustas de anställda för att klara omställningar, nya arbetsuppgifter och vid behov även yrkesbyten.Med en åldrande befolkning där allt fler lever allt längre behöver vi arbeta till en högre ålder i framtiden för att pensionssystemet ska hålla. Men ”morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi. Det kräver också att vi ändrar våra attityder och förhållningssätt till äldre på arbetsmarknaden, vilket vi bäst gör genom att organisationer och företag får incitament till och erbjuder mer individanpassade arbetsvillkor, särskilt för personer i högre ålder. Låt oss därför använda den framtagna kunskapen i praktiken för att göra arbetslivet friskt och hållbart för alla åldrar.
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| 44. |
- Nilsson, Kerstin, et al.
(författare)
-
Vi är oroade över senare ålderspension
- 2017
-
Ingår i: Dagens Samhälle. - 1652-6511.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Var fjärde person blir i dag sjuk till följd av sitt arbete. Att höja pensionsåldern för alla yrkesgrupper, utan konkreta åtgärder för att minska ohälsan, är därför problematiskt och mycket oroande. Det är, enligt forskarna, inte långsiktigt samhällsekonomiskt lönsamt att utan andra åtgärder höja pensionsåldern för alla. Vi – 54 forskare – är mycket oroade över konsekvenserna av att, som föreslagits, senarelägga ålderspensionen.Förslaget utgår i princip från arbetskraftsdeltagande i princip enbart styrs av ekonomin, medan forskningen visar att det bara är en av flera faktorer som styr hur länge och hur mycket människor väljer att arbeta.Det här sättet att lösa problemet med en åldrande befolkning och ett sviktande pensionssystem är inte samhällsekonomiskt lönsamt på lång sikt, utan riskerar bara att flytta runt folk mellan olika ersättningssystem. Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att tjäna in vår pension. Vi bör dock inte enbart utgå ifrån ålder eller antalet år sedan en person föddes då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De med kortare utbildningstid har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har också oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Ta nytta av den forskning som vi har tagit fram. Ekonomin är självklart viktigt för att vi ska vilja arbeta, men den är som sagt enbart en av flera faktorer med betydelse vårt arbetsliv.Hälsotillståndet, både det fysiska och det mentala, har en avgörande betydelse för hur länge och hur mycket vi orkar arbeta. Ett fysiskt och mentalt belastande arbete är en stark riskfaktor för en nedsatt hälsa i slutet av arbetslivet. Arbetstid, arbetstakt och möjlighet till återhämtning spelar en allt större roll ju äldre vi blir. Andra aspekter är arbetsinnehåll, hur meningsfulla och stimulerande arbetsuppgifterna är, balansen mellan arbete och familjesituation och fritidsaktiviteter. Organisationskultur, ledarskapet, stöd i arbetet och kompetens har stor betydelse för om vi ska kunna och vilja arbeta till en högre ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.Ett hållbart och acceptabelt pensionssystem måste därför utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas samt de attityder som är kopplade till ålder.
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| 45. |
- Ohlsson, Lisbeth, et al.
(författare)
-
Schools´ efforts to create inclusive learning environments
- 2016
-
Konferensbidrag (refereegranskat)abstract
- The study is part of a three-year schoolimprovement program in Sweden on creating inclusive learning environments, comprising several organizational levels from policy and management level to classroom praxis (http://www.ifous.se/programomradenforskning/inkludering/). Research on inclusive education in an international context frequently focuses the placement of individual students, administrative and organizational problems and attitudes towards policy and steering documents (Forlin, Douglas & Hattie, 1996 ; Ainscow & Miles, 2008 ). Often, a praxis of exclusion is built into educational systems (Van de Putte & De Schauwer, 2013 ) where thinking of students in categories forces pedagogues into locked positions (Tetler, 2000 ). In school development, the formation of teachers into teams may play a central part as an improvement strategy (Nordholm and Blossing, 2014 ). The aim of the present study is to document and analyze the processes experienced by 32 school teams, chosen by their school leaders in 12 municipalities to implement the intentions to create inclusive learning environments in their schools. The research interest focuses how the informants describe pedagogical and didactic prerequisites and organizational conditions and how they acted when implementing inclusive learning environments in the local school context, their role and legitimacy, the support structures and the signs of change they have seen towards a more inclusive learning environment during the developmental program. The methodological approach is inspired by on Social Justice, Equality and Solidarity in Education PAPERS 157 going evaluation (Ahnberg, Lundgren, Messing & von Schantz Lundgren, 2010) as a way to contribute knowledge about longitudinal developmental processes in school development close to local school context and praxis. Group interviews with the members of the teams were conducted each year in a dialogic manner with the ambition to give continuous feed back to the school teams as a way to promote developmental learning during the program. Except for visits to the schools and interviews, the researchers took part in seminars within the program and collected written documentation from the schools. The research interest concerns intentions expressed by the teams in the beginning of the program, the processes during the implementation phases and a final evaluation after three years. Data was analyzed according to qualitative content analysis and contains a rich variety of experiences and thick descriptions from the participants. Significant shifts of perspectives during the three years appear in the findings displaying how school problems and student-perspectives were understood, how the concept of inclusion was interpreted and enacted, how the teachers used analysis and reflection to promote inclusive learning environments and how frustration and insecurity among staff was transferred into collegial cooperation. The main shifts can be described in terms of taking steps from ideology to implementation, from being stuck in locked group constellations to finding flexible solutions, from seeing the teacher as the carrier of problems to collegial professionalism, and from viewing the student as the carrier of problems to analysing difficulties on several levels. School development related to inclusive learning environment is a democratic issue relevant in a Nordic as well as a global educational context and the complexity of educational organisation on different levels (Scheerens, 2015).
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| 46. |
- Ohlsson, Lisbeth, et al.
(författare)
-
Schools' efforts to create inclusive learning environments
- 2016
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The study is part of a three-year school-improvement program in Sweden on creating inclusive learning environments, comprising several organizational levels from policy and management level to classroom praxis (http://www.ifous.se/programomraden-forskning/inkludering/). Research on inclusive education in an international context frequently focuses the placement of individual students, administrative and organizational problems and attitudes towards policy and steering documents (Forlin, Douglas & Hattie, 1996 ; Ainscow & Miles, 2008 ). Often, a praxis of exclusion is built into educational systems (Van de Putte & De Schauwer, 2013 ) where thinking of students in categories forces pedagogues into locked positions (Tetler, 2000 ). In school development, the formation of teachers into teams may play a central part as an improvement strategy (Nordholm and Blossing, 2014 ). The aim of the present study is to document and analyze the processes experienced by 32 school teams, chosen by their school leaders in 12 municipalities to implement the intentions to create inclusive learning environments in their schools. The research interest focuses how the informants describe pedagogical and didactic prerequisites and organizational conditions and how they acted when implementing inclusive learning environments in the local school context, their role and legitimacy, the support structures and the signs of change they have seen towards a more inclusive learning environment during the developmental program. The methodological approach is inspired by on-going evaluation (Ahnberg, Lundgren, Messing & von Schantz Lundgren, 2010) as a way to contribute knowledge about longitudinal developmental processes in school development close to local school context and praxis. Group interviews with the members of the teams were conducted each year in a dialogic manner with the ambition to give continuous feed back to the school teams as a way to promote developmental learning during the program. Except for visits to the schools and interviews, the researchers took part in seminars within the program and collected written documentation from the schools. The research interest concerns intentions expressed by the teams in the beginning of the program, the processes during the implementation phases and a final evaluation after three years. Data was analyzed according to qualitative content analysis and contains a rich variety of experiences and thick descriptions from the participants. Significant shifts of perspectives during the three years appear in the findings displaying how school problems and student-perspectives were understood, how the concept of inclusion was interpreted and enacted, how the teachers used analysis and reflection to promote inclusive learning environments and how frustration and insecurity among staff was transferred into collegial cooperation. The main shifts can be described in terms of taking steps from ideology to implementation, from being stuck in locked group constellations to finding flexible solutions, from seeing the teacher as the carrier of problems to collegial professionalism, and from viewing the student as the carrier of problems to analysing difficulties on several levels. School development related to inclusive learning environment is a democratic issue relevant in a Nordic as well as a global educational context and the complexity of educational organisation on different levels (Scheerens, 2015).
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| 47. |
- Ohlsson, Lisbeth, et al.
(författare)
-
Schools´ efforts to create inclusive learning environments
- 2016
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The study is part of a three-year schoolimprovement program in Sweden on creating inclusive learning environments, comprising several organizational levels from policy and management level to classroom praxis (http://www.ifous.se/programomradenforskning/inkludering/). Research on inclusive education in an international context frequently focuses the placement of individual students, administrative and organizational problems and attitudes towards policy and steering documents (Forlin, Douglas & Hattie, 1996 ; Ainscow & Miles, 2008 ). Often, a praxis of exclusion is built into educational systems (Van de Putte & De Schauwer, 2013 ) where thinking of students in categories forces pedagogues into locked positions (Tetler, 2000 ). In school development, the formation of teachers into teams may play a central part as an improvement strategy (Nordholm and Blossing, 2014 ). The aim of the present study is to document and analyze the processes experienced by 32 school teams, chosen by their school leaders in 12 municipalities to implement the intentions to create inclusive learning environments in their schools. The research interest focuses how the informants describe pedagogical and didactic prerequisites and organizational conditions and how they acted when implementing inclusive learning environments in the local school context, their role and legitimacy, the support structures and the signs of change they have seen towards a more inclusive learning environment during the developmental program. The methodological approach is inspired by on Social Justice, Equality and Solidarity in Education PAPERS 157 going evaluation (Ahnberg, Lundgren, Messing & von Schantz Lundgren, 2010) as a way to contribute knowledge about longitudinal developmental processes in school development close to local school context and praxis. Group interviews with the members of the teams were conducted each year in a dialogic manner with the ambition to give continuous feed back to the school teams as a way to promote developmental learning during the program. Except for visits to the schools and interviews, the researchers took part in seminars within the program and collected written documentation from the schools. The research interest concerns intentions expressed by the teams in the beginning of the program, the processes during the implementation phases and a final evaluation after three years. Data was analyzed according to qualitative content analysis and contains a rich variety of experiences and thick descriptions from the participants. Significant shifts of perspectives during the three years appear in the findings displaying how school problems and student-perspectives were understood, how the concept of inclusion was interpreted and enacted, how the teachers used analysis and reflection to promote inclusive learning environments and how frustration and insecurity among staff was transferred into collegial cooperation. The main shifts can be described in terms of taking steps from ideology to implementation, from being stuck in locked group constellations to finding flexible solutions, from seeing the teacher as the carrier of problems to collegial professionalism, and from viewing the student as the carrier of problems to analysing difficulties on several levels. School development related to inclusive learning environment is a democratic issue relevant in a Nordic as well as a global educational context and the complexity of educational organisation on different levels (Scheerens, 2015).
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| 48. |
- Olafsdottir, Eydis, et al.
(författare)
-
Early detection of type 2 diabetes mellitus and screening for retinopathy are associated with reduced prevalence and severity of retinopathy
- 2016
-
Ingår i: Acta Ophthalmologica. - Hoboken, USA : Wiley-Blackwell Publishing Inc.. - 1755-375X .- 1755-3768. ; 94:3, s. 232-239
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore whether the prevalence and severity of retinopathy differ in diabetes cohorts diagnosed through screening as compared with conventional health care.Methods: A total of 257 diabetes patients, 151 detected through screening and 106 through conventional clinical care, were included. Retinopathy was evaluated by fundus photography. The modified Airlie House adaptation of the Early Treatment Retinopathy Study protocol was used to grade the photographs. Averages of clinically collected fasting blood glucose (FBG), blood pressure and body mass index values were compiled from diabetes diagnosis until the eye examination. Blood chemistry, smoking habits and peripheral neuropathy were assessed at the time of the eye examination.Results: Among the screening-detected patients, 22% had retinopathy as compared to 51% among those clinically detected (p < 0.0001). In a multivariate analysis, patients with retinopathy were more likely to have increased average FBG (OR 1.42, 95% CI 1.19-1.70 per mmol/l) and peripheral neuropathy (OR 2.75, 95% CI 1.40-5.43), but less likely to have screening-detected diabetes (OR 0.31, 95% CI 0.17-0.57). Similar results were found using increasing severity grade of retinopathy as outcome. The cumulative retinopathy prevalence for the screening-detected diabetes cohort as compared with the clinically diagnosed cohort was significantly lower from 10 years' follow-up and onwards (p = 0.0002).Conclusions: Among patients with screening-detected diabetes, the prevalence of retinopathy and increasing severity of retinopathy were significantly lower than among those who had their diabetes diagnosed through conventional care, even when other risk factors for retinopathy such as duration, hyperglycaemia and blood pressure were considered. Early detection of diabetes reduces prediagnostic time spent with hyperglycaemia. In combination with early and regular screening for retinopathy, more effective prevention against retinopathy can be provided.
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| 49. |
- Pandya, Jayesh M., et al.
(författare)
-
Blood chemokine profile in untreated early rheumatoid arthritis: CXCL10 as a disease activity marker
- 2017
-
Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- © 2017 The Author(s).Background: We have recently analyzed the profile of T-cell subtypes based on chemokine receptor expression in blood from untreated early rheumatoid arthritis (ueRA) patients compared to healthy controls (HC). Here, we compared the levels of the respective chemokines in blood plasma of ueRA patients with those of HC. We also studied the association of chemokine levels with the proportions of circulating T-cell subsets and the clinical disease activity. Methods: Peripheral blood was obtained from 43 patients with ueRA satisfying the ACR 2010 criteria and who had not received any disease-modifying anti-rheumatic drugs (DMARD) or prednisolone, and from 14 sex- and age-matched HC. Proportions of T helper cells in blood, including Th0, Th1, Th2, Th17, Th1Th17, TFh, and regulatory T cells, were defined by flow cytometry. Fifteen chemokines, including several CXCL and CCL chemokines related to the T-cell subtypes as well as to other major immune cells, were measured in blood plasma using flow cytometry bead-based immunoassay or ELISA. Clinical disease activity in patients was evaluated by assessing the following parameters: Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), swollen joint counts (SJC), tender joint counts (TJC), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The data were analyzed using multivariate factor analyses followed by univariate analyses. Results: Multivariate discriminant analysis showed that patients with ueRA were separated from HC based on the blood plasma chemokine profile. The best discriminators were CXCL9, CXCL10, CXCL13, CCL4, and CCL22, which were significantly higher in ueRA compared to HC in univariate analyses. Among the chemokines analyzed, only CXCL10 correlated with multiple disease activity measures, including DAS28-CRP, DAS28-ESR, CDAI, SJC in 66 joints, CRP, and ESR. Conclusions: High circulating levels of CXCL10 in the plasma of ueRA patients and the association with the clinical disease activity suggests that CXCL10 may serve as a disease activity marker in early rheumatoid arthritis.
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| 50. |
- Pandya, Jayesh M., et al.
(författare)
-
Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects
- 2016
-
Ingår i: Journal of Leukocyte Biology. - 0741-5400. ; 100:4, s. 823-833
-
Tidskriftsartikel (refereegranskat)abstract
- The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral bloodmononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age-and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25(+) CD127(low) and also FOXP3. CXCR5(+) cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4(+)CXCR3(-) (Th2 and Th17), CTLA4(+) and FOXP3(+) subsets were present in significantly higher frequencies, whereas CCR42 (Th1/Th17, CCR6(+)CCR4(-) CXCR3(-), and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3(+)/interferon gamma-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4(+) CXCR3(-) T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of these cells in early stages of the disease.
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