| 1. |
- Loth, Daan W, et al.
(författare)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 2. |
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| 3. |
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| 4. |
- Hannukainen, J, et al.
(författare)
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In Vivo Measurements of Glucose Uptake in Human Achilles Tendon During Different Exercise Intensities
- 2005
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Ingår i: International Journal of Sports Medicine. - : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 26, s. 727-731
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Tidskriftsartikel (refereegranskat)abstract
- Muscular contraction and loading of adjacent tendons has been demonstrated to cause increased blood flow and metabolic activity in the peritendinous region. However, it is poorly known to what extent the human tendon itself takes up glucose during exercise. Thus, the purpose of this study was to measure tendon glucose uptake with increasing exercise intensity and to compare it to muscle glucose uptake at the same intensities. Eight young men were examined on three separate days during which they performed 35 min of cycling at 30, 55 and 75 % of VO2max, respectively. Glucose uptake was measured directly by positron emission tomography (PET) with 2-[ (18)F]fluoro-2-deoxyglucose ([18F]FDG). [18F]FDG was injected after 10 min of exercise that was continued for a further 25 min after the injection. PET scanning of the thigh and Achilles region was performed after the exercise. Glucose uptake of the Achilles tendon (AT) remained unchanged (7.1 +/- 1.5, 6.6 +/- 1.1, and 6.0 +/- 1.1 micromol.kg(-1).min(-1)) with the increasing workload, although the glucose uptake in m. quadriceps femoris simultaneously clearly increased (48 +/- 35, 120 +/- 35, and 152 +/- 74 micromol.kg(-1).min(-1), p < 0.05). In conclusion, the AT takes up glucose during exercise but in significantly smaller amounts than the skeletal muscle does. Furthermore, glucose uptake in the AT is not increased with the increasing exercise intensity. This may be partly explained by the cycle ergometry exercise used in the present study, which probably causes only a little increase in strain to the AT with increasing exercise intensity.
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| 5. |
- Kaprio, J, et al.
(författare)
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The Older Finnish Twin Cohort - 45 Years of Follow-up
- 2019
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Ingår i: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 22:4, s. 240-254
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Tidskriftsartikel (refereegranskat)abstract
- The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.
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| 6. |
- Nygård, K., et al.
(författare)
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ForMAX – a beamline for multiscale and multimodal structural characterization of hierarchical materials
- 2024
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Ingår i: Journal of Synchrotron Radiation. - : International Union of Crystallography (IUCr). - 0909-0495 .- 1600-5775. ; 31:Pt 2, s. 363-377
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Tidskriftsartikel (refereegranskat)abstract
- The ForMAX beamline at the MAX IV Laboratory provides multiscale and multimodal structural characterization of hierarchical materials in the nanometre to millimetre range by combining small- and wide-angle X-ray scattering with full-field microtomography. The modular design of the beamline is optimized for easy switching between different experimental modalities. The beamline has a special focus on the development of novel fibrous materials from forest resources, but it is also well suited for studies within, for example, food science and biomedical research.
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| 7. |
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| 8. |
- Aoun, M., et al.
(författare)
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Antigen-presenting autoreactive B cells activate regulatory T cells and suppress autoimmune arthritis in mice
- 2023
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Ingår i: Journal of Experimental Medicine. - Stockholm : Karolinska Institutet, Dept of Medical Biochemistry and Biophysics. - 0022-1007 .- 1540-9538. ; 220:11
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Tidskriftsartikel (refereegranskat)abstract
- B cells undergo several rounds of selection to eliminate potentially pathogenic autoreactive clones, but in contrast to T cells, evidence of positive selection of autoreactive B cells remains moot. Using unique tetramers, we traced natural autoreactive B cells (C1-B) specific for a defined triple-helical epitope on collagen type-II (COL2), constituting a sizeable fraction of the physiological B cell repertoire in mice, rats, and humans. Adoptive transfer of C1-B suppressed arthritis independently of IL10, separating them from IL10-secreting regulatory B cells. Single-cell sequencing revealed an antigen processing and presentation signature, including induced expression of CD72 and CCR7 as surface markers. C1-B presented COL2 to T cells and induced the expansion of regulatory T cells in a contact-dependent manner. CD72 blockade impeded this effect suggesting a new downstream suppressor mechanism that regulates antigen-specific T cell tolerization. Thus, our results indicate that autoreactive antigen-specific naive B cells tolerize infiltrating T cells against self-antigens to impede the development of tissue-specific autoimmune inflammation.
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| 9. |
- Dimmock, Andrew P., et al.
(författare)
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Modeling the Geomagnetic Response to the September 2017 Space Weather Event Over Fennoscandia Using the Space Weather Modeling Framework : Studying the Impacts of Spatial Resolution
- 2021
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Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- We must be able to predict and mitigate against geomagnetically induced current (GIC) effects to minimize socio-economic impacts. This study employs the space weather modeling framework (SWMF) to model the geomagnetic response over Fennoscandia to the September 7-8, 2017 event. Of key importance to this study is the effects of spatial resolution in terms of regional forecasts and improved GIC modeling results. Therefore, we ran the model at comparatively low, medium, and high spatial resolutions. The virtual magnetometers from each model run are compared with observations from the IMAGE magnetometer network across various latitudes and over regional-scales. The virtual magnetometer data from the SWMF are coupled with a local ground conductivity model which is used to calculate the geoelectric field and estimate GICs in a Finnish natural gas pipeline. This investigation has lead to several important results in which higher resolution yielded: (1) more realistic amplitudes and timings of GICs, (2) higher amplitude geomagnetic disturbances across latitudes, and (3) increased regional variations in terms of differences between stations. Despite this, substorms remain a significant challenge to surface magnetic field prediction from global magnetohydrodynamic modeling. For example, in the presence of multiple large substorms, the associated large-amplitude depressions were not captured, which caused the largest model-data deviations. The results from this work are of key importance to both modelers and space weather operators. Particularly when the goal is to obtain improved regional forecasts of geomagnetic disturbances and/or more realistic estimates of the geoelectric field.
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| 10. |
- Hallsten, K, et al.
(författare)
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Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:12, s. 3479-3485
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Tidskriftsartikel (refereegranskat)abstract
- Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone (P < 0.05) and metformin (P < 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% (P < 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% (P < 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1) improves insulin responsiveness in resting skeletal muscle and 2) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise.
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| 11. |
- Lonnblom, E, et al.
(författare)
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AUTOANTIBODIES TO JOINT PROTEINS AS NOVEL BIOMARKERS FOR THE DIAGNOSIS OF UNTREATED EARLY RHEUMATOID ARTHRITIS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 546-546
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Autoantibodies to citrullinated protein (ACPA; measured as anti-CCP; aCCP) and rheumatoid factor (RF) appear years before clinical onset of RA and are essential tools in today’s classification criteria for RA. In animal models, antibodies to joint specific proteins (JP) can induce arthritis, and they are also present at onset of RA [1]. As there is a need for increased precision for early diagnosis of RA as well as identification of different subtypes of the disease, we aim to assess whether autoantibodies to native or modified JP can be used for early and precise diagnosis of RA.ObjectivesTo study whether antibodies to JP, alone or in combination with ACPA/RF, could increase the diagnostic sensitivity and specificity in untreated early (ue)RA patients.MethodsAntibodies to JP were analysed in serum from patients in three independent ueRA cohorts as well as from population controls without rheumatic diseases (WINGA, Gothenburg and MFM-ÅUS, Malmö n=1062). ERAp (n=66), the smallest and most recent cohort was chosen for screening, and BARFOT and TIRA-2 (n=1939) for validation. We have developed a bead-based multianalyte flow immunoassay [2] and screened approx. 350 peptides derived from JPs of interest. We included monoclonal antibodies as assay calibrators and determined limit of detection (LoD). To assess positivity for autoantibodies to JP of interest above LoD, we used 5MAD (median absolute deviation) of the control populations as the cut-off.ResultsIn the ERAp cohort, 5 autoantibodies discriminated RA patients from controls with 81% sensitivity and 100% specificity (Table 1). The same autoantibodies had 68% sensitivity and 98% specificity in the combined BARFOT and TIRA-2 cohorts. Together with RF and aCCP, only 2 of the 5 autoantibodies added statistically significant diagnostic value, increasing the sensitivity from 48% to 61% with 99% specificity. In aCCP- and RF-negative ueRA patients (n=536), the novel biomarkers identified 22.5% of the patients with 99% specificity compared to controls.Table 1.Diagnostic capacity of the joint-specific antibodiesTest panelPerformanceGroup of patientsaCCP+RF+JP+SensitivitySpecificityAUC(ROC)ERApAll patients (n=66)--X81%100%89%RF and aCCP-neg patients (n=7)1------BARFOT and TIRA-2, combined dataAll patients (N=1939)--X68%98%86%All patients (N=1939)X--58%99%78%All patients (N=1939)2XX-48%100%84%All patients (N=1939)2, 3XXX61%99%86%RF and/or aCCP-pos patients (N=1403)--X84%99%93%RF and aCCP-neg patients (N=536)--X22%99%67%RA, literature valuesAnti-CCP testXN/AN/A53–71%95–96%N/A1Not analysed due to lack of power2This patient population is both aCCP+ and RF+3Only 2 of the 5 autoantibodies added statistically significant to the diagnostic valueAUC, Area under the curve; ROC, receiver operating characteristic curve; N/A, not applicable. Controls without rheumatic diseases: N=935 for BARFOT / TIRA-2 and N=27 for ERAp.ConclusionAutoantibodies to JP discriminate ueRA patients better then aCCP and RF alone and add an increased diagnostic value in particular for seronegative patients.References[1]Holmdahl, R., V. Malmstrom, and H. Burkhardt, Autoimmune priming, tissue attack and chronic inflammation - the three stages of rheumatoid arthritis. Eur J Immunol, 2014. 44(6): p. 1593-9.[2]Viljanen, J., et al., Synthesis of an Array of Triple-Helical Peptides from Type II Collagen for Multiplex Analysis of Autoantibodies in Rheumatoid Arthritis. ACS Chem Biol, 2020. 15(9): p. 2605-2615. Correction: ACS Chem Biol, 2020. 15(11): p. 3072AcknowledgementsBARFOT study group.Disclosure of InterestsErik Lönnblom: None declared, Monica Leu Agelii: None declared, Outi Sareila Employee of: Part time employee in Vacara AB, Ingiäld Hafström: None declared, Maria Andersson: None declared, Lei Cheng: None declared, Göran Bergström: None declared, Anna-Karin H Ekwall: None declared, Anna Rudin: None declared, Alf Kastbom: None declared, Christopher Sjowall: None declared, Bingze Xu: None declared, Lennart T.H. Jacobsson: None declared, Johan Viljanen: None declared, Jan Kihlberg: None declared, Inger Gjertsson: None declared, Rikard Holmdahl Shareholder of: Rikard Holmdahl the founder of Vacara AB.
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| 12. |
- Amm, O., Janhunen, P., Kauristie, K., Opgenoorth, H.J., Pulkkinen, T.I. and Viljanen, A.
(författare)
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Mesoscale ionospheric electrodynamics observed with the MIRACLE network: 1. Analysis of a pseudobreakup spiral.
- 2001
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Ingår i: Journal of Geophysical Research. ; 106:111, s. 24675-24690
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Tidskriftsartikel (refereegranskat)abstract
- A short-lived auroral spiral is observed on February 3, 1999, around 2204 UT, using the Multi-Instrument Array for Ionosphere-Magnetosphere Coupling Studies (MIRACLE) network of ground-based instruments in Fennoscandia, which consists of magnetometers, co
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| 13. |
- Dimmock, Andrew P., et al.
(författare)
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On the Regional Variability ofdB/dtand Its Significance to GIC
- 2020
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Ingår i: Space Weather. - : AMER GEOPHYSICAL UNION. - 1542-7390. ; 18:8
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Tidskriftsartikel (refereegranskat)abstract
- Faraday's law of induction is responsible for setting up a geoelectric field due to the variations in the geomagnetic field caused by ionospheric currents. This drives geomagnetically induced currents (GICs) which flow in large ground-based technological infrastructure such as high-voltage power lines. The geoelectric field is often a localized phenomenon exhibiting significant variations over spatial scales of only hundreds of kilometers. This is due to the complex spatiotemporal behavior of electrical currents flowing in the ionosphere and/or large gradients in the ground conductivity due to highly structured local geological properties. Over some regions, and during large storms, both of these effects become significant. In this study, we quantify the regional variability ofdB/dtusing closely placed IMAGE stations in northern Fennoscandia. The dependency between regional variability, solar wind conditions, and geomagnetic indices are also investigated. Finally, we assess the significance of spatial geomagnetic variations to modeling GICs across a transmission line. Key results from this study are as follows: (1) Regional geomagnetic disturbances are important in modeling GIC during strong storms; (2)dB/dtcan vary by several times up to a factor of three compared to the spatial average; (3)dB/dtand its regional variation is coupled to the energy deposited into the magnetosphere; and (4) regional variability can be more accurately captured and predicted from a local index as opposed to a global one. These results demonstrate the need for denser magnetometer networks at high latitudes where transmission lines extending hundreds of kilometers are present.
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| 14. |
- Dimmock, Andrew P., et al.
(författare)
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The GIC and Geomagnetic Response Over Fennoscandia to the 7-8 September 2017 Geomagnetic Storm
- 2019
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Ingår i: Space Weather. - 1542-7390. ; 17:7, s. 989-1010
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Tidskriftsartikel (refereegranskat)abstract
- Between 7 and 8 September 2017, Earth experienced extreme space weather events. We have combined measurements made by the IMAGE magnetometer array, ionospheric equivalent currents, geomagnetically induced current (GIC) recordings in the Finnish natural gas pipeline, and multiple ground conductivity models to study the Fennoscandia ground effects. This unique analysis has revealed multiple interesting physical and technical insights. We show that although the 7-8 September event was significant by global indices (Dst similar to 150 nT), it produced an unexpectedly large peak GIC. It is intriguing that our peak GIC did not occur during the intervals of largest geomagnetic depressions, nor was there any clear upstream trigger. Another important insight into this event is that unusually large and rare GIC amplitudes (>10 A) occurred in multiple Magnetic Local Time (MLT) sectors and could be associated with westward and eastward electrojets. We were also successfully able to model the geoelectric field and GIC using multiple models, thus providing a further important validation of these models for an extreme event. A key result from our multiple conductivity model comparison was the good agreement between the temporal features of 1-D and 3-D model results. This provides an important justification for past and future uses of 1-D models at Mantsala which is highly relevant to additional uses of this data set. Although the temporal agreement (after scaling) was good, we found a large (factor of 4) difference in the amplitudes between local and global ground models due to the difference in model conductivities. Thus, going forward, obtaining accurate ground conductivity values are key for GIC modeling.
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| 15. |
- Hagg, S, et al.
(författare)
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Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
- 2017
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:4, s. e1100-
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Tidskriftsartikel (refereegranskat)abstract
- The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=−0.053; 95% CI: −0.087, −0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10−5), whereas carriers performed better in STROOP (β=−0.074; 95% CI: −0.140, −0.009; P=0.03). Causal associations were found for STROOP only (β=−0.598 per s.d.-increase of TL; 95% CI: −1.125, −0.072; P=0.026), with a larger effect in ɛ4-carriers (β=−0.699; 95% CI: −1.330, −0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.
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| 16. |
- Kaurisitie, K., Syrjsuo, M., Amm, O., Viljanen, A., Pulkkinen, T.I. and Opgenoorth, H.J.
(författare)
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A statistical study of evening sectorarcs and electrojets.
- 2001
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Ingår i: Advances in Space Research. ; 28, s. 16045-1610
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Tidskriftsartikel (refereegranskat)abstract
- We present results of a statistical study of evening sector auroral arcs associated with electrojets. The study (including similar to 1000 all-sky camera (ASC) frames) is based on data of the MIRACLE instrument network. An automatic search engine is used
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| 17. |
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| 18. |
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| 19. |
- Orava, J., et al.
(författare)
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Blunted Metabolic Responses to Cold and Insulin Stimulation in Brown Adipose Tissue of Obese Humans
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 21:11, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. Design and Methods: Using positron emission tomography (PET), cold-and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans were quantified. Further, cold-induced glucose uptake was measured in obese subjects before and after a 5-month conventional weight loss. Results: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. Conclusions: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.
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| 20. |
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| 21. |
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| 22. |
- Syrjäsuo, M., Pulkkinen, T.I., Pellinen, R.P., Janhunen, P., Kauristie, K., Viljanen, A., Opgenoorth, H.J., Karllson, P., Wallman, S., Eglitis, P., Nielsen, E. and Thomas, C.
(författare)
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Observations of substorm electrodynamics using the miracle network.
- 2001
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Ingår i: The 4th International Conference on Substorms, ICS4. - : Terra Scient. Publ. Comp. Tokyo, Japan. Kaje Hamana, Japan.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 23. |
- Viljanen, E.K., et al.
(författare)
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Degree of conversion and flexural properties of a dendrimer/methyl methacrylate copolymer: Design of experiments and statistical screening
- 2005
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Ingår i: Dental Materials. - : Elsevier BV. - 0109-5641 .- 1879-0097. ; 21:2, s. 172-177
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate the effect of photosensitive initiator and activator concentrations on the degree of conversion and flexural properties of an experimental photopolymerized dental copolymer containing dendrimer. Methods: The experimental resin system consisted of a dendrimer with 12 methacrylate groups and methyl methacrylate in a mass ratio of 80:20. The initiator and activator used were camphorquinone and 2-(N,N-dimethylamino)ethyl methacrylate, whose concentrations varied individually from 1 to 4wt%. The degree of conversion was determined with FTIR spectroscopy, and flexural strength and flexural modulus with the three-point bending test. The experiments were designed and analyzed, and the results plotted with Modde 5.0 software. Results: The highest degree of conversion was obtained with 2.5wt% initiator and activator concentrations, the highest flexural strength with 2.5wt% initiator and 1.0wt% activator concentration, and the highest flexural modulus with 1.0wt% initiator and activator concentrations. Significance: The results indicated that the degree of conversion increased, and flexural strength and flexural modulus decreased, with increasing initiator and activator concentrations. The high concentrations of initiator probably inhibited the transmittance of the active wavelengths to the depths of the samples (the inner filter effect), resulting in inhomogeneous conversion and thus decreased mechanical properties. © 2004 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.
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| 24. |
- Viljanen, Johan, et al.
(författare)
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Surface-assisted delivery of fluorescent groups to hGST A1-1 and a lysine mutant
- 2006
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Ingår i: Bioconjugate Chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 17:2, s. 429-437
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Tidskriftsartikel (refereegranskat)abstract
- Human glutathione transferase (hGST) Al-l and a lysine mutant(A216K) can both be rapidly and site-specifically acylated on Y9 and K216, respectively, using a range of thiolesters of glutathione (GS-thiolesters) as modifying reagents. The present investigation was aimed at developing a method with which to deliver a fluorescent acyl group from a solid support under conditions compatible with standard protein purification schemes. A number of fluorescent GS-thiolesters with modified peptide backbones were therefore prepared and tested for reactivity toward hGST Al-l and the A216K mutant. Substitutions at the alpha-NH2 part of the glutathione backbone were not tolerated by the proteins. However, two fluorescent reagents that carry a biotin moiety at the C-terminal part of glutathione were found through MALDI-MS experiments to react in solution with Y9 of the wild-type protein and one reagent with K216 of A216K. The reaction can take place in the presence of glutathione and even in a crude E. coli lysate of cells expressing A216K. Delivery of the fluorescent group to Y9 or K216 was possible using, NeutrAvidin (NA) beads that had been preincubated with biotinylated reagent. Alternatively, excess reagent can be removed by a brief incubation with NA beads. We have thus now developed a system for protein labeling with easy removal of excess and used up low-molecular weight reagent. This strategy can conceivably be utilized in future protein purification and labeling experiments.
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| 25. |
- Viljanen, Johan V., et al.
(författare)
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Synthesis of an Array of Triple-Helical Peptides from Type II Collagen for Multiplex Analysis of Autoantibodies in Rheumatoid Arthritis
- 2020
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 15:9, s. 2605-2615
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Tidskriftsartikel (refereegranskat)abstract
- Type II collagen (CII) is the most abundant protein in joint cartilage. Antibodies to CII appear around the clinical onset of the autoimmune disease rheumatoid arthritis (RA) in a subset of patients. They target specific epitopes on CII and can be pathogenic or protective. Assays for early detection of such autoantibodies may provide new opportunities for selecting effective treatment strategies of RA. We report the efficient and reproducible assembly of an array of covalently branched native and citrullinated triple helical peptides (THPs) from CII that contain defined autoantibody epitopes. Both monoclonal antibodies and sera from experimental mouse models show a unique reactivity toward the THPs, compared to cyclic peptides containing the epitopes, revealing the importance that the epitopes are displayed in a triple-helical conformation. Importantly, antibodies against three of the THPs that contain major CII epitopes were found to be increased in sera from patients with RA, compared to control persons. These results indicate that such synthetic THPs should be included in multiplex analysis of autoantibodies that are uniquely occurring in individuals with early RA, to provide valuable information on disease prognosis and on what type of therapy should be chosen for individual patients. Copyright © 2020 American Chemical Society.
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| 26. |
- Virtanen, KA, et al.
(författare)
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Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects
- 2003
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:2, s. 283-290
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the effects of rosiglitazone (4 mg b.i.d.) and metformin (1 g b.i.d.) monotherapy for 26 weeks on adipose tissue insulin-stimulated glucose uptake in patients (n = 41) with type 2 diabetes. Before and after the treatment, glucose uptake was measured using 2-[18F]fluoro-2-deoxyglucose and positron emission tomography and adipose tissue masses were quantified using magnetic resonance imaging. Rosiglitazone improved insulin-stimulated whole-body glucose uptake by 44% (P < 0.01 vs. placebo). Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2.0 kg in the metformin group (P < 0.05 vs. placebo). In visceral adipose tissue, glucose uptake increased by 29% (from 17.8 ± 2.0 to 23.0 ± 2.6 μmol · kg−1 · min−1, P < 0.05 vs. placebo) in the rosiglitazone group but to a lesser extent (17%) in the metformin group (from 16.2 ± 1.5 to 18.9 ± 1.7 μmol · kg−1 · min−1, P < 0.05 vs. baseline). Because the visceral adipose tissue mass simultaneously decreased with both treatments (P < 0.05), no change was observed in total visceral glucose uptake per depot. Rosiglitazone significantly enhanced glucose uptake in the femoral subcutaneous area, either when expressed per tissue mass (from 10.8 ± 1.2 to 17.1 ± 1.7 μmol · kg−1 · min−1, P < 0.01 vs. placebo) or per whole-fat depot (P < 0.05 vs. placebo). In conclusion, metformin treatment resulted in improvement of glycemic control without enhancement of peripheral insulin sensitivity. The improved insulin sensitivity of the nonabdominal subcutaneous adipose tissue during treatment with rosiglitazone partly explains the enhanced whole-body insulin sensitivity and underlies the central role of adipose tissue for action of peroxisome proliferator-activated receptor γ agonist in vivo.
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