| 1. |
- Ge, Changrong P, et al.
(author)
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Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage
- 2017
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In: JCI INSIGHT. - : AMER SOC CLINICAL INVESTIGATION INC. - 2379-3708. ; 2:13
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Journal article (peer-reviewed)abstract
- Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.
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| 2. |
- Kaprio, J, et al.
(author)
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The Older Finnish Twin Cohort - 45 Years of Follow-up
- 2019
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In: 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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Journal article (peer-reviewed)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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| 3. |
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| 4. |
- Virtanen, KA, et al.
(author)
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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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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:2, s. 283-290
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Journal article (peer-reviewed)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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| 5. |
- Hagg, S, et al.
(author)
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Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
- 2017
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:4, s. e1100-
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Journal article (peer-reviewed)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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| 6. |
- Hallsten, K, et al.
(author)
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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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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:12, s. 3479-3485
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Journal article (peer-reviewed)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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| 7. |
- Hannukainen, J, et al.
(author)
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In Vivo Measurements of Glucose Uptake in Human Achilles Tendon During Different Exercise Intensities
- 2005
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In: International Journal of Sports Medicine. - : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 26, s. 727-731
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Journal article (peer-reviewed)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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| 8. |
- Nygård, K., et al.
(author)
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ForMAX – a beamline for multiscale and multimodal structural characterization of hierarchical materials
- 2024
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In: Journal of Synchrotron Radiation. - : International Union of Crystallography (IUCr). - 0909-0495 .- 1600-5775. ; 31:Pt 2, s. 363-377
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Journal article (peer-reviewed)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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| 9. |
- Orava, J., et al.
(author)
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Blunted Metabolic Responses to Cold and Insulin Stimulation in Brown Adipose Tissue of Obese Humans
- 2013
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In: Obesity. - : Wiley. - 1930-7381. ; 21:11, s. 2279-2287
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Journal article (peer-reviewed)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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| 10. |
- Amm, O., Janhunen, P., Kauristie, K., Opgenoorth, H.J., Pulkkinen, T.I. and Viljanen, A.
(author)
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Mesoscale ionospheric electrodynamics observed with the MIRACLE network: 1. Analysis of a pseudobreakup spiral.
- 2001
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In: Journal of Geophysical Research. ; 106:111, s. 24675-24690
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Journal article (peer-reviewed)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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| 11. |
- Andersson, Maria L.E., et al.
(author)
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Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis
- 2023
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:7, s. 1110-1119
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Journal article (peer-reviewed)abstract
- Objective. This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.Methods. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).Results. Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.Conclusion. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.
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| 12. |
- Dimmock, Andrew P., et al.
(author)
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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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In: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 19:5
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Journal article (peer-reviewed)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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| 13. |
- Dimmock, Andrew P., et al.
(author)
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On the Regional Variability ofdB/dtand Its Significance to GIC
- 2020
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In: Space Weather. - : AMER GEOPHYSICAL UNION. - 1542-7390. ; 18:8
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Journal article (peer-reviewed)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. |
- Kaurisitie, K., Syrjsuo, M., Amm, O., Viljanen, A., Pulkkinen, T.I. and Opgenoorth, H.J.
(author)
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A statistical study of evening sectorarcs and electrojets.
- 2001
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In: Advances in Space Research. ; 28, s. 16045-1610
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Journal article (peer-reviewed)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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| 15. |
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| 16. |
- Loth, Daan W, et al.
(author)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Journal article (peer-reviewed)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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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- 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.
(author)
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Observations of substorm electrodynamics using the miracle network.
- 2001
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In: The 4th International Conference on Substorms, ICS4. - : Terra Scient. Publ. Comp. Tokyo, Japan. Kaje Hamana, Japan.
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Conference paper (other academic/artistic)
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| 22. |
- T. Tegler, Lotta, et al.
(author)
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Synthetic binder molecules that discriminate between isoforms of human Carbonic Anhydrase in blood.
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Other publication (other academic/artistic)abstract
- From a 16-membered set of 42 residue polypeptide conjugates designed to bind human Carbonic Anhydrases (HCA), two binder candidates 4-C37L34-B och 3-C15L8-B were shown to bind the isoform HCAII with high affinity in a fluorescence based screening assay. To determine their specificity for Carbonic Anhydrases the binders were immobilized on polystyrene beads and submerged in lysed blood, washed three times, cleaved from the beads, analyzed by SDS-PAGE and shown to specifically extract Carbonic Anhydrases from the complex biological mixture. Two Carbonic Anhydrase isoforms with 60% homology exist in human blood with HCAI being present in 5-7 fold excess over HCAII and the ability of the binder molecules to discriminate between HCAI and HCAII was investigated. Due to the high degree of homology HCAI and HCAII could not be separated by electrophoresis and the instead affinities were determined by SPR biosensor analysis. The polypeptide conjugate 4-C37L34-B bound HCAII with a KD of 12 nM whereas it was 90 nM for the binding of HCAI, a ratio of 7.5. The corresponding dissociation constants for the complexes formed from 3-C15L8-B and the two Carbonic Anhydrases were X and Y. This demonstration of selectivity between two very similar proteins is conspicuous in view of the fact that the molecular weight of each one of the binder molecules is little more than 5000, the fold is unordered and the polypeptide sequences are designed from scratch and have no prior relationship to Carbonic Anhydrases. The results suggest that synthetic polypeptide conjugates can be prepared with properties that make them attractive alternatives to biologically generated binders in biotechnology and biomedicine.
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| 23. |
- Tegler, Lotta T., et al.
(author)
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Polypeptide Conjugate Binders that Discriminate between Two Isoforms of Human Carbonic Anhydrase in Human Blood
- 2011
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In: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 12:4, s. 559-566
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Journal article (peer-reviewed)abstract
- Two binder candidates 4-C37L34-B and 3-C15L8-B from a 16-membered set of 42-residue polypeptide conjugates designed to bind human carbonic anhydrase II (HCAII), were shown to bind HCAII with high affinity in a fluorescence-based screening assay. Two carbonic anhydrase isoforms with 60% homology exist in human blood with HCAI being present in five-to sevenfold excess over HCAII. The ability of the binders to discriminate between HCAI and HCAII was evaluated with regard to what selectivity could be achieved by the conjugation of polypeptides from a 16-membered set to a small organic molecule that binds both isoforms with similar affinities. The polypeptide conjugate 4-C37L34-B bound HCAII with a K-D of 17 nm and HCAI with a K-D of 470 nm, that is, with a 30-fold difference in affinity. The corresponding dissociation constants for the complexes formed from 3-C15L8-B and the two carbonic anhydrases were 60 and 390 nm, respectively. This demonstration of selectivity between two very similar proteins is striking in view of the fact that the molecular weight of each one of the conjugate molecules is little more than 5000, the fold is unordered, and the polypeptide sequences were designed de novo and have no prior relationship to carbonic anhydrases. The results suggest that synthetic polypeptide conjugates can be prepared from organic molecules that are considered to be weak binders with low selectivity, yielding conjugates with properties that make them attractive alternatives to biologically generated binders in biotechnology and biomedicine.
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