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Institution

University of Turku

EducationTurku, Finland
About: University of Turku is a education organization based out in Turku, Finland. It is known for research contribution in the topics: Population & Galaxy. The organization has 16296 authors who have published 45124 publications receiving 1505428 citations. The organization is also known as: Turun yliopisto & Åbo universitet.


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Journal ArticleDOI
TL;DR: It is shown that the prognosis is unsatisfactory in warfarin-treated patients irrespective of the drug combination used, and aspirin plus Warfarin combination seems to be inadequate to prevent stent thrombosis.
Abstract: Aim The aim of this study was to evaluate the antithrombotic treatment adopted after coronary stenting in patients requiring long-term anticoagulation. Methods and results We analysed retrospectively all consecutive patients on warfarin therapy ( n = 239, mean age 70 years, men 74%) who underwent percutaneous coronary intervention (PCI) in 2003–04 in six hospitals. An age- and sex-matched control group with similar disease presentation (unstable or stable symptoms) was selected from the study period. Primary endpoint was defined as the occurrence of death, myocardial infarction, target vessel revascularization, or stent thrombosis at 12 months. Warfarin treatment was an independent predictor of both primary endpoint (OR 1.7, 95% CI 1.0–3.0, P = 0.05) and major bleeding (OR 3.4, 95% CI 1.2–9.3, P = 0.02). Triple therapy with aspirin and clopidogrel was the most common (48%) option in stented patients in warfarin group, and there was a significant ( P = 0.004) difference between the drug combinations in stent thrombosis with the highest (15.2%) incidence in patients receiving warfarin plus aspirin combination. Conclusion Our study shows that the prognosis is unsatisfactory in warfarin-treated patients irrespective of the drug combination used. Aspirin plus warfarin combination seems to be inadequate to prevent stent thrombosis.

287 citations

Journal ArticleDOI
TL;DR: It is demonstrated that IL-17 had detrimental effects on human islet cells in vitro; it potentiated both inflammatory and proapoptotic responses.
Abstract: Th17 immunity has been shown to regulate autoimmune diabetes in mice. IL-17 neutralization prevented development of diabetes when given postinitiation of insulitis but not earlier, suggesting interference with the effector phase of the disease. Islet-cell Ag-specific Th17 cells converted into IFN-γ–secreting Th1-like cells and caused diabetes in mice recipients. The role of IL-17 in human type 1 diabetes (T1D) is, however, not established. In this study, we show upregulation of Th17 immunity in peripheral blood T cells from children with T1D. This was characterized by increased IL-17 secretion and expression of IL-17, IL-22, and retinoic acid-related orphan receptor C isoform 2, but also FOXP3 transcripts upon T cell activation in vitro. Also, circulating memory CD4 cells from children with T1D showed the same pattern of IL-17, IL-22 and FOXP3 mRNA upregulation, indicating IL-17 pathway activation in vivo. IL-17–positive T cells appeared to be CD4+ cells expressing TCR-αβ and CCR6, and a subpopulation showed coproduction of IFN-γ. Given the Th17 immunity in T1D, we demonstrated that IL-17 had detrimental effects on human islet cells in vitro; it potentiated both inflammatory and proapoptotic responses. Our findings highlight the role of IL-17 immunity in the pathogenesis of human T1D and point to a potential therapeutic strategy.

286 citations

Journal ArticleDOI
Marleen H. M. de Moor1, Stéphanie Martine van den Berg2, Karin J. H. Verweij3, Karin J. H. Verweij1, Robert F. Krueger4, Michelle Luciano5, Alejandro Arias Vasquez6, Lindsay K. Matteson4, Jaime Derringer7, Tõnu Esko8, Najaf Amin9, Scott D. Gordon3, Narelle K. Hansell3, Amy B. Hart10, Ilkka Seppälä, Jennifer E. Huffman5, Bettina Konte11, Jari Lahti12, Minyoung Lee13, Michael B. Miller4, Teresa Nutile14, Toshiko Tanaka15, Alexander Teumer16, Alexander Viktorin17, Juho Wedenoja12, Gonçalo R. Abecasis18, Daniel E. Adkins13, Arpana Agrawal19, Jüri Allik20, Jüri Allik8, Katja Appel16, Timothy B. Bigdeli13, Fabio Busonero13, Harry Campbell5, Paul T. Costa21, George Davey Smith22, Gail Davies5, Harriet de Wit10, Jun Ding15, Barbara E. Engelhardt23, Johan G. Eriksson, Iryna O. Fedko1, Luigi Ferrucci15, Barbara Franke6, Ina Giegling11, Richard A. Grucza19, Annette M. Hartmann11, Andrew C. Heath19, Kati Heinonen12, Anjali K. Henders3, Georg Homuth16, Jouke-Jan Hottenga1, William G. Iacono4, Joost G. E. Janzing6, Markus Jokela12, Robert Karlsson17, John P. Kemp22, John P. Kemp24, Matthew G. Kirkpatrick10, Antti Latvala12, Antti Latvala25, Terho Lehtimäki, David C. Liewald5, Pamela A. F. Madden19, Chiara Magri26, Patrik K. E. Magnusson17, Jonathan Marten5, Andrea Maschio27, Sarah E. Medland3, Evelin Mihailov8, Yuri Milaneschi1, Grant W. Montgomery3, Matthias Nauck16, Klaasjan G. Ouwens1, Aarno Palotie12, Aarno Palotie28, Erik Pettersson17, Ozren Polasek29, Yong Qian15, Laura Pulkki-Råback12, Olli T. Raitakari30, Anu Realo8, Richard J. Rose31, Daniela Ruggiero14, Carsten Oliver Schmidt16, Wendy S. Slutske32, Rossella Sorice14, John M. Starr5, Beate St Pourcain22, Angelina R. Sutin33, Angelina R. Sutin15, Nicholas J. Timpson22, Holly Trochet5, Sita H. Vermeulen6, Eero Vuoksimaa12, Elisabeth Widen12, Jasper Wouda2, Jasper Wouda1, Margaret J. Wright3, Lina Zgaga34, Lina Zgaga5, David J. Porteous5, Alessandra Minelli26, Abraham A. Palmer10, Dan Rujescu11, Marina Ciullo14, Caroline Hayward5, Igor Rudan5, Andres Metspalu5, Jaakko Kaprio25, Jaakko Kaprio12, Ian J. Deary5, Katri Räikkönen12, James F. Wilson5, Liisa Keltikangas-Järvinen12, Laura J. Bierut19, John M. Hettema13, Hans Joergen Grabe13, Cornelia M. van Duijn9, David M. Evans22, David M. Evans24, David Schlessinger15, N. L. Pedersen14, Antonio Terracciano33, Matt McGue35, Matt McGue4, Brenda W.J.H. Penninx1, Nicholas G. Martin3, Dorret I. Boomsma1 
TL;DR: This study identifies a novel locus for neuroticism located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies and shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants.
Abstract: Importance Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). Objectives To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. Design, Setting, and Participants Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. Main Outcomes and Measures Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. Results A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10−9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10−8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10−12 < P < .05) and MDD (4.02 × 10−9 < P < .05) in the 2 other cohorts. Conclusions and Relevance This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism

286 citations

Journal ArticleDOI
TL;DR: Flexibility indices and profiles can be used in the design of more stable proteins by site-directed mutagenesis and the relevance of reduced flexibility to overall stability of proteins is discussed.
Abstract: Thermostability of proteins arises from the simultaneous effect of several forces, which in fact lead to decreased flexibility of the polypeptide chain. This is verified by flexibility indices, which are derived from normalized B-values of individual amino acids in several refined three-dimensional structures. Flexibility indices show that overall flexibility is reduced when thermostability is increased. Protein molecules require both flexibility and rigidity to function, but the higher the temperature optimum and stability the more rigid is the structure needed to compensate for increased thermal fluctuations. Flexibilities of proteins performing the same catalytic activity seem to be about the same at their temperature optima, but the more rigid thermostable proteins reach the flexibility of thermolabile proteins at higher temperatures. In several proteins such as allosteric enzymes, some local sites of flexibility are highly conserved. The relevance of reduced flexibility to overall stability of proteins is also discussed. Flexibility indices and profiles can be used in the design of more stable proteins by site-directed mutagenesis.

286 citations

Journal ArticleDOI
Norihiro Kato, Marie Loh1, Marie Loh2, Marie Loh3  +253 moreInstitutions (73)
TL;DR: The trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry finds genetic variants at 12 new loci to be associated with blood pressure, providing new evidence for the role of DNA methylation in blood pressure regulation.
Abstract: We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

286 citations


Authors

Showing all 16461 results

NameH-indexPapersCitations
Kari Alitalo174817114231
Mika Kivimäki1661515141468
Jaakko Kaprio1631532126320
Veikko Salomaa162843135046
Markus W. Büchler148154593574
Eugene C. Butcher14644672849
Steven Williams144137586712
Terho Lehtimäki1421304106981
Olli T. Raitakari1421232103487
Pim Cuijpers13698269370
Jeroen J. Bax132130674992
Sten Orrenius13044757445
Aarno Palotie12971189975
Stefan W. Hell12757765937
Carlos López-Otín12649483933
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023102
2022290
20212,673
20202,688
20192,407
20182,189