Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

BACKGROUND: Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50-60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk. OBJECTIVES: To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results. METHODS: 3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data. RESULTS: After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers. CONCLUSIONS: In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained

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Sebastian Olden-Jørgensen anmelder: Nicolaus Steno. Biography and Original Papers of a 17th Century Scientist.Edited and Translated by Troels Kardel and Paul Maquet, Springer,Heidelberg, Dordrecht, London, New York 2013, 739 sider, ill., ISBN978-3-642-25078-1, €83,29 (e-bog), €106,95 (indbundet). Henrik Horstbøll anmelder: Kristian Jensen: Revolution and the Antiquarian Book. Reshaping the Past, 1780-1815. Cambridge University Press, Cambridge 2011, 318 sider.ISBN 978-1-107-00051-3. Jesper Düring Jørgensen anmelder: Michael H. Clemmesen: Det lille land før den store krig. De danske farvande, stormagtsstrategier, efterretninger og forsvarsforberedelser omkring kriserne1911-13. Syddansk Universitet/Syddansk Universitetsforlag, Odense,2012. 557 sider, ISBN 978-87-7674-617-9 Lisbeth Bonde anmelder: Erik Aschengreen, Anne Middelboe Christensen og Kirsten Sørensen:Dansen i spejlet. John R. Johnsens balletfotos. Det Kongelige Bibliotek ogGads Forlag, København 2012, 342 sider, ill. ISBN 978-87-12-04687-5,Kr. 349. Niels D. Lund anmelder: Jesper Düring Jørgensen: Den smilende kamæleon. Karl Larsen (1860-1931) – Digter, journalist, militarist. Danish Humanist Texts and Studies, 47.Det Kongelige Bibliotek og Museum Tusculanums Forlag, København2013, 593 s. , illustreret. ISBN 978-87-635-4080-3. Claus Woschenko: J.P.E. Hartmann: Klaverværker/Piano Works/Klavierwerke. Udg. af/Hrsg.von Niels Krabbe. Det Kongelige Bibliotek: Dansk Center for Musikudgivelse.2012. Vol. 1-2. i-lii, 328 s.; liii-lxxxviii, ss. 329-652. Fol. (J.P.E.Hartmann: Udvalgte Værker/Selected Works/Ausgewählte Werke. Udg. afHartmann Udgaven, Det Kongelige Bibliotek/Publ. by The HartmannEdition, The Royal Library / Hrsg. von der Hartmann-Ausgabe, Diekönigliche Bibliothek. Hovedredaktør/Editor-in-chief/Redaktionsleiter:Niels Krabbe. Serie III, bind 1-2/Series III, Vol. 1-2/Serie III, Band1-2). ISMN 979-0706763-12-5 & 979-0706763-13-2. Kr. 1.600,

Steroid hydroxylation by basidiomycete peroxygenases: A combined experimental and computational study, Applied and environmental microbiology

The goal of this study is the selective oxyfunctionalization of steroids under mild and environmentally friendly conditions using fungal enzymes. With this purpose, peroxygenases from three basidiomycete species were tested for the hydroxylation of a variety of steroidal compounds, using H2O2 as the only cosubstrate. Two of them are wild-type enzymes from Agrocybe aegerita and Marasmius rotula, and the third one is a recombinant enzyme from Coprinopsis cinerea. The enzymatic reactions on free and esterified sterols, steroid hydrocarbons, and ketones were monitored by gas chromatography, and the products were identified by mass spectrometry. Hydroxylation at the side chain over the steroidal rings was preferred, with the 25-hydroxyderivatives predominating. Interestingly, antiviral and other biological activities of 25-hydroxycholesterol have been reported recently (M. Blanc et al., Immunity 38:106–118, 2013, http://dx.doi.org/10.1016/j.immuni.2012.11.004). However, hydroxylation in the ring moiety and terminal hydroxylation at the side chain also was observed in some steroids, the former favored by the absence of oxygenated groups at C-3 and by the presence of conjugated double bonds in the rings. To understand the yield and selectivity differences between the different steroids, a computational study was performed using Protein Energy Landscape Exploration (PELE) software for dynamic ligand diffusion. These simulations showed that the active-site geometry and hydrophobicity favors the entrance of the steroid side chain, while the entrance of the ring is energetically penalized. Also, a direct correlation between the conversion rate and the side chain entrance ratio could be established that explains the various reaction yields observed.This study was supported by the INDOX (KBBE-2013-7-613549), PEROXICATS (KBBE-2010-4-265397), and PELE (ERC-2009-Adg 25027) EU projects.Peer Reviewe

The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy

Mesenchymal stromal cells have proven capable of improving cardiac pump function in patients with chronic heart failure, yet little is known about their mode of action. The aim of the study was to investigate the short-term effect of cryopreserved allogeneic rat adipose tissue-derived stromal cells (ASC) on cardiac composition, cellular subpopulations, and gene transcription in a rat model of chronic ischemic cardiomyopathy (ICM). Myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery. After 6 weeks, the rats were treated with ASCs, saline, or no injection, using echo-guided trans-thoracic intramyocardial injections. The cardiac tissue was subsequently collected for analysis of cellular subpopulations and gene transcription 3 and 7 days after treatment. At day 3, an upregulation of genes associated with angiogenesis were present in the ASC group. On day 7, increases in CCR2+ and CD38+ macrophages (p = 0.047 and p = 0.021), as well as in the CD4/CD8 lymphocyte ratio (p = 0.021), were found in the ASC group compared to the saline group. This was supported by an upregulation of genes associated with monocytes/macrophages. In conclusion, ASC treatment initiated an immune response involving monocytes/macrophages and T-cells and induced a gene expression pattern associated with angiogenesis and monocyte/macrophage differentiation

Steroid hydroxylation by basidiomycete peroxygenases: A combined experimental and computational study, Applied and environmental microbiology

The goal of this study is the selective oxyfunctionalization of steroids under mild and environmentally friendly conditions using fungal enzymes. With this purpose, peroxygenases from three basidiomycete species were tested for the hydroxylation of a variety of steroidal compounds, using H2O2 as the only cosubstrate. Two of them are wild-type enzymes from Agrocybe aegerita and Marasmius rotula, and the third one is a recombinant enzyme from Coprinopsis cinerea. The enzymatic reactions on free and esterified sterols, steroid hydrocarbons, and ketones were monitored by gas chromatography, and the products were identified by mass spectrometry. Hydroxylation at the side chain over the steroidal rings was preferred, with the 25-hydroxyderivatives predominating. Interestingly, antiviral and other biological activities of 25-hydroxycholesterol have been reported recently (M. Blanc et al., Immunity 38:106–118, 2013, http://dx.doi.org/10.1016/j.immuni.2012.11.004). However, hydroxylation in the ring moiety and terminal hydroxylation at the side chain also was observed in some steroids, the former favored by the absence of oxygenated groups at C-3 and by the presence of conjugated double bonds in the rings. To understand the yield and selectivity differences between the different steroids, a computational study was performed using Protein Energy Landscape Exploration (PELE) software for dynamic ligand diffusion. These simulations showed that the active-site geometry and hydrophobicity favors the entrance of the steroid side chain, while the entrance of the ring is energetically penalized. Also, a direct correlation between the conversion rate and the side chain entrance ratio could be established that explains the various reaction yields observed.This study was supported by the INDOX (KBBE-2013-7-613549), PEROXICATS (KBBE-2010-4-265397), and PELE (ERC-2009-Adg 25027) EU projects.Peer Reviewe

Report on developing bottom-up Marginal abatement cost curves (MACCS) for representative farm type

Developing efficient policy instruments and incentive schemes to promote the uptake of greenhouse gas mitigation measures requires some kind of prioritisation of the mitigation measures. An important consideration in this process is the estimated cost and costefficiency the measures. The high number of reports done in developed countries show a high variability in the country-level cost-effectiveness estimates, and suggest that approaches providing higher granularity at the spatial and farm type could suit better to the purpose of regional policy development. At the same time, there is still a gap in our understanding of economic mitigation potential of agriculture in developing and newly industrialised countries.[br/] To address these questions this report presents three studies. The first is a literature review of the cost-effectiveness estimates of mitigation measures published in the past 15 years, discussing the variability in these estimates. The second study reports on marginal abatement cost curves for beef cattle production in Brazil. Finally, the last report presents the conceptual basis of a tool to assess the financial implications of the mitigation measures to be used in parallel with the FarmAC model, ultimately providing mitigation measure costeffectiveness estimates specific to individual farms. Additionally, it describes the selection of mitigation measures which have been assessed at the farm level in Component 3 of the AnimalChange project