Lamina C.,Innsbruck Medical University |
Haun M.,Innsbruck Medical University |
Coassin S.,Innsbruck Medical University |
Kloss-Brandstatter A.,Innsbruck Medical University |
And 10 more authors.
PLoS ONE | Year: 2014
Structural genetic variants as short tandem repeats (STRs) are not targeted in SNP-based association studies and thus, their possible association signals are missed. We systematically searched for STRs in gene regions known to contribute to total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels in two independent studies (KORA F4, n = 2553 and SAPHIR, n = 1648), resulting in 16 STRs that were finally evaluated. In a combined dataset of both studies, the sum of STR alleles was regressed on each phenotype, adjusted for age and sex. The association analyses were repeated for SNPs in a 200 kb region surrounding the respective STRs in the KORA F4 Study. Three STRs were significantly associated with total cholesterol (within LDLR, the APOA1/C3/A4/A5/BUD13 gene region and ABCG5/8 ), five with HDL cholesterol (3 within CETP, one in LPL and one inAPOA1/C3/A4/A5/BUD13 ), three with LDL cholesterol (LDLR, ABCG5/8 and CETP) and two with triglycerides (APOA1/C3/A4/A5/BUD13 and LPL). None of the investigated STRs, however, showed a significant association after adjusting for the lead or adjacent SNPs within that gene region. The evaluated STRs were found to be well tagged by the lead SNP within the respective gene regions. Therefore, the STRs reflect the association signals based on surrounding SNPs. In conclusion, none of the STRs contributed additionally to the SNP-based association signals identified in GWAS on lipid traits. © 2014 Lamina et al.
Marziale A.N.,King Abdullah University of Science and Technology |
Jantke D.,King Abdullah University of Science and Technology |
Faul S.H.,King Abdullah University of Science and Technology |
Reiner T.,TechnischeUniversitatMunchen |
And 2 more authors.
Green Chemistry | Year: 2011
The palladacyclic catalyst precursor received by ortho-palladation of ([1,1′-biphenyl]-2-yloxy)diisopropyl-phosphine represents a highly active system for Suzuki-Miyaura cross-coupling reactions when used in neat water. An efficient, broadly applicable and sustainable aqueous protocol was developed using 2.5 eq. of Na2CO3 as base, allowing the reaction to be performed under air and at ambient temperature with Pd loadings of 0.04 mol%. Coupling products are obtained in high yields and excellent purity by simple filtration with no organic solvents needed throughout the whole reaction. A broad variety of functional groups are tolerated and a large number of substrates can be applied with this protocol. The crystal structure of the palladacyclic catalyst precursor is presented as well as investigations targeting the nature of catalyst activation and the active catalytic species. © 2011 The Royal Society of Chemistry.
Hoenig E.,TU Hamburg - Harburg |
Leicht U.,Ludwig Maximilians University of Munich |
Winkler T.,TU Hamburg - Harburg |
Mielke G.,TU Hamburg - Harburg |
And 5 more authors.
Tissue Engineering - Part A | Year: 2013
The implantation of osteochondral constructs-tissue-engineered (TE) cartilage on a bone substitute carrier-is a promising method to treat defects in articular cartilage. Currently, however, the TE cartilage's mechanical properties are clearly inferior to those of native cartilage. Their improvement has been the subject of various studies, mainly focusing on growth factors and physical loading during cultivation. With the approach of osteochondral constructs another aspect arises: the permeability of the carrier materials. The purpose of this study was to investigate whether and how the permeability of the subchondral bone influences the properties of native cartilage and whether the bone substitute carrier's permeability influences the TE cartilage of osteochondral constructs accordingly. Consequently, the influence of the subchondral bone's permeability on native cartilage was determined: Native porcine cartilage-bone cylinders were cultivated for 2 weeks in a bioreactor under mechanical loading with and without restricted permeability of the bone. For the TE cartilage these two permeability conditions were investigated using permeable and impermeable tricalciumphosphate carriers under equivalent cultivation conditions. All specimens were evaluated mechanically, biochemically, and histologically. The restriction of the bone's permeability significantly decreased the Young's modulus of native cartilage in vitro. No biochemical differences were found. This finding was confirmed for TE cartilage: While the biochemical parameters were not affected, a permeable carrier improved the cell morphology and mechanical properties in comparison to an impermeable one. In conclusion, the carrier permeability was identified as a determining factor for the mechanical properties of TE cartilage of osteochondral constructs. © 2013, Mary Ann Liebert, Inc.
Xu T.,Helmholtz Center Munich |
Brandmaier S.,Helmholtz Center Munich |
Messias A.C.,Helmholtz Center Munich |
Herder C.,Heinrich Heine University Dusseldorf |
And 70 more authors.
Diabetes Care | Year: 2015
OBJECTIVE Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. RESEARCH DESIGN AND METHODS We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131metabolites in fasting serumsamples and usedmultivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metforminassociated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways. RESULTS We found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groupswhowere not using glucose-lowering oralmedication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of thesemetabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target. CONCLUSIONS Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease. © 2015 by the American Diabetes Association.
Koeck D.E.,TechnischeUniversitatMunchen |
Zverlov V.V.,TechnischeUniversitatMunchen |
Zverlov V.V.,Russian Academy of Sciences |
Liebl W.,TechnischeUniversitatMunchen |
Systematic and Applied Microbiology | Year: 2014
Clostridium thermocellum is among the most prevalent of known anaerobic cellulolytic bacteria. In this study, genetic and phenotypic variations among C. thermocellum strains isolated from different biogas plants were determined and different genotyping methods were evaluated on these isolates. At least two C. thermocellum strains were isolated independently from each of nine different biogas plants via enrichment on cellulose. Various DNA-based genotyping methods such as ribotyping, RAPD (Random Amplified Polymorphic DNA) and VNTR (Variable Number of Tandem Repeats) were applied to these isolates. One novel approach - the amplification of unknown target sequences between copies of a previously discovered Random Inserted Mobile Element (RIME) - was also tested. The genotyping method with the highest discriminatory power was found to be the amplification of the sequences between the insertion elements, where isolates from each biogas plant yielded a different band pattern. Cellulolytic potentials, optimal growth conditions and substrate spectra of all isolates were characterized to help identify phenotypic variations. Irrespective of the genotyping method used, the isolates from each individual biogas plant always exhibited identical patterns. This is suggestive of a single C. thermocellum strain exhibiting dominance in each biogas plant. The genotypic groups reflect the results of the physiological characterization of the isolates like substrate diversity and cellulase activity. Conversely, strains isolated across a range of biogas plants differed in their genotyping results and physiological properties. Both strains isolated from one biogas plant had the best specific cellulose-degrading properties and might therefore achieve superior substrate utilization yields in biogas fermenters. © 2014 Elsevier GmbH.