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- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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- Böhmer, Jens, 1981, et al.
(författare)
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Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study.
- 2023
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - 0934-0874 .- 1432-2277. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- In this prospective study we investigated a cohort after heart transplantation with a novel PCR-based approach with focus on treated rejection. Blood samples were collected coincidentally to biopsies, and both absolute levels of dd-cfDNA and donor fraction were reported using digital PCR. 52 patients (11 children and 41 adults) were enrolled (NCT03477383, clinicaltrials.gov), and 557 plasma samples were analyzed. 13 treated rejection episodes >14days after transplantation were observed in 7 patients. Donor fraction showed a median of 0.08% in the cohort and was significantly elevated during rejection (median 0.19%, p < 0.0001), using a cut-off of 0.1%, the sensitivity/specificity were 92%/56% (AUC ROC-curve: 0.78). Absolute levels of dd-cfDNA showed a median of 8.8 copies/mL and were significantly elevated during rejection (median 23, p = 0.0001). Using a cut-off of 7.5 copies/mL, the sensitivity/specificity were 92%/43% for donor fraction (AUC ROC-curve: 0.75). The results support the feasibility of this approach in analyzing dd-cfDNA after heart transplantation. The obtained values are well aligned with results from other trials. The possibility to quantify absolute levels adds important value to the differentiation between ongoing graft damage and quiescent situations.
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- Huang, Mingtao, 1984, et al.
(författare)
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Microfluidic screening and whole-genome sequencing identifies mutations associated with improved protein secretion by yeast
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:34, s. E4689-E4696
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Tidskriftsartikel (refereegranskat)abstract
- There is an increasing demand for biotech-based production of recombinant proteins for use as pharmaceuticals in the food and feed industry and in industrial applications. Yeast Saccharomyces cerevisiae is among preferred cell factories for recombinant protein production, and there is increasing interest in improving its protein secretion capacity. Due to the complexity of the secretory machinery in eukaryotic cells, it is difficult to apply rational engineering for construction of improved strains. Here we used high-throughput microfluidics for the screening of yeast libraries, generated by UV mutagenesis. Several screening and sorting rounds resulted in the selection of eight yeast clones with significantly improved secretion of recombinant a-amylase. Efficient secretion was genetically stable in the selected clones. We performed whole-genome sequencing of the eight clones and identified 330 mutations in total. Gene ontology analysis of mutated genes revealed many biological processes, including some that have not been identified before in the context of protein secretion. Mutated genes identified in this study can be potentially used for reverse metabolic engineering, with the objective to construct efficient cell factories for protein secretion. The combined use of microfluidics screening and whole-genome sequencing to map the mutations associated with the improved phenotype can easily be adapted for other products and cell types to identify novel engineering targets, and this approach could broadly facilitate design of novel cell factories.
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- Kassa, Elias, 1975, et al.
(författare)
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Simulation of dynamic interaction between train and railway turnout
- 2006
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Ingår i: Vehicle System Dynamics. - : Informa UK Limited. - 1744-5159 .- 0042-3114. ; 44:3, s. 247-258
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic train–track interaction is more complex in railway turnouts (switches and crossings) than that in ordinary tangent or curved tracks. Multiple contacts between wheel and rail are common, and severe impact loads with broad frequency contents are induced, when nominal wheel–rail contact conditions are disturbed because of the continuous variation in rail profiles and the discontinuities in the crossing panel. The absence of transition curves at the entry and exit of the turnout, and the cant deficiency, leads to large wheel–rail contact forces and passenger discomfort when the train is switching into the turnout track. Two alternative multibody system (MBS) models of dynamic interaction between train and a standard turnout design are developed. The first model is derived using a commercial MBS software. The second model is based on a multibody dynamics formulation, which may account forthe structural flexibility of train and track components (based on finite element models and coordinate reduction methods). The variation in rail profile is accounted for by sampling the cross-section of each rail at several positions along the turnout. Contact between the back of the wheel flange and the check rail, when the wheelset is steered through the crossing, is considered. Good agreement in results from the two models is observed when the track model is taken as rigid.
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