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- Svala, Emilia, et al.
(författare)
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Effects of interleukin-6 and interleukin-1 beta on expression of growth differentiation factor-5 and Wnt signaling pathway genes in equine chondrocytes
- 2014
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Ingår i: American Journal of Veterinary Research. - : American Veterinary Medical Association (AVMA). - 0002-9645 .- 1943-5681. ; 75:2, s. 132-140
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Tidskriftsartikel (refereegranskat)abstract
- Objective-To determine the effects of interleukin (IL)-6 and IL-1 beta stimulation on expression of growth differentiation factor (GDF)-5 and Wnt signaling pathway genes in equine chondrocytes. Sample-Macroscopically normal articular cartilage samples from 6 horses and osteochondral fragments (OCFs) from 3 horses. Procedures-Chondrocyte pellets were prepared and cultured without stimulation or following stimulation with IL-6 or IL-1 beta for 1, 2, 12, and 48 hours; expression of GDF-5 was determined with a quantitative real-time PCR assay. Expression of genes in various signaling pathways was determined with microarrays for pellets stimulated for 1 and 2 hours. Immunohistochemical analysis was used to detect GDF-5, glycogen synthase kinase 3 beta (GSK-3 beta), and beta-catenin proteins in macroscopically normal cartilage samples and OCFs. Results-Chondrocytes stimulated with IL-6 had significantly higher GDF-5 expression within 2 hours versus unstimulated chondrocytes. Microarray analysis of Wnt signaling pathway genes indicated expression of GSK-3 beta and coiled-coil domain containing 88C increased after 1 hour and expression of beta-catenin decreased after 2 hours of IL-6 stimulation. Results of immunohistochemical detection of proteins were similar to microarray analysis results. Chondrocytes in macroscopically normal articular cartilage and OCFs had immunostaining for GDF-5. Conclusion and Clinical Relevance-Results indicated IL-6 stimulation decreased chondrocyte expression of the canonical Wnt signaling pathway transactivator beta-catenin, induced expression of inhibitors of the Wnt pathway, and increased expression of GDF-5. This suggested IL-6 may inhibit the Wnt signaling pathway with subsequent upregulation of GDF-5 expression. Anabolic extracellular matrix metabolism in OCFs may be attributable to GDF-5 expression. This information could be useful for development of cartilage repair methods.
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| 2. |
- Ståhl, Niclas, 1990-, et al.
(författare)
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Deep Convolutional Neural Networks for the Prediction of Molecular Properties : Challenges and Opportunities Connected to the Data
- 2018
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Ingår i: Journal of Integrative Bioinformatics. - : De Gruyter Open. - 1613-4516. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a flexible deep convolutional neural network method for the analysis of arbitrary sized graph structures representing molecules. This method, which makes use of the Lipinski RDKit module, an open-source cheminformatics software, enables the incorporation of any global molecular (such as molecular charge and molecular weight) and local (such as atom hybridization and bond orders) information. In this paper, we show that this method significantly outperforms another recently proposed method based on deep convolutional neural networks on several datasets that are studied. Several best practices for training deep convolutional neural networks on chemical datasets are also highlighted within the article, such as how to select the information to be included in the model, how to prevent overfitting and how unbalanced classes in the data can be handled.
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