TY - JOUR A1 - Franco-Obregon, Alfredo A1 - Cambria, Elena A1 - Greutert, Helen A1 - Wernas, Timon A1 - Hitzl, Wolfgang A1 - Egli, Marcel A1 - Sekiguchi, Miho A1 - Boos, Norbert A1 - Hausmann, Oliver A1 - Ferguson, Stephen J. A1 - Kobayashi, Hiroshi A1 - Würtz-Kozak, Karin T1 - TRPC6 in simulated microgravity of intervertebral disc cells JF - European Spine Journal N2 - Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. Conclusions Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies. KW - Intervertebral disc KW - Simulated microgravity KW - Senescence KW - TRP channels KW - Mechanotransduction KW - Gene expression Y1 - 2018 U6 - https://doi.org/10.1007/s00586-018-5688-8 SN - 0940-6719 SN - 1432-0932 VL - 27 IS - 10 SP - 2621 EP - 2630 PB - Springer CY - New York ER - TY - JOUR A1 - Scheiner, Ricarda A1 - Kulikovskaja, Leonora A1 - Thamm, Markus T1 - The honey bee tyramine receptor AmTYR1 and division of foraging labour JF - The journal of experimental biology N2 - Honey bees display a fascinating division of labour among foragers. While some bees solely collect pollen, others only collect nectar. It is assumed that individual differences in sensory response thresholds are at the basis of this division of labour. Biogenic amines and their receptors are important candidates for regulating the division of labour, because they can modulate sensory response thresholds. Here, we investigated the role of the honey bee tyramine receptor AmTYR1 in regulating the division of foraging labour. We report differential splicing of the Amtyr1 gene and show differential gene expression of one isoform in the suboesophageal ganglion of pollen and nectar foragers. This ganglion mediates gustatory inputs. These findings imply a role for the honey bee tyramine receptor in regulating the division of foraging labour, possibly through the suboesophageal ganglion. KW - Splicing KW - Tyramine KW - Gene expression KW - Pollen KW - Nectar KW - Biogenic amines Y1 - 2014 U6 - https://doi.org/10.1242/jeb.098475 SN - 0022-0949 SN - 1477-9145 VL - 217 IS - 8 SP - 1215 EP - 1217 PB - Company of Biologists Limited CY - Cambridge ER - TY - JOUR A1 - Huynen, Leon A1 - Suzuki, Takayuki A1 - Ogura, Toshihiko A1 - Watanabe, Yusuke A1 - Millar, Craig D. A1 - Hofreiter, Michael A1 - Smith, Craig A1 - Mirmoeini, Sara A1 - Lambert, David M. T1 - Reconstruction and in vivo analysis of the extinct tbx5 gene from ancient wingless moa (Aves: Dinornithiformes) JF - BMC evolutionary biology N2 - Background: The forelimb-specific gene tbx5 is highly conserved and essential for the development of forelimbs in zebrafish, mice, and humans. Amongst birds, a single order, Dinornithiformes, comprising the extinct wingless moa of New Zealand, are unique in having no skeletal evidence of forelimb-like structures. Results: To determine the sequence of tbx5 in moa, we used a range of PCR-based techniques on ancient DNA to retrieve all nine tbx5 exons and splice sites from the giant moa, Dinornis. Moa Tbx5 is identical to chicken Tbx5 in being able to activate the downstream promotors of fgf10 and ANF. In addition we show that missexpression of moa tbx5 in the hindlimb of chicken embryos results in the formation of forelimb features, suggesting that Tbx5 was fully functional in wingless moa. An alternatively spliced exon 1 for tbx5 that is expressed specifically in the forelimb region was shown to be almost identical between moa and ostrich, suggesting that, as well as being fully functional, tbx5 is likely to have been expressed normally in moa since divergence from their flighted ancestors, approximately 60 mya. KW - tbx5 KW - Moa KW - Gene expression KW - Ancient DNA KW - Development KW - Forelimb Y1 - 2014 U6 - https://doi.org/10.1186/1471-2148-14-75 SN - 1471-2148 VL - 14 PB - BioMed Central CY - London ER - TY - JOUR A1 - Lukoszek, Radoslaw A1 - Müller-Röber, Bernd A1 - Ignatova, Zoya T1 - Interplay between polymerase II- and polymerase III-assisted expression of overlapping genes JF - FEBS letters : the journal for rapid publication of short reports in molecular biosciences N2 - Up to 15% of the genes in different genomes overlap. This architecture, although beneficial for the genome size, represents an obstacle for simultaneous transcription of both genes. Here we analyze the interference between RNA-polymerase II (Pol II) and RNA-polymerase III (Pol III) when transcribing their target genes encoded on opposing strands within the same DNA fragment in Arabidopsis thaliana. The expression of a Pol II-dependent protein-coding gene negatively correlated with the transcription of a Pol III-dependent, tRNA-coding gene set. We suggest that the architecture of the overlapping genes introduces an additional layer of control of gene expression. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. KW - Gene expression KW - Transcription KW - tRNA KW - Nested and overlapping genes KW - Arabidopsis thaliana Y1 - 2013 U6 - https://doi.org/10.1016/j.febslet.2013.09.033 SN - 0014-5793 SN - 1873-3468 VL - 587 IS - 22 SP - 3692 EP - 3695 PB - Elsevier CY - Amsterdam ER - TY - GEN A1 - Perscheid, Cindy A1 - Uflacker, Matthias T1 - Integrating Biological Context into the Analysis of Gene Expression Data T2 - Distributed Computing and Artificial Intelligence, Special Sessions, 15th International Conference N2 - High-throughput RNA sequencing produces large gene expression datasets whose analysis leads to a better understanding of diseases like cancer. The nature of RNA-Seq data poses challenges to its analysis in terms of its high dimensionality, noise, and complexity of the underlying biological processes. Researchers apply traditional machine learning approaches, e. g. hierarchical clustering, to analyze this data. Until it comes to validation of the results, the analysis is based on the provided data only and completely misses the biological context. However, gene expression data follows particular patterns - the underlying biological processes. In our research, we aim to integrate the available biological knowledge earlier in the analysis process. We want to adapt state-of-the-art data mining algorithms to consider the biological context in their computations and deliver meaningful results for researchers. KW - Gene expression KW - Machine learning KW - Feature selection KW - Association rule mining KW - Biclustering KW - Knowledge bases Y1 - 2019 SN - 978-3-319-99608-0 SN - 978-3-319-99607-3 U6 - https://doi.org/10.1007/978-3-319-99608-0_41 SN - 2194-5357 SN - 2194-5365 VL - 801 SP - 339 EP - 343 PB - Springer CY - Cham ER - TY - JOUR A1 - Nagel, Rebecca A1 - Kirschbaum, Frank A1 - Tiedemann, Ralph T1 - Electric organ discharge diversification in mormyrid weakly electric fish is associated with differential expression of voltage-gated ion channel genes JF - Journal of comparative physiology : A, Neuroethology, sensory, neural, and behavioral physiology N2 - In mormyrid weakly electric fish, the electric organ discharge (EOD) is used for species recognition, orientation and prey localization. Produced in the muscle-derived adult electric organ, the EOD exhibits a wide diversity across species in both waveform and duration. While certain defining EOD characteristics can be linked to anatomical features of the electric organ, many factors underlying EOD differentiation are yet unknown. Here, we report the differential expression of 13 Kv1 voltage-gated potassium channel genes, two inwardly rectifying potassium channel genes, two previously studied sodium channel genes and an ATPase pump in two sympatric species of the genus Campylomormyrus in both the adult electric organ and skeletal muscle. Campylomormyrus compressirostris displays a basal EOD, largely unchanged during development, while C. tshokwe has an elongated, putatively derived discharge. We report an upregulation in all Kv1 genes in the electric organ of Campylomormyrus tshokwe when compared to both skeletal muscle and C. compressirostris electric organ. This pattern of upregulation in a species with a derived EOD form suggests that voltage-gated potassium channels are potentially involved in the diversification of the EOD signal among mormyrid weakly electric fish. KW - Weakly electric fish KW - Ion channels KW - Electric organ KW - Gene expression KW - Campylomormyrus Y1 - 2017 U6 - https://doi.org/10.1007/s00359-017-1151-2 SN - 0340-7594 SN - 1432-1351 VL - 203 SP - 183 EP - 195 PB - Springer CY - New York ER - TY - JOUR A1 - Luckert, Claudia A1 - Hessel, Stefanie A1 - Lenze, Dido A1 - Lampen, Alfonso T1 - Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis JF - Toxicology in vitro N2 - 1,2-unsaturated pyrrolizidine alkaloids (PA) are plant metabolites predominantly occurring in the plant families Asteraceae and Boraginaceae. Acute and chronic PA poisoning causes severe hepatotoxicity. So far, the molecular mechanisms of PA toxicity are not well understood. To analyze its mode of action, primary human hepatocytes were exposed to a non-cytotoxic dose of 100 mu M of four structurally different PA: echimidine, heliotrine, senecionine, senkirkine. Changes in mRNA expression were analyzed by a whole genome microarray. Employing cut-off values with a vertical bar fold change vertical bar of 2 and a q-value of 0.01, data analysis revealed numerous changes in gene expression. In total, 4556, 1806, 3406 and 8623 genes were regulated by echimidine, heliotrine, senecione and senkirkine, respectively. 1304 genes were identified as commonly regulated. PA affected pathways related to cell cycle regulation, cell death and cancer development. The transcription factors TP53, MYC, NF kappa B and NUPR1 were predicted to be activated upon PA treatment. Furthermore, gene expression data showed a considerable interference with lipid metabolism and bile acid flow. The associated transcription factors FXR, LXR, SREBF1/2, and PPAR alpha/gamma/delta were predicted to be inhibited. In conclusion, though structurally different, all four PA significantly regulated a great number of genes in common. This proposes similar molecular mechanisms, although the extent seems to differ between the analyzed PA as reflected by the potential hepatotoxicity and individual PA structure. (C) 2015 Elsevier Ltd. All rights reserved. KW - Pyrrolizidine alkaloids KW - Transcriptomics KW - Gene expression KW - Hepatotoxicity Y1 - 2015 U6 - https://doi.org/10.1016/j.tiv.2015.06.021 SN - 0887-2333 VL - 29 IS - 7 SP - 1669 EP - 1682 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Perscheid, Cindy T1 - Comprior BT - Facilitating the implementation and automated benchmarking of prior knowledge-based feature selection approaches on gene expression data sets JF - BMC Bioinformatics N2 - Background Reproducible benchmarking is important for assessing the effectiveness of novel feature selection approaches applied on gene expression data, especially for prior knowledge approaches that incorporate biological information from online knowledge bases. However, no full-fledged benchmarking system exists that is extensible, provides built-in feature selection approaches, and a comprehensive result assessment encompassing classification performance, robustness, and biological relevance. Moreover, the particular needs of prior knowledge feature selection approaches, i.e. uniform access to knowledge bases, are not addressed. As a consequence, prior knowledge approaches are not evaluated amongst each other, leaving open questions regarding their effectiveness. Results We present the Comprior benchmark tool, which facilitates the rapid development and effortless benchmarking of feature selection approaches, with a special focus on prior knowledge approaches. Comprior is extensible by custom approaches, offers built-in standard feature selection approaches, enables uniform access to multiple knowledge bases, and provides a customizable evaluation infrastructure to compare multiple feature selection approaches regarding their classification performance, robustness, runtime, and biological relevance. Conclusion Comprior allows reproducible benchmarking especially of prior knowledge approaches, which facilitates their applicability and for the first time enables a comprehensive assessment of their effectiveness KW - Feature selection KW - Prior knowledge KW - Gene expression KW - Reproducible benchmarking Y1 - 2021 U6 - https://doi.org/10.1186/s12859-021-04308-z SN - 1471-2105 VL - 22 SP - 1 EP - 15 PB - Springer Nature CY - London ER - TY - JOUR A1 - Müller, S. M. A1 - Finke, Hannah A1 - Ebert, Franziska A1 - Kopp, Johannes Florian A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Francesconi, Kevin A. A1 - Raber, G. A1 - Schwerdtle, Tanja T1 - Arsenic-containing hydrocarbons BT - effects on gene expression, epigenetics, and biotransformation in HepG2 cells JF - Archives of toxicology : official journal of EUROTOX N2 - Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-specific endonuclease 1 (FEN1) as well as xeroderma pigmentosum group A complementing protein (XPA) and (cytosine-5)-methyltransferase 3A (DNMT3A) showed time- and concentration-dependent alterations in gene expression, thereby indicating an impact on genomic stability. In the subsequent analysis of epigenetic markers, within 72 h, neither AsHC 332 nor AsHC 360 showed an impact on the global DNA methylation level, whereas incubation with AsHC 360 increased the global DNA hydroxymethylation level. Analysis of cell extracts and cell media by HPLC-mass spectrometry revealed that both AsHCs were considerably biotransformed. The identified metabolites include not only the respective thioxo-analogs of the two AsHCs, but also several arsenic-containing fatty acids and fatty alcohols, contributing to our knowledge of biotransformation mechanisms of arsenolipids. KW - Arsenolipids KW - Gene expression KW - Arsenic-containing hydrocarbons KW - Global DNA methylation KW - Arsenic speciation KW - Metabolism Y1 - 2018 U6 - https://doi.org/10.1007/s00204-018-2194-z SN - 0340-5761 SN - 1432-0738 VL - 92 IS - 5 SP - 1751 EP - 1765 PB - Springer CY - Heidelberg ER -