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Kaynig V.,ETH Zurich | Fischer B.,European Molecular Biology Laboratory Heidelberg EMBL | Muller E.,ETH Zurich | Buhmann J.M.,ETH Zurich
Journal of Structural Biology | Year: 2010

In electron microscopy, a large field of view is commonly captured by taking several images of a sample region and then by stitching these images together. Non-linear lens distortions induced by the electromagnetic lenses of the microscope render a seamless stitching with linear transformations impossible. This problem is aggravated by large CCD cameras, as they are commonly in use nowadays. We propose a new calibration method based on ridge regression that compensates non-linear lens distortions, while ensuring that the geometry of the image is preserved. Our method estimates the distortion correction from overlapping image areas using automatically extracted correspondence points. Therefore, the estimation of the correction transform does not require any special calibration samples. We evaluate our method on simulated ground truth data as well as on real electron microscopy data. Our experiments demonstrate that the lens calibration robustly corrects large distortions with an average stitching error exceeding 10 pixels to sub-pixel accuracy within two iteration steps. © 2010 Elsevier Inc.

Pougach K.,Catholic University of Leuven | Pougach K.,Laboratory for Systems Biology | Voet A.,RIKEN | Kondrashov F.A.,Center for Genomic Regulation | And 15 more authors.
Nature Communications | Year: 2014

The emergence of new genes throughout evolution requires rewiring and extension of regulatory networks. However, the molecular details of how the transcriptional regulation of new gene copies evolves remain largely unexplored. Here we show how duplication of a transcription factor gene allowed the emergence of two independent regulatory circuits. Interestingly, the ancestral transcription factor was promiscuous and could bind different motifs in its target promoters. After duplication, one paralogue evolved increased binding specificity so that it only binds one type of motif, whereas the other copy evolved a decreased activity so that it only activates promoters that contain multiple binding sites. Interestingly, only a few mutations in both the DNA-binding domains and in the promoter binding sites were required to gradually disentangle the two networks. These results reveal how duplication of a promiscuous transcription factor followed by concerted cis and trans mutations allows expansion of a regulatory network. © 2014 Macmillan Publishers Limited. All rights reserved.

Hollerer I.,University of Heidelberg | Hollerer I.,Molecular Medicine Partnership Unit MMPU | Hollerer I.,European Molecular Biology Laboratory Heidelberg EMBL | Grund K.,University of Heidelberg | And 5 more authors.
EMBO Molecular Medicine | Year: 2014

Recent advances reveal mRNA 3′end processing as a highly regulated process that fine-tunes posttranscriptional gene expression. This process can affect the site and/or the efficiency of 3′end processing, controlling the quality and the quantity of substrate mRNAs. The regulation of 3′end processing plays a central role in fundamental physiology such as blood coagulation and innate immunity. In addition, errors in mRNA 3′end processing have been associated with a broad spectrum of human diseases, including cancer. We summarize and discuss the paradigmatic shift in the understanding of 3′end processing as a mechanism of posttranscriptional gene regulation that has reached clinical medicine. © 2013 The Authors..

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