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Sik, A.

Publications and source records attributed to Sik, A..

3 recordsLinked to original sources

Automatic Detection of Larval Zebrafish ECG: Computational Tool for High-throughput Cardiac Activity Analysis

Automatic analysis of larval zebrafish electrocardiographs (ECG) is essential for high-throughput measurements in environmental toxicity assays, cardiotoxicity measurements and drug screening. We have developed a MATLAB based software is built on methods that have previously been used to analyze human ECG, such as the Pan-Tompkins algorithm and Wavelet. For the first time these sophisticated tools have been applied to larval zebrafish ECG to automatically characterize the heart-beat waveforms. The ability of the automated algorithm to detect the QT interval for both normal and pharmacologically altered larval ECG is found and compared to previously used software that is built into LabChart(R) (AD Instruments). Using wavelet transforms it is shown that the typical larval ECG features are within the frequency range of 1 to 31 Hz. It is also shown that the automated software is capable of detecting QTc (heartrate corrected heartbeat interval) changes within pharmacologically altered zebrafish larval ECG. The automated process is a significant improvement on the approaches that were previously applied to the zebrafish ECG. The automated process described here that is based on established techniques of analyzing ECG can sensitively measure pharmacologically induced changes in the ECG. The novel, automated software is faster, more sensitive at detecting ECG changes and less dependent on user involvement, thus minimizing user error and human bias. The automated process can also be applied to human ECG.

physiology↗

A lightweight segmentation and lineage tracking tool for noisy, low frame rate 4D fluorescence microscopy data

4D fluorescence microscopy allows the study of spatiotemporal cell dynamics in embryonic development in unprecedented detail, yet the uneven scattering of light within developing embryos presents challenges in discerning fine details. We present a tool which pre-processes large in vivo 4D microscopy datasets and can then track the movements and lineage histories of rapidly dividing embryonic stem cells. This solution offers a robust, simple segmentation technique to segment high intensity fluorescent features in highly scattered datasets, such as from deep within a developing zebrafish embryo. This tool then offers lineage tracing functionality by tracking rapidly dividing nuclei and their progeny, while also accounting for the jumps rapidly moving features make between frames in low frame rate data. Based on the user having prior knowledge of their imaging subject, this tool has applications in datasets with limitations with signal to noise, and frame rate. It can provide information regarding the position and movement of rapidly dividing nuclei. We demonstrate this pipeline in developing early zebrafish embryos.

bioinformatics↗

A cell cycle-coordinated nuclear compartment for Polymerase II transcription encompasses the earliest gene expression before global genome activation

Most metazoan embryos commence development with rapid cleavages without zygotic gene expression and their genome activation is delayed until the mid-blastula transition (MBT). However, a set of genes escape global repression during the extremely fast cell cycles, which lack gap phases and their transcription is activated before the MBT. Here we describe the formation and the spatio-temporal dynamics of a distinct transcription compartment, which encompasses the earliest detectable transcription during the first wave of genome activation. Simultaneous 4D imaging of expression of pri-miR430 and zinc finger genes by a novel, native transcription imaging approach reveals a pair of shared transcription compartments regulated by homolog chromosome organisation. These nuclear compartments carry the majority of nascent RNAs and transcriptionally active Polymerase II, are depleted of compact chromatin and represent the main sites for detectable transcription before MBT. We demonstrate that transcription occurs in the S-phase of the cleavage cycles and that the gradual slowing of these cell cycles are permissive to transcription before global genome activation. We propose that the demonstrated transcription compartment is part of the regulatory architecture of nucleus organisation, and provides a transcriptionally competent, supporting environment to facilitate early escape from the general nuclear repression before global genome activation.

developmental biology↗