Automatic Morphological Subtyping Reveals New Roles of Caspases in Mitochondrial Dynamics

Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases, but the lack of standard quantification of mitochondrial morphology impedes systematic investigation. This paper presents an automated system for the quantification and classification of mitochondrial morphology. We discovered six morphological subtypes of mitochondria for objective quantification of mitochondrial morphology. These six subtypes are small globules, swollen globules, straight tubules, twisted tubules, branched tubules and loops. The subtyping was derived by applying consensus clustering to a huge collection of more than 200 thousand mitochondrial images extracted from 1422 micrographs of Chinese hamster ovary (CHO) cells treated with different drugs, and was validated by evidence of functional similarity reported in the literature. Quantitative statistics of subtype compositions in cells is useful for correlating drug response and mitochondrial dynamics. Combining the quantitative results with our biochemical studies about the effects of squamocin on CHO cells reveals new roles of Caspases in the regulatory mechanisms of mitochondrial dynamics. This system is not only of value to the mitochondrial field, but also applicable to the investigation of other subcellular organelle morphology

Epigenetic mechanisms in cancer: push and pull between kneaded erasers and fate writers

Ammad Ahmad Farooqi,1 Jen-Yang Tang,2–4 Ruei-Nian Li,5 Muhammad Ismail,1 Yung-Ting Chang,6 Chih-Wen Shu,7 Shyng-Shiou F Yuan,8,9 Jing-Ru Liu,5 Qaisar Mansoor,1 Chih-Jen Huang,2,3,* Hsueh-Wei Chang5,9–11,*1Institute of Biomedical and Genetic Engineering (IBGE), KRL Hospital, Islamabad, Pakistan, 2Department of Radiation Oncology, Faculty of Medicine, College of Medicine, 3Department of Radiation Oncology, Kaohsiung Medical University Hospital, 4Department of Radiation Oncology, Kaohsiung Municipal Ta-Tung Hospital, 5Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Doctor Degree Program in Marine Biotechnology, National Sun Yat-sen University/Academia Sinica, 7Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 8Translational Research Center, 9Cancer Center, Kaohsiung Medical University Hospital, 10Institute of Medical Science and Technology, National Sun Yat-sen University, 11Research Center of Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan*These authors contributed equally to this workAbstract: Research concerning the epigenome over the years has systematically and sequentially shown substantial development and we have moved from global inhibition of modifications of the epigenome toward identification and targeted therapy against tumor-specific epigenetic mechanisms. In accordance with this approach, several drugs with epigenetically modulating activity have received considerable attention and appreciation, and recently emerging scientific evidence is uncovering details of their mode of action. High-throughput technologies have considerably improved our existing understanding of tumor suppressors, oncogenes, and signaling pathways that are key drivers of cancer. In this review, we summarize the general epigenetic mechanisms in cancer, including: the post-translational modification of DNA methyltransferase and its mediated inactivation of Ras association domain family 1 isoform A, Sonic hedgehog signaling, Wnt signaling, Notch signaling, transforming growth factor signaling, and natural products with epigenetic modification ability. Moreover, we introduce the importance of nanomedicine for delivery of natural products with modulating ability to epigenetic machinery in cancer cells. Such in-depth and comprehensive knowledge regarding epigenetic dysregulation will be helpful in the upcoming era of molecular genomic pathology for both detection and treatment of cancer. Epigenetic information will also be helpful when nanotherapy is used for epigenetic modification.Keywords: epigenetic, modification, methylation, natural products, cance

A review on assembly sequence planning and assembly line balancing optimisation using soft computing approaches

Assembly optimisation activities occur across development and production stages of manufacturing goods. Assembly Sequence Planning (ASP) and Assembly Line Balancing (ALB) problems are among the assembly optimisation. Both of these activities are classified as NP-hard. Several soft computing approaches using different techniques have been developed to solve ASP and ALB. Although these approaches do not guarantee the optimum solution, they have been successfully applied in many ASP and ALB optimisation works. This paper reported the survey on research in ASP and ALB that use soft computing approaches for the past 10years. To be more specific, only Simple Assembly Line Balancing Problem (SALBP) is considered for ALB. The survey shows that three soft computing algorithms that frequently used to solve ASP and ALB are Genetic Algorithm, Ant Colony Optimisation and Particle Swarm Optimisation. Meanwhile, the research in ASP and ALB is also progressing to the next level by integration of assembly optimisation activities across product development stages