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

Chinese translation of strengths and difficulties questionnaire requires urgent review before field trials for validity and reliability

<p>Abstract</p> <p/> <p>Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire for children and teenagers aged 3 to 16 years. It is available in 66 languages, and gaining more popularity world wide. Chinese translation of SDQ is available and has been used in clinical practice and research. We undertook the exercise to back-translate the current Chinese translation and it showed a number of differences compared to the original English SDQ. The differences and concerns include: (1) the flow and grammar of Chinese translation as well as wrongly written Chinese characters; (2) translated words that have deviated from the original meaning; (3) significant numbers of wording that are somewhat different from the original English version; (4) addition of auxiliary verbs that do not exist in original English version; and (5) the current Chinese SDQ is a general questionnaire for all age groups that does not observe the differences of wording that exist in the English versions.</p> <p>Conclusion</p> <p>An accurate translated Chinese version is important for researchers, clinicians and educators who work in the Chinese communities. There is an urgent need to review the translation of the Chinese SDQ version before more studies use it in the field.</p

Association between milk intake and childhood growth: results from a nationwide cross-sectional survey

Purpose: The literature is inconsistent regarding milk intake and physical growth. This study aims to evaluate the association of milk intake with body height and weight in a nationally representative sample of Chinese children. Methods: A total of 41,439 children ages 6–17 were recruited from 30 provinces in mainland China in 2013–2016 using a multistage stratified cluster sampling approach. Milk intake information was collected using a questionnaire aided with standard containers. Weight and height were measured using a standard physician beam scale with a height rod. Milk intake was categorized into no-, low-, and high-intake groups based on the intake rate, and weight status into normal, overweight, and obese groups based on the body-mass-index (BMI). Associations between height/weight status and milk intake were evaluated using multivariate weighted linear and logistic regression models. Results: Chinese children had low milk intake: 1/5 of children did not drink milk, and those drinking milk had a median intake of 100 ml/month. The low- and high-intake groups were 0.83 cm (95% confidence interval: 0.00, 1.68 cm) and 1.26 cm (0.34, 2.19 cm) taller than the no-intake group for girls, respectively, after adjusting for confounding factors. Boys with high milk intake had lower BMI (−0.56, 95% CI: −1.00, −0.12 kg/m2) and risk of obesity (OR = 0.67, 95% CI: 0.46, 0.97) than those without milk intake. Conclusions: This study revealed the association of increased milk intake with increased body height and lowered obesity risk among Chinese children. Given the cross-sectional nature of the study and the possibility of residual confounding, further research is warranted to uncover the role of milk intake in promoting children’s growth