MYCT1-TV, A Novel MYCT1 Transcript, Is Regulated by c-Myc and May Participate in Laryngeal Carcinogenesis

BACKGROUND: MYCT1, a putative target of c-Myc, is a novel candidate tumor suppressor gene cloned from laryngeal squamous cell carcinoma (LSCC). Its transcriptional regulation and biological effects on LSCC have not been clarified. METHODOLOGY/PRINCIPAL FINDINGS: Using RACE assay, we cloned a 1106 bp transcript named Myc target 1 transcript variant 1 (MYCT1-TV) and confirmed its transcriptional start site was located at 140 bp upstream of the ATG start codon of MYCT1-TV. Luciferase, electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed c-Myc could regulate the promoter activity of MYCT1-TV by specifically binding to the E-box elements within -886 to -655 bp region. These results were further verified by site-directed mutagenesis and RNA interference (RNAi) assays. MYCT1-TV and MYCT1 expressed lower in LSCC than those in paired adjacent normal laryngeal tissues, and overexpression of MYCT1-TV and MYCT1 could inhibit cell proliferation and invasion and promote apoptosis in LSCC cells. CONCLUSIONS/SIGNIFICANCE: Our data indicate that MYCT1-TV, a novel MYCT1 transcript, is regulated by c-Myc and down-regulation of MYCT1-TV/MYCT1 could contribute to LSCC development and function

Was Julian Right? A Re-Evaluation of Augustine’s and Mani’s Doctrines of Sexual Concupiscence and the Transmission of Sin: Part 1

The article focuses on the question: Was Julian of Eclanum (c. 380–454) right in accusing Augustine (354–430) of still being a Manichaean, based on his view of sexual concupiscence and the transmission of (original) sin? In order to find an answer to this (still hotly debated) question, a sketch of Augustine’s acquaintance with Manichaeism is first provided. Thereafter follows the (first ever) overview of the Manichaean doctrines of the origin of sexual concupiscence, its distinctive features, and its role in the transmission of sin. The third part of the article focuses on the essentials of Augustine’s views of sexual concupiscence and the transmission of original sin, in particular as they were expounded (and further developed) in his controversy with the ‘Pelagian’ bishop, Julian of Eclanum. It is concluded that, in particular, Augustine’s stress on the ‘random motion’ (motus inordinatus) as typical of the sinfulness of sexual concupiscence, is strikingly similar to Manichaean views on the subject. In this respect, then, Julian seems to be right. Finally, some preliminary remarks are made on early Jewish and Jewish-Christian views of sexual concupiscence and (original) sin which may have influenced not only Mani and his followers, but also Augustine and his precursors in the tradition of Roman North Africa. The current article is the first in a series of two essays on the topic.The National Research Foundation (NRF) in South Africa.https://www.tandfonline.com/loi/rech20hj2019Church History and Church Polic