Science, Ethics, and Politics: Conversations and Investigations

Gregory R. Peterson (with Kevin S. Reimer, and Michael Spezio, Warren Brown, James Van Slyke, and Kristen Renwick Monroe) is a contributing author, “Virtuous Courage: New Methods for the Interdisciplinary Study of Virtue. Book description: The relationship between science and ethics has been subject to much debate. This volume demonstrates the mutually beneficial relationship that can take place between ethics and science. It presents work that utilises the tools of science - broadly conceptualised - to elucidate ethical issues, showing that careful scientific analysis of ethical issues can reveal new insights. This is supplemented by conversations with the authors - some of them pre-eminent scientists addressing issues of ethics, including two Nobel laureates - to learn how they came to the study of ethics and ask how they conceptualise and think about ethical issues. Science, Ethics and Politics provides substantive insight into particular ethical issues, ranging from issues of torture during war to parents\u27 obligations to children. This book is designed as a complement to traditional texts on ethics and should appeal to students of ethics as well as to the general public.https://openprairie.sdstate.edu/hppr_book/1012/thumbnail.jp

Viral Particle-Mediated SAMHD1 Depletion Sensitizes Refractory Glioblastoma to DNA-Damaging Therapeutics by Impairing Homologous Recombination

The current standard-of-care treatment for glioblastoma includes DNA damaging agents, γ-irradiation (IR) and temozolomide (TMZ). These treatments fail frequently and there is limited alternative strategy. Therefore, identifying a new therapeutic target is urgently needed to develop a strategy that improves the efficacy of the existing treatments. Here, we report that tumor samples from GBM patients express a high level of SAMHD1, emphasizing SAMHD1’s importance. The depletion of SAMHD1 using virus-like particles containing Vpx, VLP(+Vpx), sensitized two independent GBM cell lines (LN-229 and U-87) to veliparib, a well-established PARP inhibitor, and slowed cell growth in a dose-dependent manner. In the mouse GBM xenograft model, Vpx-mediated SAMHD1 depletion reduced tumor growth and SAMHD1 knockout (KO) improved survival. In combination with IR or TMZ, SAMHD1 KO and exposure to 50% growth inhibitory dose (gID50) of VLP(+Vpx) displayed a synergistic effect, resulting in impaired HR, and improved LN-229 cells’ sensitivity to TMZ and IR. In conclusion, our finding demonstrates that SAMHD1 promotes GBM resistance to treatment, and it is a plausible therapeutic target to improve the efficacy of TMZ and IR in GBM. Furthermore, we show that Vpx could be a potential therapeutic tool that can be utilized to deplete SAMHD1 in GBM