The ubiquitin-related modifier Urm1 can be covalently conjugated to lysine residues of other proteins, such as yeast Ahp1 and human MOCS3, through a mechanism involving the E1-like protein Uba4 (MOCS3 in humans). Similar to ubiquitination, urmylation requires a thioester intermediate and forms isopeptide bonds between Urm1 and its substrates. In addition, the urmylation process can be significantly enhanced by oxidative stress. Recent findings have demonstrated that Urm1 also acts as a sulfur carrier in the thiolation of eukaryotic tRNA via a mechanism that requires the formation of a thiocarboxylated Urm1. This role is very similar to that of prokaryotic sulfur carriers such as MoaD and ThiS. Evidence strongly supports the hypothesis that Urm1 is the molecular fossil in the evolutionary link between prokaryotic sulfur carriers and eukaryotic ubiquitin-like proteins. In the present review, we discuss the dual role of Urm1 in protein and tRNA modification.
Animals ; Humans ; Models, Biological ; RNA, Transfer ; metabolism ; Sulfur ; metabolism ; Ubiquitin ; metabolism ; Ubiquitins ; metabolism

Bayesian statistics is an approach for learning from evidences as it accumulates, combining prior distribution with current information on a quantity of interest, in which posterior distribution and inferences are being updated each time new data become available using Bayes' Theorem. Though frequentist approach has dominated medical studies, Bayesian approach has been more and more widely recognized by its flexibility and efficiency. Research and development (R&D) on anti-cancer new drugs have been so hot globally in recent years in spite of relatively high failure rate. It is the common demand of pharmaceutical enterprises and researchers to identify the optimal dose, regime and right population in the early-phase R&D stage more accurately and efficiently, especially when the following three major changes have been observed. The R&D on anticancer drugs have transformed from chemical drugs to biological products, from monotherapy to combination therapy, and the study design has also gradually changed from traditional way to innovative and adaptive mode. This also raises a number of subsequent challenges on decision-making of early R&D, such as inability to determine MTD, flexibility to deal with delayed toxicity, delayed response and dose-response changing relationships. It is because of the above emerging changes and challenges that the Bayesian approach is getting more and more attention from the industry. At least, Bayesian approach has more information for decision-making, which could potentially help enterprises achieve higher efficiency, shorter period and lower investment. This study also expounds the application of Bayesian statistics in the early R&D on anticancer new drugs, and compares and analyzes its idea and application scenarios with frequentist statistics, aiming to provide macroscopic and systematic reference for all related stakeholders.
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Humans ; Bayes Theorem ; Lung Neoplasms/drug therapy* ; Research Design ; Antineoplastic Agents/therapeutic use* ; Biological Products ; Pharmaceutical Preparations