E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development.

Pyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that plays an essential role during brain development. Using genetically engineered mouse model and primary neuronal cells, we identify the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U).

Ovarian carcinoma in patients aged ≥80 years: A retrospective multicenter study of management and survival in the FRANCOGYN population.

Introduction: The aims of this study were to describe survival outcomes in patients with ovarian cancer aged ≥80 years and to explore predictors of poor prognosis.

Methods: We collected clinical, demographic, histologic, surgical and follow-up data for patients with ovarian cancer aged ≥80 years from a multicenter French cohort (FRANCOGYN) who underwent surgery from 1999 to 2019. Primary endpoints were overall survival (OS) and disease-free survival (DFS).

Deciphering oxygen distribution and hypoxia profiles in the tumor microenvironment: a data-driven mechanistic modeling approach.

. The distribution of hypoxia within tissues plays a critical role in tumor diagnosis and prognosis. Recognizing the significance of tumor oxygenation and hypoxia gradients, we introduce mathematical frameworks grounded in mechanistic modeling approaches for their quantitative assessment within a tumor microenvironment.