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).
View Article and Find Full Text PDFBackground: Patients with familial fibrotic interstitial lung disease (ILD) experience worse survival than patients with sporadic disease. Current guidelines do not consider family aggregation or genetic information in the diagnostic algorithm for idiopathic pulmonary fibrosis or other fibrotic ILDs. Better characterizing familial cases could help in diagnostic and treatment decision-making.
View Article and Find Full Text PDFOn September 29, 2023, the Republic of Ecuador convened a meeting to address surgical system strengthening and urge political leaders to invest in surgical infrastructure. The meeting included experts in health diplomacy, innovative financing, implementation strategy and national surgical plans. The event occurred in parallel with the Sixtieth Directing Council of the Pan American Health Organization, Seventy-fifth session of the World Health Organization Regional Committee for the Americas.
View Article and Find Full Text PDF, the rat lungworm, is a zoonotic parasite mainly of rats which act as definitive hosts. If humans become accidentally infected, the nematode is capable of migrating to the brain causing meningoencephalitis. Intermediate hosts are snails and slugs.
View Article and Find Full Text PDF