All kingdoms of life have more than 150 different forms of RNA alterations, with tRNA accounting for around 80% of them. These chemical alterations include, among others, methylation, sulfuration, hydroxylation, and acetylation. These changes are necessary for the proper codon recognition and stability of tRNA. In Escherichia coli, sulfur modification at the wobble uridine (34) of lysine, glutamic acid, and glutamine is essential for codon and anticodon binding and prevents frameshifting during translation. Two important proteins that are involved in this thiolation modification are the L-cysteine desulfurase IscS, the initial sulfur donor, and tRNA-specific 2-thiouridylase MnmA, which adenylates and finally transfers the sulfur from IscS to the tRNA. tRNA-specific 2-thiouridylases are iron–sulfur clusters (Fe-S), either dependent or independent depending on the organism. Here, we dissect the controversy of whether the E. coli MnmA protein is an Fe-S cluster-dependent or independent protein. We show that when Fe-S clusters are bound to MnmA, tRNA thiolation is inhibited, making MnmA an Fe-S cluster-independent protein. We further show that 2-thiouridylase only binds to tRNA from its own organism.

Ebola virus disease (EVD) remains a significant public health threat, with sporadic outbreaks occurring in Sub-Saharan Africa. Survivors of EVD may experience various post-infection symptoms, collectively known as post-Ebola virus syndrome (PES), which include chronic arthralgia, uveitis, headache, and psychosocial stressors. In this review, we discuss the persistence of Ebola virus in survivors and its possible role in the reemergence of current outbreaks. We highlight that waning immunity of survivors enhances viral persistence and may lead to viral reactivation and recurrence of disease in previously affected tissues. The delicate equilibrium between diminished immune cell surveillance and limited viral replication may lead to enduring chronic inflammation. Our systematic review, based on an extensive survivor cohort, underscores the importance of continued research and preparedness efforts to combat future outbreaks through adequate surveillance and timely public health interventions. This review serves as a comprehensive guide to understanding the complexities of EVD survivorship, the challenges of PES, and the strategies to mitigate its impact.

Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, and dementia with Lewy bodies, still pose a serious challenge to global public health due to the non-availability of disease-modifying therapeutic modalities. Emerging evidence shows the important role of neuroinflammation in contributing to disease progression, driven by the activation of glial cells (microglia and astrocytes) and cytokine dysfunction. The functional polarization of microglia and astrocytes is critical to disease mechanisms. Pro- inflammatory M1 microglia and A1 astrocytes contribute to neurotoxic mediator production and M2 and A2 polarize towards repair mechanisms andrestore neuronal homeostasis. Recent breakthroughs in translational medicine have been geared towards exploiting inflammatory pathways with the help of kinase inhibitors, cytokine modulators, and biologicals to attain neuroimmune homeostasis. This review reports the intricacies of neuronal inflammation pathways and current trial-based therapeutic modalities, with attention focused on Phase 1-3 trials of potential therapeutic candidates. These mechanism-based and biomarker-guided approaches are shaping a new generation of precision therapies that hold promise for slowing or preventing neurodegeneration.