Lethe

Abstract: Type 2 diabetes mellitus is a complex, systemic metabolic disease characterized by insulin resistance and resulting hyperglycemia, which is associated with impaired wound healing. The clinical complications associated with hyperglycemia are attributed, in part, to the increased production of reactive oxygen species (ROS). Recent studies revealed that long non-coding RNAs (lncRNAs) play important regulatory roles in many biological processes. Specifically, lncRNA Lethe has been described as exhibiting an anti-inflammatory effect by binding to the p65 subunit of NFκB and blocking its binding to DNA and the subsequent activation of downstream genes. We therefore hypothesize that dysregulation of Lethe's expression plays a role in hyperglycemia-induced ROS production. To test our hypothesis, we treated RAW264.7 macrophages with low glucose (5 mM) or high glucose (25 mM) for 24h. High glucose conditions significantly induced ROS production and NOX2 gene expression in RAW cells, while significantly decreasing Lethe gene expression. Overexpression of Lethe in RAW cells eliminated the increased ROS production induced by high glucose conditions, while also attenuating the upregulation of NOX2 expression. Similar results was found also in non-diabetic and diabetic primary macrophage, bone marrow derived macrophage (BMM). Furthermore, overexpression of Lethe in RAW cells treated with high glucose significantly reduced the translocation of p65-NFkB to the nucleus, which resulted in decreased NOX2 expression and ROS production. Interestingly, these findings are consistent with the decreased Lethe gene expression and increased NOX2 gene expression observed in a mouse model of diabetic wound healing. These findings provide the first evidence that lncRNA Lethe is involved in the regulation of ROS production in macrophages through modulation of NOX2 gene expression via NFκB signaling. Moreover, this is the first report to describe a role of lncRNAs, in particular Lethe, in impaired diabetic wound healing. Further studies are warranted to determine if correction of Lethe expression in diabetic wounds could improve healing.

Abstract: Introduction: Be Our Ghost 1. Birth of a Nation from the Spirit of Tragedy: The Historical Sublime in Richard II 2. All Is Truancy: Rebellious Uses of the Past in 1 Henry IV 3. "Washed in Lethe": Laundering the Past in 2 Henry IV 4. Wars of Memory in Henry V 5. Coda: The History Play as Palimpsest in King John

Abstract: This article is a reflection on organizational oblivion, viewed as an archetypical antonym of learning. The consequences of this kind of forgetting for organizational identity construction are described as a narrative project. We refer to the image of Lethe, an archetype of forgetting, to depict how forgetting directly affects the process of identity narrative construction. In this perspective, drinking from the waters of Lethe implies not just the loss of knowledge or memories of how things are done, but the loss of identity so that the individuals do not know who they are anymore. In this context, forgetting disrupts organizational narrative which ceases to be a coherent story and results in organizational identity loss.