The roots of romantic cognitivism:(post) Kantian intellectual intuition and the unity of creation and discovery

During the romantic period, various authors expressed the belief that through creativity, we can directly access truth. To modern ears, this claim sounds strange. In this paper, I attempt to render the position comprehensible, and to show how it came to seem plausible to the romantics. I begin by offering examples of this position as found in the work of the British romantics. Each thinks that the deepest knowledge can only be gained by an act of creativity. I suggest the belief should be seen in the context of the post-Kantian embrace of “intellectual intuition.” Unresolved tensions in Kant's philosophy had encouraged a belief that creation and discovery were not distinct categories. The post-Kantians held that in certain cases of knowledge (for Fichte, knowledge of self and world; for Schelling, knowledge of the Absolute) the distinction between discovering a truth and creating that truth dissolves. In this context, the cognitive role assigned to acts of creativity is not without its own appeal

Alternative-splicing defects in cancer: Splicing regulators and their downstream targets, guiding the way to novel cancer therapeutics.

Defects in alternative splicing are frequently found in human tumors and result either from mutations in splicing-regulatory elements of specific cancer genes or from changes in the regulatory splicing machinery. RNA splicing regulators have emerged as a new class of oncoproteins and tumor suppressors, and contribute to disease progression by modulating RNA isoforms involved in the hallmark cancer pathways. Thus, dysregulation of alternative RNA splicing is fundamental to cancer and provides a potentially rich source of novel therapeutic targets. Here, we review the alterations in splicing regulatory factors detected in human tumors, as well as the resulting alternatively spliced isoforms that impact cancer hallmarks, and discuss how they contribute to disease pathogenesis. RNA splicing is a highly regulated process and, as such, the regulators are themselves tightly regulated. Differential transcriptional and posttranscriptional regulation of splicing factors modulates their levels and activities in tumor cells. Furthermore, the composition of the tumor microenvironment can also influence which isoforms are expressed in a given cell type and impact drug responses. Finally, we summarize current efforts in targeting alternative splicing, including global splicing inhibition using small molecules blocking the spliceosome or splicing-factor-modifying enzymes, as well as splice-switching RNA-based therapeutics to modulate cancer-specific splicing isoforms. This article is categorized under: RNA in Disease and Development \u3e RNA in Disease RNA Processing \u3e Splicing Regulation/Alternative Splicing