RNF213 loss of function reshapes vascular transcriptome and spliceosome leading to disrupted angiogenesis and aggravated vascular inflammatory responses

Genetics, Genomics, Molecular Biology, Immunology.

This research operates within the established paradigm of molecular biology and genetics, specifically focusing on the role of gene mutations in disease. The study investigates the impact of RNF213 loss of function on vascular cells, aiming to understand its contribution to Moyamoya disease. This aligns with normal science as it seeks to refine existing knowledge within the dominant paradigm, rather than challenging or replacing it. While the research presents novel findings regarding the effects of RNF213 on angiogenesis, inflammation, and cell communication, it does so within the existing framework of genetic and molecular mechanisms of disease. The authors also propose a refined model for MMD based on their findings, which is characteristic of normal science's focus on puzzle-solving within a paradigm. While there are some innovative aspects to their approach, such as investigating the impact of RNF213 on alternative splicing and proposing a link to turbulence hemodynamics, these explorations still build upon the established understanding of genetics and vascular biology. There is no evidence presented to suggest a paradigm shift or model crisis. The research strengthens the existing paradigm by adding to the body of knowledge regarding the role of RNF213 in vascular pathophysiology. This justifies a classification as normal science. However, the proposal of a new model for MMD based on RNF213 interaction between immune stimulation of ECs, disrupted mechanosensitive responses to blood hemodynamics, and alteration in vSMCs suggests a competing model and thus could hint at a Model Drift as this new model seeks to extend and refine existing knowledge in a novel mechanistic direction.