Fibril motion improves peptide signaling
Artificial scaffolds that bear the peptide-signaling sequences of proteins for tissue regeneration often have limited effectiveness. Álvarez
et al
. synthesized supramolecular peptide fibril scaffolds bearing two peptide sequences that promote nerve regeneration, one that reduces glial scarring and another that promotes blood vessel formation (see the Perspective by Wojciechowski and Stevens). In a mouse model of paralyzing human spinal cord injury, mutations in a tetrapeptide domain outside of the signaling regions improved recovery by promoting intense supramolecular motion within the fibrils. The mutation with the most intense dynamics resulted in corticospinal axon regrowth and myelination, functional revascularization, and motor neuron survival. —PDS
The quality of colonic cleansing and the detection of flat lesions are significantly improved when the preparation is taken on the day of the colonoscopy.
Highlights d C9-HRE alters subcellular localization of proteins involved in RNA and protein metabolism d eRF1 accumulates in complex nuclear invaginations in C9-ALS neurons d C9-ALS neurons display hyperactive NMD and reduced translation d eRF1 and UPF1 are modulators of C9-HRE toxicity in vivo
The somatic DNA methylation (DNAme) landscape is established early in development but remains highly dynamic within focal regions that overlap with gene regulatory elements. The significance of these dynamic changes, particularly in the central nervous system, remains unresolved. Here, we utilize a powerful human embryonic stem cell differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNAme machinery. We quantitatively dissect the role of DNAme in directing somatic cell fate with high-resolution genome-wide bisulfite-, bulk-, and single-cell-RNA sequencing. We find defects in neuralization and MN differentiation in DNMT3A knockouts (KO) that can be rescued by the targeting of DNAme to key developmental loci using catalytically inactive dCas9. We also find decreased dendritic arborization and altered electrophysiological properties in DNMT3A KO MNs. Our work provides a list of DNMT3A-regulated targets and a mechanistic link between de novo DNAme, cellular differentiation, and human MN function.
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