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Translin/TRAX Deficiency Affects Mesenchymal Differentiation Programs and Induces Bone Marrow Failure
The decision regarding self-renewal versus differentiation of hematopoietic stem cells (HSCs) is a crucial issue in bone marrow hematopoiesis. We have generated mice homozygous for an inactivating mutation of ...
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Article
Open AccessAneuploidy generates proteotoxic stress and DNA damage concurrently with p53-mediated post-mitotic apoptosis in SAC-impaired cells
The molecular mechanism responsible that determines cell fate after mitotic slippage is unclear. Here we investigate the post-mitotic effects of different mitotic aberrations—misaligned chromosomes produced by...
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Article
Open AccessCLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor
CDC-like kinase phosphorylation of serine/arginine-rich proteins is central to RNA splicing reactions. Yet, the genomic network of CDC-like kinase-dependent RNA processing events remains poorly defined. Here, ...
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Article
Open AccessPharmacological systems analysis defines EIF4A3 functions in cell-cycle and RNA stress granule formation
The RNA helicase EIF4A3 regulates the exon junction complex and nonsense-mediated mRNA decay functions in RNA transcript processing. However, a transcriptome-wide network definition of these functions has been...
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Polygenic architecture informs potential vulnerability to drug-induced liver injury
Drug-induced liver injury (DILI) is a leading cause of termination in drug development programs and removal of drugs from the market; this is partially due to the inability to identify patients who are at risk1. ...
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Open AccessSoticlestat, a novel cholesterol 24-hydroxylase inhibitor shows a therapeutic potential for neural hyperexcitation in mice
Cholesterol 24-hydroxylase (CH24H) is a brain-specific enzyme that converts cholesterol into 24S-hydroxycholesterol, the primary mechanism of cholesterol catabolism in the brain. The therapeutic potential of CH24...
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Article
Open AccessGene regulatory network analysis defines transcriptome landscape with alternative splicing of human umbilical vein endothelial cells during replicative senescence
Endothelial cell senescence is the state of permanent cell cycle arrest and plays a critical role in the pathogenesis of age-related diseases. However, a comprehensive understanding of the gene regulatory netw...
