| 1. |
- Xu, An, et al.
(författare)
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Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas.
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| 2. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 3. |
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| 4. |
- Malla, Sandhya, et al.
(författare)
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ZFP207 sustains pluripotency by coordinating OCT4 stability, alternative splicing and RNA export
- 2022
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Ingår i: EMBO Reports. - : John Wiley & Sons. - 1469-221X .- 1469-3178. ; 23:3
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Tidskriftsartikel (refereegranskat)abstract
- The pluripotent state is not solely governed by the action of the core transcription factors OCT4, SOX2, and NANOG, but also by a series of co-transcriptional and post-transcriptional events, including alternative splicing (AS) and the interaction of RNA-binding proteins (RBPs) with defined subpopulations of RNAs. Zinc Finger Protein 207 (ZFP207) is an essential transcription factor for mammalian embryonic development. Here, we employ multiple functional analyses to characterize its role in mouse embryonic stem cells (ESCs). We find that ZFP207 plays a pivotal role in ESC maintenance, and silencing of Zfp207 leads to severe neuroectodermal differentiation defects. In striking contrast to human ESCs, mouse ZFP207 does not transcriptionally regulate neuronal and stem cell-related genes but exerts its effects by controlling AS networks and by acting as an RBP. Our study expands the role of ZFP207 in maintaining ESC identity, and underscores the functional versatility of ZFP207 in regulating neural fate commitment.
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| 5. |
- Wang, Kui, et al.
(författare)
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Efficient electro-demulsification of O/W emulsions and simultaneous oil removal enabled by a multiscale porous biocarbon electrode
- 2024
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Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947 .- 1873-3212. ; 481
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Tidskriftsartikel (refereegranskat)abstract
- Emulsion wastewater contain substantial amounts of oil and various additives, which pose threats to the environment and human health. Demulsification is a crucial pretreatment stage for wastewater. This study aims to identify a novel electro-demulsification method with high oil removal efficiency and low energy consumption. Modified carbonized birch wood with a unique isotropic multiscale pore structure is used as a self-standing electrode to treat a toluene oil-in-water (O/W) emulsion. The electrode must have a highly porous structure to facilitate efficient water diffusion and oil adsorption. It must also have high electronic conductivity to expedite polarized molecular electrophoresis to realize penetration into the pores and, subsequently, demulsification. Guided by an applied electric field force, polarized O/W droplets are drawn toward the electrode, revealing electrical characteristics distinct from those of polarized organic molecules. This electric field force augments the capture and adhesion of droplets by the electric double layer at the electrode interface. Consequently, adsorbed droplets in close proximity to the electrode rupture due to the combined influence of the electric field force and the electrostatic effects stemming from the electrode's multiscale porous structure. This synergistic action enables demulsification to occur efficiently at low energy consumption levels. This study has revealed that electro-demulsification can effectively treat toluene emulsions stabilized by various surfactants and microemulsion containing toluene. Therefore, this electro-demulsification technology can be further developed for various types of water pollution.
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