| 1. |
- 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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| 2. |
- Meng, Weida, et al.
(författare)
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Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:8, s. 4367-4382
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
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| 3. |
- 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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| 4. |
- Xu, Fengqin, et al.
(författare)
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Effects of an Innovative Training Program for New Graduate Registered Nurses : A Comparison Study
- 2021
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Ingår i: SAGE Open. - : SAGE Open. - 2158-2440. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- New graduate registered nurses (NGRNs) face a great challenge during the transition from school to clinical practice. We conducted a quasi-randomized controlled study to evaluate the effects of a new training mode for newly recruited NGRNs in a Chinese teaching hospital. A total of 150 NGRNs were recruited from a teaching hospital and assigned into two groups. The conventional training and a new training program were taken for the control group and the research group, respectively. At the end of the training, the two groups were evaluated and compared for theoretical knowledge and operation skills using a mutual-evaluation examination and the Chinese Registered Nurse Core Competency Scale. The scores of theoretical knowledge (88.4 vs. 81.7, p < .001) and operation skills (94.8 vs. 90.3, p < .001), and the total core competencies score (156.2 vs. 148.8, p < .05) in the research group were statistically significantly higher than those in the control group. Compared with the control group, the research group also had statistically significantly higher scores in education and consultation (2.47 vs. 2.40), clinical nursing (2.87 vs. 2.62), interpersonal relationship (2.56 vs. 2.43), and critical thinking and scientific research (2.78 vs. 2.61). The innovative pre-job training program for NGRNs conducted in Chinese clinical nursing skill training bases might significantly improve the training effects and is worthy of broader implementation.
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