| 1. |
- Zhang, Xiao-Jie, et al.
(författare)
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Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation
- 2024
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Ingår i: Nature Structural & Molecular Biology. - : NATURE PORTFOLIO. - 1545-9993 .- 1545-9985. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored. Here we show that a large low-complexity domain (LCD), located in the catalytic part of Tet enzymes, negatively regulates the dioxygenase activity. Recombinant Tet3 lacking LCD is shown to be hyperactive in converting 5mC into oxidized species in vitro. Endogenous expression of the hyperactive Tet3 mutant in mouse oocytes results in genome-wide 5mC oxidation. Notably, the occurrence of aberrant 5mC oxidation correlates with a consequent loss of the repressive histone mark H3K9me3 at ERVK retrotransposons. The erosion of both 5mC and H3K9me3 causes ERVK derepression along with upregulation of their neighboring genes, potentially leading to the impairment of oocyte development. These findings suggest that Tet dioxygenases use an intrinsic auto-regulatory mechanism to tightly regulate their enzymatic activity, thus achieving spatiotemporal specificity of methylome reprogramming, and highlight the importance of methylome integrity for development. Here the authors show that TET dioxygenases, the erasers of DNA methylation, use a self-limiting mechanism via their LCD domain to ensure adaptable methylome status and protect the genome from excessive oxidative methylation.
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| 2. |
- Li, Yadi, et al.
(författare)
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Virtual and In vitro bioassay screening of phytochemical inhibitors from flavonoids and isoflavones against Xanthine oxidase and Cyclooxygenase-2 for gout treatment
- 2013
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Ingår i: Chemical Biology and Drug Design. - : John Wiley & Sons. - 1747-0277 .- 1747-0285. ; 81:4, s. 537-544
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic drugs such as allopurinol and benzbroarone are commonly used to treat the complex pathogenesis of gout, a metabolic disease that results from an inflammation of the joints caused by precipitation of uric acid. We seek to discover novel phytochemicals that could treat gout, by targeting the xanthine oxidase (XO) and cyclooxygenase 2 (COX-2) enzymes. In this study, we report the screening of 9 compounds of flavonoids from the ZINC and PubChem databases (containing 2,092 flavonoids) using the iGEMDOCK software tool against the XO and COX-2 3D protein structures. Each compound was also evaluated by an in vitro bioassay testing the inhibition of XO and COX-2. Myricetin and luteolin were found to be the potential dual inhibitors of XO and COX-2 as demonstrated by IC50: 62.7 and 3.29μg/mL (XO) / 70.8 and 16.38μg/mL (COX-2), respectively. In addition, structure activity relationships and other important factors of the flavonoids binding to the active site of XO and COX-2 were discussed, which is expected for further rational drug design.
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| 3. |
- Wang, Fengjuan, et al.
(författare)
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Physical–cyber–human framework‐based resilience evaluation toward urban power system: Case study from China
- 2024
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Ingår i: Risk Analysis. - : Wiley. - 0272-4332 .- 1539-6924.
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Tidskriftsartikel (refereegranskat)abstract
- Because the increased frequency, intensity, and duration of extreme weather events have significantly challenged power systems, there has been an increased interest in resilient power systems. This article establishes a multicriteria resilience evaluation framework for urban power systems from a physical-cyber-human system perspective, in which the two principal elements responsible for power system function degradation are described, the three major domains comprising urban power systems are explained, four core capacities that positively contribute to power system resilience are proposed, and 15 (11 objective and four subjective) power system resilience evaluation indicators are identified. Fuzzy hesitant judgment and a Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) aggregation method are employed to minimize the expert divergence and maximize the group consensus. A validation method is designed and a comparison with commonly applied performance-based and attributes-based evaluation methods is conducted. The applicability of the evaluation framework is verified using data from four Chinese municipalities: Shanghai, Beijing, Chongqing, and Tianjin. It was found that Shanghai's resilience was the best, and Chongqing's physical resistance disadvantages would result in the greatest difficulties in coping with extreme event disturbances. Physical, cyber, and human domain resilience enhancement strategies are given for different cities separately. This study provides a practical tool to evaluate, compare, and enhance power system resilience for governments and public utilities.
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| 4. |
- Wang, Fengjuan, et al.
(författare)
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Resilience evaluation framework towards urban power system
- 2021
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Ingår i: Energy Proceedings. - : Scanditale AB.
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Konferensbidrag (refereegranskat)abstract
- As the increased frequency, intensity and duration of extreme weather events have significantly challenged power systems, greater attention has been focused on the development of resilient power systems. Taking a physical-cyber-human system perspective, this paper establishes a multi-criteria resilience evaluation framework for urban power systems, in which two principal elements responsible for power system function degradation are described, and fifteen (eleven objective and four subjective) power system resilience evaluation indicators are identified. Fuzzy hesitant judgement and a TOPSIS aggregation method are applied for the evaluation to minimize expert divergence and maximize group consensus. The evaluation method is then applied to four Chinese municipalities: Shanghai, Beijing and Chongqing, and Tianjin. It was found that Beijing’s resilience was the best of the four but overall the urban power system resiliencies were not enough in the face of extreme event challenges.
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| 5. |
- Wang, Yangyang, et al.
(författare)
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UHRF2 promotes DNA damage response by decreasing p21 via RING finger domain
- 2018
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Ingår i: Biotechnology letters. - : SPRINGER. - 0141-5492 .- 1573-6776. ; 40:8, s. 1181-1188
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the interaction of E3 ubiquitin ligase UHRF2 with p21 and the mechanism of UHRF2 in repairing DNA damage caused by hydroxyurea (HU) in HEK293 cells. Western blotting indicated that the overexpression of UHRF2 reduced the level of p21, particularly in HEK293 cells. Immunoprecipitation and immunofluorescence staining reveled that UHRF2 combined with p21 in the nucleus. In addition, UHRF2 degraded p21 through ubiquitination and shortened the half-life of p21. UHRF2 could repair DNA damage caused by HU treatment, which was impaired by the inhibition of p21 in HEK293 cells. UHRF2 may negatively modulate p21 to regulate DNA damage response, suggesting a novel pathway of UHRF2 repairing DNA damage through the partial regulation of p21.
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