| 1. |
- Li, Ao, et al.
(författare)
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Genome architecture and selective signals compensatorily shape plastic response to a new environment
- 2023
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Ingår i: The Innovation. - 2666-6758. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional plasticity interacts with natural selection in complex ways and is crucial for the survival of species under rapid climate change. How 3D genome architecture affects transcriptional plasticity and its interaction with genetic adaptation are unclear. We transplanted estuarine oysters to a new environment and found that genes located in active chromatin regions exhibited greater transcriptional plasticity, and changes in these regions were negatively correlated with selective signals. This indicates a trade-off be- tween 3D active regions and selective signals in shaping plastic responses to a new environment. Specifically, a mutation, lincRNA, and changes in the accessibility of a distal enhancer potentially affect its interaction with the ManIIa gene, which regulates the muscle function and survival of oysters. Our findings reveal that 3D genome architecture compensates for the role of genetic adaptation in environmental response to new environments and provide insights into synergetic genetic and epigenetic interactions critical for fitness-related trait and survival in a model marine species.
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| 2. |
- Oppi, Sara, et al.
(författare)
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Macrophage NCOR1 protects from atherosclerosis by repressing a pro-atherogenic PPAR gamma signature
- 2020
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 41:9, s. 995-1005
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Tidskriftsartikel (refereegranskat)abstract
- Aims Nuclear receptors and their cofactors regulate key pathophysiological processes in atherosclerosis development. The transcriptional activity of these nuclear receptors is controlled by the nuclear receptor corepressors (NCOR), scaffolding proteins that form the basis of large corepressor complexes. Studies with primary macrophages demonstrated that the deletion of Ncor1 increases the expression of atherosclerotic molecules. However, the role of nuclear receptor corepressors in atherogenesis is unknown. Methods and results We generated myeloid cell-specific Ncor1 knockout mice and crossbred them with low-density lipoprotein receptor and results (Ldlr) knockouts to study the role of macrophage NCOR1 in atherosclerosis. We demonstrate that myeloid cellspecific deletion of nuclear receptor corepressor 1 (NCOR1) aggravates atherosclerosis development in mice. Macrophage Ncorl-deficiency leads to increased foam cell formation, enhanced expression of pro-inflammatory cytokines, and atherosclerotic lesions characterized by larger necrotic cores and thinner fibrous caps. The immunometabolic effects of NCOR1 are mediated via suppression of peroxisome proliferator-activated receptor gamma (PPAR gamma) target genes in mouse and human macrophages, which lead to an enhanced expression of the CD36 scavenger receptor and subsequent increase in oxidized low-density lipoprotein uptake in the absence of NCOR1. Interestingly, in human atherosclerotic plaques, the expression of NCOR1 is reduced whereas the PPAR gamma signature is increased, and this signature is more pronounced in ruptured compared with non-ruptured carotid plaques. Conclusions Our findings show that macrophage NCOR1 blocks the pro-atherogenic functions of PPAR gamma in atherosclerosis and suggest that stabilizing the NCOR1-PPAR gamma binding could be a promising strategy to block the pro-atherogenic functions of plaque macrophages and lesion progression in atherosclerotic patients.
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| 3. |
- Wei, Jianhua, et al.
(författare)
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Genome and proteomic analysis of risk factors for fatal outcome in children with severe community-acquired pneumonia caused by human adenovirus 7
- 2023
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Ingår i: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 95:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Human adenovirus 7 (HAdV-7) is an important viral pathogen of severe pneumonia in children and a serious threat to health. Methods: A cohort of 45 pediatric patients diagnosed with HAdV-7-associated severe pneumonia and admitted to the Pediatric Intensive Care Unit at the Children's Hospital of Chongqing Medical University from May 2018 to January 2020 were included. Risk factors of death were analyzed by the Cox proportional risk mode with Clinical data, serum, and nasopharyngeal aspirate adenovirus load, Genome analysis, Olink proteomics, and cytokine profile between dead and surviving patients were also analyzed. Results: A total of 45 children with a median age of 12.0 months (interquartile range [IQR]: 6.5, 22.0) were included (female 14), including 14 (31.1%) who died. High serum viral load was an independent risk factor for mortality (hazard ratio [HR] = 2.16, 95% confidence interval [CI], 1.04-4.49, p = 0.039). BTB and CNC homology 1 (BACH1), interleukin-5 (IL-5), and IL-9 levels were significantly correlated with serum viral load (p = 0.0400, 0.0499, and 0.0290; r = 0.4663, 0.3339, and -0.3700, respectively), with significant differences between the dead and survival groups (p = 0.021, 0.001, and 0.021). Conclusions: Severe cytokine storm-associated high serum viral load after HAdV-7 infection may be the main mechanism responsible for poor prognosis in children.
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