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991.
Libin Ni Jian Xiao Di Zhang Zhenxuan Shao Chongan Huang Sheng Wang Yaosen Wu Naifeng Tian Liaojun Sun Aimin Wu Yifei Zhou Xiangyang Wang Xiaolei Zhang 《Cell death & disease》2022,13(2)
The pathophysiology of spinal cord injury (SCI) involves primary injury and secondary injury. Secondary injury is a major target for SCI therapy, whereas microglia play an important role in secondary injury. The immunoresponsive gene 1 (Irg-1) has been recorded as one of the most significantly upregulated genes in SCI tissues in gene chip data; however, its role in SCI remains unclear. This study aims to illustrate the role of Irg-1 as well as its regulated metabolite itaconate in SCI. It was demonstrated that the expression of Irg-1 was increased in spinal cord tissues in mice as well as in microglia stimulated by lipopolysaccharides (LPS). It was also shown that overexpression of Irg-1 may suppress LPS-induced inflammation in microglia, while these protective effects were attenuated by Nrf2 silencing. In vivo, overexpression of Irg-1 was shown to suppress neuroinflammation and improve motor function recovery. Furthermore, treatment of microglia with itaconate demonstrated similar inflammation suppressive effects as Irg-1 overexpression in vitro and improved motor function recovery in vivo. In conclusion, the current study shows that Irg-1 and itaconate are involved in the recovery process of SCI, either Irg-1 overexpression or itaconate treatment may provide a promising strategy for the treatment of SCI.Subject terms: Apoptosis, Cell death in the nervous system, Microglia, Trauma 相似文献
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Background Rhizoctonia solani is a pathogenic fungus that causes serious diseases in many crops, including rice, wheat, and soybeans. In crop production, it is very important to understand the pathogenicity of this fungus, which is still elusive. It might be helpful to comprehensively understand its genomic information using different genome annotation strategies.MethodsAiming to improve the genome annotation of R. solani, we performed a proteogenomic study based on the existing data. Based on our study, a total of 1060 newly identified genes, 36 revised genes, 139 single amino acid variants (SAAVs), 8 alternative splicing genes, and diverse post-translational modifications (PTMs) events were identified in R. solani AG3. Further functional annotation on these 1060 newly identified genes was performed through homology analysis with its 5 closest relative fungi.ResultsBased on this, 2 novel candidate pathogenic genes, which might be associated with pathogen-host interaction, were discovered. In addition, in order to increase the reliability and novelty of the newly identified genes in R. solani AG3, 1060 newly identified genes were compared with the newly published available R. solani genome sequences of AG1, AG2, AG4, AG5, AG6, and AG8. There are 490 homologous sequences. We combined the proteogenomic results with the genome alignment results and finally identified 570 novel genes in R. solani.ConclusionThese findings extended R. solani genome annotation and provided a wealth of resources for research on R. solani. 相似文献
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INTEGRATE: Model-based multi-omics data integration to characterize multi-level metabolic regulation
998.
Lia Di Saymon Akther Edgaras Bezrucenkovas Larisa Ivanova Brian Sulkow Bing Wu Saad Mneimneh Maria Gomes-Solecki Wei-Gang Qiu 《The ISME journal》2022,16(2):447
Natural populations of pathogens and their hosts are engaged in an arms race in which the pathogens diversify to escape host immunity while the hosts evolve novel immunity. This co-evolutionary process poses a fundamental challenge to the development of broadly effective vaccines and diagnostics against a diversifying pathogen. Based on surveys of natural allele frequencies and experimental immunization of mice, we show high antigenic specificities of natural variants of the outer surface protein C (OspC), a dominant antigen of a Lyme Disease-causing bacterium (Borrelia burgdorferi). To overcome the challenge of OspC antigenic diversity to clinical development of preventive measures, we implemented a number of evolution-informed strategies to broaden OspC antigenic reactivity. In particular, the centroid algorithm—a genetic algorithm to generate sequences that minimize amino-acid differences with natural variants—generated synthetic OspC analogs with the greatest promise as diagnostic and vaccine candidates against diverse Lyme pathogen strains co-existing in the Northeast United States. Mechanistically, we propose a model of maximum antigen diversification (MAD) mediated by amino-acid variations distributed across the hypervariable regions on the OspC molecule. Under the MAD hypothesis, evolutionary centroids display broad cross-reactivity by occupying the central void in the antigenic space excavated by diversifying natural variants. In contrast to vaccine designs based on concatenated epitopes, the evolutionary algorithms generate analogs of natural antigens and are automated. The novel centroid algorithm and the evolutionary antigen designs based on consensus and ancestral sequences have broad implications for combating diversifying pathogens driven by pathogen–host co-evolution.Subject terms: Population genetics, Bacterial genetics 相似文献
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Yunqing Gu Jun Cao Xinyu Zhang Hai Gao Yuyan Wang Jia Wang Juan He Xiaoyi Jiang Jinlan Zhang Guanghui Shen Jie Yang Xichen Zheng Gaowei Hu Yuanfei Zhu Shujuan Du Yunkai Zhu Rong Zhang Jianqing Xu Fei Lan Di Qu Guoliang Xu Yun Zhao Dong Gao Youhua Xie Min Luo Zhigang Lu 《Cell research》2022,32(1):24-37
Host cellular receptors play key roles in the determination of virus tropism and pathogenesis.However,little is known about SARS-CoV-2 host receptors with the e... 相似文献
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Michael S. Dahabieh Fan Huang Christophe Goncalves Raúl Ernesto Flores Gonzlez Sathyen Prabhu Alicia Bolt Erminia Di Pietro Elie Khoury John Heath Zi Yi Xu Joelle Rmy-Sarrazin Koren K. Mann Alexandre Orthwein Franois-Michel Boisvert Nancy Braverman Wilson H. Miller Sonia V. del Rincn 《Autophagy》2022,18(3):540