RNA病毒作为疫苗载体的研究与应用

在目前的疫苗研究中,对新疫苗免疫效果的要求越来越高。减毒或无毒的病毒疫苗载体能够激发高效持久的系统和黏膜免疫,并且具有较高的安全性,为研究新疫苗提供了一条途径。RNA病毒作为疫苗载体,在可操作性和免疫效果方面有着显著的优势,近年来已成为疫苗研究领域的热点。综述了几种RNA病毒载体目前的研究状况及其在疫苗载体方面的应用。     

Gadolinium promoted proliferation in mouse embryo fibroblast NIH3T3 cells through Rac and PI3K/Akt signaling pathways

Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder disease developed in patients with underlying renal insufficiency following exposure to gadolinium-based contrast agents (GBCAs). Previous studies have demonstrated that GdCl₃ can promote NIH3T3 fibroblast cell proliferation, which provide a new clue to the role of GBCAs in the development of NSF. In the present study, we further clarify the molecular mechanism of Gd-promoted proliferation. The results showed that intervention with the Rac inhibitor NSC23766 abrogated Gd-promoted proliferation. The levels of active Rac1 significantly increased in Gd-treated cells detected by pull-down assays. In addition, the phosphorylation of Akt was significantly elevated in the treatment group, which was blocked by NSC23766. NSC23766 also reduced the migration of NIH3T3 cells enhanced by Gd. Moreover, the F-actin cytoskeleton was strengthened and the mitotic cell numbers was significantly increased after exposure to Gd. These results suggest that Rac and PI3K/Akt signaling pathways, as well as integrin-mediated signal pathway may play important roles in Gd-induced cell proliferation. In addition, under serum-free condition, Gd could decrease ROS accumulation and increase NIH3T3 cell survival.     

Development of a Loop-Mediated Isothermal Amplification Assay for Porcine Circovirus Type 2

In this study, the loop-mediated isothermal amplification (LAMP) method was used to develop a rapid and simple detection system for porcine circovirus type 2 (PCV2). According to the PCV2 sequences published in GenBank, multiple LAMP primers were designed targeting conserved sequences of PCV2. Using the DNA extracted from PCV2 isolates HUN-09 and SD-09 as the template, LAMP reactions in a PCV2 LAMP system was performed, the amplification products were detected by adding SYBR Green I and could be observed di...     

综述与专论: 机械敏感性离子通道TMEM63A在髓鞘形成障碍相关疾病中的作用

跨膜蛋白63A（transmembrane protein 63,TMEM63A）是一种机械敏感性离子通道（mechanosensitive ion channel,MSC）,在髓鞘形成过程中发挥重要作用。TMEM63A于2019年与髓鞘形成低下性脑白质营养不良19型（hypomyelinating leukodystrophy 19,HLD19）相关联,确定为HLD19的致病基因。髓鞘是神经系统中由少突胶质细胞形成的兼具营养轴突和加速动作电位传导的结构,髓鞘形成障碍可表现为髓鞘形成低下、髓鞘囊性化和髓鞘变性。髓鞘中脂质含量丰富,不同脂质参与髓鞘形成、修复和胶质细胞与轴突识别等重要过程。TMEM63A变异导致的HLD19为髓鞘形成低下性疾病。TMEM63A变异可引起渗透压改变,细胞上TMEM63A跨膜蛋白受机械刺激产生电流,从而影响少突胶质细胞分化、成熟,导致髓鞘形成异常;同时,TMEM63A变异也可引起细胞膜脂质的分布异常,影响脂质正常功能,异常的脂质通过参与不同的髓鞘形成环节最终导致了髓鞘形成障碍。     

Phosphorylation of the SSBP2 and ABL proteins by the ZNF198‐FGFR1 fusion kinase seen in atypical myeloproliferative disorders as revealed by phosphopeptide‐specific MS

The ZNF198‐fibroblast growth factor receptor‐1 (FGFR1) fusion kinase is a constitutively activated tyrosine kinase associated with a specific atypical myeloproliferative disease. The chimeric protein localizes to the cytoplasm, unlike the wild type FGFR1 receptor kinase, and presumably inappropriately phosphorylates specific targets as part of the oncogenic signaling cascade. Other than known targets of the FGFR1 kinase itself, few specific targets of ZNF198‐FGFR1 have been identified. Using a genetically engineered HEK 293 cell system, we have identified proteins that are specifically phosphorylated in the presence of the fusion kinase using anti‐phosphotyrosine immunoprecipitation and MS. Compared with 293 cells expressing exongenous wild type FGFR1, ZNF198‐FGFR1 is associated with phosphorylation of several proteins including SSBP2, ABL, FLJ14235, CALM and TRIM4 proteins. The specificity of the phosphorylation events in the SSBP2 and ABL proteins, which have previously been implicated in leukemogenesis, was further confirmed independently using immunoprecipitation with protein‐specific antibodies and Western blotting. The MS analysis also identified the phosphorylation events in the ZNF198 moiety in the chimeric protein that might be related to its function. These studies identify the intersection of several different leukemia‐related pathways in the development of this myeloproliferative disorder and provide new insights into the substrates of FGFR1 under defined conditions.