Identification of a Novel Universal Potential Epitope on the Cytoplasmic Tail of H7N9 Virus Hemagglutinin

<正>Dear Editor,H7 N9 is a recently identified subtype of influenza A virus that caused a major outbreak in humans in China in 2013.According to the latest data provided by the Chinese Center for Disease Control and Prevention(http://www.moh.gov.cn/zwgk/yqbb3/ejlist.shtml, updated on October 31, 2018),the mortality rate of H7 N9 infections in China amounts to     

Autographa Californica Multiple Nucleopolyhedrovirus P48 (Ac103) Is Required for the Efficient Formation of Virus-Induced Intranuclear Microvesicles

Our previous study has shown that the Autographa californica multiple nucleopolyhedrovirus(AcMNPV) p48(ac103)gene is essential for the nuclear egress of nucleocapsids and the formation of occlusion-derived virions(ODVs). However,the exact role of p48 in the morphogenesis of ODVs remains unknown. In this study, we demonstrated that p48 was required for the efficient formation of intranuclear microvesicles. To further understand its functional role in intranuclear microvesicle formation, we characterized the distribution of the P48 protein, which was found to be associated with the nucleocapsid and envelope fractions of both budded virions and ODVs. In Ac MNPV-infected cells, P48 was predominantly localized to nucleocapsids in the virogenic stroma and the nucleocapsids enveloped in ODVs, with a limited but discernible distribution in the plasma membrane, nuclear envelope, intranuclear microvesicles, and ODV envelope. Furthermore,coimmunoprecipitation assays showed that among the viral proteins required for intranuclear microvesicle formation, P48 associated with Ac93 in the absence of viral infection.     

DNA Methylation and SNPs in VCX are Correlated with Sex Differences in the Response to Chronic Hepatitis B

The study was conducted to explore the mechanisms of sex differences in the response to chronic hepatitis B(CHB) in terms of DNA methylation, SNP genotype, and gene expression. Genomic DNA was isolated from peripheral blood mononuclear cells(PBMCs) of CHB patients and healthy controls and evaluated using the Human Methylation 450 K Assay. The DNA methylation level at hg37 chromosome(CHR) X: 7810800 was further validated using pyrosequencing.SNP genotypes, VCX m RNA expression of PBMCs, and plasma VCX protein concentration were further examined using SNaPshot, RT-qPCR, and Western blot, respectively. Results showed that a total of 5529 CpG loci were differentially methylated between male and female CHB patients. DNA methylation level and CC+CT frequency at CHR X: 7810800,VCX mRNA expression of PBMCs, and plasma VCX protein concentration were higher in female than in male CHB patients. The CHR X: 7810800 locus was hypermethylated in CHB patients with CC+CT genotypes in comparison with those with the TT genotype. In cases of CC+CT genotypes, VCX mRNA expression was negatively correlated with the DNA methylation level. CHB patients with higher levels of HBV DNA, AST, and GGT or higher GPRI scores exhibited lower VCX expression. In conclusion, SNPs and DNA methylation at the CHR X: 7810800 locus cooperatively regulate VCX expression in CHB. The upregulated VCX expression in female CHB patients might represent a mechanism of protection from more severe liver dysfunction and extensive fibrosis, as observed in male CHB patients.     

SmGGPPS2对丹参酮合成的影响

香叶基香叶基焦磷酸合酶(GGPPS)是植物二萜类次生代谢物合成过程中的重要调控位点。在药用模式植物丹参(Salvia miltiorrhiza)中, GGPPS基因家族成员SmGGPPS2的生物学功能及其在丹参酮有效成分合成过程中的作用尚不明确。分别在丹参植株中过表达和RNA干涉SmGGPPS2基因, 并对转基因丹参中丹参酮含量和丹参酮合成相关基因表达量 以及转基因植物生理指标进行检测, 结果表明, 过表达SmGGPPS2株系中的丹参酮IIA和铁锈醇等脂溶性成分含量高于野生型; RNA干涉SmGGPPS2株系中的丹参酮IIA和铁锈醇等脂溶性成分含量均低于野生型。调节表达SmGGPPS2后, 丹参株系中SmHMGR1和SmCPS1等多个关键酶基因的表达都呈现明显的变化。此外, 调节表达SmGGPPS2还影响丹参植株抗性。以上结果表明, SmGGPPS2在丹参酮等萜类物质的合成中起重要的调控作用。     

水稻细菌性穗枯病的病原特性和抗性研究进展

水稻(Oryza sativa)细菌性穗枯病是世界性的重要病害之一, 严重威胁全球范围水稻的高产稳产。虽然该病目前仍被列为我国的检疫性病害, 但近几年的研究表明, 穗枯病随时有在内地蔓延的潜在危险, 因此除了加强检疫工作, 开展针对性的防控技术研发也十分必要。水稻细菌性穗枯病菌在侵染过程中涉及多种毒力因子, 同时, 水稻在与病原菌的长期互作过程中演化出了多种防卫机制, 抗性基因是主要的防卫机制之一。挖掘水稻基因组中抗细菌性穗枯病遗传位点并培育抗病品种是最安全且经济有效的防治途径。该文综述了水稻细菌性穗枯病的病原菌特性、发病特征、发病机制、病害循环和对水稻细菌性穗枯病的抗性研究现状, 以期为挖掘和分离水稻穗枯病抗性位点提供参考。     

Death domain of p75 neurotrophin receptor: a structural perspective on an intracellular signalling hub

The death domain (DD) is a globular protein motif with a signature feature of an all‐helical Greek‐key motif. It is a primary mediator of a variety of biological activities, including apoptosis, cell survival and cytoskeletal changes, which are related to many neurodegenerative diseases, neurotrauma, and cancers. DDs exist in a wide range of signalling proteins including p75 neurotrophin receptor (p75^NTR), a member of the tumour necrosis factor receptor superfamily. The specific signalling mediated by p75^NTR in a given cell depends on the type of ligand engaging the extracellular domain and the recruitment of cytosolic interactors to the intracellular domain, especially the DD, of the receptor. In solution, the p75^NTR‐DDs mainly form a symmetric non‐covalent homodimer. In response to extracellular signals, conformational changes in the p75^NTR extracellular domain (ECD) propagate to the p75^NTR‐DD through the disulfide‐bonded transmembrane domain (TMD) and destabilize the p75^NTR‐DD homodimer, leading to protomer separation and exposure of binding sites on the DD surface. In this review, we focus on recent advances in the study of the structural mechanism of p75^NTR‐DD signalling through recruitment of diverse intracellular interactors for the regulation and control of diverse functional outputs.     

Transgenic creeping bentgrass overexpressing Osa‐miR393a exhibits altered plant development and improved multiple stress tolerance

MicroRNA393 (miR393) has been implicated in plant growth, development and multiple stress responses in annual species such as Arabidopsis and rice. However, the role of miR393 in perennial grasses remains unexplored. Creeping bentgrass (Agrostis stolonifera L.) is an environmentally and economically important C3 cool‐season perennial turfgrass. Understanding how miR393 functions in this representative turf species would allow the development of novel strategies in genetically engineering grass species for improved abiotic stress tolerance. We have generated and characterized transgenic creeping bentgrass plants overexpressing rice pri‐miR393a (Osa‐miR393a). We found that Osa‐miR393a transgenics had fewer, but longer tillers, enhanced drought stress tolerance associated with reduced stomata density and denser cuticles, improved salt stress tolerance associated with increased uptake of potassium and enhanced heat stress tolerance associated with induced expression of small heat‐shock protein in comparison with wild‐type controls. We also identified two targets of miR393, AsAFB2 and AsTIR1, whose expression is repressed in transgenics. Taken together, our results revealed the distinctive roles of miR393/target module in plant development and stress responses between creeping bentgrass and other annual species, suggesting that miR393 would be a promising candidate for generating superior crop cultivars with enhanced multiple stress tolerance, thus contributing to agricultural productivity.     

Development of Beet necrotic yellow vein virus‐based vectors for multiple‐gene expression and guide RNA delivery in plant genome editing

Many plant viruses with monopartite or bipartite genomes have been developed as efficient expression vectors of foreign recombinant proteins. Nonetheless, due to lack of multiple insertion sites in these plant viruses, it is still a big challenge to simultaneously express multiple foreign proteins in single cells. The genome of Beet necrotic yellow vein virus (BNYVV) offers an attractive system for expression of multiple foreign proteins owning to a multipartite genome composed of five positive‐stranded RNAs. Here, we have established a BNYVV full‐length infectious cDNA clone under the control of the Cauliflower mosaic virus 35S promoter. We further developed a set of BNYVV‐based vectors that permit efficient expression of four recombinant proteins, including some large proteins with lengths up to 880 amino acids in the model plant Nicotiana benthamiana and native host sugar beet plants. These vectors can be used to investigate the subcellular co‐localization of multiple proteins in leaf, root and stem tissues of systemically infected plants. Moreover, the BNYVV‐based vectors were used to deliver NbPDS guide RNAs for genome editing in transgenic plants expressing Cas9, which induced a photobleached phenotype in systemically infected leaves. Collectively, the BNYVV‐based vectors will facilitate genomic research and expression of multiple proteins, in sugar beet and related crop plants.     

The TrkB‐T1 receptor mediates BDNF‐induced migration of aged cardiac microvascular endothelial cells by recruiting Willin

The mechanism of age‐related decline in the angiogenic potential of the myocardium is not yet fully understood. Our previous report revealed that the aging of cardiac microvascular endothelial cells (CMECs) led to changes in their expression of receptor Trk isoforms: among the three isoforms (TrkB‐FL, TrkB‐T1 and TrkB‐T2), only the truncated TrkB‐T1 isoform continued to be expressed in aged CMECs, which led to decreased migration of CMECs in aging hearts. Thus far, how BDNF induces signalling through the truncated TrkB‐T1 isoform in aged CMECs remains unclear. Here, we first demonstrated that aged CMECs utilize BDNF–TrkB‐T1 signalling to recruit Willin as a downstream effector to further activate the Hippo pathway, which then promotes migration. These findings suggest that the aging process shifts the phenotype of aged CMECs that express TrkB‐T1 receptors by transducing BDNF signals via the BDNF–TrkB‐T1–Willin–Hippo pathway and that this change might be an important mechanism and therapeutic target of the dysfunctional cardiac angiogenesis observed in aged hearts.     

Rho‐associated coiled‐coil kinase 1 activation mediates amyloid precursor protein site‐specific Ser655 phosphorylation and triggers amyloid pathology

Rho‐associated coiled‐coil kinase 1 (ROCK1) is proposed to be implicated in Aβ suppression; however, the role for ROCK1 in amyloidogenic metabolism of amyloid precursor protein (APP) to produce Aβ was unknown. In the present study, we showed that ROCK1 kinase activity and its APP binding were enhanced in AD brain, resulting in increased β‐secretase cleavage of APP. Furthermore, we firstly confirmed that APP served as a substrate for ROCK1 and its major phosphorylation site was located at Ser655. The increased level of APP Ser655 phosphorylation was observed in the brain of APP/PS1 mice and AD patients compared to controls. Moreover, blockade of APP Ser655 phosphorylation, or inhibition of ROCK1 activity with either shRNA knockdown or Y‐27632, ameliorated amyloid pathology and improved learning and memory in APP/PS1 mice. These findings suggest that activated ROCK1 targets APP Ser655 phosphorylation, which promotes amyloid processing and pathology. Inhibition of ROCK1 could be a potential therapeutic approach for AD.