35 research outputs found

    Epidermal Growth Factor Receptor-PI3K Signaling Controls Cofilin Activity To Facilitate Herpes Simplex Virus 1 Entry into Neuronal Cells

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    Herpes simplex virus type 1 (HSV-1) establishes latency in neurons and can cause severe disseminated infection with neurological impairment and high mortality. This neurodegeneration is thought to be tightly associated with virus-induced cytoskeleton disruption. Currently, the regulation pattern of the actin cytoskeleton and the involved molecular mechanisms during HSV-1 entry into neurons remain unclear. Here, we demonstrate that the entry of HSV-1 into neuronal cells induces biphasic remodeling of the actin cytoskeleton and an initial inactivation followed by the subsequent activation of cofilin, a member of the actin depolymerizing factor family that is critical for actin reorganization. The disruption of F-actin dynamics or the modulation of cofilin activity by mutation, knockdown, or overexpression affects HSV-1 entry efficacy and virus-mediated cell ruffle formation. Binding of the HSV-1 envelope initiates the epidermal growth factor receptor (EGFR)-phosphatidylinositide 3-kinase (PI3K) signaling pathway, which leads to virus-induced early cofilin phosphorylation and F-actin polymerization. Moreover, the extracellular signal-regulated kinase (ERK) kinase and Rho-associated, coiled-coil-containing protein kinase 1 (ROCK) are recruited as downstream mediators of the HSV-1-induced cofilin inactivation pathway. Inhibitors specific for those kinases significantly reduce the virus infectivity without affecting virus binding to the target cells. Additionally, lipid rafts are clustered to promote EGFR-associated signaling cascade transduction. We propose that HSV-1 hijacks cofilin to initiate infection. These results could promote a better understanding of the pathogenesis of HSV-1-induced neurological diseases

    Monitoring the Process and Characterizing Symptoms of Suckling Mouse Inoculation Promote Isolating Viruses from Ticks

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    Suckling mouse inoculation is an important method that has been used for years to isolate viruses from ticks; however, this method has usually been briefly described in the literature on a case-by-case basis upon successful isolation rather than providing extensive details. This study describes the procedure from preparation of tick homogenates to identification of virus isolation using the suckling mouse inoculation method. The transient and persistent features were characterized and the incidence of manifestations that developed in the suckling mice, especially in mice from which viruses were isolated, is reported. We identified 22 symptoms that developed in mice, including 13 transient symptoms that recovered by the end of the observation period and 7 persistent symptoms that the mice suffered from throughout the observation period. Persistent symptoms (lateral positioning and dead) and transient symptoms (malaise, emaciation, and difficulty turning over) were the main symptoms based on the high overall incidence. Moreover, we showed that mice from which viruses were isolated had a concentrated period and advanced days of disease onset. This study provides detailed information necessary for better use of suckling mouse inoculation to isolate viruses from ticks, which may benefit optimization of this method to identify, discover, and acquire tick-borne viruses

    Study on the Spatial Convergence Club and Growth Momentum of China’s Regional Economies

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    The purpose of this paper is to clarify the convergence pattern of China’s regional economies, explore the driving force of their coordinated development, and provide policy suggestions for coordinated and high-quality development. We used nighttime light data from 1992 to 2020 and combined an exploratory spatial data analytical method and a log-t test of a nonlinear time-varying factor model to identify the spatial convergence clubs of regional economic growth and the economic growth drivers of different clubs based on a spatial econometric model. We found that the eastern region is strong while the development of the central, western, and northeastern regions follows China’s long-term trend. Three high-level economic clubs (Shanghai, Jiangsu, and Zhejiang belong to Club 1; Shandong, Hebei, Anhui, Henan, and Liaoning belong to Club 2; Hainan, Fujian, and Guangdong belong to Club 3) have formed in the eastern coastal and central regions, while a low-level one (Inner Mongolia, Hubei, Chongqing, Qinghai, Guizhou, Sichuan, Guangxi, Yunnan, Xizang, Shaanxi, Gansu, Hunan, Ningxia, Xinjiang, Jiangxi, Heilongjiang, and Jilin) has formed in the central, western, and northeastern regions. Beijing, Tianjin, and Shanxi are not convergent. The coordinated development of these regions requires improving the levels of economic growth in the western and northeastern regions to give full play to the role of the Yangtze River Delta as a growth pole and its economic radiation capacity. An analysis of the influence mechanism and spatial spillover effects shows that industrial development and market vitality are the most important driving forces for economic growth. For the low-level club, service industry development, human capital, and resource consumption are also key factors for achieving sustained and stable economic growth

    Study on the Spatial Convergence Club and Growth Momentum of China’s Regional Economies

    No full text
    The purpose of this paper is to clarify the convergence pattern of China’s regional economies, explore the driving force of their coordinated development, and provide policy suggestions for coordinated and high-quality development. We used nighttime light data from 1992 to 2020 and combined an exploratory spatial data analytical method and a log-t test of a nonlinear time-varying factor model to identify the spatial convergence clubs of regional economic growth and the economic growth drivers of different clubs based on a spatial econometric model. We found that the eastern region is strong while the development of the central, western, and northeastern regions follows China’s long-term trend. Three high-level economic clubs (Shanghai, Jiangsu, and Zhejiang belong to Club 1; Shandong, Hebei, Anhui, Henan, and Liaoning belong to Club 2; Hainan, Fujian, and Guangdong belong to Club 3) have formed in the eastern coastal and central regions, while a low-level one (Inner Mongolia, Hubei, Chongqing, Qinghai, Guizhou, Sichuan, Guangxi, Yunnan, Xizang, Shaanxi, Gansu, Hunan, Ningxia, Xinjiang, Jiangxi, Heilongjiang, and Jilin) has formed in the central, western, and northeastern regions. Beijing, Tianjin, and Shanxi are not convergent. The coordinated development of these regions requires improving the levels of economic growth in the western and northeastern regions to give full play to the role of the Yangtze River Delta as a growth pole and its economic radiation capacity. An analysis of the influence mechanism and spatial spillover effects shows that industrial development and market vitality are the most important driving forces for economic growth. For the low-level club, service industry development, human capital, and resource consumption are also key factors for achieving sustained and stable economic growth

    The complete plastome sequence of Platanthera japonica (Orchidaceae): an endangered medicinal and ornamental plant

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    Platanthera japonica (Thunb. ex A. Marray) Lindl belongs to the genus Platanthera within family Orchidaceae, is an endangered herbal species in the East Asia area. In this study, the complete plastome sequence (cpDNA) of P. japonica was determined by next-generation Illumina sequencing. The cpDNA of this herbal plant is 155,409 bp in size, with a pair of inverted repeat (IR) regions of 26,933 bp that separate a large single-copy (LSC) region of 84,049 bp and a small single-copy (SSC) region of 17,494 bp. The GC content in plastome is 36.9%, and the IR region (43.2%) is higher than that of the LSC and SSC region (34.4% and 29.7%, respectively), which is similar with other Orchidaceae plastomes. The assembled plastome encoded 133 genes, which included 38 tRNA genes, 8 rRNA genes, and 87 protein-coding genes. A total of 24 species were used to construct the phylogenetic relationships among P. japonica and other related species within Orchidaceae. The results showed that P. japonica is closely related to Platanthera chlorantha

    A Long Noncoding RNA Derived from lncRNA–mRNA Networks Modulates Seed Vigor

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    The discovery of long noncoding RNAs (lncRNAs) has filled a great gap in our understanding of posttranscriptional gene regulation in a variety of biological processes related to plant stress responses. However, systematic analyses of the lncRNAs expressed in rice seeds that germinate under cold stress have been elusive. In this study, we performed strand-specific whole transcriptome sequencing in germinated rice seeds under cold stress and normal temperature. A total of 6258 putative lncRNAs were identified and expressed in a stage-specific manner compared to mRNA. By investigating the targets of differentially expressed (DE) lncRNAs of LT-I (phase I of low temperature)/NT-I (phase I of normal temperature), it was shown that the auxin-activated signaling pathway was significantly enriched, and twenty-three protein-coding genes with most of the members of the SAUR family located in chromosome 9 were identified as the candidate target genes that may interact with five lncRNAs. A seed vigor-related lncRNA, SVR, which interplays with the members of the SAUR gene family in cis was eventually identified. The CRISPR/Cas 9 engineered mutations in SVR cause delay of germination. The findings provided new insights into the connection between lncRNAs and the auxin-activated signaling pathway in the regulation of rice seed vigor

    Identification and Analysis of Differentially-Expressed microRNAs in Japanese Encephalitis Virus-Infected PK-15 Cells with Deep Sequencing

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    Japanese encephalitis virus (JEV), a mosquito-borne Flavivirus, causes acute viral encephalitis with high morbidity and mortality in humans and animals. MicroRNAs (miRNAs) are small noncoding RNAs that are important modulators of the intricate host-pathogen interaction networks. However, our knowledge of the changes that occur in miRNAs in host cells after JEV infection is still limited. To understand the molecular pathogenesis of JEV at the level of posttranscriptional regulation, we used Illumina deep sequencing to sequence two small RNA libraries prepared from PK-15 cells before and after JEV infection. We identified 522 and 427 miRNAs in the infected and uninfected cells, respectively. Overall, 132 miRNAs were expressed significantly differently after challenge with JEV: 78 were upregulated and 54 downregulated. The sequencing results for selected miRNAs were confirmed with RT-qPCR. GO analysis of the host target genes revealed that these dysregulated miRNAs are involved in complex cellular pathways, including the metabolic pathway, inflammatory response and immune response. To our knowledge, this is the first report of the comparative expression of miRNAs in PK-15 cells after JEV infection. Our findings will underpin further studies of miRNAs’ roles in JEV replication and identify potential candidates for antiviral therapies against JEV
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