Viral pathogens are a major threat to rice production worldwide. Although RNA interference (RNAi) is known to mediate antiviral immunity in plant and animal models, the mechanism of antiviral RNAi in rice and other economically important crops is poorly understood. Here, we report that rice resistance to evolutionarily diverse viruses requires Argonaute18 (AGO18). Genetic studies reveal that the antiviral function of AGO18 depends on its activity to sequester microRNA168 (miR168) to alleviate repression of rice AGO1 essential for antiviral RNAi. Expression of miR168-resistant AGO1a in ago18 background rescues or increases rice antiviral activity. Notably, stable transgenic expression of AGO18 confers broad-spectrum virus resistance in rice. Our findings uncover a novel cooperative antiviral activity of two distinct AGO proteins and suggest a new strategy for the control of viral diseases in rice.DOI: http://dx.doi.org/10.7554/eLife.05733.001
The Wnt signaling pathway is well known to play major roles in skeletal development and homeostasis. In certain aspects, fracture repair mimics the process of bone embryonic development. Thus, the importance of Wnt signaling in fracture healing has become more apparent in recent years. Here, we summarize recent research progress in the area, which may be conducive to the development of Wnt-based therapeutic strategies for bone repair. [BMB Reports 2014; 47(12): 666-672]
Lymphatic vessels constitute a specialized vasculature that is involved in development, cancer, obesity, and immune regulation. The migration of lymphatic endothelial cells (LECs) is critical for vessel growth (lymphangiogenesis) and vessel remodeling, processes that modify the lymphatic network in response to developmental or pathological demands. Using the publicly accessible results of our genome-wide siRNA screen, we characterized the migratome of primary human LECs and identified individual genes and signaling pathways that regulate LEC migration. We compared our data set with mRNA differential expression data from endothelial and stromal cells derived from two in vivo models of lymphatic vessel remodeling, viral infection and contact hypersensitivity-induced inflammation, which identified genes selectively involved in regulating LEC migration and remodeling. We also characterized the top candidates in the LEC migratome in primary blood vascular endothelial cells to identify genes with functions common to lymphatic and blood vascular endothelium. On the basis of these analyses, we showed that , which encodes the glycan-binding protein Galectin-1, promoted lymphatic vascular growth in vitro and in vivo and contributed to maintenance of the lymphatic endothelial phenotype. Our results provide insight into the signaling networks that control lymphangiogenesis and lymphatic remodeling and potentially identify therapeutic targets and biomarkers in disease specific to lymphatic or blood vessels.
Passive seismic methods in highly populated urban areas have gained much attention from geophysics and civil engineering communities because traditional seismic surveys, especially in complex urbanized environments, might be improperly applied. In passive seismic methods, directional noise sources will inevitably bring azimuthal effects and spatial aliasing to dispersion measurements due to the fact that true randomness of ambient noise cannot be achieved in reality. To solve these problems, multichannel analysis of passive surface (MAPS) waves based on long noise sequence crosscorrelations is proposed. We have introduced a hybrid method of seismic interferometry and the roadside passive multichannel analysis of surface waves (MASW) using crosscorrelation to produce common virtual source gathers from 1 h multichannel noise records. Common virtual source gathers are then used to do dispersion analysis with an active scheme based on phase-shift measurement. Synthetic tests demonstrated the advantages of this method with azimuthal adjustment and dispersion imaging for directional noise source distribution. Two field applications were conducted, and results from the roadside passive MASW, MAPS, and spatial autocorrelation method were compared. Our study indicated the superiority of MAPS over the roadside passive MASW on the validity of azimuth detection, feasibility of combining the active MASW and MAPS, and accuracy in determining dispersion energy trends, especially at a relative low-frequency range ([Formula: see text]) in urban areas.
Connexin (Cx) 43 forms gap junctions and hemichannels that mediate communication between osteocytes and adjacent cells or the extracellular environment in bone, respectively. To investigate the role of each channel type in response to mechanical unloading, two transgenic mouse models overexpressing dominant-negative Cx43 predominantly in osteocytes driven by a 10 kb dentin matrix protein 1 (Dmp1) promoter were generated. The R76W mutation resulted in gap junction inhibition and enhancement of hemichannels, whereas the 130-136 mutation inhibited both gap junctions and hemichannels. Both mutations led to cortical bone loss with increased endocortical osteoclast activity during unloading. Increased periosteal osteoclasts with decreased apoptotic osteocytes were observed only in R76W mice. These findings indicated that inhibiting osteocytic Cx43 channels promotes bone loss induced by unloading, mainly in the cortical area; moreover, hemichannels protect osteocytes against apoptosis and promote periosteal bone remodeling, whereas gap junctions modulate endocortical osteoclast activity in response to unloading.
Connexin 43 (Cx43) hemichannels and gap junctions in osteocytes are responsive to mechanical loading, which is important for bone formation and remodeling. However, the mechanism of these Cx43-forming channels in the process of mechanical unloading is still not very clear. In this study, unloading caused by weightlessness was simulated by using a random position machine (RPM). Osteocytic MLO-Y4 cells were subjected to 2 h of RPM treatment, and levels of Cx43 mRNA and total and cell surface expressed protein were determined by quantitative real-time PCR, western blotting, and biotinylation analysis. Although mRNA was elevated by RPM, total protein level of Cx43 was not altered; however, surface biotinylated Cx43 was significantly reduced. Interestingly, RPM promoted the retention of Cx43 in the Golgi apparatus detected by co-immunofluorescence with antibodies against Cx43 and 58 K Golgi marker protein. Dye uptake assay showed that hemichannels were induced open after RPM for 2 h. Consistently, prostaglandin E2 release was increased and this increase was completely attenuated with the treatment of a Cx43 hemichannel blocking antibody. Together, this study demonstrates increased activity of Cx43 hemichannels to RPM, and active Cx43 hemichannels with prostaglandin E2 release are likely to module biological function under simulated weightless conditions.
Viral pathogens are a major threat to rice production worldwide. Although RNA interference (RNAi) is known to mediate antiviral immunity in plant and animal models, the mechanism of antiviral RNAi in rice and other economically important crops is poorly understood. Here, we report that rice resistance to evolutionarily diverse viruses requires Argonaute18 (AGO18). Genetic studies reveal that the antiviral function of AGO18 depends on its activity to sequester microRNA168 (miR168) to alleviate repression of rice AGO1 essential for antiviral RNAi. Expression of miR168-resistant AGO1a in ago18 background rescues or increases rice antiviral activity. Notably, stable transgenic expression of AGO18 confers broad-spectrum virus resistance in rice. Our findings uncover a novel cooperative antiviral activity of two distinct AGO proteins and suggest a new strategy for the control of viral diseases in rice.
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