Rhinovirus (RV), a member of the Picornaviridae family, accounts for many virus-induced asthma exacerbations. RV induces airway cell chemokine expression both in vivo and in vitro. Because of the ...known interactions of proteases with cellular functions, we hypothesized that RV 3C protease is sufficient for cytokine up-regulation. A cDNA encoding RV16 3C protease was constructed by PCR amplification and transfected into 16HBE14o- human bronchial epithelial cells. 3C protease induced expression of both IL-8 and GM-CSF, as well as transcription from both the IL-8 and GM-CSF promoters. 3C expression also induced activator protein 1 and NF-kappaB transcriptional activation. Finally, mutation of IL-8 promoter AP-1 and NF-kappaB promoter sequences significantly reduced 3C-induced responses. Together, these data suggest expression of RV16 3C protease is sufficient to induce chemokine expression in human bronchial epithelial cells, and does so in an AP-1- and NF-kappaB-dependent manner.
Genetic diversity and relationships among Chinese traditional cabbage landraces have not yet been well investigated. To explore the diversity, 83 landraces originating in Northern China, Southern ...China, Eastern Europe, Western Europe as well as other countries were evaluated by using AFLP markers. Results indicated that cabbage landraces exhibited a relatively low level of diversity. Among the 575 markers, 41.9% were polymorphic with an average PIC value of 0.354. Unweighted pair group method with arithmetic averages (UPGMA) cluster and population structure analysis consistently divided all landraces into two major groups reflecting geographic origins. Group 1 was a distinct group comprised of Northern China landraces and Eastern European landraces, whereas Group 2 was comprised of populations of Southern China landraces, Western European populations and other countries. Landraces with varied maturing times or head types could not be distinguished based on molecular data. The Northern China population was closely allied to the Eastern Europe population (D = 0.037). The integration of our data with historical documents confirmed that traditional cabbage landraces cultivated in North of China were first introduced from Russia.
Objective This study was to investigate the molecular mechanisms underlying the 27nt-miRNA-mediated regulation of expression of the endothelial nitric oxide synthase (eNOS) gene. Methods Cell lines ...overexpressing 27nt-miRNA or its mutant were established by transfecting the miRNA expression vector into the endothelial cells. eNOS mRNA and protein expression were examined by RT-PCR and Western Blotting, respectively. Luciferase activity reporter system was used to study the target of 27nt-miRNA. Results The results showed that overexpression of 27nt-miRNA significantly inhibited eNOS mRNA level and protein expression, and reduced the eNOS transcriptional efficiency. Such inhibitory effects of 27nt-miRNA were attenuated by the sequence mutations in 27nt-miRNA. Interestingly, the transcription factor SP-1 expression was reduced by 27nt-miRNA. Meanwhile, overxpression of SP-1 protein partially restored eNOS expression, and rescued the 27nt-miRNA-mediated reduction of endothelial cell proliferation. Moreover, certain sites in the SP-1 mRNA were found to be the direct target of 27nt-miRNA by a luciferase reporter system. Conclusions These results demonstrate that the 27nt-miRNA suppresses eNOS gene expression and SP-1 expression in vascular endothelial cells. The 27nt-miRNA directly target to SP-1 mRNA, thereby contributing to proliferation of endothelial cells.
Total steroidal saponins extracted from the rhizome of Paris polyphylla Sm. var. yunnanensis (TSSPs) have been widely used in China for the treatment of abnormal uterine bleeding. We previously ...studied the main active constituents of TSSPs and their structure-activity relationships with respect to rat myometrial contractions. Tg (pennogenin tetraglycoside) was identified as one of the active ingredients in TSSPs able to induce rat myometrial contractions. However, the mechanisms underlying the pharmacological actions on uterine activity have not been described clearly.
Here Tg was screened for effects on contractile activity in isolated uterine strips from estrogen-primed rats and on MLC20 phosphorylation and related signaling pathways in cultured rat myometrial cells as determined by Western blot. Intracellular calcium (Ca(2+)(i)) was monitored under a confocal microscope using Fluo-4 AM-loaded myometrial cells.
Tg dose-dependently stimulated rat myometrial contractions as well as MLC20 phosphorylation in vitro, which could be completely suppressed by an inhibitor of myosin light chain kinase (MLCK). Use of Ca(2+) channel blockers and kinase inhibitors demonstrated that Tg-induced myometrial contractions are mediated by activation of the phospholipase C (PLC)-inositol triphosphate (IP3) signaling pathway, resulting in increased MLC20 phosphorylation. Furthermore, Y27632, a specific inhibitor of Rho kinase (ROK), notably suppressed Tg-stimulated myometrial contractions and decreased MLC20 phosphorylation.
These data provide evidence that rat myometrial contractility induced by Tg results from enhanced MLC20 phosphorylation, while both PLC-IP3 and RhoA/ROK signaling pathways mediate the process. These mechanisms may be responsible for the therapeutic effects of TSSPs on abnormal uterine bleeding.
The recent GPU-based clusters that handle deep learning (DL) tasks have the features of GPU device heterogeneity, a variety of deep neural network (DNN) models, and high computational complexity. ...Thus, the traditional power capping methods for CPU-based clusters or small-scale GPU devices cannot be applied to the GPU-based clusters handling DL tasks. This article develops a cooperative distributed GPU power capping (CD-GPC) system for GPU-based clusters, aiming to minimize the training completion time of invoked DL tasks without exceeding the limited power budget. Specifically, we first design the frequency scaling approach using the online model estimation based on the recursive least square method. This approach achieves the accurate tuning for DL task training time and power usage of GPU devices without needing offline profiling. Then, we formulate the proposed FS problem as a Lagrangian dual decomposition-based economic model predictive control problem for large-scale heterogeneous GPU clusters. We conduct both the NVIDIA GPU-based lab-scale real experiments and real job trace-based simulation experiments for performance evaluation. Experimental results validate that the proposed system improves the power capping accuracy to have a mean absolute error of <inline-formula><tex-math notation="LaTeX">$< \!1\%$</tex-math></inline-formula>, and reduces the deadline violation ratio of invoked DL tasks by 21.5% compared with other recent counterparts.
Oxygen K-edge X-ray absorption spectra of liquid water are computed based on the configurations from advanced ab initio molecular dynamics simulations, as well as an electron excitation theory from ...the GW method. One one hand, the molecular structures of liquid water are accurately predicted by including both van der Waals interactions and hybrid functional (PBE0). On the other hand, the dynamic screening effects on electron excitation are approximately described by the recently developed enhanced static Coulomb hole and screened exchange approximation by Kang and Hybertsen Phys. Rev. B 82, 195108 (2010). The resulting spectra of liquid water are in better quantitative agreement with the experimental spectra due to the softened hydrogen bonds and the slightly broadened spectra originating from the better screening model.
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