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21.
Objectives
There has been increased interest in the possible role of human cytomegalovirus (HCMV) in carcinogenesis during the last decade. HCMV seroprevalence was enhanced in patients with hepatocellular carcinoma (HCC) but a possible relationship between HCC and HCMV infection remained to be assessed. The aim of this work was to investigate the pro-tumor influence of HCMV on primary human hepatocytes (PHH) and HepG2 cells.Methods
Following infection of PHH and HepG2 cells by two different strains of HCMV, we measured the production of IL-6 in culture supernatants by ELISA and the protein levels of STAT3, pSTAT3, JAK, cyclin D1, survivin, p53, p21, and Mdm2 by western Blotting in infected and uninfected cells. Cell proliferation and transformation were investigated using Ki67Ag expression measurement and soft-agar colony formation assay respectively.Results
Infection of HepG2 cells and PHH by HCMV resulted in the production of IL-6 and the subsequent activation of the IL-6R-JAK-STAT3 pathway. HCMV increased the expression of cyclin D1 and survivin. Cell proliferation was enhanced in HepG2 and PHH infected with HCMV, despite a paradoxical overexpression of p53 and p21. More importantly, we observed the formation of colonies in soft agar seeded with PHH infected with HCMV and when we challenged the HepG2 cultures to form tumorspheres, we found that the HCMV-infected cultures formed 2.5-fold more tumorspheres than uninfected cultures.Conclusion
HCMV activated the IL-6-JAK-STAT3 pathway in PHH and HepG2 cells, favored cellular proliferation, induced PHH transformation and enhanced HepG2 tumorsphere formation. Our observations raise the possibility that HCMV infection might be involved in the genesis of hepatocellular carcinoma. 相似文献22.
Madeleine Scharf Stefan Neef Robert Freund Cornelia Geers-Kn?rr Mirita Franz-Wachtel Almuth Brandis Dorothee Krone Heike Schneider Stephanie Groos Manoj B. Menon Kin-Chow Chang Theresia Kraft Joachim D. Meissner Kenneth R. Boheler Lars S. Maier Matthias Gaestel Renate J. Scheibe 《Molecular and cellular biology》2013,33(13):2586-2602
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Epigenetic mechanisms of plant stress responses and adaptation 总被引:3,自引:0,他引:3
Pranav Pankaj Sahu Garima Pandey Namisha Sharma Swati Puranik Mehanathan Muthamilarasan Manoj Prasad 《Plant cell reports》2013,32(8):1151-1159
Epigenetics has become one of the hottest topics of research in plant functional genomics since it appears promising in deciphering and imparting stress-adaptive potential in crops and other plant species. Recently, numerous studies have provided new insights into the epigenetic control of stress adaptation. Epigenetic control of stress-induced phenotypic response of plants involves gene regulation. Growing evidence suggest that methylation of DNA in response to stress leads to the variation in phenotype. Transposon mobility, siRNA-mediated methylation and host methyltransferase activation have been implicated in this process. This review presents the current status of epigenetics of plant stress responses with a view to use this knowledge towards engineering plants for stress tolerance. 相似文献
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Manoj Cheriyan Chandra Sekhar Pedamallu Kazuo Tori Francine Perler 《The Journal of biological chemistry》2013,288(9):6202-6211
Inteins are naturally occurring intervening sequences that catalyze a protein splicing reaction resulting in intein excision and concatenation of the flanking polypeptides (exteins) with a native peptide bond. Inteins display a diversity of catalytic mechanisms within a highly conserved fold that is shared with hedgehog autoprocessing proteins. The unusual chemistry of inteins has afforded powerful biotechnology tools for controlling enzyme function upon splicing and allowing peptides of different origins to be coupled in a specific, time-defined manner. The extein sequences immediately flanking the intein affect splicing and can be defined as the intein substrate. Because of the enormous potential complexity of all possible flanking sequences, studying intein substrate specificity has been difficult. Therefore, we developed a genetic selection for splicing-dependent kanamycin resistance with no significant bias when six amino acids that immediately flanked the intein insertion site were randomized. We applied this selection to examine the sequence space of residues flanking the Nostoc punctiforme Npu DnaE intein and found that this intein efficiently splices a much wider range of sequences than previously thought, with little N-extein specificity and only two important C-extein positions. The novel selected extein sequences were sufficient to promote splicing in three unrelated proteins, confirming the generalizable nature of the specificity data and defining new potential insertion sites for any target. Kinetic analysis showed splicing rates with the selected exteins that were as fast or faster than the native extein, refuting past assumptions that the naturally selected flanking extein sequences are optimal for splicing. 相似文献
27.
The incidence of salinity-induced plant stress as a result of natural and anthropogenic factors in arid and semi-arid agricultural lands is great. In South Africa alone, 9 % of irrigated agricultural land is salt-affected. Commercial fertilizers used for improving soil nutrient levels are costly and affect the quality, lifespan and sustainability of soil and water resources. Organic farming practices are based on cost-effective and environmentally-aware management systems. Vermicompost leachate (VCL) is a vermicompost-derived liquid product that has become recognised as a suitable soil amendment product. Commercial tomato (Lycopersicon esculentum Mill var. Heinz-1370) seedlings were subjected to sodium chloride (NaCl) concentrations of 0, 25, 50 and 100 mM and were treated with 1:10 (v/v) WizzardWorms VCL prepared in Hoagland’s nutrient solution under greenhouse conditions. Morphological characters of VCL-treated tomato seedlings showed improved root growth and stimulated overall aboveground growth with significantly higher numbers of leaves, greater stem thickness and increased leaf area, even at a high NaCl-tested concentration (100 mM). The accumulation of compatible solutes such as proline and total soluble sugars indicate an induced salt tolerance or adaptive mechanism in VCL-treated tomato seedlings. The current investigation demonstrates the potential of an organic liquid to maximise tomato productivity by improving seedling growth performance under salt stress conditions. 相似文献
28.
Manoj Bhosale Anujith Kumar Mrinmoy Das Chetana Bhaskarla Vikas Agarwal Dipankar Nandi 《Microbiological research》2013,168(1):56-64
Peptidase N (PepN), the sole M1 family member in Escherichia coli, displays broad substrate specificity and modulates stress responses: it lowers resistance to sodium salicylate (NaSal)-induced stress but is required during nutritional downshift and high temperature (NDHT) stress. The expression of PepN does not significantly change during different growth phases in LB or NaSal-induced stress; however, PepN amounts are lower during NDHT stress. To gain mechanistic insights on the roles of catalytic activity of PepN in modulating these two stress responses, alanine mutants of PepN replacing E264 (GAMEN motif) and E298 (HEXXH motif) were generated. There are no major structural changes between purified wild type (WT) and mutant proteins, which are catalytically inactive. Importantly, growth profiles of ΔpepN upon expression of WT or mutant proteins demonstrated the importance of catalytic activity during NDHT but not NaSal-induced stress. Further fluorescamine reactivity studies demonstrated that the catalytic activity of PepN is required to generate higher intracellular amounts of free N-terminal amino acids; consequently, the lower growth of ΔpepN during NDHT stress increases with high amounts of casamino acids. Together, this study sheds insights on the expression and functional roles of the catalytic activity of PepN during adaptation to NDHT stress. 相似文献
29.
Sami Khanal Robert P. Anex Christopher J. Anderson Daryl E. Herzmann Manoj K. Jha 《Global Change Biology Bioenergy》2013,5(6):713-722
Large‐scale conversion of traditional agricultural cropping systems to biofuel cropping systems is predicted to have significant impact on the hydrologic cycle. Changes in the hydrologic cycle lead to changes in rainfall and its erosive power, and consequently soil erosion that will have onsite impacts on soil quality and crop productivity, and offsite impacts on water quality and quantity. We examine regional change in rainfall erosivity and soil erosion resulting from biofuel policy‐induced land use/land cover (LULC) change. Regional climate is simulated under current and biofuel LULC scenarios for the period 1979–2004 using the Weather Research Forecast (WRF) model coupled to the NOAH land surface model. The magnitude of change in rainfall erosivity under the biofuel scenario is 1.5–3 times higher than the change in total annual rainfall. Over most of the conterminous United States (~56%), the magnitude of the change in erosivity is between ?2.5% and +2.5%. A decrease in erosivity of magnitude 2.5–10% is predicted over 23% of the area, whereas an increase of the same magnitude is predicted over 14% of the area. Corresponding to the changes in rainfall erosivity and crop cover, a decrease in soil loss is predicted over 60% of the area under the biofuel scenario. In Kansas and Oklahoma, the states in which a large fraction of land area is planted with switchgrass under the biofuel scenario, soil loss is estimated to decrease 12% relative to the baseline. This reduction in soil loss is due more to changes in the crop cover factor than changes in rainfall or rainfall erosivity. This indicates that the changes in LULC, due to future cellulosic biofuel feedstock production, can have significant implications for regional soil and water resources in the United States and we recommend detailed investigation of the trade‐offs between land use and management options. 相似文献
30.
Manoj K. Mishra Pankaj Chaturvedi Ruchi Singh Gaurav Singh Lokendra K. Sharma Vibha Pandey Nishi Kumari Pratibha Misra 《PloS one》2013,8(4)