Aims: The BRAFV600E oncogene, reported in 40-60% of papillary thyroid carcinoma (PTC), has an important role in the pathogenesis of PTC. It is associated with the loss of thyroid iodide-metabolizing genes, such as sodium/iodide symporter (NIS) and therefore with radioiodide-refractoriness. Inhibition of MAPK pathway, constitutively activated by BRAFV600E, is not always efficient in resistant tumors suggesting that other compensatory mechanisms contribute to a BRAFV600E adaptive resistance. Recent studies pointed to a key role of TGF-β in BRAFV600E-induced effects. The reactive oxygene species (ROS)-generating NADPH oxidase NOX4, which is increased in PTC, has been identified as a new key effector of TGF-β in cancer, suggestive of a potential role in BRAFV600E-induced thyroid tumors. Results: Here, using two human BRAFV600E mutated thyroid cell lines and a rat thyroid cell line expressing BRAFV600E in a conditional manner we show that NOX4 up-regulation is controlled at the transcriptional level by the oncogene via the TGF-β/Smad3 signaling pathway. Importantly, treatment of cells with NOX4-targeted siRNA downregulates BRAFV600E-induced NIS repression. Innovation and Conclusion: Our results establish a link between BRAFV600E and NOX4, which is confirmed by a comparative analysis of NOX4 expression in human (TCGA) and mouse thyroid cancers. Remarkably, analysis of human and murine BRAFV600E-mutated thyroid tumors highlights that the level of NOX4 expression is inversely correlated to thyroid differentiation suggesting that other genes involved in thyroid differentiation in addition to NIS might be silenced by a mechanism controlled by NOX4-derived ROS. This study opens a new opportunity to optimize thyroid cancer therapy
1 March 2012 in International Journal of Phytoremediation
The aim of this work was to test Lupinus luteus plants, inoculated with metal resistant rhizobacteria, in order to phytostabilise metals in contaminated soils. The resistance to heavy metals of strains isolated from nodules of Lupinus plants was evaluated. The strain MSMC541 showed multi-resistance to several metals (up to 13.3 mM As, 2.2 mM Cd, 2.3 mM Cu, 9 mM Pb and 30 mM Zn), and it was selected for further characterization. Furthermore, this strain was able to biosorb great amounts of metals in cell biomass. 16S rDNA sequencing positioned this strain within the genus Serratia. The presence of arsenic resistance genes was confirmed by southern blot and PCR amplification. A rhizoremediation pot experiment was conducted using Lupinus luteus grown on sand supplemented with heavy metals and inoculated with MSMC541. Plant growth parameters and metal accumulation were determined in inoculated vs. non-inoculated Lupinus luteus plants. The results showed that inoculation with MSMC541 improved the plant tolerance to metals. At the same time, metal translocation to the shoot was significantly reduced upon inoculation. These results suggest that Lupinus luteus plants, inoculated with the metal resistant strain Serratia sp. MSMC541, have a great potential for phytostabilization of metal contaminated soils.
Heat stress occurring during the reproductive stage of wheat has a detrimental effect on productivity. A durum wheat core set was exposed to simulated terminal heat stress by applying plastic tunnels at the time of flowering over two seasons. Mean grain yield was reduced by 54% compared to control conditions, and grain number was the most critical trait for tolerance to this stress. The combined use of tolerance indices and grain yield identified five top performing elite lines: Kunmiki, Berghouata1, Margherita2, IDON37-141, and Ourgh. The core set was also subjected to genome wide association study using 7652 polymorphic single nucleotide polymorphism (SNPs) markers. The most significant genomic regions were identified in association with spike fertility and tolerance indices on chromosomes 1A, 5B, and 6B. Haplotype analysis on a set of 208 elite lines confirmed that lines that carried the positive allele at all three quantitative trait loci (QTLs) had a yield advantage of 8% when field tested under daily temperatures above 31° C. Three of the QTLs were successfully validated into Kompetitive Allele Specific PCR (KASP) markers and explained >10% of the phenotypic variation for an independent elite germplasm set. These genomic regions can now be readily deployed via breeding to improve resilience to climate change and increase productivity in heat-stressed areas.
The phenotypic characteristics of 48 isolates obtained from root nodules of four Acacia species (Acacia cyanophylla, A. gummifera, A. horrida and A. raddiana) growing in soils collected from the arid...
The objective of this study was to understand and characterize the physiological and biochemical tolerance mechanisms of Argania spinosa under drought stress for selection tolerant ecotypes. Significant differences were observed among ecotypes in indices of leaf water status studied: stomatal conductance (gs), predawn leaf water potential (Ψpd) and leaf relative water content. There was a significant decrease in these physiological traits with increasing degree of drought stress in all ecotypes. Drought stress significantly increased endogenous H2O2 and lipid peroxidation. Moderate and severe drought stress increased significantly the catalase, superoxide dismutase, peroxidase, polyphenoloxidase and lipoxygenase activities, depending on time. Their constitutive activities were higher in inland ecotypes than in coastal ecotypes. According to canonical discriminant analysis, the inland ecotypes were essentially distinguished from the coastal ecotypes by the following physiological and biochemical traits: Ψpd, gs, polyphenol oxidase, superoxide dismutase and malonyldialdehyde. Inland ecotypes seem to be more tolerant to drought stress than coastal ecotypes.