104 research outputs found
Functional interactions of the Tax and p13 proteins of Human T-cell Leukemia Virus Type I
No full textHuman T-cell leukemia virus type 1 (HTLV-1) establishes a lifelong persistent infection in humans. Approximately 3% of the infected individuals will develop adult T-cell leukemia/lymphoma (ATLL), an aggressive malignancy of mature CD4+ T-cells. The viral protein Tax plays a major role in HTLV-1 pathogenicity by activating the NF-κB pathway. Tax activates both the canonical and non-canonical NF-κB pathways, promoting NF-κB translocation to the nucleus and transcription of genes that favour T-cell proliferation and survival. Our previous studies showed that the p13 protein of HTLV-1 enhances mitochondrial ROS production, resulting in activation of normal T-cells. ROS constitute a homeostatic rheostat that controls the activity of several key pathways, including the NF-κB pathway.Thus, we hypothesized that the effects of p13 on ROS production could affect the activation of the NF-κB pathway by Tax in primary T-cells.
The work described in the present thesis was aimed at testing the hypothesis that Tax and p13 might act in concert to activate the NF-κB signal transduction pathway in primary T-cells. To this end, we optimized a transfection protocol for primary T-cells using an innovative approach based on the electroporation of in vitro-transcribed RNA. Activation of the NF-κB pathway was then analysed by measuring expression of the NF-κB target genes CD25 and 4-1BB.
Results showed that the co-transfection of Tax and p13 resulted in a synergistic activation of the NF-κB pathway in primary T-cells measured as an increase in the expression levels of both CD25 and 4-1BB. In addition to being a transcriptional target of NF-κB, CD25 is also an early marker of T-cell activation. To further test the effects of Tax and p13 on cell activation, we measured CD38 expression by flow cytometry. Jurkat T-cells, which exhibit a constitutively activated CD38 positive phenotype, were used as a control. Results of this analysis confirmed the synergy of Tax and p13, although the effect was not so prominent as that observed for the CD25 marker, suggesting that, within the time frame of our experiments, Tax and p13 drove T-cells to an early-intermediate stage of activation.
Taken together, these findings suggest that, in contrast to the well-established role of Tax as an activator of the NF-κB pathway in tumor cell lines, in the context of normal T-cells, the induction of NF-κB target genes requires the concerted action of Tax and p13.
Current studies are aimed at verifying the ROS-dependence of this effect and testing the functional interaction of Tax and p13 in the context of the complete HTLV-1 genome using wild type HTLV-1 and a p13-knock-out HTLV-1 molecular clone. These experiments will be carried out in primary T-cells as well as in dendritic cells, which have recently emerged as an important target of the virus in vivo
Decreasing handoff-related care failures in children\u27s hospitals
No full textBigham, M. T., Logsdon, T. R., Manicone, P. E., Landrigan, C. P., Hayes, L. W., Randall, K. H., . . . Sharek, P. J. (2014). Decreasing handoff-related care failures in children\u27s hospitals. Pediatrics, 134(2), e572-e579
What information could the main actors of liquid biopsy provide? A representative case of non-small cell lung cancer (NSCLC)
No full textIn non-small cell lung cancer (NSCLC), there is a consensus regarding the use of liquid biopsy, generally, to detect "druggable" mutations and, in particular, to monitor tyrosine kinase inhibitor (TKI) treatments. However, whether circulating tumor cells (CTCs) are better tools than cell-free DNA (cfDNA), is still a matter of debate, mainly concerning which antigen(s) we should use to investigating simultaneously both epithelial and epithelial-to-mesenchymal transient (EMT) phenotype in the same sample of CTCs. To address this item, we exploited here a single-tube liquid biopsy, to detect both epithelial cell adhesion molecule (EpCAM)-positive CTCs and EpCAM-low/negative CTCs, because down-modulation of EpCAM is considered the first step in EMT. Furthermore, we analyzed the DNA from CTCs of four different phenotypes (ctcDNA), according to their EpCAM expression and cytokeratin pattern, and circulating tumor DNA (ctDNA) by droplet digital PCR (ddPCR), in order to disclose activating and resistancedriving mutations. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution
Carriers of the TCF7L2 rs7903146 variant with GMD have an increate risk of developing impaired glucose regulation after pregnancy.
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Sustainable irrigation strategy in fruit orchards: environmental impact at farm scale
No full textClimate change is gradually affecting regional and global food production. Warming temperatures and a greater incidence and intensity of extreme weather events may lead to significant reductions in crop yields. The LIFE AgroClimaWater project provides adaptation strategies to increase water productivity in fruit orchards, reducing pollution and resource use.
Experimental trials were conducted in fruit orchards of citrus, peach and olive, that were divided into two plots: one managed with sustainable practices (no soil tillage, compost addition, mulching of pruning residues, cover crops and guided irrigation through optimized water balance, reduced Kc and monitoring of soil moisture) and another one traditionally managed (weeding, empirical addition of mineral fertilizers and empirical irrigation).
Effectiveness of cultivation practices applied in sustainable plots was assessed by Water Productivity (WP), Water Footprint (WF), Nutrient Use Efficiency (NUE); these parameters and indicators were compared to conventionally managed plots.
Results revealed that the sustainable management leads to a maximum decrease of 11.64% in the WF, an increase in the WP till 13.28% and a nitrogen use efficiency (NUE) greater than 3 times in the sustainable orchard compared to the conventional one.
The adoption of optimized irrigation management at farm scale, if properly adopted, could reduce the environmental impact at territorial level, increasing fruit quality and water productivity, with beneficial effect on natural resources (soil and water) conservation and restoration
Sustainable irrigation strategy in fruit orchards: environmental impact at farm scale
No full textClimate change is gradually affecting regional and global food production. Warming temperatures and a greater incidence and intensity of extreme weather events may lead to significant reductions in crop yields. The LIFE AgroClimaWater project provides adaptation strategies to increase water productivity in fruit orchards, reducing pollution and resource use. Experimental trials were conducted in fruit orchards of citrus, peach and olive, that were divided into two plots: one managed with sustainable practices (no soil tillage, compost addition, mulching of pruning residues, cover crops and guided irrigation through optimized water balance, reduced Kc and monitoring of soil moisture) and another one traditionally managed (weeding, empirical addition of mineral fertilizers and empirical irrigation). Effectiveness of cultivation practices applied in sustainable plots was assessed by water productivity (WP), water footprint (WF), nutrient use efficiency (NUE); these parameters and indicators were compared to conventionally managed plots. Results revealed that the sustainable management leads to a maximum decrease of 11.64% in the WF, an increase in the WP till 13.28% and a nitrogen use efficiency (NUE) greater than 3 times in the sustainable orchard compared to the conventional one. The adoption of optimized irrigation management at farm scale, if properly adopted, could reduce the environmental impact at territorial level, increasing fruit quality and water productivity, with beneficial effect on natural resources (soil and water) conservation and restoration
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