Functional interactions of the Tax and p13 proteins of Human T-cell Leukemia Virus Type I

Human 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

The Use of Dining Data to Increase Retention and Academic Success in Residential First-Year Students

Higher education leaders have been conducting research over the last 50 years to pinpoint why students enroll in college and then end up leaving. Research shows that there is not a single factor that influences a student’s decision, but it is a variety of factors. Influential factors include class attendance, a sense of belonging, motivation, academic rigor and performance, finances, and more. A student’s physical wellness and mental state can also impact their academic success and life while in college. First-year students often experience depression, anxiety, and loneliness as they try to successfully transition to college. Most of these influential factors are quantified and measured by institutions in real-time through predictive analytics to identify students at risk of leaving. One data point that has not been thoroughly researched is dining data. This non-experimental, causal-comparison study investigated the relationship between dining data and academic success and retention. Analysis of the data showed that dining data can predict academic success and retention, however, the strongest correlation existed between a significant change in dining habits predicting persistence into the next semester. The findings indicate that dining data should be collected by institutions and integrated into predictive analytics to identify at-risk students. Further research should be conducted to generalize the use of dining data in predictive analytics as well as investigate how dining data can be paired with other data points to further identify students in need of assistance

What information could the main actors of liquid biopsy provide? A representative case of non-small cell lung cancer (NSCLC)

In 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

Virtualized eNB Latency Limits

In flexible functional split, functions of a virtualized evolved NodeB (eNB) can be disaggregated in distributed computational resources. One of the main constraints for their placement is the latency experienced by the communication between the Virtual Machines (VM) hosting the functions. This paper evaluates experimentally the latency limits for different functional splits providing insights on flexible functional split implementationThis work has been partially funded by the EU H2020 5G-Transformer Project (grant no. 761536

La pratica filosofica: una possibile genealogia

Lo scritto si pone l’obiettivo di una ricostruzione genealogica della filosofia intesa come pratica; in questo tentativo, si cerca di mettere in evidenza il ruolo fondamentale che ha rivestito l’avvento della scienza. Più precisamente, la tesi che il presente lavoro vuole proporre è che l’impresa scientifica abbia portato alla luce, intrecciandoli in vario modo, tre elementi essenziali per questa genealogia, ovvero il tempo, la prassi e il concetto di relazione.The philosophical practice: a possible genealogyAim of this writing is to give a genealogical reconstruction of philosophy meant as practice; in this attempt, we try to point out the fundamental role played by the coming of science. More precisely, according to the thesis proposed by the present work, the scientific practice brought to light, weaving them together, three essential elements for this genealogy: time, praxis and the concept of relation

La tassazione diretta nel Regno di Napoli tra la fine del XIII e la metà del XV secolo: la Basilicata angioina e aragonese in una prospettiva comparativa

L'articolo mira ad investigare il sistema della tassazione diretta («subventio generalis» o «collectae») nell’Italia meridionale durante il Medioevo, con particolare attenzione alla provincia amministrativa della Basilicata nel periodo della dominazione angioina e aragonese da Alfonso il Magnanimo a Ferdinando I di Napoli, attraverso una ricerca documentaria nei Registi della Cancelleria angioina, nell’Archivo de la Corona de Aragón e nell’Archivo de la Ciudad de Barcelona. This article points to investigate direct taxation («subventio generalis» or «collectae») in late medieval southern Italy, paying specific attention to the province of Basilicata during Angevin and Aragonese domination (from Alfonso the Magnanimous to Ferdinand I of Naples), through a documentary research in the Registri della cancelleria angioina, in the Archivo de la Corona de Aragón and in the Archivo de la Ciudad de Barcelona

Knowledge Graph Completion to Predict Polypharmacy Side Effects

The polypharmacy side effect prediction problem considers cases in which two drugs taken individually do not result in a particular side effect; however, when the two drugs are taken in combination, the side effect manifests. In this work, we demonstrate that multi-relational knowledge graph completion achieves state-of-the-art results on the polypharmacy side effect prediction problem. Empirical results show that our approach is particularly effective when the protein targets of the drugs are well-characterized. In contrast to prior work, our approach provides more interpretable predictions and hypotheses for wet lab validation.Comment: 13th International Conference on Data Integration in the Life Sciences (DILS2018