Prediction of human targets for viral-encoded microRNAs by thermodynamics and empirical constraints

MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression through degradation of specific mRNAs and/or repression of their translation. miRNAs are involved in both physiological and pathological processes, such as apoptosis and cancer. Their presence has been demonstrated in several organisms as well as in viruses. Virus encoded miRNAs can act as viral gene expression regulators, but they may also interfere with the expression of host genes. Viral miRNAs may control host cell proliferation by targeting cell-cycle and apoptosis regulators. Therefore, they could be involved in cancer pathogenesis. Computational prediction of miRNA/target pairs is a fundamental step in these studies. Here, we describe the use of miRiam, a novel program based on both thermodynamics features and empirical constraints, to predict viral miRNAs/human targets interactions. miRiam exploits target mRNA secondary structure accessibility and interaction rules, inferred from validated miRNA/mRNA pairs. A set of genes involved in apoptosis and cell-cycle regulation was identified as target for our studies. This choice was supported by the knowledge that DNA tumor viruses interfere with the above processes in humans. miRNAs were selected from two cancer-related viruses, Epstein-Barr Virus (EBV) and Kaposi-Sarcoma-Associated Herpes Virus (KSHV). Results show that several transcripts possess potential binding sites for these miRNAs. This work has produced a set of plausible hypotheses of involvement of v-miRNAs and human apoptosis genes in cancer development. Our results suggest that during viral infection, besides the protein-based host regulation mechanism, a post-transcriptional level interference may exist. miRiam is freely available for downloading at http://ferrolab.dmi.unict.it/miriam

Factors predicting poor survival after resection of stage IA non–small cell lung cancer

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EFFICIENT SIMULATION TOOL TO CHARACTERIZE THE RADAR CROSS SECTION OF A PEDESTRIAN IN NEAR FIELD

none4A simulation tool to characterize the radar cross section of a pedestrian in near field is presented in the paper. The tool has been developed in order to predict and optimize the performance of the short-range radar systems employed in autonomous vehicle operations. It is based on an analytical model which joins the modeling of the human body with the theory of the physical optics. Our studies first focused on the implementation of the electromagnetic code where the human body, the radiation properties of the antenna and the scenario to be analyzed have been analytically expressed. Then, the proposed model has been validated in terms of accuracy comparing simulated and experimental data regarding the radar cross section of a metal sphere and of an adult, in the frequency range 23-28 GHz. In the end, an evaluation of the performance in terms of required computer memory and execution time has been carried out, comparing the proposed simulation tool with other numerical computational methods.openManfredi, Giovanni; Russo, Paola; De Leo, Alfredo; Cerri, GrazianoManfredi, Giovanni; Russo, Paola; De Leo, Alfredo; Cerri, Grazian

Waterborne outbreak of Norwalk-like virus gastroenteritis at a tourist resort, Italy.

In July 2000, an outbreak of gastroenteritis occurred at a tourist resort in the Gulf of Taranto in southern Italy. Illness in 344 people, 69 of whom were staff members, met the case definition. Norwalk-like virus (NLV) was found in 22 of 28 stool specimens tested. The source of illness was likely contaminated drinking water, as environmental inspection identified a breakdown in the resort water system and tap water samples were contaminated with fecal bacteria. Attack rates were increased (51.4%) in staff members involved in water sports. Relative risks were significant only for exposure to beach showers and consuming drinks with ice. Although Italy has no surveillance system for nonbacterial gastroenteritis, no outbreak caused by NLV has been described previously in the country

Estrogenic activity and cytotoxicity of six anticancer drugs detected in water systems

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Comprehensive reconstruction and visualization of non-coding regulatory networks in human

Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established online repositories. The interactions involve RNA, DNA, proteins and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command line and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape

Eco-genotoxicity of six anticancer drugs using comet assay in daphnids

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Mechanisms of antidiarrhoeal effects by diosmectite in human intestinal cells

Rotavirus (RV) induces diarrhoea through a sequence of enterotoxic and cytotoxic effects. The former are NSP4-dependent, induce calcium-dependent chloride secretion and involve oxidative stress. Diosmectite (DS) is a natural clay that has been recommended as an active therapy for diarrhoea, but the mechanism of its effect is not clear. Electrical parameters may be used to measure the direct enterotoxic and cytotoxic effects in polar epithelial intestinal cells. To investigate the effects of DS on RV-induced enterotoxic and cytotoxic damage. Caco-2 cells were used as a model of RV infection to evaluate chloride secretion, epithelial integrity, oxidative stress and viral infectivity in Ussing chambers

Enhancement of 5-FU sensitivity by the proapoptotic rpL3 gene in p53 null colon cancer cells through combined polymer nanoparticles

Colon cancer is one of the leading causes of cancer-related death worldwide and the therapy with 5-fluorouracil (5-FU) is mainly limited due to resistance. Recently, we have demonstrated that nucleolar stress upon 5-FU treatment leads to the activation of ribosome-free rpL3 (L3) as proapoptotic factor. In this study, we analyzed L3 expression profile in colon cancer tissues and demonstrated that L3 mRNA amount decreased with malignant progression and the intensity of its expression was inversely related to tumor grade and Bcl-2/Bax ratio. With the aim to develop a combined therapy of 5-FU plus plasmid encoding L3 (pL3), we firstly assessed the potentiation of the cytotoxic effect of 5-FU on colon cancer cells by L3. Next, 10 μM 5-FU and 2 μg of pL3 were encapsulated in biocompatible nanoparticles (NPs) chemically conjugated with HA to achieve active tumor-targeting ability in CD44 overexpressing cancer cells. We showed the specific intracellular accumulation of NPs in cells and a sustained release for 5-FU and L3. Analysis of cytotoxicity and apoptotic induction potential of combined NPs clearly showed that the 5-FU plus L3 were more effective in inducing apoptosis than 5-FU or L3 alone. Furthermore, we show that the cancer-specific chemosensitizer effect of combined NPs may be dependent on L3 ability to affect 5-FU efflux by controlling P-gp (P-glycoprotein) expression. These results led us to propose a novel combined therapy with the use of 5-FU plus L3 in order to establish individualized therapy by examining L3 profiles in tumors to yield a better clinical outcomes

Acute and chronic toxicity of six anticancer drugs on rotifers and crustaceans

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