Critical Role of the Virus-Encoded MicroRNA-155 Ortholog in the Induction of Marek's Disease Lymphomas

Notwithstanding the well-characterised roles of a number of oncogenes in neoplastic transformation, microRNAs (miRNAs) are increasingly implicated in several human cancers. Discovery of miRNAs in several oncogenic herpesviruses such as KSHV has further highlighted the potential of virus-encoded miRNAs to contribute to their oncogenic capabilities. Nevertheless, despite the identification of several possible cancer-related genes as their targets, the direct in vivo role of virus-encoded miRNAs in neoplastic diseases such as those induced by KSHV is difficult to demonstrate in the absence of suitable models. However, excellent natural disease models of rapid-onset Marek's disease (MD) lymphomas in chickens allow examination of the oncogenic potential of virus-encoded miRNAs. Using viruses modified by reverse genetics of the infectious BAC clone of the oncogenic RB-1B strain of MDV, we show that the deletion of the six-miRNA cluster 1 from the viral genome abolished the oncogenicity of the virus. This loss of oncogenicity appeared to be primarily due to the single miRNA within the cluster, miR-M4, the ortholog of cellular miR-155, since its deletion or a 2-nucleotide mutation within its seed region was sufficient to inhibit the induction of lymphomas. The definitive role of this miR-155 ortholog in oncogenicity was further confirmed by the rescue of oncogenic phenotype by revertant viruses that expressed either the miR-M4 or the cellular homolog gga-miR-155. This is the first demonstration of the direct in vivo role of a virus-encoded miRNA in inducing tumors in a natural infection model. Furthermore, the use of viruses deleted in miRNAs as effective vaccines against virulent MDV challenge, enables the prospects of generating genetically defined attenuated vaccines

A surface science study of the initial stages of hydrogen corrosion on uranium metal and the role played by grain microstructure

Controlled formation of UH3 on uranium metal surfaces was induced by a precisely limited uptake of hydrogen at 250 degrees C and 320 degrees C with 500 mbar H-2 pressure. The hydride (UH3) growth sites on the sample surfaces were studied using focused ion beam (FIB) milling with high resolution secondary electron imaging. Electron backscatter diffraction (EBSD) analysis was also used to examine grain orientation of the metal in the region of the corrosion sites.Results of the analysis indicated that the location of hydride sites was predominantly found to be associated with grain boundaries at the metal surface. In addition, FIB cross-sectioning of multiple hydride sites indicates the observed morphology of very small hydride growths to be consistent with nucleation at, and not beneath, the oxide-metal interface. Crown Copyright (c) 2013 Published by Elsevier B.V. All rights reserved.</p

An investigation of the reaction of uranium with nitrogen - A thermogravimetric analysis study

In this work, the heating corrosion reaction of uranium with dry air and with dry nitrogen gas was investigated. Metallic uranium samples of different specific surface area and mass were reacted in a thermogravimetric analysis system at temperature ramping from 323 K to 1273 K at 15 K.min −1 . Ignition was achieved during all heating profiles of the samples reacting with air, with the reported ignition temperature decreasing with increasing specific surface area. Heating cycles were conducted for the uranium and dry nitrogen gas system to investigate if ignition could be attained. These experiments were conducted by varying the specific surface area, sample mass, initial oxide thickness, nitrogen flow rate, and heating ramp rate. None of these experiments showed signs of clear ignition under dry nitrogen. It is hence suggested that uranium ignition under a dry nitrogen atmosphere is not readily attainable and would require a combination of extreme conditions, such as high heating ramp rate for a non-oxidised sample of high surface area and mass