22 research outputs found
The hepatitis C viral nonstructural protein 5A stabilizes growth-regulatory human transcripts
Numerous mammalian proto-oncogene and other growth-regulatory transcripts are upregulated in malignancy due to abnormal mRNA stabilization. In hepatoma cells expressing a hepatitis C virus (HCV) subgenomic replicon, we found that the viral nonstructural protein 5A (NS5A), a protein known to bind to viral RNA, also bound specifically to human cellular transcripts that encode regulators of cell growth and apoptosis, and this binding correlated with transcript stabilization. An important subset of human NS5A-target transcripts contained GU-rich elements, sequences known to destabilize mRNA. We found that NS5A bound to GU-rich elements in vitro and in cells. Mutation of the NS5A zinc finger abrogated its GU-rich element-binding and mRNA stabilizing activities. Overall, we identified a molecular mechanism whereby HCV manipulates host gene expression by stabilizing host transcripts in a manner that would promote growth and prevent death of virus-infected cells, allowing the virus to establish chronic infection and lead to the development of hepatocellular carcinoma. © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research
Individual expression features of GPX2, NQO1 and SQSTM1 transcript variants induced by hydrogen peroxide treatment in HeLa cells
Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation
Turning a molecule into a coherent two-level quantum system
The use of molecules in quantum optical applications has been hampered by incoherent internal vibrations and other phononic interactions with their environment. Here we show that an organic molecule placed into an optical microcavity behaves as a coherent two-level quantum system. This allows the observation of 99% extinction of a laser beam by a single molecule, saturation with less than 0.5 photons and non-classical generation of few-photons super-bunched light. Furthermore, we demonstrate efficient interaction of the molecule–microcavity system with single photons generated by a second molecule in a distant laboratory. Our achievements represent an important step towards linear and nonlinear quantum photonic circuits based on organic platforms
Nanoscopic charge fluctuations in a gallium phosphide waveguide measured by single molecules
We present efficient coupling of single organic molecules to a gallium phosphide subwavelengthwaveguide (nanoguide). By examining and correlating the temporal dynamics of various single-molecule resonances at different locations along the nanoguide, we reveal light-induced fluctuationsof their Stark shifts. Our observations are consistent with the predictions of a simple model basedon the optical activation of a small number of charges in the GaP nanostructure
The hepatitis C viral nonstructural protein 5A stabilizes growth-regulatory human transcripts
RNA-binding protein CELF6 is cell cycle regulated and controls cancer cell proliferation by stabilizing p21
Genome-wide shRNA screen reveals increased mitochondrial dependence upon mTORC2 addiction
Release from growth factor dependence and acquisition of signalling pathway addiction are critical steps in oncogenesis. To identify genes required on mammalian target of rapamycin (mTOR) addiction, we performed a genome-wide short hairpin RNA screen on a v-H-ras-transformed Pten-deficient cell line that displayed two alternative growth modes, interleukin (IL)-3-independent/mTOR-addicted proliferation (transformed growth mode) and IL-3-dependent/mTOR-non-addicted proliferation (normal growth mode). We screened for genes required only in the absence of IL-3 and thus specifically for the transformed growth mode. The top 800 hits from this conditional lethal screen were analyzed in silico and 235 hits were subsequently rescreened in two additional Pten-deficient cell lines to generate a core set of 47 genes. Hits included genes encoding mTOR and the mTOR complex 2 (mTORC2) component rictor and several genes encoding mitochondrial functions including components of the respiratory chain, adenosine triphosphate synthase, the mitochondrial ribosome and mitochondrial fission factor. Small interfering RNA knockdown against a sizeable fraction of these genes triggered apoptosis in human cancer cell lines but not in normal fibroblasts. We conclude that mTORC2-addicted cells require mitochondrial functions that may be novel drug targets in human cancer.Oncogene advance online publication, 20 December 2010; doi:10.1038/onc.2010.539
The influence of Latin on North Germanic languages, especially on Norwegian
The thesis concentrates on Latin influence on North Germanic languages, especially on Norwegian. First part deals with this topic from sociolinguistic point of view: relationship between Latin and domestic languages in Middle Ages, discerning contexts, where Latin was used, emphasizing the role of church, schools and literature. Second part concentrates on concrete examples of Latin influence, persisting to the modern times, especially loanwords, prefixes and suffixes, irregular declension, idioms. Original research concentrates on Norwegian letters from Middle Age, in Diplomatarium Norwegicum. Research about numbers of Latin letters and letters in domestic language, according to topic and time, in comparison with similar informations from Denmark and Sweden