@article{JunGholamiSongetal.2014,
  author    = {Jun, Kyong-Hwa and Gholami, Spedideh and Song, Tae-Jin and Au, Joyce and Haddad, Dana and Carson, Joshua and Chen, Chun-Hao and Mojica, Kelly and Zanzonico, Pat and Chen, Nanhai G. and Zhang, Qian and Szalay, Aladar and Fong, Yuman},
  title     = {A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter},
  series = {Journal of Experimental \& Clinical Cancer Research},
  volume    = {33},
  journal   = {Journal of Experimental \& Clinical Cancer Research},
  number    = {2},
  issn      = {1756-9966},
  doi       = {10.1186/1756-9966-33-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117716},
  year      = {2014},
  abstract  = {Background: Gastric cancers have poor overall survival despite recent advancements in early detection methods, endoscopic resection techniques, and chemotherapy treatments. Vaccinia viral therapy has had promising therapeutic potential for various cancers and has a great safety profile. We investigated the therapeutic efficacy of a novel genetically-engineered vaccinia virus carrying the human sodium iodide symporter (hNIS) gene, GLV-1 h153, on gastric cancers and its potential utility for imaging with Tc-99m pertechnetate scintigraphy and I-124 positron emission tomography (PET). Methods: GLV-1 h153 was tested against five human gastric cancer cell lines using cytotoxicity and standard viral plaque assays. In vivo, subcutaneous flank tumors were generated in nude mice with human gastric cancer cells, MKN-74. Tumors were subsequently injected with either GLV-1 h153 or PBS and followed for tumor growth. Tc-99m pertechnetate scintigraphy and I-124 microPET imaging were performed. Results: GFP expression, a surrogate for viral infectivity, confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1, GLV-1 h153 achieved > 90\% cytotoxicity in MNK-74, OCUM-2MD3, and AGS over 9 days, and >70\% cytotoxicity in MNK-45 and TMK-1. In vivo, GLV-1 h153 was effective in treating xenografts (p < 0.001) after 2 weeks of treatment. GLV-1 h153-infected tumors were readily imaged by Tc-99m pertechnetate scintigraphy and I-124 microPET imaging 2 days after treatment. Conclusions: GLV-1 h153 is an effective oncolytic virus expressing the hNIS protein that can efficiently regress gastric tumors and allow deep-tissue imaging. These data encourages its continued investigation in clinical settings.},
  language  = {en}
}
@article{RicoYepesRodriguezetal.2014,
  author    = {Rico, Sergio and Yepes, Ana and Rodriguez, Hector and Santamaria, Jorge and Antoraz, Sergio and Krause, Eva M. and Diaz, Margarita and Santamaria, Ramon I.},
  title     = {Regulation of the AbrA1/A2 Two-Component System in Streptomyces coelicolor and the Potential of Its Deletion Strain as a Heterologous Host for Antibiotic Production},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {10},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0109844},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115151},
  pages     = {e109844},
  year      = {2014},
  abstract  = {The Two-Component System (TCS) AbrA1/A2 from Streptomyces coelicolor M145 is a negative regulator of antibiotic production and morphological differentiation. In this work we show that it is able to auto-regulate its expression, exerting a positive induction of its own operon promoter, and that its activation is dependent on the presence of iron. The overexpression of the abrA2 response regulator (RR) gene in the mutant DabrA1/A2 results in a toxic phenotype. The reason is an excess of phosphorylated AbrA2, as shown by phosphoablative and phosphomimetic AbrA2 mutants. Therefore, non-cognate histidine kinases (HKs) or small phospho-donors may be responsible for AbrA2 phosphorylation in vivo. The results suggest that in the parent strain S. coelicolor M145 the correct amount of phosphorylated AbrA2 is adjusted through the phosphorylation-dephosphorylation activity rate of the HK AbrA1. Furthermore, the ABC transporter system, which is part of the four-gene operon comprising AbrA1/A2, is necessary to de-repress antibiotic production in the TCS null mutant. Finally, in order to test the possible biotechnological applications of the DabrA1/A2 strain, we demonstrate that the production of the antitumoral antibiotic oviedomycin is duplicated in this strain as compared with the production obtained in the wild type, showing that this strain is a good host for heterologous antibiotic production. Thus, this genetically modified strain could be interesting for the biotechnology industry.},
  language  = {en}
}
@article{ZukherNovikovaTikhonovetal.2014,
  author    = {Zukher, Inna and Novikova, Maria and Tikhonov, Anton and Nesterchuk, Mikhail V. and Osterman, Ilya A. and Djordjevic, Marko and Sergiev, Petr V. and Sharma, Cynthia M. and Severinov, Konstantin},
  title     = {Ribosome-controlled transcription termination is essential for the production of antibiotic microcin C},
  series = {Nucleic Acids Research},
  volume    = {42},
  journal   = {Nucleic Acids Research},
  number    = {19},
  issn      = {0305-1048},
  doi       = {10.1093/nar/gku880},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114839},
  pages     = {11891-11902},
  year      = {2014},
  abstract  = {Microcin C (McC) is a peptide-nucleotide antibiotic produced by Escherichia coli cells harboring a plasmid-borne operon mccABCDE. The heptapeptide MccA is converted into McC by adenylation catalyzed by the MccB enzyme. Since MccA is a substrate for MccB, a mechanism that regulates the MccA/MccB ratio likely exists. Here, we show that transcription from a promoter located upstream of mccA directs the synthesis of two transcripts: a short highly abundant transcript containing the mccA ORF and a longer minor transcript containing mccA and downstream ORFs. The short transcript is generated when RNA polymerase terminates transcription at an intrinsic terminator located in the intergenic region between the mccA and mccB genes. The function of this terminator is strongly attenuated by upstream mcc sequences. Attenuation is relieved and transcription termination is induced when ribosome binds to the mccA ORF. Ribosome binding also makes the mccA RNA exceptionally stable. Together, these two effects-ribosome induced transcription termination and stabilization of the message-account for very high abundance of the mccA transcript that is essential for McC production. The general scheme appears to be evolutionary conserved as ribosome-induced transcription termination also occurs in a homologous operon from Helicobacter pylori.},
  language  = {en}
}