@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{RodriguezRicoYepesetal.2015,
  author    = {Rodriguez, H{\´e}ctor and Rico, Sergio and Yepes, Ana and Franco-Echevarr{\´i}a, Elsa and Antoraz, Sergio and Santamar{\´i}a, Ram{\´o}n I. and D{\´i}az, Margerita},
  title     = {The two kinases, AbrC1 and AbrC2, of the atypical two-component system AbrC are needed to regulate antibiotic production and differentiation in Streptomyces coelicolor},
  series = {Frontiers in Microbiology},
  volume    = {6},
  journal   = {Frontiers in Microbiology},
  number    = {450},
  doi       = {10.3389/fmicb.2015.00450},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143048},
  year      = {2015},
  abstract  = {Two-component systems (TCSs) are the most important sensing mechanisms in bacteria. In Streptomyces, TCSs-mediated responses to environmental stimuli are involved in the regulation of antibiotic production. This study examines the individual role of two histidine kinases (HKs), AbrC1 and AbrC2, which form part of an atypical TCS in Streptomyces coelicolor. gRT-PCR analysis of the expression of both kinases demonstrated that both are expressed at similar levels in NB and NMMP media. Single deletion of abrC1 elicited a significant increase in antibiotic production, while deletion of abrC2 did not have any clear effect. The origin of this phenotype, probably related to the differential phosphorylation ability of the two kinases, was also explored indirectly, analyzing the toxic phenotypes associated with high levels of phosphorylated RR. The higher the AbrC3 regulator phosphorylation rate, the greater the cell toxicity. For the first time, the present work shows in Streptomyces the combined involvement of two different HKs in the response of a regulator to environmental signals. Regarding the possible applications of this research, the fact that an abrC1 deletion mutant overproduces three of the S. coelicolor antibiotics makes this strain an excellent candidate as a host for the heterologous production of secondary metabolites.},
  language  = {en}
}
@article{TrafimowAmrheinAreshenkoffetal.2018,
  author    = {Trafimow, David and Amrhein, Valentin and Areshenkoff, Corson N. and Barrera-Causil, Carlos J. and Beh, Eric J. and Bilgi{\c{c}}, Yusuf K. and Bono, Roser and Bradley, Michael T. and Briggs, William M. and Cepeda-Freyre, H{\´e}ctor A. and Chaigneau, Sergio E. and Ciocca, Daniel R. and Correa, Juan C. and Cousineau, Denis and de Boer, Michiel R. and Dhar, Subhra S. and Dolgov, Igor and G{\´o}mez-Benito, Juana and Grendar, Marian and Grice, James W. and Guerrero-Gimenez, Martin E. and Guti{\´e}rrez, Andr{\´e}s and Huedo-Medina, Tania B. and Jaffe, Klaus and Janyan, Armina and Karimnezhad, Ali and Korner-Nievergelt, Fr{\"a}nzi and Kosugi, Koji and Lachmair, Martin and Ledesma, Rub{\´e}n D. and Limongi, Roberto and Liuzza, Marco T. and Lombardo, Rosaria and Marks, Michael J. and Meinlschmidt, Gunther and Nalborczyk, Ladislas and Nguyen, Hung T. and Ospina, Raydonal and Perezgonzalez, Jose D. and Pfister, Roland and Rahona, Juan J. and Rodr{\´i}guez-Medina, David A. and Rom{\~a}o, Xavier and Ruiz-Fern{\´a}ndez, Susana and Suarez, Isabel and Tegethoff, Marion and Tejo, Mauricio and van de Schoot, Rens and Vankov, Ivan I. and Velasco-Forero, Santiago and Wang, Tonghui and Yamada, Yuki and Zoppino, Felipe C. M. and Marmolejo-Ramos, Fernando},
  title     = {Manipulating the Alpha Level Cannot Cure Significance Testing},
  series = {Frontiers in Psychology},
  volume    = {9},
  journal   = {Frontiers in Psychology},
  number    = {699},
  issn      = {1664-1078},
  doi       = {10.3389/fpsyg.2018.00699},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189973},
  year      = {2018},
  abstract  = {We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable.},
  language  = {en}
}