Differential miRNA expression profiling reveals miR-205-3p to be a potential radiosensitizer for low- dose ionizing radiation in DLD-1 cells

Indexación: Scopus.Departamento de Oncología Básico-Clínica, Facultad de Medicina, Universidad de Chile, Santiago, Chile 2Comisión Chilena de Energía Nuclear, Santiago, Chile 3Center for Research and Applications in Plasma Physics and Pulsed Power, P4, Chile 4Departamento de Ciencias Físicas, Universidad Andres Bello, Santiago, Chile 5Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile 6Current Address: Center of Excellence in Precision Medicine, Pfizer, Chile. on IR responsive modeling. This work was supported by Anillo grant ACT1115 and ACT172101, PIA Program, CONICYT; the Chilean doctoral fellowship 21130246Enhanced radiosensitivity at low doses of ionizing radiation (IR) (0.2 to 0.6 Gy) has been reported in several cell lines. This phenomenon, known as low doses hyperradiosensitivity (LDHRS), appears as an opportunity to decrease toxicity of radiotherapy and to enhance the effects of chemotherapy. However, the effect of low single doses IR on cell death is subtle and the mechanism underlying LDHRS has not been clearly explained, limiting the utility of LDHRS for clinical applications. To understand the mechanisms responsible for cell death induced by low-dose IR, LDHRS was evaluated in DLD-1 human colorectal cancer cells and the expression of 80 microRNAs (miRNAs) was assessed by qPCR array. Our results show that DLD-1 cells display an early DNA damage response and apoptotic cell death when exposed to 0.6 Gy. miRNA expression profiling identified 3 over-expressed (miR-205-3p, miR-1 and miR-133b) and 2 downregulated miRNAs (miR-122-5p, and miR-134-5p) upon exposure to 0.6 Gy. This miRNA profile differed from the one in cells exposed to high-dose IR (12 Gy), supporting a distinct low-dose radiation-induced cell death mechanism. Expression of a mimetic miR- 205-3p, the most overexpressed miRNA in cells exposed to 0.6 Gy, induced apoptotic cell death and, more importantly, increased LDHRS in DLD-1 cells. Thus, we propose miR-205-3p as a potential radiosensitizer to low-dose IR. © Andaur et al.http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=25405&path[]=7956

Gluino signals in 4jet events and vertex tagging at LEP1

Heavy flavour tagging provides a broad range of possibilities in testing QCD features at LEP. We present here a study of 4jets events at LEP I where the so-called light gluinos could be directly produced. We show that microvertex techniques offer a unique chance to exploit simple kinematical distributions in order to optimise the signal coming from gluino production with respect to the background of ordinary QCD events. Our results indicate that experimental analyses along the lines suggested here can exclude or reveal the presence of a gluino for masses up to 10 GeV and lifetimes below 10$^{-9}$ sec. We also point out that a large fraction of gluino events could decay in configurations carrying large missing energy, so to escape the usual selection criteria of 4jet samples. In our study, mass effects of quarks and gluinos have been taken into account exactly. Our results are independent from both the jet algorithm and its resolution parameter.}Comment: 28 pages, 9 figures embedded with epsfig, Latex. Major revision taking into account latest bounds. Version to appear in Zeit. f. Phys.

Mesoscopic Model for Free Energy Landscape Analysis of DNA sequences

A mesoscopic model which allows us to identify and quantify the strength of binding sites in DNA sequences is proposed. The model is based on the Peyrard-Bishop-Dauxois model for the DNA chain coupled to a Brownian particle which explores the sequence interacting more importantly with open base pairs of the DNA chain. We apply the model to promoter sequences of different organisms. The free energy landscape obtained for these promoters shows a complex structure that is strongly connected to their biological behavior. The analysis method used is able to quantify free energy differences of sites within genome sequences.Comment: 7 pages, 5 figures, 1 tabl

Comparative Transcriptomics of Rice Genotypes with Contrasting Responses to Nitrogen Stress Reveals Genes Influencing Nitrogen Uptake through the Regulation of Root Architecture

The indiscriminate use of nitrogenous fertilizers continues unabated for commercial crop production, resulting in air and water pollution. The development of rice varieties with enhanced nitrogen use efficiency (NUE) will require a thorough understanding of the molecular basis of a plant\u27s response to low nitrogen (N) availability. The global expression profiles of root tissues collected from low and high N treatments at different time points in two rice genotypes, Pokkali and Bengal, with contrasting responses to N stress and contrasting root architectures were examined. Overall, the number of differentially expressed genes (DEGs) in Pokkali (indica) was higher than in Bengal (japonica) during low N and early N recovery treatments. Most low N DEGs in both genotypes were downregulated whereas early N recovery DEGs were upregulated. Of these, 148 Pokkali-specific DEGs might contribute to Pokkali\u27s advantage under N stress. These DEGs included transcription factors and transporters and were involved in stress responses, growth and development, regulation, and metabolism. Many DEGs are co-localized with quantitative trait loci (QTL) related to root growth and development, chlorate-resistance, and NUE. Our findings suggest that the superior growth performance of Pokkali under low N conditions could be due to the genetic differences in a diverse set of genes influencing N uptake through the regulation of root architecture

Ethanol Cellular Defense Induce Unfolded Protein Response in Yeast

Ethanol is a valuable industrial product and a common metabolite used by many cell types. However, this molecule produces high levels of cytotoxicity affecting cellular performance at several levels. In the presence of ethanol, cells must adjust some of their components, such as the membrane lipids to maintain homeostasis. In the case of microorganism as Saccharomyces cerevisiae, ethanol is one of the principal products of their metabolism and is the main stress factor during fermentation. Although, many efforts have been made, mechanisms of ethanol tolerance are not fully understood and very little evidence is available to date for specific signaling by ethanol in the cell. This work studied two S. cerevisiae strains, CECT10094, and Temohaya-MI26, isolated from flor wine and agave fermentation (a traditional fermentation from Mexico) respectively, which differ in ethanol tolerance, in order to understand the molecular mechanisms underlying the ethanol stress response and the reasons for different ethanol tolerance. The transcriptome was analyzed after ethanol stress and, among others, an increased activation of genes related with the unfolded protein response (UPR) and its transcription factor, Hac1p, was observed in the tolerant strain CECT10094. We observed that this strain also resist more UPR agents than Temohaya-MI26 and the UPR-ethanol stress correlation was corroborated observing growth of 15 more strains and discarding UPR correlation with other stresses as thermal or oxidative stress. Furthermore, higher activation of UPR pathway in the tolerant strain CECT10094 was observed using a UPR mCherry reporter. Finally, we observed UPR activation in response to ethanol stress in other S. cerevisiae ethanol tolerant strains as the wine strains T73 and EC1118. This work demonstrates that the UPR pathway is activated under ethanol stress occurring in a standard fermentation and links this response to an enhanced ethanol tolerance. Thus, our data suggest that there is a room for ethanol tolerance improvement by enhancing UPR response.EN was supported by a FPU grant from the Ministerio de Educación, Cultura y Deporte (ref. AP2009-0787). RP was supported by a JAEDOC postdoctoral program (IATA-CSIC), co-funded by FSE. This work has been supported by grants AGL2012-39937-C02-01 from the Spanish Government, FEDER and Generalitat Valenciana PROMETEOII/2014/042 to AQ. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe