Regulación de los factores de transcripción ATF2 y c-Jun por la quinasa humana VRK1

Director: Pedro A. Lazo-ZbikowskiPeer reviewe

Vaccinia-related kinase 1 (VRK1) is an upstream nucleosomal kinase required for the assembly of 53BP1 foci in response to ionizing radiation-induced DNA damage

Cellular responses to DNA damage require the formation of protein complexes in a highly organized fashion. The complete molecular components that participate in the sequential signaling response to DNA damage remain unknown. Here we demonstrate that vaccinia-related kinase 1 (VRK1) in resting cells plays an important role in the formation of ionizing radiationinduced foci that assemble on the 53BP1 scaffold protein during the DNA damage response. The kinase VRK1 is activated by DNA double strand breaks induced by ionizing radiation (IR) and specifically phosphorylates 53BP1 in serum-starved cells. VRK1 knockdown resulted in the defective formation of 53BP1 foci in response to IR both in number and size. This observed effect on 53BP1 foci is p53- and ataxia-telangiectasia mutated (ATM)-independent and can be rescued with VRK1 mutants resistant to siRNA. VRK1 knockdown also prevented the activating phosphorylation of ATM, CHK2, and DNA-dependent protein kinase in response to IR. VRK1 activation in response to DNA damage is a novel and early step in the signaling of mammalian DNA damage responses.This work was supported in part by Ministerio de Ciencia e Innovación Grants SAF2010-14935 and CSD2007-0017, Junta de Castilla y León Grants CSI006A11-2 and GR-15, and the Kutxa-Fundación Inbiomed. Supported by Junta para la Ampliación de Estudios-CSIC-Fondo Social Europeo fellowships.Peer Reviewe

The cyanobacterial ribosomal-associated protein LrtA from Synechocystis sp. PCC 6803 is an oligomeric protein in solution with chameleonic sequence properties

The LrtA protein of Synechocystis sp. PCC 6803 intervenes in cyanobacterial post-stress survival and in stabilizing 70S ribosomal particles. It belongs to the hibernating promoting factor (HPF) family of proteins, involved in protein synthesis. In this work, we studied the conformational preferences and stability of isolated LrtA in solution. At physiological conditions, as shown by hydrodynamic techniques, LrtA was involved in a self-association equilibrium. As indicated by Nuclear Magnetic Resonance (NMR), circular dichroism (CD) and fluorescence, the protein acquired a folded, native-like conformation between pH 6.0 and 9.0. However, that conformation was not very stable, as suggested by thermal and chemical denaturations followed by CD and fluorescence. Theoretical studies of its highly-charged sequence suggest that LrtA had a Janus sequence, with a context-dependent fold. Our modelling and molecular dynamics (MD) simulations indicate that the protein adopted the same fold observed in other members of the HPF family ( - - - - - ) at its N-terminal region (residues 1–100), whereas the C terminus (residues 100–197) appeared disordered and collapsed, supporting the overall percentage of overall secondary structure obtained by CD deconvolution. Then, LrtA has a chameleonic sequence and it is the first member of the HPF family involved in a self-association equilibrium, when isolated in solution.Ministerio de Economía y Competitividad CTQ2015-64445-RMinisterio de Economía y Competitividad BIO2016-78020-RMinisterio de Economía y Competitividad FIS2014-52212-RMinisterio de Economía y Competitividad BIO2016-75634-PFundación Séneca 19353/PI/1

Situación actual del banco de recursos genéticos de la raza bovina Serrana de Teruel

raza Serrana de TeruelPublishe

Influencia de las TIC en el proceso administrativo

This article analyzes the influence of ICT in the administrative process of the tobacco company Perdomo Cigar S.A, as well as identifying the benefits of implementing these tools. Different data collection techniques and instruments (surveys, interviews and observation guide) were used for the scope of the objectives set out; these instruments were selected because their design provides the basis for exiting the objectives because it facilitates everything from the most general and abstract aspects to the more specific issues. The methodological design selected for research provides the elements necessary to collect and analyze the variables, as well as respond to the hypothesis. Among the most important results are that the company has introduced better technological tools in order to facilitate, streamline and automate administrative processes. The company provides its employees with the tools you would need to carry out their activities depending on the nature of their functions. Technological applications make it easier to capture the data at the place and time it is generated, and to access the information where and when it is needed; the implementation of the systems has been improving the processes in all the activities that the company develops, makes it more agile, are increasingly supported makes each area of the company interconnected and more functional. Both administrative staff and management agree that the implementation of ICTs in processes is of paramount importance as the success of the implementation does not depends on them if not the handling and use they are given.Este articulo analiza la influencia de las TIC en el proceso administrativo de la empresa tabacalera Perdomo Cigar S.A, así mismo, identifica los beneficios de la implementación de estas herramientas. Para el alcance de los objetivos planteados se utilizaron diferentes técnicas e instrumentos de recolección de datos (encuestas, entrevistas y guía de observación); se seleccionaron estas herramientas debido a que su diseño proporciona las bases para darle salida a los objetivos debido a que facilita desde los aspectos más generales y abstractos hasta las cuestiones más específicas. El diseño metodológico seleccionado para la investigación proporciona los elementos necesarios para recolectar y analizar las variables, así mismo, dar respuesta a la hipótesis. Entre los resultados más importantes destacan que la empresa a medida del tiempo ha introducido mejores herramientas tecnológicas con el fin de facilitar, agilizar y automatizar los procesos administrativos. La empresa proporciona a sus colaboradores las herramientas necesitarías para la realización de sus actividades en dependencia de la naturaleza de sus funciones. Mediante las aplicaciones tecnológicas se facilita tanto el captar el dato en el lugar y el momento que este se genere, como el acceder a la información dónde y cuándo se precise; la implementación de los sistemas ha venido mejorando los procesos en todas las actividades que desarrolla la empresa, lo hace más ágil, están cada vez más soportados hace que cada área de la empresa este interconectada y sea más funcional. Tanto el personal administrativo como la gerencia coinciden que la aplicación de las TIC en los procesos es de suma importancia ya que del éxito de la implementación no depende de ellos si no del manejo y uso que se les da

An Esrrb and nanog cell fate regulatory module controlled by feed forward loop interactions

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions' coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors, plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb module

Heavy-metal contents in oysters (Crassostrea gigas) cultivated on the southeastern coast of the Gulf of California, Mexico

Background. For its flesh and flavor, the Pacific oyster Crassostrea gigas is cultivated worldwide, but as filter feeders, this bivalve bioaccumulates heavy metals from different pollution sources, rendering them unsafe for human consumption. Goals. We carried out this study to assess the heavy metal concentrations in cultivated oysters from a farm located on the southeastern coast of the Gulf of California during 2011. Methods. Oyster samples were analyzed monthly (March- December 2011) for cooper (Cu), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), zinc (Zn), arsenic (As), and mercury (Hg). Results. The mean values (?g g-1, dry weight) for each metal were Cu = 51.42 ± 25.92, Cr = 24.97 ± 32.38, Cd = 13.84 ± 4.22, Ni = 10.26 ± 12.18, Pb = 2.18 ± 1.28, As = 0.37 ± 0.08, Zn = 267.42 ± 92.29, and Hg = 0.02 ± 0.01.Conclusions. The results suggest that metal burdens could be influenced by anthropogenic activities such as agriculture and aquaculture surrounding the culture zone. Cu, Cr, Cd, and Pb levels (?g g-1, fresh weight) were above the maximum permissible values and thus pose a threat to human health. Metal concentrations must be monitored periodically.Background. For its flesh and flavor, the Pacific oyster Crassostrea gigas is cultivated worldwide, but as filter feeders, this bivalve bioaccumulates heavy metals from different pollution sources, rendering them unsafe for human consumption. Goals. We carried out this study to assess the heavy metal concentrations in cultivated oysters from a farm located on the southeastern coast of the Gulf of California during 2011. Methods. Oyster samples were analyzed monthly (March- December 2011) for cooper (Cu), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), zinc (Zn), arsenic (As), and mercury (Hg). Results. The mean values (?g g-1, dry weight) for each metal were Cu = 51.42 ± 25.92, Cr = 24.97 ± 32.38, Cd = 13.84 ± 4.22, Ni = 10.26 ± 12.18, Pb = 2.18 ± 1.28, As = 0.37 ± 0.08, Zn = 267.42 ± 92.29, and Hg = 0.02 ± 0.01.Conclusions. The results suggest that metal burdens could be influenced by anthropogenic activities such as agriculture and aquaculture surrounding the culture zone. Cu, Cr, Cd, and Pb levels (?g g-1, fresh weight) were above the maximum permissible values and thus pose a threat to human health. Metal concentrations must be monitored periodically

Effectiveness of the 13-valent pneumococcal conjugate vaccine in preventing invasive pneumococcal disease in children aged 7-59 months. A matched case-control study

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7-59 months in a population with suboptimal vaccination coverage of 55%. Methods The study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI). Results 169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1-87.2) and 90% (95% CI, 63.9-97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7-97.9) against serotype 1 and 86.0% (95% CI, 51.2-99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8). Conclusions The effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7-59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually

Impact of the 13-valent conjugated pneumococcal vaccine on the direct costs of invasive pneumococcal disease requiring hospital admission in children aged < 5 years. A prospective study

The lack of invasive pneumococcal disease (IPD) cost studies may underestimate the effect of pneumococcal polysaccharide conjugated vaccines (PCV). The objective of this study was to estimate the direct costs of hospitalized IPD cases. A prospective study was made in children aged <5 years diagnosed with IPD in two high-tech hospitals in Catalonia (Spain) between 2007-2009 (PCV7 period) and 2012-2015 (PCV13 period). Costs were calculated according to 2014 Catalan Health Service rates using diagnostic-related groups. In total, 319 and 154 cases were collected, respectively. Pneumonia had the highest cost (65.7% and 62.0%, respectively), followed by meningitis (25.8% and 26.1%, respectively). During 2007-2015, the costs associated with PCV7 serotypes (Pearson coeffcient (Pc) = 0.79; p = 0.036) and additional PCV13 serotypes (Pc = 0.75; p = 0.05) decreased, but those of other serotypes did not (Pc = 0.23 p = 0.62). The total mean cost of IPD increased in the PCV13 period by 31.4% (¿3016.1 vs. ¿3963.9), mainly due to ICU stay (77.4%; ¿1051.4 vs. ¿1865.6). During the PCV13 period, direct IPD costs decreased due to a reduction in the number of cases, but cases were more severe and had a higher mean cost. During 2015, IPD costs increased due to an increase in the costs associated with non-PCV13 serotypes and serotype 3 and this requires further investigation

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E-4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E-4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease