5,827 research outputs found
Clustering U.S. 2016 presidential candidates through linguistic appraisals
Producción CientíficaThe main purpose of this paper is to cluster the United States (U.S.) 2016 presidential candidates taking the linguistic appraisals made by a random representative sample of adults living in the U.S. as our starting point. To do this, we have used the concept of ordinal proximity measure (see García-Lapresta and Pérez-Román), which allows to determine the degree of consensus in a group of agents when a set of alternatives is evaluated through non-necessarily qualitative scales.Ministerio de Economía, Industria y Competitividad (project ECO2016-77900-P
An ordinal multi-criteria decision-making procedure in the context of uniform qualitative scales
Producción CientíficaIn this contribution, we propose a multi-criteria decision-making procedure that has been devised in a purely ordinal way. Agents evaluate the alternatives regarding several criteria by assigning one or two consecutive terms of a uniform ordered qualitative scale to each alternative in each criterion. Weights assigned to criteria are managed through replications of the corresponding ratings, and alternatives are ranked according to the medians of their ratings after the replications
SUMOylation regulates LKB1 localization and its oncogenic activity in liver cancer
BACKGROUND:
Even though liver kinase B1 (LKB1) is usually described as a tumor suppressor in a wide variety of tissues, it has been shown that LKB1 aberrant expression is associated with bad prognosis in Hepatocellular Carcinoma (HCC).
METHODS:
Herein we have overexpressed LKB1 in human hepatoma cells and by using histidine pull-down assay we have investigated the role of the hypoxia-related post-translational modification of Small Ubiquitin-related Modifier (SUMO)ylation in the regulation of LKB1 oncogenic role. Molecular modelling between LKB1 and its interactors, involved in regulation of LKB1 nucleocytoplasmic shuttling and LKB1 activity, was performed. Finally, high affinity SUMO binding entities-based technology were used to validate our findings in a pre-clinical mouse model and in clinical HCC.
FINDINGS:
We found that in human hepatoma cells under hypoxic stress, LKB1 overexpression increases cell viability and aggressiveness in association with changes in LKB1 cellular localization. Moreover, by using site-directed mutagenesis, we have shown that LKB1 is SUMOylated by SUMO-2 at Lys178 hampering LKB1 nucleocytoplasmic shuttling and fueling hepatoma cell growth. Molecular modelling of SUMO modified LKB1 further confirmed steric impedance between SUMOylated LKB1 and the STe20-Related ADaptor cofactor (STRADα), involved in LKB1 export from the nucleus. Finally, we provide evidence that endogenous LKB1 is modified by SUMO in pre-clinical mouse models of HCC and clinical HCC, where LKB1 SUMOylation is higher in fast growing tumors.
INTERPRETATION:
Overall, SUMO-2 modification of LKB1 at Lys178 mediates LKB1 cellular localization and its oncogenic role in liver cancer. FUND: This work was supported by grants from NIH (US Department of Health and Human services)-R01AR001576-11A1 (J.M.M and M.L.M-C.), Gobierno Vasco-Departamento de Salud 2013111114 (to M.L.M.-C), ELKARTEK 2016, Departamento de Industria del Gobierno Vasco (to M.L.M.-C), MINECO: SAF2017-87301-R and SAF2014-52097-R integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M., respectively), BFU2015-71017/BMC MINECO/FEDER, EU (to A.D.Q. and I.D.M.), BIOEF (Basque Foundation for Innovation and Health Research): EITB Maratoia BIO15/CA/014; Instituto de Salud Carlos III:PIE14/00031, integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovacion 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M), Asociación Española contra el Cáncer (T.C.D, P·F-T and M.L.M-C), Daniel Alagille award from EASL (to T.C.D), Fundación Científica de la Asociación Española Contra el Cancer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M and M.A), La Caixa Foundation Program (to M.L.M), Programma di Ricerca Regione-Università 2007-2009 and 2011-2012, Regione Emilia-Romagna (to E.V.), Ramón Areces Foundation and the Andalusian Government (BIO-198) (A.D.Q. and I.D.M.), ayudas para apoyar grupos de investigación del sistema Universitario Vasco IT971-16 (P.A.), MINECO:SAF2015-64352-R (P.A.), Institut National du Cancer, FRANCE, INCa grant PLBIO16-251 (M.S.R.), MINECO - BFU2016-76872-R to (E.B.). Work produced with the support of a 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (M.V-R). Finally, Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). Funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication
Silico identification, molecular characterization and expression analysis of the Trypanosoma brucei paraflagellar rod protein PFR3
En el presente artículo se describen la identificación y el aislamiento del gen codificante para la proteínaPFR3 del T. brucei. La secuencia deducida de aminoácidos produce una proteína de 592 residuos conun punto isoeléctrico de 5,14 y presenta una identidad de secuencia del 68,9% con la proteína PFR3 delT. cruzi. Sin embargo, el porcentaje de homología entre la proteína PFR3 de T. brucei y otras secuenciasdisponibles de PFRs de T. brucei y T. cruzi es inferior al 22%. En contraste con lo descrito para losmiembros de la familia de proteínas de filamento paraflagelar, la mayor divergencia entre las proteínasPFR3 de T. cruzi y T. brucei se encuentra en la región central de la proteína, con una similitud del 38%en 200 aminoácidos. Estimamos que existen dos copias de la proteína PFR3 de T. brucei por genomahaploide. El gen se transcribe como mARN de aproximadamente 3,6 kb de longitud, presente con lamisma abundancia en formas parasitarias procíclicas y del torrente sanguíneo.In the present paper we describe the identification and isolation of the gene coding for T. brucei PFR3protein. The deduced amino acid sequence produces a protein of 592 residues with an isoelectric pointof 5.14 and shows a 68.9% sequence identity with T. cruzi PFR3 protein. However, the percentage ofhomology among T. brucei PFR3 and other available PFRs sequences from T. brucei and T. cruzi islower than 22%. In contrast to that described for members of paraflagellar rod protein family, thehighest divergence between T. cruzi and T. brucei PFR3 proteins is located at the central region of theprotein with a 38% of similarity over 200 amino acid. We estimate that there exist two copies of theT. brucei PFR3 protein per haploid genome. The gene is transcribed as a mRNA of approximately 3.6kb in length, equally abundant in both procyclic and bloodstream parasite forms
Development and validation of the Spanish hazard perception test
Objective: The aim of the current study is to develop and obtain validity evidence for a Hazard Perception test suitable for the Spanish driving population. To obtain validity evidence to support the use of the test, the effect of hazardous and quasi-hazardous situations on the participants’ Hazard Prediction is analysed and the pattern of results of drivers of different driving experience: learner, novice and expert drivers and re-offender vs. non-offender drivers, is compared. Potentially hazardous situations are those that develop without involving any real hazard (i.e., the driver didn’t actually have to decelerate or make any evasive manoeuvre to avoid a potential collision). The current study analysed multiple offender drivers attending compulsory re-education programmes as a result of reaching the maximum number of penalty points on their driving licence, due to repeated violations of traffic laws. Method: A new video-based hazard perception test was developed, using a total of 20 hazardous situation videos plus 8 quasi-hazardous situation videos. They were selected from 167 recordings of natural hazards in real Spanish driving settings
Elevated CO<sub>2</sub> alleviates high PAR and UV stress in the unicellular Chlorophyte Dunaliella tertiolecta
The effects of increased CO2 and irradiance on the physiological performance of the chlorophyte Dunaliella tertiolecta were studied at different PAR and UVR (UVA+UVB) irradiances, simulating the solar radiation at different depths, under present (390 ppmv, LC) and predicted CO2 levels (1000 ppmv, HC). Cell stress after UVR-exposure was mostly attenuated under HC levels, as evidenced by a decrease in reactive oxygen species accumulation. DNA damage showed a 42-fold increase in cyclobutane-pyrimidine dimers formation under the highest irradiance in LC with respect to the lowest irradiance. Photolyase gene expression was upregulated under HC resulting in a drastic decrease in CPDs accumulation to only 25% with respect to LC. However, the expression of genes related to the replacement of photosynthetic apparatus proteins (PsbA and LHCII) were downregulated at HC compared to LC. Proliferating cell nuclear antigen (PCNA) accumulation was always higher in HC and the accumulation pattern indicated its involvement in DNA repair or growth depending on the irradiance doses. Our results suggest that marine unicellular chlorophytes might possibly become more resilient to UVR exposure under future CO2 regimes.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech
Prevalence of vitamin D deficiency: cross-sectional study of a hospital cohort of HIV-1 infected outpatients
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