Loss of PRDX6 aborts proliferative and migratory signaling in hepatocarcinoma cell lines

Peroxiredoxin 6 (PRDX6), the only mammalian 1-Cys member of the peroxiredoxin family, has peroxidase, phospholipase A2 (PLA2), and lysophosphatidylcholine (LPC) acyltransferase (LPCAT) activities. It has been associated with tumor progression and cancer metastasis, but the mechanisms involved are not clear. We constructed an SNU475 hepatocarcinoma cell line knockout for PRDX6 to study the processes of migration and invasiveness in these mesenchymal cells. They showed lipid peroxidation but inhibition of the NRF2 transcriptional regulator, mitochondrial dysfunction, metabolic reprogramming, an altered cytoskeleton, down-regulation of PCNA, and a diminished growth rate. LPC regulatory action was inhibited, indicating that loss of both the peroxidase and PLA2 activities of PRDX6 are involved. Upstream regulators MYC, ATF4, HNF4A, and HNF4G were activated. Despite AKT activation and GSK3β inhibition, the prosurvival pathway and the SNAI1-induced EMT program were aborted in the absence of PRDX6, as indicated by diminished migration and invasiveness, down-regulation of bottom-line markers of the EMT program, MMP2, cytoskeletal proteins, and triggering of the “cadherin switch”. These changes point to a role for PRDX6 in tumor development and metastasis, so it can be considered a candidate for antitumoral therapies

Identification of new immunoprotective surface protein vaccine candidates against streptococcus suis infection by proteomics

Comunicaciones a congreso

Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality

This is an open-access article distributed under the terms of the Creative Commons Attribution License.Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56 NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56 NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94/HLADR phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.This work has been partially supported by the following grants: FIS 02/1244-FEDER, DTS 15/00119-FEDER, RTICC RD06/0020/0035-FEDER and RTICC RD12/0036/0048-FEDER from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain; SA103/03 and SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain. The research activities of the EuroFlow Consortium were supported by the European Commission (grant STREP EU-FP6, LSHB-CT-2006–018708, entitled ‘Flow cytometry for fast and sensitive diagnosis and follow-up of hematological malignancies’).Peer Reviewe

Noble gas signals in corals predict submarine volcanic eruptions

Deep-water corals growing in close proximity to the 2011 submarine eruption at Tagoro (El Hierro Island; Canary Archipielago, Spain) have revealed their ability to record the magmatic helium (3He) signal during a period of months prior to the eruption with magmatic 3He/4He ratios of 3.6-5.0 RA This is similar to the range of He isotope values (3-10 Ra) obtained from olivine samples from basinites erupted during the 2011 Tagoro eruption. Whip-like black corals (Anthozoa: Antipatharia: Antipathidae: Stichopathes) growing on basaltic rocks trapped 3He within their skeletons. We used a theoretical growth rate to estimate the time of trapping of 3He between release from the magmatic source at depth to trapping by the aquatic organisms. Our findings suggest that magmatic 3He emission occurred a few months before the beginning of the seismic activity in the region, the latter occurring four months in advance of the beginning of the eruption. This discovery implies that corals living in submarine volcanic areas may act as archives of noble gases released before the beginning of an eruption, and that the continuous monitoring of 3He may help to constrain the arrival time of a subaqueous eruption with potential applications in volcano eruption forecasting.En prens

Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer

Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages. There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signaling pathways leading to cell survival/death. The induction of apoptosis and cell cycle arrest widely related to the antitumoral properties of TKIs result from tightly controlled events involving different cellular compartments and signaling pathways. The aim of the present review is to update the most relevant studies dealing with the impact of TKI treatment on cell function. The induction of endoplasmic reticulum (ER) stress and Ca2+ disturbances, leading to alteration of mitochondrial function, redox status and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways that involve cell metabolism reprogramming in cancer cells will be covered. Emphasis will be given to studies that identify key components of the integrated molecular pattern including receptor tyrosine kinase (RTK) downstream signaling, cell death and mitochondria-related events that appear to be involved in the resistance of cancer cells to TKI treatments.This study was funded by Institute of Health Carlos III (ISCiii) (PI16/00090, PI19/00838 and PI19/01266), Spanish Ministry of Economy and Competitiveness (BFU2016-80006-P), Andalusian Ministry of Economy, Innovation, Science and Employment (BIO-216 and CTS-6264), Andalusian Ministry of Equality, Health and Social Policies (PI-0198-2016) and Valencian Ministry of Education, Culture and Sports (PROMETEO/2019/027). P de la C-O was supported by FPU predoctoral fellowship (FPU17/00026) from Spanish Ministry of Education, Culture and Sports. E N-V was supported by the the predoctoral i-PFIS IIS-enterprise contract in science and technologies in health (IFI18/00014) from ISCiii. We thank the Biomedical Research Network Center for Cardiovascular Diseases (CIBERcv), and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by the ISCiii and co-financed by European Regional Development Fund (ERDF) "A way to achieve Europe" for their financial support

Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy

Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival. From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding (p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34+/CD7+ and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment (p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival. In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.This work was supported by the Fundación Científica de la Asociación Española Contra el Cáncer (AECC, Madrid, Spain) and the Fundación Rafael del Pino (Madrid, Spain) and both CIBERONC (CB16/12/00400, CB16/12/00233, CB16/12/00480) and grant PI16/00787 from Instituto de Salud Carlos III (Ministerio de Economía y Competitividad, Madrid, Spain)

Use of interactive response devices for the improvement of teaching in the degrees of the Faculty of Sciences

La implantación de los nuevos Grados dentro del EEES supone un nuevo enfoque metodológico, pero sobre todo evaluador. El profesor debe esforzarse en ser capaz de valorar no sólo el nivel de conocimientos del alumnado sobre los contenidos, ya que la sociedad actual demanda un perfil de los egresados más completo basado en la formación por competencias. La adquisición de ambas facetas por parte del alumnado se basa principalmente en actividades presenciales y metodologías docentes aplicadas en el desarrollo de las asignaturas, tanto en grupo reducido como en grupo completo. Por tanto, cualquier herramienta adicional que ayude al docente a facilitar esta doble tarea es bien recibida, pues permitirá evaluar el rendimiento académico global del alumnado. Recientemente la Facultad de Ciencias ha puesto en marcha una experiencia piloto mediante la cual un nutrido grupo de profesores ha incorporado en su docencia un sistema de mandos inalámbricos de respuesta. Actualmente, la Facultad de Ciencias dispone de un total de 82 mandos inalámbricos de respuesta y tres antenas receptoras. Esta nueva tecnología ha permitido al docente realizar, de forma interactiva, preguntas colectivas al alumnado y recoger las respuestas individuales de forma inmediata. Los resultados obtenidos en este proyecto nos permiten ser muy optimistas con el uso de esta herramienta y nos animan a continuar en la misma línea. El profesorado participante se ha mostrado dispuesto a continuar empleando esta TIC en su docencia, tratando de abarcar más asignaturas, diversificar el tipo de pruebas, y emplear los mandos de respuesta en grupo completo, cuando el número de alumnos lo permita. La puesta en común de los resultados revela que, de forma general, este tipo de sistemas de respuesta incrementa el nivel de atención del alumnado, ya que se les demanda de forma continuada su participación activa durante la sesión. Se potencia la retención de conceptos, al suministrar en el acto la respuesta correcta a cada pregunta realizada. Permite también al profesorado conocer el nivel previo de conocimientos sobre la materia a impartir, ya que se puede realizar este tipo de preguntas al comienzo de la sesión y enfocar entonces su atención en las debilidades manifestadas. Asimismo se puede testar el grado de adquisición de dichos conocimientos, realizando este tipo de cuestionarios después de la sesión. Además, el tratamiento posterior de los resultados, de forma individualizada, permite gestionar de forma ágil el nivel de conocimientos y adquisición de competencias en lo que es un sistema de evaluación continua, tan necesario en los nuevos enfoques metodológicos nacidos de la implantación del EEES. Por último destacar que el profesorado participante ha considerado que se trata de una herramienta de gran utilidad para la consecución del objetivo de excelencia en la docencia, que además es eficaz y de fácil manejo, y entiende que no debe ser una actividad puntual, sino un proceso transformador en la actividad docente e interacción alumno-profesor, configurándose como una herramienta habitual en los sistemas de enseñanza-aprendizaje.Implementation of the new degrees in the EHEA involve a new methodological approach, but above all evaluation. The teacher should strive to be able to assess not only the level of knowledge of the students on the content, as the current society demands a profile of the most complete graduates based on training by competencies. The acquisition of both facets by students is based mainly on face-to-face activities and teaching methodologies applied in the development of the subjects, both in small group and in whole group. Therefore, any additional tool that helps the teacher to facilitate this double task is well received, since it will allow to evaluate the overall academic performance of the students. Recently the Faculty of Sciences has launched a pilot experience through which a large group of teachers has incorporated into their teaching a system of interactive response devices. Currently, the Faculty of Sciences has a total of 82 wireless response controllers and three receiving antennas. This new technology has enabled the teacher to interact interactively with the students and collect the individual answers immediately. The results obtained in this project allow us to be very optimistic with the use of this tool and encourage us to continue in the same line. The participating teachers have been willing to continue using this ICT in their teaching, trying to cover more subjects, diversify the type of tests, and use the full group response commands, when the number of students allows. The sharing of results reveals that, in a general way, this type of response systems increases the level of attention of the students, since they are continuously demanded their active participation during the session. The retention of concepts is strengthened by providing the correct answer to every question asked. It also allows the faculty to know the previous level of knowledge about the subject to be taught, since this type of questions can be asked at the beginning of the session and then focus their attention on the weaknesses manifested. It is also possible to test the degree of acquisition of this knowledge, performing this type of questionnaire after the session. In addition, the subsequent treatment of the results, in an individualized way, allows to manage in an agile way the level of knowledge and acquisition of competences in what is a system of continuous evaluation, so necessary in the new methodological approaches born from the implantation of the EHEA. Finally, it should be pointed out that the participating teachers have considered that this is a very useful tool for achieving the objective of excellence in teaching, which is also efficient and easy to use and understands that it should not be a specific activity, but a transforming process in the teaching activity and student-teacher interaction, being configured as a habitual tool in the teaching-learning systems

Cachimbos europeus de cerâmica branca, séculos XVI ao XIX: parâmetros básicos para análise arqueológica

O tabaco foi introduzido na Europa no final do século XV. Desde então, uma das formas mais comuns para o seu consumo foi o cachimbo, além do rapé, do tabaco de mascar, do charuto e, mais recentemente, dos cigarros. Os cachimbos de cerâmica branca, largamente produzidos e utilizados na Europa desde o século XV, são encontrados em sítios arqueológicos históricos ao redor do mundo, incluindo no Brasil, em decorrência do comércio internacional, que gradualmente se intensificou após o início da conquista europeia. Eles funcionam como excelentes elementos para datação de sítios e estratos arqueológicos, tendo sido estudados em vários países a partir dessa abordagem. Ainda, esse tipo de artefato, mais que fornecer datações, permite identificar redes comerciais entre nações e desenvolver discussões de cunho social e cultural. Contudo, eles foram pouco estudados no Brasil. Visando contribuir com os estudos nacionais dessa categoria material, este artigo oferece uma revisão da literatura internacional acerca do histórico da produção dos cachimbos europeus de caulim, incluindo apresentação dos principais centros produtores; da morfologia e decoração desses produtos, considerando a cronologia do fabrico; e dos métodos de análise dos diferentes cachimbos de caulim no âmbito da arqueologia histórica.Tobacco was introduced in Europe at the end of the 15th century. Since then, one of the most traditional means for its use has been the pipe, next to the powder version, chewing, cigars, and, more recently, cigarettes. White clay tobacco pipes, widely produced and used in Europe since the 15th century, are found in historical archaeological sites around the world, including Brazil, due to international trade, which gradually intensified with the European conquest of the New World. They are excellent guides for dating archaeological sites and layers. In addition, this type of artifact, more than a dating tool, permits identifying trading networks between nations and developing discussions of cultural and social nature. These pipes, however, have been understudied in Brazil. In order to contribute to studies of this type of artifact in our country, this paper offers a revision of the international literature on the history of clay pipe production in Europe, including the presentation of main production centers; morphology and decoration of these products, considering issues of fabrication chronology; and the methods used in Historical Archaeology for analyzing clay tobacco pipes

Evaluación de la calidad en colecciones de germoplasma autóctono de trigo harinero

Two grain quality parameters, four morphological characters of spike and HMW-glutenins were evaluated in 185 Spanish landraces of bread wheat. High variability was obtained in SDS sedimentation volume, protein content and HMW-glutenins frecuencies of several poor quality alleles were high red grain varieties had higher protein content than white ones.Trabajo realizado dentro del proyecto CICYT de referencia PA 85-0233.Peer reviewe