Characterization of the biological and molecular activity of PML in breast cancer

253 p.Oncogene addiction postulates that the survival and growth of certain tumor cells is dependent upon the activity of one oncogene, despite their multiple genetic and epigenetic abnormalities. This phenomenon provides a foundation for molecular targeted therapy and a rationale for oncogene-based stratification. We previously reported that the Promyelocytic Leukemia protein (PML) is upregulated in triple negative breast cancer (TNBC) and it regulates cancer-initiating cell function, thus suggesting that this protein can be therapeutically targeted in combination with PML-based stratification. However, the effects of PML perturbation on the bulk of tumor cells remained poorly understood. In this thesis work we demonstrated that TNBC cells are addicted to the expression of this nuclear protein. PML inhibition led to a remarkable growth arrest combined with features of senescence in vitro and in vivo. Mechanistically, we observed that growth arrest and senescence were associated to a decrease in MYC and PIM1 kinase levels, with the subsequent accumulation of cyclin-dependent kinase inhibitor 1B (CDKN1B, p27), a trigger of senescence. In line with this notion, we found that PML is associated to thepromoter regions of MYC and PIM1, consistent with their direct correlation in breast cancer specimens. Altogether, our results provide a feasible explanation for the functional similarities of MYC, PIM1, and PML in TNBC and encourage further study of PML targeting strategies for the treatment of this breast cancer subtype.CICbioGUN

La mujer y el mundo del trabajo en la Vitoria del siglo XVIII

Los gremios prohibían a las mujeres el acceso al oficio. Las casadas trabajaban en tareas subalternas y bajo la dirección del esposo. Cuando éste estaba enfermo o impedido, podían hacerse cargo del taller. A la viuda de maestro se la permitía mantener el taller, en unos casos durante un año y en otros de manera ilimitada. Las solteras y viudas sin recursos debían trabajar para sobrevivir como criadas, maestras, costureras, vendiendo comestibles, como cereras, cajeras, zapateras, albarqueras o parteras.Gremioek galarazi egiten zuten emakumeek lanbiderik izatea. Ezkonduriko emakumeek menpeko eginkizunetan lan egiten zuten, senarraren agindupean betiere. Senarra gaixo edo ezindurik zegoenean, beren gain har zezaketen tailerraren ardura. Maisuaren alargunari, batzuetan urte batez bestetan denbora mugarik gabe, uzten zieten tailerra beren esku edukitzea Baliabiderik gabeko ezkongabeek zein alargunek bizi ahal izateko lan jakinetan jardun beharra zuten:neskame, maistra, jostun, janari saltzaile, kandelagile, zapatari, abarkagile edo emagin.Les corporations interdisaient aux femmes l'accès aux métiers. Les femmes mariées travaillaient à des tâches subalternes et sous la direction du mari. Lorsque celui-ci était malade ou impotent, elles pouvaient se charger de l'atelier. On permettait à la veuve d'un maître de garder l'atelier, durant une année dans certains cas et dans d'autres pour une durée illimitée. Les femmes célibataires et les veuves sans ressources devaient, pour survivre, travailler comme domestiques, institutrices, couturières, vendeuses de comestibles, comme cireuses, caissières, savetières ou sage-femmes.Guilds forbade women to accede to a trade. Maried women worked in subordinate tasks under their husband's supervision. When the husbands were ill or handicapped, women could then take over the workshop. The artisan's widow was allowed to maintain the workshop, in some cases during a year and in others for unlimited periods of time. Single women and widows without resources had to work to survive as maids, teachers, seamstresses, seling food, as cashiers, cobblers or midwives

Characterization of the biological and molecular activity of PML in breast cancer

253 p.Oncogene addiction postulates that the survival and growth of certain tumor cells is dependent upon the activity of one oncogene, despite their multiple genetic and epigenetic abnormalities. This phenomenon provides a foundation for molecular targeted therapy and a rationale for oncogene-based stratification. We previously reported that the Promyelocytic Leukemia protein (PML) is upregulated in triple negative breast cancer (TNBC) and it regulates cancer-initiating cell function, thus suggesting that this protein can be therapeutically targeted in combination with PML-based stratification. However, the effects of PML perturbation on the bulk of tumor cells remained poorly understood. In this thesis work we demonstrated that TNBC cells are addicted to the expression of this nuclear protein. PML inhibition led to a remarkable growth arrest combined with features of senescence in vitro and in vivo. Mechanistically, we observed that growth arrest and senescence were associated to a decrease in MYC and PIM1 kinase levels, with the subsequent accumulation of cyclin-dependent kinase inhibitor 1B (CDKN1B, p27), a trigger of senescence. In line with this notion, we found that PML is associated to thepromoter regions of MYC and PIM1, consistent with their direct correlation in breast cancer specimens. Altogether, our results provide a feasible explanation for the functional similarities of MYC, PIM1, and PML in TNBC and encourage further study of PML targeting strategies for the treatment of this breast cancer subtype.CICbioGUN

Histona desazetilasa inhibitzaileek giza melanoman duten efektuaren azterketa

HDAC inhibitzaileek melanoman duten efektua argitzeko asmoz, 5 inhibitzaile testatzen dira A375 eta HT-144 lerro zelularretan. Helburua, teknika desberdinetaz baliatuz, inhibitzaile hauek bideragarritasunean, apoptosian eta morfologian zein efektu duten ikustea izango da

La Escuela Activa: de la teoría a la práctica a través de un estudio de caso

La finalidad de este trabajo es dar a conocer la Escuela Activa y sus características por medio de la investigación y el acercamiento a un caso real. Para ello, se recopila información sobre la transición educativa desde los comienzos de la conocida como Educación Tradicional del Siglo XVII hasta el impacto de la Escuela Activa a principios del Siglo XX. Se proponen además las principales diferencias entre ambos estilos educativos y una profundización en la Escuela Activa junto a su definición, sus postulados, sus características y la pedagogía en la que se basa. Por otro lado, se realiza un estudio de caso para poder profundizar de forma real en la temática escogida y comprobar las similitudes y diferencias entre la realidad observada en la escuela y la teoría. Como conclusión de este trabajo se puede decir que la Escuela Activa genera un cambio en la educación y en la sociedad que muestra la necesidad por cambio en el Sistema Educativo.The purpose of this work is to make known the Active School and its characteristics through research and approach to a real case. To this end, information is collected on the educational transition from the beginning of the so-called Traditional Education of the17th century to the impact of the Active School at the beginning of the 20th century. It also proposes the main differences between the two educational styles and a deepening in the active school together with its definition, its postulates, its characteristics and the pedagogy on which it is based. On the other hand, a case study is made in order to be able to go deeper into the chosen subject and to verify the similarities and differences between the reality observed in the school and the theory. As a conclusion of this work, it can be said that the Active School generates a change in education and in society that shows the need for change in the Educational System.Grado en Educación Infanti

Las acciones de comunicación, la web 2.0 y la actividad promocional

This research addresses an understudied area of knowledge in Academia: the communication actions, Web 2.0 and promotional activities. All these areas have been widely studied separately, but the relationships between them has not been addressed so extensively and from a global perspective.La presente investigación aborda un área de conocimiento poco estudiado en el ámbito académico: las acciones de comunicación, la web 2.0 y la actividad promocional. Si bien es cierto que todas estas áreas han sido estudiadas por separado, no lo han sido tanto respecto a la interacción que se produce entre ellas, ni desde una perspectiva de globalidad

Are children with unrecognised psychiatric disorders being excluded from school? A secondary analysis of the British Child and Adolescent Mental Health Surveys 2004 and 2007

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this record.Background There is limited research that explores the association between exclusion from school and mental health, but it seems intuitively plausible that the recognition of mental difficulties by key teachers and parents would influence the likelihood of exclusion from school Methods A secondary analysis of the British Child and Adolescent Mental Health (BCAMH) survey 2004, (n=7997) and the 2007 follow-up (n= 5326) was conducted. Recognition of difficulty was assessed via a derived variable that combined the first item of the Impact supplement of the Strengths and Difficulties Questionnaire (SDQ) which asked parents and teachers if they thought that the child has difficulties with emotions, behaviour and concentration, and the presence / absence of psychiatric disorder measured by the Development and Well-being Assessment (DAWBA). Results Adjusted logistic regression models demonstrated that children with recognised difficulties were more likely to be excluded [adjusted odds ratio (OR) 5.78, confidence interval (CI) 3.45-9.64, p<0.001], but children with unrecognised difficulties [adjusted OR 3.58 (1.46-8.81) p<0.005] or recognised subclinical difficulties [adjusted OR 3.42 (2.04-5.73) p<0.001] were also more likely to be excluded than children with no difficulties. Children with conduct disorder and attention deficit hyperactivity disorder were most likely to be excluded compared to other types of disorder. Conclusion Exclusion from school may result from a failure to provide timely and effective support rather than a failure to recognise psychopathology.This paper presents independent research funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula

Blogs: attitudes towards sustainability through its semantic study

El objetivo de esta investigación es conocer a través de los Blogs lo que las personas entienden por sostenibilidad y cuáles son los mensajes y/o acciones que subyacen al concepto. La metodología se basa en la idea de palimpsesto al considerar el conocimiento como un constructo compuesto de capas de significados y significantes que van acumulando y superponiendo contenidos semánticos interrelacionados. Este estudio se lleva a cabo en dos fases, en la primera se realiza un análisis semántico cualitativo a una muestra de personas, y la segunda fase se efectúa con los principales blogs sobre sostenibilidad en España, basado en el análisis semántico previo. Los resultados confirman la ambigüedad del término sostenibilidad en el discurso social a través de los Blogs. También destacan conceptos tales como la flexibilidad y variedad en torno a la sostenibilidad desde el área de la Comunicación y Responsabilidad Social Corporativa.The aim of this research is to provide knowledge through the Blogs about what people understand by sustainability, as well as, what are the messages and actions underlying the concept. Methodology is based on Palimpsest’s idea of considering knowledge as a construct made up of layers of meanings and significant that they are accumulating and overlapping interrelated semantic content. The study is carried out in two phases. The first is a qualitative semantic analysis to a sample of people and the second phase is carried out through the major blogs on sustainability in Spain, based on the prior semantic analysis. Results confirm the ambiguity of the term sustainability in the social discourse through Blogs. They also highlight the flexibility and choice about sustainability in this medium. Aspects of communication and corporate social responsibility are discussed in this regard.Depto. de Teorías y Análisis de la ComunicaciónFac. de Ciencias de la InformaciónTRUEpu

Las acciones de comunicación, la web 2.0 y la actividad promocional

La presente investigación aborda un área de conocimiento poco estudiado en el ámbito académico: las acciones de comunicación, la web 2.0 y la actividad promocional. Si bien es cierto que todas estas áreas han sido estudiadas por separado, no lo han sido tanto respecto a la interacción que se produce entre ellas, ni desde una perspectiva de globalidad

Data Resource Profile: The Mental Health of Children and Young People Surveys (MHCYP).

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record.England’s Department of Health and Social Car