IL-7R-mediated signaling in T-cell acute lymphoblastic leukemia: an update

© 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/)Interleukin 7 (IL-7) and its receptor (IL-7R, a heterodimer of IL-7Rα and γc) are essential for normal lymphoid development. In their absence, severe combined immunodeficiency occurs. By contrast, excessive IL-7/IL-7R-mediated signaling can drive lymphoid leukemia development, disease acceleration and resistance to chemotherapy. IL-7 and IL-7R activate three main pathways: STAT5, PI3K/Akt/mTOR and MEK/Erk, ultimately leading to the promotion of leukemia cell viability, cell cycle progression and growth. However, the contribution of each of these pathways towards particular functional outcomes is still not completely known and appears to differ between normal and malignant states. For example, IL-7 upregulates Bcl-2 in a PI3K/Akt/mTOR-dependent and STAT5-independent manner in T-ALL cells. This is a 'symmetric image' of what apparently happens in normal lymphoid cells, where PI3K/Akt/mTOR does not impact on Bcl-2 and regulates proliferation rather than survival. In this review, we provide an updated summary of the knowledge on IL-7/IL-7R-mediated signaling in the context of cancer, focusing mainly on T-cell acute lymphoblastic leukemia, where this axis has been more extensively studied.Publication costs were supported by LISBOA-01-0145-FEDER-007391, project cofunded by FEDER, through POR Lisboa2020 Programa Operacional Regional de Lisboa, PORTUGAL 2020, and Fundação para a Ciência e a Tecnologia (FCT, Portugal). The research work in JTB's lab related to the present review was supported by the grants FAPESP/20015/2014 and PTDC/MEC-HEM/31588/2017, from FCT; and by the consolidator grant ERC CoG-648455 from the European Research Council, under the European Union's Horizon 2020 research and innovation programme. JTB is an FCT investigator (consolidator). MLO is a LisbonBioMed PhD student and received a fellowship from FCT. PA received a PhD fellowship from the EU Marie Sklodowska-Curie ITN Protein Conjugates.info:eu-repo/semantics/publishedVersio

As escolas portuguesas são organizações aprendentes? Um estudo empírico

The paradigm of learning organizations has been the subject of growing attention, but few studies investigate its practical application to the processes and structures of schools. Thus, instruments are needed that can measure the levels of organizational learning in schools, enabling the planning of interventions for improvement. This article examines in an exploratory way the reliability and validity of the Portuguese version of an instrument to assess schools as learning organizations. It also describes the results of its application to teachers and senior staff (n=1266) of public schools in Viseu county. The analyses indicate that the psychometric properties of the adapted instrument are identical to the original instrument, which is promising. Although the type of sample used prevents the generalization of results, this work is one of the first applications of an instrument for measuring the level of organizational learning of primary and secondary Portuguese schools. Principals and teachers of these schools can use the results to create a school climate more conducive to improving their teaching and learning processes.O paradigma das organizações aprendentes tem sido alvo de crescente atenção, mas poucos estudos investigam a sua aplicação prática aos processos e estruturas das escolas. Assim, são necessários instrumentos que possam medir os níveis de aprendizagem organizacional das escolas, permitindo o planeamento de intervenções de melhoria. Este artigo examina de forma exploratória a fiabilidade e validade da versão portuguesa de um instrumento para avaliar as escolas enquanto organizações aprendentes. Descreve ainda os resultados da sua aplicação a docentes e técnicos superiores (n=1266) das escolas públicas do concelho de Viseu. As análises efetuadas indicam que as propriedades psicométricas do instrumento adaptado são idênticas às do instrumento original, o que é promissor. Apesar de o tipo de amostra utilizada impedir a generalização dos resultados, este trabalho constitui uma das primeiras aplicações de um instrumento para aferir o nível de aprendizagem organizacional das escolas portuguesas dos ensinos básico e secundário. Os diretores e professores destas escolas podem utilizar os resultados para criar um clima escolar mais favorável à melhoria dos seus processos de ensino-aprendizagem

Mashups: An Approach to Overcoming the Business/IT Gap in Service-Oriented Architectures

For quite a long time already, great importance has been attached to the concept of Service-Oriented Architectures for future IT-architectures. However, a major challenge in implementing this concept lies in the gap between the functional department and IT department. Mashups, an architecture also based on services, try to avoid this gap by letting the user himself integrate the services. The following article analyzes similarities and differences between both architecture approaches, and explains to what extent and in which cases Mashups could complement a Service-Oriented Architecture