Heterocellular cadherin connections: coordinating adhesive cues in homeostasis and cancer

This short insight covers some of the recent topics relevant to the field of cadherin-catenin adhesion in mediating connections between different cell types, so-called heterotypic or heterocellular connections, in both homeostasis and cancer. These scientific discoveries are increasing our understanding of how multiple cells residing in complex tissues can be instructed by cadherin adhesion receptors to regulate tissue architecture and function and how these cadherin-mediated heterocellular connections spur tumor growth and the acquisition of malignant characteristics in tumor cells. Overall, the findings that have emerged over the past few years are elucidating the complexity of the functional roles of the cadherin-catenin complexes. Future exciting research lies ahead in order to understand the physical basis of these heterotypic interactions and their influence on the behavior of heterogeneous cellular populations as well as their roles in mediating phenotypic and genetic changes as cells evolve through complex environments during morphogenesis and cancer.The Perez-Moreno lab is supported by grants from the Spanish Ministry of Economy and Competitiveness/European Regional Development Fund (ERDF), European Union (BFU2015-71376-R), and the Worldwide Cancer Research UK Foundation (15-1219 to Mirna Perez-Moreno). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

O Balanced Scorecard e a sua aplicação a empresas revendedoras de combustível

Num mercado cada vez mais competitivo e exigente em que as empresas se inserem nos dias de hoje, é notória a necessidade de estas adoptarem uma ferramenta de gestão e planeamento estratégico que possibilite aos gestores encarar outras realidades além da perspectiva financeira. Tratando-se de empresas inseridas num sector que está a atravessar uma profunda crise económica, como é o caso das empresas revendedoras de combustível, o desafio de alcançar altos níveis de exigência e competitividade agrava-se. O Balanced Scorecard (BSC) revela-se uma vantagem competitiva para estas organizações, constituindo uma ferramenta útil para monitorar o desempenho estratégico, já que integra os diversos aspectos da organização. O BSC permite considerar quatro perspectivas para medir o desempenho das organizações, nomeadamente Financeira, Clientes, Processos Internos e Aprendizagem e Crescimento. A formulação dos objectivos, das iniciativas estratégicas, das metas e dos indicadores, pelas quatro perspectivas e considerando as relações de causa-efeito entre elas, permitirá um processo de tomada de decisão mais coerente com a realidade em que as organizações se situam. Partindo desta problemática, os objectivos principais que guiaram este estudo foram os seguintes: averiguar se as empresas revendedoras de combustível utilizam o BSC para monitorização estratégica ou algum sistema de medida e avaliação de desempenho que, de alguma forma, se aproxima a este modelo e propor um possível modelo de BSC para estas empresas que possam ajustar a cada caso em particular (definindo as metas e acções específicas). Da análise dos resultados dos questionários aplicados aos responsáveis das empresas em estudo, concluiu-se que o facto que as une – a marca GASPE - não faz com que estas sigam uma estratégia uniforme, mas sim se enquadrem numa de três orientações estratégicas distintas: “Maximização da rendibilidade”, “Criação de valor e relacionamento com os clientes” ou “Optimização de custos e melhoria da produtividade e qualidade”. Por último é apresentada uma proposta de BSC para cada uma das orientações estratégicas identificadas. In a market increasingly competitive and demanding environment where companies are included today, it is notorious the need for them to adopt a management tool and strategic planning that enables managers to consider other realities beyond the financial perspective. In the case of companies operating in a sector facing a profound economic crisis, as it is the case of fuel retailers companies, the challenge of achieving high levels of demand and competitiveness worsens. The Balanced Scorecard (BSC) appears to be a competitive advantage for these organizations, providing a useful tool to monitor the strategic performance, as it integrates the various aspects of the organization. The BSC allows us to consider four perspectives to measure the performance of organizations, including Financial, Customers, Internal Processes and Learning and Growth. The formulation of objectives, strategic initiatives, goals and indicators, by the four perspectives and considering the relations of cause and effect between them, will allow a decision-making process more consistent with the reality that organizations are located. On this issue, the main purposes that guided this study were: to investigate whether the fuel retailers companies use BSC for strategic monitoring or any system of measurement and evaluation of performance, which somehow comes close to this model and to propose a possible model of BSC for these companies that can adjust to each particular case (by setting goals and specific actions). The analysis of results from the questionnaires to the heads of companies under investigation, it was concluded that the fact that unites them - the mark GASPE – does not make these follow a uniform strategy, but fall into one of three different strategic orientations: “Maximizing profitability”, “Value creation and customer relationships” or “Optimizing costs and improving productivity and quality”. Finally a proposal of BSC is presented for each of the strategic directions identified. En un mercado cada vez más competitivo y exigente donde se sitúan las empresas hoy en día, es evidente la necesidad de adoptar un instrumento de gestión y planificación estratégico, que permita a los gerentes considerar otras realidades más allá de las perspectivas financieras. En el caso de las sociedades situadas en un sector que se enfrenta a una profunda crisis económica, como es el caso de las empresas concesionarias de combustible, el desafío de lograr altos niveles de demanda y competitividad empeora. El Balanced Scorecard (BSC) parece ser una ventaja competitiva para estas organizaciones, proporcionando una herramienta útil para controlar la estrategia, ya que integra diferentes aspectos de la organización. El BSC nos permite considerar cuatro areas para medir el desempeño de las organizaciones, que son: Financiera, Clientes, Procesos Internos y Aprendizaje y Desarrollo. La definición de objetivos, iniciativas estratégicas, metas e indicadores de las cuatro areas y teniendo en cuenta las relaciones de causa y efecto entre ellas, permitirá un proceso de toma de decisiones más coherente con la realidad en que las organizaciones se encuentran. A este respecto, los principales objetivos que han guiado este estudio fueron: investigar si las empresas concesionarias de combustible utilizan el BSC para la monitorización estratégica del desempeño o cualquier otro sistema de medición y evaluación del desempeño, que de alguna manera se acerca a este modelo y proponer un posible modelo de BSC para estas empresas, que puede adaptarse a cada caso en particular (por el establecimiento de metas y acciones específicas). El análisis de los resultados de las encuestas a los jefes de las empresas objeto de la investigación, concluyó que el hecho que los une - la marca GASPE - no causa una estrategia uniforme, sino que los sitúa en una de las tres ubicaciones estratégicas: “Maximización de la rentabilidad”, “Creación de valor y relaciones con los clientes” o “Optimización de los costos y mejora de la productividad y calidad”. Por último, se presenta una propuesta del BSC para cada una de las orientaciones estratégicas identificadas

Effect of native gastric mucus on in vivo hybridization therapies directed at Helicobacter pylori

Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid mimics are a promising alternative. In particular, locked nucleic acids (LNA)/2'-OMethyl RNA (2'OMe) have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical barriers-the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without permeabilization and fixation of the bacteria, which is normally part of in vitro studies, the ability of LNA/2'OMe to efficiently hybridize with H. pylori was hampered by the presence of mucus. Future research should focus on developing nanocarriers that shield LNA/2'OMe from components in the gastric mucus, while remaining capable of diffusing through the mucus and delivering these nucleic acid mimics directly into the bacteria

Fluorescence In Vivo Hybridization (FIVH) for Detection of Helicobacter pylori Infection in a C57BL/6 Mouse Model

Introduction In this study, we applied fluorescence in vivo hybridization (FIVH) using locked nucleic acid (LNA) probes targeting the bacterial rRNA gene for in vivo detection of H. pylori infecting the C57BL/6 mouse model. A previously designed Cy3_HP_LNA/2OMe_PS probe, complementary to a sequence of the H. pylori 16S rRNA gene, was used. First, the potential cytotoxicity and genotoxicity of the probe was assessed by commercial assays. Further, the performance of the probe for detecting H. pylori at different pH conditions was tested in vitro, using fluorescence in situ hybridization (FISH). Finally, the efficiency of FIVH to detect H. pylori SS1 strain in C57BL/6 infectedmice was evaluated ex vivo in mucus samples, in cryosections and paraffin-embedded sections by epifluorescence and confocal microscopy. Results H. pylori SS1 strain infecting C57BL/6 mice was successfully detected by the Cy3_HP_LNA/2OMe_PS probe in the mucus, attached to gastric epithelial cells and colonizing the gastric pits. The specificity of the probe for H. pylori was confirmed by microscopy. Conclusions In the future this methodology can be used in combination with a confocal laser endomicroscope for in vivo diagnosis of H. pylori infection using fluorescent LNA probes, which would be helpful to obtain an immediate diagnosis. Our results proved for the first time that FIVH method is applicable inside the body of a higher-order animal

Carta do Bacharel João Fernandes para D. João III sobre a doença da Imperatriz D. Isabel (1528)

UIDB/04666/2020 UIDP/04666/20201528, Madrid, Setembro, 2 O bacharel João Fernandes escreve a D. João III, falando-lhe dos mais recentes episódios da doença que acometia a Imperatriz D. Isabel, sua irmã. 1528, Madrid, 2 September Bachelor João Fernandes writes to King John III to update him on the most recent developments of the disease that afflicted his sister, Empress Isabel of Portugal.publishersversionpublishe

Carta de D. Margarida de Sousa para a Rainha D. Catarina de Áustria (1563)

UIDB/04666/2020 UIDP/04666/20201563, s. l. D. Margarida de Sousa, recolhida no Convento de São Bento, pede uma esmola a D. Catarina de Áustria, para que pudesse suprir as suas necessidades básicas, tomar hábito e fazer o noviciado. 1563, s. l. Margarida de Sousa, living in the Convent of St. Benedict, asks Queen Catherine of Austria for alms to cover her basic necessities, to don the habit, and to carry out her novitiate.publishersversionpublishe

Carta do Padre Álvaro Rodrigues para D. João III sobre a doença da Imperatriz D. Isabel (1528)

UIDB/04666/2020 UIDP/04666/20201555, Toledo, Novembro, 7 O padre Álvaro Rodrigues escreve a D. João III para lhe dar notícias sobre o estado de saúde de sua irmã, a Imperatriz D. Isabel. Entre outros assuntos breves, pede-lhe ainda que tome um criado seu por escudeiro, como forma de lhe fazer mercê. 1555, Toledo, 7 November Father Álvaro Rodrigues writes to King John III to inform him about the health of his sister, Empress Isabel of Portugal. Among other matters that he touches upon briefly, he asks the King to reward him by taking one of his servants as his squire.publishersversionpublishe