Effects of the aurora kinase inhibitors AZD1152-HQPA and ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts.

BACKGROUND:
Aurora kinases play an essential role in the orchestration of chromosome separation and cytokinesis during mitosis. Small-molecule inhibition of the aurora kinases has been shown to result in inhibition of cell division, phosphorylation of histone H3 and the induction of apoptosis in a number of cell systems. These characteristics have led aurora kinase inhibitors to be considered as potential therapeutic agents.
DESIGN AND METHODS:
Aurora kinase gene expression profiles were assessed in 101 samples from patients with acute myeloid leukemia. Subsequently, aurora kinase inhibitors were investigated for their in vitro effects on cell viability, histone H3 phosphorylation, cell cycle and morphology in acute myeloid leukemia cell lines and primary acute myeloid leukemia samples.
RESULTS:
The aurora kinase inhibitors AZD1152-HQPA and ZM447439 induced growth arrest and the accumulation of hyperploid cells in acute myeloid leukemia cell lines and primary acute myeloid leukemia cultures. Furthermore, both agents inhibited histone H3 phosphorylation and this preceded perturbations in cell cycle and the induction of apoptosis. Single cell cloning assays were performed on diploid and polyploid cells to investigate their colony-forming capacities. Although the polyploid cells showed a reduced capacity for colony formation when compared with their diploid counterparts, they were consistently able to form colonies.
CONCLUSIONS:
AZD1152-HQPA- and ZM447439 are effective apoptosis-inducing agents in acute myeloid leukemia cell lines and primary acute myeloid leukemia cultures. However, their propensity to induce polyploidy does not inevitably result in apoptosis.

Maria Edgeworth: Nineteenth century Irish female pioneer of science education.

Maria Edgeworth was a nineteenth century novelist, primarily remembered for her adult and children's novels. Yet her book, Letters for literary ladies discussed the importance of science education for girls and in conjunction with her father, Richard Edgeworth, she wrote several treatises on education. Their book Practical education advocates an inquiry approach to teaching science and also using scientific practices, such as observation and data collection, to examine and plan children's education. They emphasised the importance and the role of experimentation, observation and critical thinking in the development of children's knowledge, skills and attitudes towards learning. However, the history of science education has to date ignored this seminal work and Maria's contributions to women's science education.

Aurora-A expression, hormone receptor status and clinical outcome in hormone related cancers

Aims: We investigated the correlation between protein expression of Aurora-A with hormone receptor expression and clinicopathological parameters in ovarian, breast and prostate cancer.

Maria Victoria Atencia: Legend of Myself

In this collection of 65 short poems, Roberta Quance exemplifies the range, vitality and mysticism of work by one of Spain’s foremost, if controversial, contemporary female poets, drawing on the contents of a number of Spanish collections.

miR-433 overexpression attenuates the spindle assembly checkpoint response to paclitaxel

Paclitaxel is a microtubule inhibitory chemotherapeutic drug that is increasingly used for the treatment of solid tumours. In vitro studies have demonstrated that attenuating the spindle assemble checkpoint (SAC) alters the post-mitotic responses to paclitaxel. Furthermore, the aberrant expression of a number of the SAC proteins, MAD2, BUBR1, and Aurora A kinase, are associated with poor patient prognosis. We have identified a microRNA, miR-433, that regulates the expression of MAD2. Overexpression of miR-433 in Hela cells induced downregulation of MAD2 mRNA and protein expression. We have also shown that Hela cells overexpressing miR-433 and treated with paclitaxel are no longer capable of cyclin B stabilisation, and thus have lost the ability to activate the SAC in response to paclitaxel. In addition, cell viability assays showed that Hela cells overexpressing miR-433 and treated with paclitaxel have an attenuated response to paclitaxel compared with microRNA scrambled controls. We have characterised the levels of miR-433, MAD2 gene expression and MAD2 protein levels in a cohort of ovarian cancer cell lines. Cell viability assays on this cohort revealed that responsiveness to paclitaxel is associated with high MAD2 protein expression and lower miR-433 expression. We hypothesise that the expression of miR-433 when deregulated in cancer leads to altered MAD2 expression and a compromised SAC, a key feature underlying drug resistance to paclitaxel. In a pilot study of paired human breast tumour and normal breast tissue samples we have shown that expression levels of miR-433 are elevated in cancer tissue. Targeting this microRNA in cancer may improve the efficacy of paclitaxel in treating breast cancer and ovarian cancer.

Comportamentos agressivos entre pares e padrões de vinculação: um estudo com jovens adolescentes

O presente estudo, desenvolvido com 237 jovens de três escolas do distrito de Évora, teve como objetivos caracterizar e analisar os comportamentos relacionados com situações de bullying (vitimação, do agressão e observação); e analisar a existência de eventuais relações entre padrões de vinculação e comportamentos agressivos entre pares. Utilizaram-se dois questionários de auto-relato, nomeadamente o QEVE – Questionário de Exclusão Social e Violência Escolar (Martins, 2003), que mede os comportamentos de agressão, vitimação e observação; e o IVIA – Inventário sobre Vinculação para a Infância e a Adolescência (Carvalho, Soares & Baptista, 2006), que analisa um conjunto de comportamentos e representações da vinculação na infância e na adolescência. Ambos os instrumentos mostraram boas qualidades psicométricas. Os resultados mostraram uma clara prevalência de situações de observação, relativamente às situações de agressão e de vitimação. Em todas estas situações, os comportamentos relacionados com a Exclusão Social e Agressão Verbal são os mais frequentes, comparativamente aos comportamentos relacionados com a Agressão Física. Os rapazes apresentaram médias mais elevadas em todas as escalas; os estudantes com menor percepção de suporte social na escola eram os que evidenciavam mais comportamentos de vitimação. No que se refere aos padrões de vinculação, os resultados mostraram que a vinculação segura parece funcionar como um fator protetor para a vitimação e para a agressividade. A partir dos resultados obtidos, serão analisadas pistas para uma intervenção psicoeducativa.

Tecnologia vinagreira: desenvolvimento de novos produtos vinagreiros na ESAS

O vinagre é obtido por dupla fermentação alcoólica e acética de substâncias de origem agrícola, possuindo cada tipo um flavour particular, função dos substratos e tecnologia usados, mantendo gosto sui generis ácido. A sua aptidão tecnológica viabiliza o fabrico de múltiplos produtos, macerando especiarias, plantas, etc, conduzindo ao enriquecimento da matriz, cujo perfil químico ganha complexidade e novas características sensoriais/funcionais. A picklagem fresh pack é um processo alternativo de conservação em vinagre, sem fermentação. Com vinagres de fermentação submergida, desenvolveram-se na ESAS (2009-2013), dois vinagres e um vinagrete com adições e um pickles de frutos doces, articulando ensaios tecnológicos, laboratoriais e sensoriais. Concebidos como produtos gourmet, pretendeu-se oferecer inovação e conveniência. Além do longo tempo de vida de prateleira, evidencia-se: 1) no vinagre de vinho branco com mirtilo –a mais-valia de preservar o fruto inteiro, por efeito de picklagem; 2) no vinagre agridoce, de vinho tinto Touriga Nacional com mel e especiarias –uma tónica agridoce equilibrada e actual; 3) no vinagrete de laranja aromatizado –a complexidade aromática aliada à sensação de frescura na boca; 4) no pickles fresh pack de pera-abacaxi agridoce –novidade e dupla utilização: consumida a fruta, a infusão utiliza-se como vinagre de mesa (aptidão incomum em pickles).---Vinegar is obtained by double fermentation alcoholic and acetic of substances from agricultural origin, each type having one particular flavor, due to the technology and the substrates used, while maintaining sui generis acid taste. Its technological aptitude enables the manufacture of multiple products, macerating spices, plants, leading to the enrichment of the matrix whose chemical profile becomes increasingly complex with new sensory/functional characteristics. The fresh pack process is an alternative process of pickling, without fermentation. With submerged fermentation vinegar, two vinegars and a vinaigrette with additions and pickled sweet fruits were developed in ESAS (2009-2013), articulating technological, laboratory and sensory tests. Designed as gourmet products, intended to provide innovation and convenience. In addition to the long shelf life, stands out: 1) in white wine vinegar with blueberries – the added value of preserving the whole fruit by pickling effect, 2) in bittersweet red wine vinegar, Touriga Nacional with honey and spices – the sweet and sour taste, balanced and fashionable; 3) in flavored orange vinaigrette – the aromatic complexity coupled with the fresh sensation in the mouth, 4) in the fresh pack sweet and sour pickles with pear-pineapple – the innovation and dual-use: consumed the fruit, infusion is used as table vinegar (unusual application for pickles).

A influência da satisfação no trabalho no desempenho profissional um estudo de caso:as ajudantes de ação direta no Centro de Apoio Social da Carregueira

Dissertação, Mestrado, Gestão de Organizações de Economia Social, Instituto Politécnico de Santarém, Escola Superior de Gestão e Tecnologia, 2016

O potencial de produção e comercialização de uvas "D. Maria" em Portugal

A produção de uva de mesa “Dona Maria”, casta 100% nacional criada e obtida nos anos 50 na antiga Estação Agronómica Nacional, em Oeiras, pelo engenheiro-agrónomo Leão Ferreira de Almeida, vem decrescendo ano após ano como resultado do desinteresse e abandono por parte dos agricultores. É uma uva muito doce, com bagos grandes e apreciada pelos portugueses que sentem cada vez mais dificuldades em encontrá-la no mercado. Este estudo de caso tem como objetivos verificar o porquê de tão pouca produção desta uva por parte dos agricultores e sugerir através de ferramentas e estratégias de marketing formas de fazer com que a uva seja mais conhecida e consumida pelo mercado português. No intuito de valorizar e consumir o que é nacional, a uva “Dona Maria” é uma excelente opção para o consumo em fresco ou na forma de passa, em cantinas de escolas e universidades. Os investimentos em novas tecnologias de produção e investigação por parte dos produtores também são uma boa opção para rentabilizar a casta e fazer com que ela não desapareça do mercado, o que seria desastroso na perspectiva cultural e económica; ### Abstract: The production of the table grape “Dona Maria”, a 100% national Portuguese grape variety, created and produced in the 1950s in the former National Agricultural Station (EAN) in Oeiras, Portugal, by Leão Ferreira de Almeida, has been decreasing year after year as a result of lack of interest and abandonment on behalf of producers. It is a very sweet grape with big berries and is highly appreciated by the Portuguese, who find it ever more difficult to find it in the marketplace. This case study´s objectives were to investigate the shortage of production by growers, and to suggest through marketing strategies and tools, ways to make this grape better known and more consumed by the Portuguese market. Within the scope of highlighting and promoting this national product, “Dona Maria” grape is an excellent option either as a fresh consumable or raisin in school and university restaurants. Investment in new production technologies and research are also a good choice and direction to promote the variety and avoid its disappearance from the market, which would be disastrous both culturally and economically.