Genetic and functional analyses of the developing asymmetric zebrafish habenula

The vertebrate brain develops anatomical and functional left-right asymmetries in localised regions, without affecting the laterality of the surrounding structures. To understand how brain laterality develops, we studied the development of robust habenular asymmetries in larval zebrafish. The left and right dorsal habenulae (dHb) have different sizes, asymmetric patterns of gene expression and establish distinct afferent and efferent connections. Although we are beginning to understand the molecular pathways that establish these asymmetries, the pathways underlying formation of the habenular progenitors remains largely elusive. Also, despite several habenular gene expression patterns being broadly asymmetric, there are no habenular markers for smaller habenular neuronal subpopulations in 4 dpf zebrafish. Lastly, we still need to investigate the importance of habenular asymmetry for its correct function and normal behaviour. This thesis aims to tackle these three gaps in habenular asymmetry research. To do so, we first characterised the A66u757 mutant, which develops a smaller and symmetric habenula. The causative mutation is in the rerea gene, which encodes a co-regulator of nuclear receptors that modulates the expression of fgf8. In line with this, the pattern of fgf8 expression is expanded in the diencephalon of mutants, and the parapineal is malformed, as observed in other FGF signalling mutants. Lastly, we show that the habenular phenotype of these mutants is concomitant with a delay in the formation of habenular progenitors. Second, to understand which neuronal subpopulations compose the zebrafish habenula at 4 dpf, we developed a protocol to obtain habenular single cells for RNA sequencing. Cells collected from the left and right nuclei still express habenular genes in an asymmetric fashion. However, to increase the number of collected cells, we harvested GFP-positive cells from a transgenic line that expresses GFP in the dHb and in the olfactory organ. Consequently, we sequenced 586 cells, which were separated into dHb, ventral habenula and olfactory organ clusters. However, due to the relatively small number of sequenced cells, we did not manage to discriminate subpopulations of the dHb. We propose optimisation steps that will allow us to finish this work. Lastly, to study the role of habenular asymmetry in behaviour, we tested two habenular mutants in an operant learning paradigm, through the ROAST assay. We show that wild-type and left-isomerised dHb mutant larvae learn to terminate an aversive stimulus by changing the direction of a stereotypical aversive-heat-response. Despite not finding differences between these mutants and wild-types, we did not exclude the role of the habenula in this assay and propose future research to further test this function

The Importance of Relationships for the Produced Knowledge in the Sector of Management Consulting

While the management consulting industry has been largely linked to the knowledge produced within the disciplines of strategic management in the academic field, the truth is that very little literature is produced in terms of research in this area, while the researchers focused more on a set of static techniques to be applied in the development of this field of research concerns. This article seeks to bridge this gap as well, showing by example that the consultancy sector is a true field of opportunities for the study of relationships management. This presentation is thus the aim of contributing both theoretically and empirically in the area of relationships through research in the context of management consulting, trying to visualize how the relationships are manifested in a context of high involvement and personal contact, and what’s the perception that must be taken into consideration by clients and consultants in terms of the benefits of their greater or lesser degree of involvement.info:eu-repo/semantics/publishedVersio

Sistema de testes para cone de suspensão de parapente

Mestrado em Sistemas e Tecnologias de Informação para as OrganizaçõesA atual crise económica de abrandamento e recessão leva a que várias empresas estejam a sentir elevadas quebras no seu volume de negócios e de produção. Deste modo a inovação e a diferenciação assumem um papel de relevo nas empresas especialmente em tempos de crise. Tradicionalmente, as empresas especializadas em reparações de parapentes utilizam meios meramente visuais para avaliar o estado do cone de suspensão dos parapentes1 Embora o parapente seja considerado um desporto seguro, existem alguns riscos associados a esta prática desportiva. O estado do material utilizado assume um papel preponderante no que diz respeito à segurança. Dependendo da sua composição, os cordões apresentam diferentes características e comportamentos: enquanto uns apresentam maior estabilidade a nível dimensional e menor flexibilidade, outros apresentam menor estabilidade dimensional e maior flexibilidade. Contudo, com o tempo e os esforços a que são sujeitos, todos vão sofrendo desgaste, provocando variações ao nível da sua dimensão e perdendo resistência. [25] . Este tipo de inspeções é pouco fiável e coloca em causa a segurança do piloto. É, neste contexto, que aqui é proposto um novo método de avaliação do cone de suspensão. Para isso, foi desenvolvido um protótipo, designado por sistema de testes para cone de suspensão de parapente que permite analisar uma amostra de cordões e desta forma avaliar o seu estado atual. Este tipo de testes possibilita ao utilizador aferir do estado da asa e daí decidir qual a melhor forma de reparar/aumentar a segurança da asa. 1 - Conjunto de linhas que suportam o peso do piloto.Abstract: The current economic slowdown conjecture leads to recession and many companies are experiencing high losses in its turnover and production. This way, the innovation and differentiation are an important role in business especially in times of crisis. Traditionally, companies that specialize in repairs of paragliders using only visual means to assess the state of the cone suspension of paragliders2 Although the glider is considered a safe sport, there are some risks associated with this sport. The state of the material takes a leading role with regard to safety. Depending on its composition, the strings have different characteristics and behaviors: while some have more stable and less dimensional flexibility, others are less dimensional stability and flexibility. However, with time and effort that they are subject, everyone will suffer wear and tear, including changes in terms of size and losing strength. [25] . Such inspections are unreliable and jeopardize the safety of the pilot. It is in this context that we propose here a new method for evaluating the cone suspension. For this, we developed a prototype, called the testing system for rear suspension that allows the glider to analyze a sample of cord and thus assess its current state. This type of testing allows the user to gauge the state of the wing and then decide the best way to fix / enhance the security of the wing 2 - Set of lines that support the weight of the pilo

The “Fashionable Knowledge” of Management Consulting

In the evolution of strategic disciplines much of the knowledge produced has been widely diffused by the management consulting industry. But can this sector be regarded as knowledge intensive activity based on true structure of expertise knowledge? One way to understand if we can consider that sector as a source of knowledge dissemination is realizing its relationship with the market in terms of knowledge, rather than identify only as a set of static techniques to be applied as in most of times they have been doing. This article presents itself as a reflection about the real reasons for the increasing use ofmanagement consulting services, indicating simultaneously that can really be a true field of opportunities for the academic class if the study will focused in the establishment and institutionalization of micropractices (strategy-as-practice) that there are used and its implications in terms of organizational results.info:eu-repo/semantics/publishedVersio

How the population’s perceptions influence their behaviours regarding the consumption of fibre rich foods

The association between dietary fibre, health benefits and healthy food has been studied in recent years. The food industry, to accompany the strong interest shown by consumers, has placed at their disposal new products, rich in dietary fibre. In order to meet this huge interest and demand for these products, this work was elaborated, which had as main objective to evaluate the degree of knowledge of the Portuguese population about fibre and its effects on health, as well as evaluating the their consumption habits in respect of fibres. To achieve this goal an inquiry was carried out by questionnaire to 182 adults. The most relevant results indicate that only 13% of the inquired eat two meals a day with vegetables and/or salads and 9% eat at least 3 pieces of fruit. Whole grains are never consumed by 41% and 18% do so at least once a week. The vast majority (90%) of respondents have the notion that fibre intake contributes to the prevention and treatment of diseases. With this work it was concluded that respondents‘ knowledge about dietary fibre is insufficient, and that although they give great importance to their role in treatment and prevention of diseases, the level of intake is too low

Conhecimento da População Portuguesa sobre Fibras Alimentares

As fibras têm sido objecto de estudo nas últimas décadas e um dos temas frequentemente abordado é a relação entre fibra alimentar e os benefícios para a saúde. Este trabalho pretendeu fazer uma análise estatística do conhecimento da população portuguesa relativa às fibras alimentares. Foi realizado um inquérito por questionário entre Abril e Junho de 2011 a uma amostra de 182 indivíduos. Foram abordados temas como hábitos de consumo, conhecimento sobre fibras, meios de divulgação e informação, rotulagem dos alimentos, relação entre fibras e saúde, entre outros. Alguns dos resultados obtidos indicam que aproximadamente 70% dos inquiridos possui idade entre 18 e 40 anos, ensino universitário e vive no meio urbano. Os resultados mais relevantes indicam que por dia apenas 13% dos inquiridos comem duas refeições com legumes e/ou saladas e 9% come no mínimo 3 peças de fruta. Os cereais integrais nunca são consumidos por 41% e apenas 18% o fazem pelo menos uma vez por semana. Cerca de 35% dos inquiridos sabem qual a origem das fibras e aproximadamente 70% afirma que existe maior quantidade de fibras nas leguminosas, fruta com casca e nos alimentos integrais. A consulta dos rótulos dos alimentos revela interesse por parte de 80% dos inquiridos, sendo que, do total de respostas, apenas 10% consulta sempre o rótulo. O teor de fibras que o alimento possui não é do interesse de 43% dos inquiridos tendo em conta que esta informação nunca é consultada ou então isso é feito raramente. Um valor semelhante (39%) refere que a quantidade de fibras não é tida em conta aquando da escolha dos alimentos. A grande maioria (90%) dos inquiridos tem a noção de que a ingestão de fibras contribui para a prevenção e tratamento de doenças. Das várias doenças referidas no inquérito, as mais citadas foram a prisão de ventre (86%), obesidade (80%), doenças cardiovasculares e colesterol (7 %) e o cancro do intestino (69%). Relativamente aos meios de divulgação e informação sobre fibras alimentares, a escola (44%) e a televisão (41%) foram considerados os meios de divulgação mais adequados para incentivar o consumo, mas, na realidade, são os centros de saúde e hospitais (25%) que têm mais informação disponível. Com a realização deste trabalho foi possível concluir que o conhecimento dos inquiridos acerca de fibras alimentares é insuficiente, e que apesar de lhes ser atribuída grande importância no tratamento e prevenção de doenças, o nível de ingestão é muito baixo

ANÁLISE EPIDEMIOLÓGICA DOS CASOS DE INTOXICAÇÃO HUMANA POR PLANTAS NO BRASIL (2015-2019)

Estima-se a existência de mais de 250 mil espécies de vegetais superiores e, dentre elas, estão as plantas ornamentais, que comumente são utilizadas em ambientes públicos. Dentre as principais plantas ornamentais, estão as da família Araceae, das quais destacam-se aquelas do gênero Dieffenbachia, que engloba as plantas conhecidas popularmente como “comigo-ninguém-pode”, que podem causar casos graves de intoxicação em humanos e animais domésticos. Nesse cenário, o objetivo deste estudo foi realizar um levantamento epidemiológico, através do Sistema de Informação de Agravos de Notificação (SINAN), acerca dos casos de intoxicação por plantas em todo território nacional no período entre 2015 até 2019. Foi possível observar que, no período analisado, foram totalizados 4.604 casos de intoxicação por plantas no Brasil, dos quais 1.552 (o que equivale a 33,70% dos casos) ocorreram na região Sudeste, fazendo com que esta região ocupe o primeiro lugar em número de intoxicações por plantas, seguido pela região Sul (28,41% dos casos), Nordeste (22,67%), Centro-Oeste (9,60%) e, com a menor taxa, a região Norte (5,60%). A principal faixa etária acometida foi de 1-4 anos, com 1.427 casos (o que representa 30,99% dos envenenamentos no Brasil). Analisando esses dados, podemos perceber a necessidade constante de estudos e de campanhas educativas e preventivas sobre este tema em todo o País, especialmente voltado para crianças, seus responsáveis ou professores da educação básica, o que poderia evitar ou diminuir esses tipos de ocorrência

EL “OUTSOURCING” COMO UN RECURSO ESTRATÉGICO DE LA COMPETITIVIDAD INTERNACIONAL DEL MERCADO ESPAÑOL

La globalización del mercado empresarial actual requiere de una visión global, lógica y de carácter funcional, vinculada a la creación de valor desde un punto de vista del coste, el tiempo y la prestación del servicio. La enfatización de nuevas formas organizacionales y nuevos procesos de trabajo en términos contractuales ha dejado de ser vista como un recurso pasando a ser entendida como una necesidad básica y fundamental. Este artículo tiene como objetivo presentar un componente teórico relacionado con una estrategia de negocio muy particular, dada la importancia que pueda tener en el actual contexto empresarial de España. En esta medida, cabe preguntarse lo siguiente: ¿es el sector del "Outsourcing" la respuesta ideal y una herramienta influyente y poderosa de cambio organizacional?, ¿podrá este sector ser uno de los focos de proyección internacional de España y una verdadera fuente de ingresos en tiempos de crisis y cerca de la recesión? En realidad, este puede ser el camino para capitalizar las ventajas de España, mejorar sus desventajas, crear empleo, generar riqueza, promover la competitividad internacional y, aún más importante, ser la medicina alternativa para curar la enfermedad que supone ahora el déficit publico español y que el tratamiento “Outsourcing” podría eventualmente ayudar a regenerar.info:eu-repo/semantics/publishedVersio

AKT can modulate the in vitro response of HNSCC cells to irreversible EGFR inhibitors

Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines. The mutational analysis in the eight HNSCC cell lines revealed an EGFR mutation (p.H773Y) and gene amplification in the HN13 cells. According to the growth inhibition score (GI), allitinib was the most cytotoxic drug, followed by afatinib and finally cetuximab. The higher AKT phosphorylation level was associated with resistance to anti-EGFR agents. Therefore, we further performed drug combinations with anti-AKT agent (MK2206) and AKT1 gene editing, which demonstrated afatinib and allitinib sensitivity restored. Additionally, in silico analysis of TCGA database showed that AKT1 overexpression was present in 14.7% (41/279) of HNSCC cases, and was associated with perineural invasion in advanced stage. In conclusion, allitinib presented a greater cytotoxic profile when compared to afatinib and cetuximab. AKT pathway constitutes a predictive marker of allitinib response and combination with AKT inhibitors could restore response and increase treatment success.FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013 - FPXII-BIOPLAT) and the Assistance Program and Incentive Research (PAIP), Barretos Cancer Hospital São Paulo, Brazil. The authors would like to acknowledge the technical support of Gabriela Lamberti in the clonogenic assays. A.L.C and R.M.R are recipients of a National Counsel of Technological and Scientific Development (CNPq) scholarship and O.C.M is recipient of a Portuguese Foundation for Science and Technology (FCT) scholarship (SFRH/BPD/108351/2015)info:eu-repo/semantics/publishedVersio

In vitro screening of cytotoxic activity of euphol from Euphorbia tirucalli on a large panel of human cancer-derived cell lines

A large number of classic antineoplastic agents are derived from plants. Euphorbia tirucalli L. (Euphorbiaceae) is a subtropical and tropical plant, used in Brazilian folk medicine against many diseases, including cancer, yet little is known about its true anticancer properties. The present study evaluated the antitumor effect of the tetracyclic triterpene alcohol, euphol, the main constituent of E. tirucalli in a panel of 73 human cancer lines from 15 tumor types. The biological effect of euphol in pancreatic cells was also assessed. The combination index was further used to explore euphol interactions with standard drugs. Euphol showed a cytotoxicity effect against several cancer cell lines (IC50 range, 1.41-38.89 µM), particularly in esophageal squamous cell (11.08 µM) and pancreatic carcinoma cells (6.84 µM), followed by prostate, melanoma, and colon cancer. Cytotoxicity effects were seen in all cancer cell lines, with more than half deemed highly sensitive. Euphol inhibited proliferation, motility and colony formation in pancreatic cancer cells. Importantly, euphol exhibited synergistic interactions with gemcitabine and paclitaxel in pancreatic and esophageal cell lines, respectively. To the best of our knowledge, this study constitutes the largest in vitro screening of euphol efficacy on cancer cell lines and revealed its in vitro anti-cancer properties, particularly in pancreatic and esophageal cell lines, suggesting that euphol, either as a single agent or in combination with conventional chemotherapy, is a potential anti-cancer drug.Amazônia Fitomedicamentos Ltda. (grant no. FITO 05/2012) and Barretos Cancer Hospital, all from Brazilinfo:eu-repo/semantics/publishedVersio