Abnormal regulation of Na,K-ATPase in Glucose Intolerant Rats.

Introduction: Glucose is the most important physiological insulin secretagogue. However, the mechanisms underlying glucose-induced insulin release are not fully understood. The role of electrogenic systems such as ionic pumps, to these events remains essentially uninvestigated. Na,K-ATPase, responsible for maintaining Na+ and K+ gradients across the plasma membrane and generates a net outward current, thus changes in its activity may contribute to the early ionic events regulating insulin secretion (Therien and Blostein, 2000). Objective: The aim of this work was to evaluate the regulation of Na,K-ATPase activity by glucose in intact -cells of normal and glucose intolerant (GI) rats and its putative contribution to the regulation of insulin secretion. Material and Methods: Pancreatic -cells, from normal or control or GI rats, were isolated and cultured (48h). Cell batches were pre-incubated (30min) with 2mM glucose to reach basal. Afterwards cells were challenged with glucose in the interval 0-11mM for 60min, for dose-dependence evaluation, or with 8mM glucose for 5-120min, for time-dependence evaluation. ATPase activity was assessed in intact cells by colorimetric quantification of Pi formed in 30min. Na,K-ATPase activity was calculated by the difference between the activities obtained in the absence and in presence the of 1mM ouabain (Costa et al., 2009). Results: In β-cells from normal rats, glucose induced a bimodal regulation of Na,K-ATPase. In the absence of glucose, Na,K-ATPase activity was 0.056±0.015 U/mg. Stimulation with 2mM glucose induced an increase of Na,K-ATPase activity of ~4 fold whereas for [glucose] above 2mM it was observed a significant inhibition of Na,K-ATPase activity (0.061±0.013, 0.080±0.009 and 0.064±0.005 U/mg for 5.6, 8.4 and 11mM glucose, respectively, compared to 0.188±0.035 U/mg observed in 2mM G; n=3-8). β-cells from GI rats does not present this profile; in the absence of glucose, Na,K-ATPase activity was 0.202±0.036 U/mg and no significant differences from this value were observed with the other glucose concentration tested. Addicionally, in β-cells from normal rats, glucose (8mM) induced a time-dependent inhibition, with a biphasic profile, of Na,K-ATPase - it was observed a decrease in the pump activity between 0 and 20min stimulation where it reached a minimum value (77%). For incubation periods over 20min, the pump activity slowly and partially recovered (54%, 55% and 52%, for 30, 60 and 120min, respectively; n=7). In β-cells from GI animals, an less accentuated decrease of Na,K-ATPase activity between 0 ans 20min was also observed (34%), and is not observed further recover in activity. Conclusions: This work demonstrates there Na,K-ATPase is strictly regulated by glucose in pancreatic β-cell. This regulation is unpaired in GI animals. Na,K-ATPase contribution to glucose-induced ionic events and insulin secretion might be relevant and must be explored as a possible therapeutic target in TD2 . 1. Therien AG, Blostein R (2000) Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol 279:C541-C566 2. Costa AR, Real J, Antunes CM, Cruz-Morais J (2009) A new approach for determination of Na,K-ATPase activity: application to intact pancreatic beta-cells. In Vitro Cell Dev Biol Ani

Implication of AMPK in glucose-evoked modulation of Na,K-ATPase

Background and aims: Na,K-ATPase is an integral membrane protein that maintains the gradients of Na+ and K+, using the energy of ATP hydrolysis, maintaining the ionic gradients that allow electrical activity to occur. It has been demonstrated that, in pancreatic β-cells, Na,K-ATPase is regulated by glucose and that this phenomenon is impaired in glucose intolerant subjects. However, the mechanism underlying glucose-induced modulation of Na,K-ATPase is still unclear. The AMP-activated protein kinase (AMPK) is a molecular key player in energy homeostasis, providing exquisite sensitivity to small changes in intracellular AMP levels and thus to intracellular [ATP]/[ADP] ratio, that is known to activate protein regulatory pathways. Since in pancreatic β-cell, glucose has marked effects on oxidative metabolism and total intracellular ATP and AMP levels, the involvement of AMPK in the cascade of events regulating Na,K-ATPase regulation in pancreatic β-cells was postulated. The aim of this work was to evaluate the putative role of AMPK in the glucose-evoked regulation of Na,K-ATPase activity in the pancreatic β-cell. Materials and methods: Pancreatic -cells from normal (control) or glucose-intolerant Wistar rats (GIR) were isolated and cultured (48h). Cell batches were pre-incubated (30min) with 2.1mM glucose to reach basal activity. Afterwards cells were challenged to 8.4mM glucose for 20min, in the presence or absence of AMPK agonists (AICAR) and antagonists (compound C; CC). ATPase activity was assessed in intact cells by colorimetric quantification of Pi formed in 30min. Na,K-ATPase activity was calculated by the difference between the activities obtained in the absence and in presence the of 1mM ouabain. Results: In basal conditions the activity of Na,K-ATPase from normal and GIR pancreatic β-cell was similar (0.184±0.030 and 0.186±0.020 molPi/min/mgProt, respectively). Challenging the control β-cells with glucose 8.4mM evoked a 62% reduction of Na,K-ATPase activity whereas in GIR β-cells a significantly lower inhibition (40%) was observed. The addition of AICAR 1mM abolished glucose-induced Na,K-ATPase inhibition (0,166±0.011 molPi/min/mg). In control β-cell, the addition of CC 10 μM had no effect on glucose-induced inhibition of Na,K-ATPase. In the contrary, in GIR β-cells it significantly potentiated glucose-evoked inhibition of Na,K-ATPase reaching values similar to that observed in the controls (66%). Conclusions: The AMPK agonist AICAR counteracts the inhibitory action of glucose on Na,K-ATPase of control β-cells whereas CC amplified the glucose-induced inhibition of Na,K-ATPase in GIR β-cells. These results suggest that AMPK plays a central role in the cascade of events underlying glucose-induced modulation of Na,K-ATPase and that the defect must be upstream of AMPK. Finally, abnormal glucose-induced regulation of Na,K-ATPase occurs prior to overt type 2 diabetes and might be a feature in the disease development

Anthropogenic actions shape biodiversity change and ecosystem functioning

Increasing rates of carbon emission, unsustainable development, and intense land cover change, led to an inevitable environmental degradation. While much of the lost biodiversity has not been described by scientists yet, we continue to lose new species at impressive rates. In this thesis, I compiled a large dataset for vertebrate assemblages in the Amazon forest, known for its extensive understudied biodiversity. The database englobes camera trap data from mammals, birds and reptile species and represents a small but important step further in the direction of filling the gap in biodiversity information for the Amazon forest. Using this dataset, I investigated the effects of human modifications on vertebrate communities in the Amazon, and the results show that, even within the gradient of low to moderate human modification, we can detect a decrease in the richness of vertebrate species. This raises a red flag for the vulnerability of species under our current scenario of changes in climate and land use. The functioning of the ecosystems involves complex processes and interactions of different species, and understanding the relationship between biodiversity change and the contribution of biodiversity to the provision of nature’s contribution to people (NCP) remains a challenge. In this thesis, I propose a macroecological framework that integrates biodiversity models and energy flux theory to link biodiversity, ecosystem function and NCP. This novel approach allows the incorporation of different aspects (such as species interactions and environmental data) to evaluate biodiversity-based NCP. Furthermore, in order to apply this framework to belowground ecosystems, I aggregated data and developed a biodiversity model to predict species abundance based on their body mass. Additionally, I also used the compiled database to explore the effects of environmental conditions on the community-abundance distribution of the communities

Iris Murdoch's 'The Unicorn' (1963): Gothicizing Morality

In a post-war panorama of secular humanism, morality has taken on new contours that allow Goodness to be achieved via the forgoing of the Self. This seems to be the lesson of the late Iris Murdoch, who dedicated her life to the study of philosophy in an attempt to create a unified moral code to offer guidance to (wo)mankind. Increasingly worried by the ethical road society was travelling down in the twentieth century, its lack of religious direction and consequent spiritual void, the novelist creates a moral philosophy based on the precept that one must reject one’s natural predisposition for egotism -a form of Evil. The soul must enter a path of knowledge that will allow man to see Reality and Truth. The secular redemption of the soul can only be achieved through a life dedicated to art and looking beyond oneself. Female Gothic, a tangential strain that developed out of the eighteenth century Gothic, has been used to express social anxieties concerning such issues as identity, sexuality, the fragmentation of the self and the redemption or damnation of the soul. This article explores how Iris Murdoch appropriates Female Gothic in order to explore these anxieties, as well as to propagate her own moral philosophy in an attempt to reform our spiritual world through a suggested model of Goodness.Num panorama de humanismo secular pós-guerra, a moralidade ganha novos contornos que permitem que a Bondade seja alcançada através da renúncia do Eu. Esta é a lição que nos deixa Iris Murdoch, autora que dedicou a sua vida ao estudo da filosofia, na tentativa de criar um código moral uno pelo qual a humanidade se pudesse reger. Largamente preocupada com o caminho ético que a sociedade estava a tomar no século XX, na sua falta de direcção religiosa e no consequente vazio espiritual, a autora cria uma filosofia moral baseada no preceito de que o indivíduo deve rejeitar a sua predisposição natural para o egoísmo enquanto uma manifestação de Mal. A alma deve procurar o caminho de conhecimento para que o Homem possa alcançar a Realidade e a Verdade. A redenção secular da alma apenas pode ser alcançada através de uma vida altruísta dedicada à arte e focada no outro. O Gótico Feminino, um subgénero do Gótico que se veio a desenvolver desde o século XVIII, tem sido usado para exprimir ansiedades sociais relacionadas com a identidade, a sexualidade, a fragmentação do Eu e a condenação ou redenção da alma. Este artigo procura investigar a forma como Iris Murdoch se apropria do Gótico Feminino para explorar estas ansiedades, bem como para difundir a sua filosofia moral, usando assim a sua obra como forma de tentar reformar o nosso mundo espiritual através de um proposto modelo de Bondad

Non–profit and investment attractiveness – best practices under a national perspective

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and EconomicsThis Work Project (WP) aims to measure the investment attractiveness of the social sector by providing a general overview of the investment strategies and motivations behind Non-Profit Initiatives (NPIs) performed by the For-Profit sector (FP), usually perceived as corporate social responsibility (CSR). Through the development of a structured survey and a structured analysis of the NPIs performed by Psi–20 companies over the last five years, the final purpose of the project is to provide a set of tools to non-profit organizations to attract investment to their projects

Responsabilidade social : estudo com uma amostra de colaboradores do sector de retalho

Tese de mestrado, Psicologia (Secção de Psicologia dos Recursos Humanos, do Trabalho e das Organizações), Universidade de Lisboa, Faculdade de Psicologia, 2012Actualmente, torna-se fundamental que as empresas conjuguem os seus objectivos financeiros e económicos às questões relacionadas com a cidadania, ética nos negócios e preservação do meio ambiente, e que reconheçam o valor da sua responsabilidade social de modo a fazer face aos constantes desafios com que são confrontadas e mantendo uma “imagem positiva” junto dos seus stakeholders. A presente investigação incide sobre o estudo da Responsabilidade Social, mais especificamente sobre a relação entre as Percepções de Responsabilidade Social (dimensões económica, legal, ética, discricionária para com os colaboradores e discricionária para com a comunidade) e as variáveis idade, sexo e antiguidade dos colaboradores. Para medir a variável em estudo foi utilizada a Escala de Cidadania Empresarial, que foi aplicada a uma amostra de 106 colaboradores de uma empresa do sector de retalho. Os resultados obtidos corroboram parcialmente a relação entre algumas dimensões da Responsabilidade Social e as variáveis sexo e idade dos colaboradores. No final, tecem-se algumas considerações para futuras propostas de investigação e limitações do presente estudo.Currently, it becomes fundamental that enterprises combine their financial and economic objectives with the questions related to citizenship, business ethics and environmental preservation, and that they recognize the value of their Corporate Social Responsibility in order to deal with the constant challenges confronting them and maintaining a “positive image” with is Stakeholders. The present investigation focuses on the study of Corporate Social Responsibility, specifically on the relation between Perceptions of Social Responsibility (economic, legal, ethic and discretionary towards employees and discretionary towards the community dimensions) and age, sex and seniority variables of the employees. To measure the variables under study, the Corporate Citizenship Scale was used, being applied to an 106 employees sample from a retail sector company. The final results partially support the relation between some Social Responsibility dimensions and the variables sex and age of the employees. At the end, some considerations about future investigation proposals and limitations of this study are stated

Ensinar e aprender através da banda desenhada digital – Pixton : no 1º CEB

A comunicação apresenta uma investigação realizada no âmbito da Prática de Ensino Supervisionada do mestrado em Educação Pré-Escolar e Ensino do 1º CEB que foi implementado na Escola Básica da Boa Esperança de Castelo Branco, numa turma de 3º ano que incluiu 21 alunos. O principal objetivo da investigação foi o de averiguar e compreender os potenciais contributos, no processo de ensino/aprendizagem, através da utilização do Software «Pixton» (suporte digital que permite a criação de uma banda desenhada digital). Os resultados da investigação vieram demonstrar que a utilização do «Pixton» despertou nos alunos o prazer em realizar as atividades, mantendo-os mais motivados para as aprendizagens, não tendo sido necessário recorrer a estratégias diferenciadas para que resolvessem as atividades propostas. Dado que os alunos referiram, através do questionário, que as atividades que mais gostavam de fazer no computador era jogar, o «Pixton» conseguiu-lhes transmitir esse ambiente lúdico que muito apreciaram. Contudo, foi sempre intenção expressa utilizar o recurso digital como forma de complementar o papel do professor, recorrendo ao professor ou ao recurso digital sempre que tal se entendesse mais pertinente.The paper presents an investigation under the Master Supervised Teaching Practice in Preschool Education and the 1st Cycle (Basic Education) which was implemented in the Basic School of «Boa Esperança» at Castelo Branco, a 3rd grade class that included 21 students. The main objective of the research was to investigate and understand the potential contributions in the process of teaching /learning through the use of software "Pixton" (digital support that enables the creation of a digital comic). The research results have shown that the use of 'Pixton’ aroused the students happy to carry out the activities, keeping them more motivated for learning and has not been necessary to use different strategies to solve the proposed activities. Since the students mentioned, through the questionnaire, that the activities they liked to do on the computer was playing the 'Pixton’ succeeded them convey this playful environment that is greatly appreciated by them. However, it was always stated intention to use digital resource as a way to complement the role of the teacher, using the teacher or digital resource whenever it is understood more relevant.info:eu-repo/semantics/publishedVersio

Herpes zoster with cutaneous dissemination: a rare presentation of an uncommon pathology in children

Herpes zoster, caused by varicella zoster virus (VZV) reactivation, affects mainly the adult population, although it can occur in children. This happens when primary infection (varicella) has occurred at a very young age or in immunocompromised patients. Complications are rare in healthy individuals. They include VZV cutaneous dissemination, which affects 2%-10% of immunocompromised patients.We present a previously healthy child, with history of varicella during her first month of life, which presented at age 8 with a severe case of herpes zoster, complicated with cutaneous dissemination. Immunity study was unremarkable. Causes, management and follow-up are discussed.(undefined

Estimation of periodontitis national and regional prevalence based on the study of periodontal health Almada-Seixal

Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas MonizAims: To estimate the risk of periodontitis in the Portuguese population at a regional level and the prevalence of periodontitis in the municipalities that make up the clusters with peri-urban characteristics. Materials and Methods: In this study, we have estimated the periodontitis risk for Portuguese population, at regional/territory-level, based on a multivariate approach, using sociodemographic, economic and health services data. The information was gathered for all 308 Portuguese municipalities and compiled in a large set of 52 variables. Principal Component Analysis (PCA), Factor Analysis (FA) and clustering techniques were used to model the nationwide geographical distribution of the disease. Estimation of periodontitis risk for each municipality was achieved by calculation of a normalized score, obtained as an adjusted linear combination of six independent factors that were extracted through PCA/FA. The municipalities were also classified according to a quartile-based risk grade, in each cluster. Additionally, linear regression was used to estimate the periodontitis prevalence within the peri-urban municipalities clusters, accounting for 30.5% of the Portuguese population. Results: A total of nine municipalities clusters were obtained with the following characteristics: mainly rural/low populated, including small villages (1), partly rural/including small cities (2), partly rural/including small and médium cities (3), mainly urban/peri-urban/including medium to large size cities (4 and 5). Uninominal clusters with their own characteristics were also obtained, grouped in clusters 6,7,8 and 9. The estimated periodontitis prevalence for the 18 municipalities included in the four peri-urban clusters, ranged from 41.2 to 69.0%. Conclusions: Periodontitis proved to be a disease with high prevalence in Portugal. The most affected population tends to be the oldest, with the highest unemployment rate, low income, precarious housing and with less schooling. To counter these values, it is foreseen the need to invest in oral health through the National Health Service.Objetivos: Estimar o risco de periodontite na população portuguesa a nível regional e a prevalência de periodontite dos municípios que integram os clusters com características periurbanas. Materiais e Métodos: Neste estudo, estimou-se o risco de periodontite para a população portuguesa, a nível regional/territorial, com base numa abordagem multivariada, utilizando dados sociodemográficos, económicos e dos serviços de saúde. A informação foi recolhida para todos os 308 municípios portugueses e compilada num conjunto de 52 variáveis. A Análise de Componentes Principais (ACP), Análise Fatorial (AF) e técnicas de agrupamento foram utilizadas para modelar a distribuição geográfica nacional da doença. A estimativa do risco de periodontite para cada município foi obtida pelo cálculo de um score normalizado, obtido como uma combinação linear ajustada de fatores independentes que foram extraídos por ACP/AF. Os municípios também foram classificados de acordo com um grau de risco baseado em quartis, em cada cluster. Adicionalmente, a regressão linear foi utilizada para estimar a prevalência de periodontite nos aglomerados de municípios periurbanos, representando 30,5% da população portuguesa. Resultados: Obteve-se um total de nove aglomerados (clusters) de municípios com as seguintes características: principalmente rural/pouco povoado, incluindo pequenas aldeias (1), parcialmente rural/incluindo pequenas cidades (2), parcialmente rural incluindo pequenas e médias cidades (3), principalmente urbano/periurbano/incluindo cidades de médio a grande porte (4 e 5). Obtiveram-se ainda aglomerados uninominais com caraterísticas próprias agrupados nos clusters 6,7,8 e 9. A prevalência estimada de periodontite para os 18 municípios incluídos nos quatro clusters periurbanos variou de 41,2 a 69,0%. Conclusão: A periodontite mostrou ser uma doença com elevada prevalência em Portugal. A população mais afetada tem tendência a ser a mais envelhecida, com maior taxa de desemprego, baixo rendimento, precariedade habitacional e com menor formação escolar. Para contrariar estes valores prevê-se a necessidade de apostar na saúde oral através do Serviço Nacional de Saúde