A construção narrativa da família em crianças com familiares alcoólicos: contributos de um estudo qualitativo

No presente artigo descreve-se um estudo cujo objetivo se centra na identificação e compreensão dos significados e sentidos, narrativamente construídos e organizados por crianças com e sem familiares alcoólicos, relativamente à sua família. Esta investigação enquadra-se na necessidade atual de aprofundar o estudo do consumo de álcool e do seu impacto a nível familiar, principalmente no desenvolvimento das crianças. Foi utilizada uma metodologia qualitativa, recorrendo-se à realização de entrevistas analisadas de acordo com a Grounded Analysis. As entrevistas decorreram com 11 crianças com idades compreendidas entre os 4 e os 10 anos de idade, inseridas nas atividades lúdico-pedagógicas de um projeto social. Seis destas crianças possuem familiares que sofrem de alcoolismo e cinco não. Os resultados apontam para a existência de diferenças entre os discursos dos dois grupos de crianças que constituíram a amostra, sendo que as crianças com familiares alcoólicos manifestaram uma concepção diferente da família, que envolve relações conflituosas e problemas de vários tipos.info:eu-repo/semantics/publishedVersio

Conceções dos alunos do 1º ciclo do ensino básico sobre o lobo ibérico

O lobo ibérico (Canis lupus signatus) é um predador de topo, cuja função ecológica é muitas vezes incompreendida. Historicamente suscitou muitos ódios e, mais recentemente, preocupações com a sua viabilidade enquanto espécie. Esta investigação diagnosticou as conceções dos alunos dos 1.º e 2.º anos do 1.º Ciclo do Ensino Básico sobre o lobo. Para tal, foram analisados 164 desenhos sobre essa espécie, os quais foram posteriormente classificados em 10 categorias de codificação. De forma geral, os resultados mostraram que os alunos possuem uma visão favorável sobre o lobo e alguns conhecimentos sobre as suas características e habitat. Concluiu-se que representaram frequentemente o lobo no seu contexto ecológico, a uivar e/ou ao luar e personificações dessa espécie e do seu contexto. Por outro lado, também se apurou que algumas crianças manifestaram conceções deturpadas e estereotipadas sobre a espécie lupina porque representaram-na como feroz, agressiva e que deve ser caçada ou presa em cativeiro. Estas conceções erradas podem servir de base para os docentes despertarem nos alunos a consciência da importância do verdadeiro papel do lobo no equilíbrio dos ecossistemas da Península Ibérica. (Abstract: The Iberian wolf (Canis lupus signatus) is a top predator whose ecological function is often misunderstood. Historically it raised many hates and, more recently, concerns with its feasibility as a species. This research determines the conceptions about the Iberian wolf of 1st and 2nd grade students of public elementary schools. For that matter, 164 drawings about that species were analyzed and posteriorly classified in 10 categories. Generally, the results show that the students have a positive vision of the wolf and some knowledge about its features and habitat. It was concluded that they often represented the wolf in its ecological context, howling and/or by moonlight, and also personifications of that species and its context. On the other hand, it was also found that a few students have manifested distorted and stereotyped conceptions regarding the wolf, as they represented it as a fierce and aggressive species that should be hunted or locked up in captivity. These misconceptions can serve as a base for the teachers to aware the students of the importance of the wolf’s real role on the balance of the Iberian Peninsula’s ecosystems.

NPY Y1 receptor is not involved in the hemodynamic response to an acute cold pressor test in mice

The vasoconstrictor neuropeptide Y (NPY) has been shown to down-regulate tyrosine hydroxylase expression in cultured adrenal chromaffin cells, which probably accounts for the higher plasma resting norepinephrine (NE) and epinephrine (E) concentrations observed in Y1 knock-out mice (Y1-/-) than in wild-type mice (Y1+/+). The aim of this work was to study the hemodynamic response of Y1-/- mice to an acute stimulation of the sympathetic nervous system (cold pressor test, CPT). Plasma catecholamine concentrations were higher in Y1-/- mice than in wild-type animals at the end of the CPT. The CPT-induced increase in mean arterial blood pressure (MAP) and heart rate (HR) was similar in both genotypes. Independently of the genotype, females had significantly slower HR than males throughout the 15 min duration of the CPT. There was no difference in the sensitivity of the baroreceptor reflex, as reflected by the change in HR divided by the concurrent change in MBP between Y1-/- and Y1+/+ mice. In conclusion, mice lacking the Y1 receptor can maintain normal hemodynamic response to an acute activation of the sympathetic system, albeit at the expense of increased catecholamine discharge.http://www.sciencedirect.com/science/article/B6T0M-4MT54Y4-3/1/f346666c9ec021eeffb80529f17474d

Caloric restriction blocks neuropathology and motor deficits in Machado–Joseph disease mouse models through SIRT1 pathway

Machado–Joseph disease (MJD) is a neurodegenerative disorder characterized by an abnormal expansion of the CAG triplet in the ATXN3 gene, translating into a polyglutamine tract within the ataxin-3 protein. The available treatments only ameliorate symptomatology and do not block disease progression. In this study we find that caloric restriction dramatically rescues the motor incoordination, imbalance and the associated neuropathology in transgenic MJD mice. We further show that caloric restriction rescues SIRT1 levels in transgenic MJD mice, whereas silencing SIRT1 is sufficient to prevent the beneficial effects on MJD pathology. In addition, the re-establishment of SIRT1 levels in MJD mouse model, through the gene delivery approach, significantly ameliorates neuropathology, reducing neuroinflammation and activating autophagy. Furthermore, the pharmacological activation of SIRT1 with resveratrol significantly reduces motor incoordination of MJD mice. The pharmacological SIRT1 activation could provide important benefits to treat MJD patients.Fonds Europeen de Developpement Economique et Regional. Competitive Factors Operational Program (CENTRO-07-ST24-FEDER-002002)Fundação para a Ciência e a Tecnologia (Portugal) (Strategic Project UID/NEU/04539/2013, E-Rare4/0003/2012)French Muscular Dystrophy Association (AFM-Téléthon)National Ataxia FoundationRichard Chin and Lily Lock Machado-Joseph Disease Research Fun

Trehalose alleviates the phenotype of Machado–Joseph disease mouse models

Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most common of the dominantly inherited ataxias worldwide and is characterized by mutant ataxin-3 aggregation and neuronal degeneration. There is no treatment available to block or delay disease progression. In this work we investigated whether trehalose, a natural occurring disaccharide widely used in food and cosmetic industry, would rescue biochemical, behavioral and neuropathological features of an in vitro and of a severe MJD transgenic mouse model.This work was funded by BioBlast Pharma, the ERDF through the Regional Operational Program Center 2020, Competitiveness Factors Operational Program (COMPETE 2020) and National Funds through FCT (Foundation for Science and Technology) - SFRH/BD/87404/2012, BrainHealth2020 projects (CENTRO-01-0145-FEDER-000008), ViraVector (CENTRO-01-0145FEDER-022095), CortaCAGs (POCI-01-0145-FEDER-016719), SpreadSilenc‑ing POCI-01-0145-FEDER-029716 and POCI-01-0145-FEDER-007440, as well as the SynSpread, ESMI and ModelPolyQ under the EU Joint ProgramNeurodegenerative Disease Research (JPND), the last two co-funded bythe European Union H2020 program, GA No. 643417; by National Ataxia Foundation (USA), the American Portuguese Biomedical Research Fund (APBRF) and the Richard Chin and Lily Lock Machado–Joseph Disease Research Fund.info:eu-repo/semantics/publishedVersio

Neuropeptide Y Enhances Progerin Clearance and Ameliorates the Senescent Phenotype of Human Hutchinson-Gilford Progeria Syndrome Cells

Hutchinson-Gilford progeria syndrome (HGPS, or classical progeria) is a rare genetic disorder, characterized by premature aging, and caused by a de novo point mutation (C608G) within the lamin A/C gene (LMNA), producing an abnormal lamin A protein, termed progerin. Accumulation of progerin causes nuclear abnormalities and cell cycle arrest ultimately leading to cellular senescence. Autophagy impairment is a hallmark of cellular aging, and the rescue of this proteostasis mechanism delays aging progression in HGPS cells. We have previously shown that the endogenous Neuropeptide Y (NPY) increases autophagy in hypothalamus, a brain area already identified as a central regulator of whole-body aging. We also showed that NPY mediates caloric restriction-induced autophagy. These results are in accordance with other studies suggesting that NPY may act as a caloric restriction mimetic and plays a role as a lifespan and aging regulator. The aim of the present study was, therefore, to investigate if NPY could delay HGPS premature aging phenotype. Herein, we report that NPY increases autophagic flux and progerin clearance in primary cultures of human dermal fibroblasts from HGPS patients. NPY also rescues nuclear morphology and decreases the number of dysmorphic nuclei, a hallmark of HGPS cells. In addition, NPY decreases other hallmarks of aging as DNA damage and cellular senescence. Altogether, these results show that NPY rescues several hallmarks of cellular aging in HGPS cells, suggesting that NPY can be considered a promising strategy to delay or block the premature aging of HGPS

The NutriClock Study Protocol - Assessing the Impact of a Chrononutrition Intervention in Patients With Cardiometabolic Disturbances

info:eu-repo/semantics/publishedVersio

The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes

Insulin resistance is a major predictor of the development of metabolic disorders. Sirtuins (SIRTs) have emerged as potential targets that can be manipulated to counteract age-related diseases, including type 2 diabetes. SIRT2 has been recently shown to exert important metabolic effects, but whether SIRT2 regulates insulin sensitivity in hepatocytes is currently unknown. The aim of this study is to investigate this possibility and to elucidate underlying molecular mechanisms. Here, we show that SIRT2 is downregulated in insulin-resistant hepatocytes and livers, and this was accompanied by increased generation of reactive oxygen species, activation of stress-sensitive ERK1/2 kinase, and mitochondrial dysfunction. Conversely, SIRT2 overexpression in insulin-resistant hepatocytes improved insulin sensitivity, mitigated reactive oxygen species production and ameliorated mitochondrial dysfunction. Further analysis revealed a reestablishment of mitochondrial morphology, with a higher number of elongated mitochondria rather than fragmented mitochondria instigated by insulin resistance. Mechanistically, SIRT2 was able to increase fusion-related protein Mfn2 and decrease mitochondrial-associated Drp1. SIRT2 also attenuated the downregulation of TFAM, a key mtDNA-associated protein, contributing to the increase in mitochondrial mass. Importantly, we found that SIRT2 expression in PBMCs of human subjects was negatively correlated with obesity and insulin resistance. These results suggest a novel function for hepatic SIRT2 in the regulation of insulin sensitivity and raise the possibility that SIRT2 activators may offer novel opportunities for preventing or treating insulin resistance and type 2 diabetes.European Regional Development Fund (ERDF), Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000012: HealthyAging2020); COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-007440, SFRH/BPD/109347/2015 to R.M.O., SFRH/BD/86655/2012 to L.N. and SFRH/BPD/111815/2015 to P.G.); FLAD Life Science 2020 Grant to A.C.R.; European Molecular Biology Organization (EMBO Installation Grant to T.F.O.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) to T.F.O

The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes

Funding Information: European Regional Development Fund (ERDF), Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000012: HealthyAging2020); COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-007440, SFRH/BPD/109347/ 2015 to R.M.O., SFRH/BD/86655/2012 to L.N. and SFRH/BPD/ 111815/2015 to P.G.); FLAD Life Science 2020 Grant to A.C.R.; European Molecular Biology Organization (EMBO Installation Grant to T.F.O.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) to T.F.O.Insulin resistance is a major predictor of the development of metabolic disorders. Sirtuins (SIRTs) have emerged as potential targets that can be manipulated to counteract age-related diseases, including type 2 diabetes. SIRT2 has been recently shown to exert important metabolic effects, but whether SIRT2 regulates insulin sensitivity in hepatocytes is currently unknown. The aim of this study is to investigate this possibility and to elucidate underlying molecular mechanisms. Here, we show that SIRT2 is downregulated in insulin-resistant hepatocytes and livers, and this was accompanied by increased generation of reactive oxygen species, activation of stress-sensitive ERK1/2 kinase, and mitochondrial dysfunction. Conversely, SIRT2 overexpression in insulin-resistant hepatocytes improved insulin sensitivity, mitigated reactive oxygen species production and ameliorated mitochondrial dysfunction. Further analysis revealed a reestablishment of mitochondrial morphology, with a higher number of elongated mitochondria rather than fragmented mitochondria instigated by insulin resistance. Mechanistically, SIRT2 was able to increase fusion-related protein Mfn2 and decrease mitochondrial-associated Drp1. SIRT2 also attenuated the downregulation of TFAM, a key mtDNA-associated protein, contributing to the increase in mitochondrial mass. Importantly, we found that SIRT2 expression in PBMCs of human subjects was negatively correlated with obesity and insulin resistance. These results suggest a novel function for hepatic SIRT2 in the regulation of insulin sensitivity and raise the possibility that SIRT2 activators may offer novel opportunities for preventing or treating insulin resistance and type 2 diabetes.publishersversionpublishe

CreativeLab_Sci&Math: Atividade outdoor no Geopark Naturtejo_7.º Ano

Este recurso consiste numa propostas de trabalho outdoor que se enquadra no âmbito da disciplina de Ciências Naturais, do 7.º ano. . A proposta de trabalho contempla uma pré-saída, uma saída com oito paragens que exploram o valor cultural, científico e educativo do património geológico do Geopark Naturtejo e uma pós-saída.info:eu-repo/semantics/publishedVersio