Interação da ataxina-2 e ataxina-3 na doença de Machado-Joseph

Mestrado em Biologia Molecular e CelularMachado-Joseph disease also known as Spinocerebellar ataxia type 3 (MJD/SCA3) is a hereditary neurodegenerative disease first described among Portuguese immigrants from Azores. Is the most common autossomal domi-nant spinocerebellar ataxia worldwide and it presents severe clinical features with a fatal outcome. This disease is caused by an unstable expansion of the trinucleotide CAG in the coding region of the MJD1 gene, the mutation is trans-lated into an expanded polyglutamine tract in the protein ataxin-3. The mutant ataxin-3 acquires toxic properties and leads to a downstream of pathogenic mechanisms that make MJD a very heterogeneous disease. Although the polyglutamine expansion in ataxin-3 is sufficient for the pathogen-esis of the disease and for the number of repeats is correlated inversely with the age of onset, clinical observations suggest that the polyQ expansion does not account for all the diversity in the age of onset and clinical manifestations. Interactions between different proteins may affect the age of onset as well as the disease progression. In a screen for modifiers of neurodegeneration in MJD, previous studies found ataxin-2, a protein involved in the spinocerebellar ataxia type 2 (SCA2) which interacts with poly (A)-binding protein (PABP) and may potentiate the neuro-degeneration in MJD. The main goal of our research was to investigate the relation between ataxin-2, PABP and ataxin-3 in MJD. Recurring to human material (brain tissue and fibroblasts), transgenic mice for MJD, a lentiviral-based MJD mouse model and a cellular model of the disease, we observed that levels of ataxin-2 and PABP suffer alterations in MJD. The ataxin-2 immunoreactivity is increased in the human tissue of MJD patients, which also occurred in the transgenic rodents. In the lentiviral model we ob-served both proteins’ recruitment into the nucleus with the progression of the disease. The cellular model revealed a positive feedback between ataxin-2 and PABP that may to be responsible for their capacity in reducing mutant ataxin-3 levels in the disease. Attesting that the levels of the three proteins seem to be inter-dependent, remaining only the question whether this interaction occurs direct or indirectly. These studies indicate that the levels and the consequent toxicity of a polyglu-tamine disease protein can be modulated by the normal activity of another. This synergicall relation may be critical for the pathogenesis of the disease and therefore be a potential therapeutic target.A doença de Machado-Joseph também conhecida como ataxia espinhocerebelosa tipo 3 (MJD/SCA3) é uma doença neurodegenerativa hereditária descrita pela primeira vez em emigrantes portugueses da região dos Açores. É a ataxia autossómica dominante mais comum e apresenta manifestações clínicas severas com um desfecho fatal. Esta doença é causada por uma expansão instável do trinucleótido CAG na região codificante do gene MJD1, que se traduz numa cadeia com um número excessivo de glutaminas na ataxina-3. A ataxina-3 mutante adquire propriedades tóxicas e desencadeia uma patogénese complexa com manifestações heterogéneas. Apesar da expansão poliglutamínica na proteína ataxina-3 ser suficiente para induzir a patogénese da doença e do número de repetições se correlacionar inversamente com a idade de início dos sintomas, não permite explicar toda a diversidade na idade de iníco e nas manifestações clínicas. Há evidências de que a interação entre diferentes proteinas pode afectar quer a idade de ínicio dos sintomas quer a progressão da doença. Na procura de modificadores da neurodegeneração da DMJ estudos recentes sugerem que a ataxina-2, uma proteína envolvida na ataxia espinocerebelosa do tipo 2 (SCA2) que interage com a proteína ligante da cadeia de poliadenina do RNA mensageiro (PABP) e poderá potenciar a neurodegeneração na DMJ. O objectivo principal deste trabalho foi investigar a interacção entre a ataxina-2, PABP e a ataxina-3 na DMJ. Utilizando material humano (tecido cerebral e fibroblastos), animais trangénicos para a doença, um modelo lentiviral em roedor e ainda um modelo celular da doença, observámos que os níveis de ataxina-2 e PABP sofrem alterações na DMJ. A imunoreactividade para a ataxina-2 encontra-se aumentada no tecido humano dos doentes, o que também ocorreu também no murganos trangénicos. No modelo lentiviral observámos um recrutamento de ambas as proteínas para o núcleo da célula coincidente com a progressão da doença. O modelo celular revelou um feedback positivo entre os níveis de ataxina-2 e PABP, que poderá estar na base da sua capacidade de reduzir os níveis de ataxina-3 mutante na doença. Provando assim que os níveis das três proteínas parecem ser interdependentes, permanecendo a questão se esta interação ocorre de forma directa ou indirecta. Estes estudos sugerem que os níveis e consequente toxicidade de uma proteína poliglutamínica mutada pode ser modulada pela actividade normal de outra. Esta relação sinérgica pode ser crítica para a patogénese da doença e desta forma constituir um potencial alvo terapêutico

Marketing Interno nas empresas: efeitos na felicidade e no comprometimento organizacional

Dissertação de mestrado apresentada à Escola Superior de Comunicação Social como parte dos requisitos para obtenção de grau de mestre em Publicidade e Marketing.Cada vez há uma maior competitividade no mercado de trabalho para atrair, contratar e reter os melhor colaboradores. O marketing interno é uma estratégia que deve ser aplicada na empresa para criar valor diferenciado ao produto “organização” aos olhos dos clientes e potenciais clientes internos, os colaboradores. Estudos anteriores comprovam que o marketing interno tem um impacto positivo na performance, motivação e satisfação dos colaboradores, mas há pouca investigação sobre o seu efeito na felicidade organizacional ou no comprometimento organizacional. A presente investigação tem como objetivo compreender quais os contornos do marketing interno, como é que este se apresenta e de que forma influência a felicidade dos colaboradores e o comprometimento organizacional. Para o fazer, optou-se por uma metodologia mista, através de pesquisa qualitativa em forma de entrevistas e pesquisa quantitativa, operacionalizada em inquéritos por questionário. Foram realizadas entrevistas semiestruturadas à Cisco, Conrad Algarve by Hilton e DHL, com o intuito de identificar quais as dimensões do marketing interno e o papel que estas têm na felicidade e comprometimento dos seus colaboradores. Paralelamente, elaborou-se e disponibilizou-se um questionário, baseado em partes de escalas testadas anteriormente, para medir o marketing interno, a felicidade e o comprometimento, através de uma amostra de conveniência (N=225 válidos). Concluiu-se que o marketing interno é constituído por seis dimensões essenciais, a pesquisa interna, as condições ou benefícios, a formação e desenvolvimento, o reconhecimento e recompensas, a liderança e a comunicação interna. Os resultados foram comparados e permitiram aferir que o marketing interno tem um efeito positivo na felicidade organizacional dos clientes internos e no seu comprometimento organizacional. Foi também possível comprovar uma forte correlação entre a felicidade e o comprometimento. Verificou-se ainda que a relação entre o marketing interno e o comprometimento organizacional é mediada pela felicidade organizacional.ABSTRACT: The competitiveness in the labor market is constantly increasing to attract, hire and retain the best employees. Internal marketing is a strategy that should be applied in a company to create differentiated value to the product “organization” for the internal customer and potential internal customer, the employee. Previous studies show that internal marketing has a positive impact on employee performance, motivation, and satisfaction, but there is still little research into its effect on organizational happiness or on organizational commitment. This investigation aims to understand the outlines of internal marketing, how it is presented and how it influences employee happiness and organizational commitment. To do so, a mixed methodology was used, through qualitative research in the form of interviews and quantitative research, operationalized in questionnaire surveys. Semi structured interviews were conducted with Cisco, Conrad Algarve by Hilton and DHL, in order to identify the dimensions of internal marketing and the role they play in the happiness and commitment of its employees. At the same time, a questionnaire was developed and spread, based on parts of previously tested scales, to measure internal marketing, happiness, and commitment, through a convenience sample (N=225 valid). The main conclusion is that internal marketing consists of six essential dimensions, internal market research, job conditions or benefits, training and development, recognition and rewards, leadership, and internal communication. The results were compared, and it was verified that internal marketing has a positive effect on the organizational happiness of internal customers and on their organizational commitment. In addition, a strong correlation between happiness and commitment was proven. Furthermore, it was found that the relationship between internal marketing and organizational commitment is mediated by organizational happiness.N/

IENE 2020 International Conference LIFE LINES – Linear Infrastructure Networks with Ecological Solutions. Abstract Book

In the past 12 to 14 of January 2021, the University of Évora, in the framework of the LIFE LINES project, and the Infrastructure and Ecology Network Europe held the online event IENE International Conference, under the theme “LIFE LINES – Linear Infrastructure Networks with Ecological Solutions”. We had 293 attendees from 40 different countries representing the five continents. During three days, participants were able to assist to 115 full oral presentations, 36 lightning talks, 13 workshops and chat with 40 posters authors, representing studies and projects worldwide. The event counted with 50 thematic sessions, running in five parallel sessions mixing live and pre-recorded interventions

IENE 2020 International Conference “LIFE LINES – Linear Infrastructure Networks with Ecological Solutions””. Programme Book,

In the past 12 to 14 of January 2021, the University of Évora, in the framework of the LIFE LINES project, and the Infrastructure and Ecology Network Europe held the online event IENE International Conference, under the theme “LIFE LINES – Linear Infrastructure Networks with Ecological Solutions”. The local organising committee of the IENE 2020 had contributors from several institutions including the Mediterranean Institute for Agriculture, Environment and Development; REN; Infrastructures of Portugal; and the Municipalities of Montemor-o-Novo and Évora. This was the first IENE International Conference entirely online and participants could attend it from home and working place, regardless of their location in the world. We had 293 confirmed attendees (from 354 registered) from 40 different countries representing the five continents. During three days, participants were able to assist to 115 full oral presentations, 36 lightning talks, 13 workshops and chat with 40 posters authors, representing studies and projects worldwide. The event counted with 50 thematic sessions, running in five parallel sessions mixing live and pre-recorded interventions

Multispecies lanscape functional connectivity enhances local bird species' diversity in a highly fragmented landscape

Local species assemblages are likely the result of habitat and landscape filtering. However, there is still limited knowledge on how landscape functional connectivity complements habitat attributes in mediating local species assemblages in real-world fragmented landscapes. In this study, we set up a non-manipulative experimental design in a standard production forest to demonstrate how functional connectivity determines the spatial distribution of a bird community. We test single- and multispecies spatially explicit, landscape functional connectivity models framed within the circuit theory, considering also patch attributes describing habitat size and quality, to weight their effects on species occurrence and community assemblage. We found that single-species functional connectivity effects contributed positively for occurrence of each species. However, they rarely provided competing alternatives in predicting community parameters when compared to multispecies connectivity models. Incorporating multispecies connectivity showed more consistent effects for all community parameters, than single-species models, since the overlap between species’ dispersal abilities in the landscape shows poor agreement. Habitat size and quality, though less important, were also determinant in explaining community parameters while possibly relating to the provision of suitable nesting and foraging conditions. Both habitat and landscape filters concur to govern community assembly, though likely influencing different processes: while landscape connectivity determines which species can reach a patch, habitat quality determines which species settle in the patch. Our results also suggest that surrogating multispecies connectivity from single species has potential to source bias by assuming species perceive landscape and its barriers similarly. Inference on this issue must be gathered from as much species as possible

The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington’s disease

Objective Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. Results We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression.This work was supported by Brainvectis and E.rare: E-Rare Joint Transnational Call for Proposals 2017 “Transnational Research Projects for Innovative Therapeutic Approaches for Rare Diseases”. CN laboratory is supported by the French Muscular Dystrophy Association (AFM-Téléthon), the Ataxia UK, and the Fundação para a Ciência e Tecnologia (project ALG-01-0145-FEDER-29480 “SeGrPolyQ”). AM is supported by a Ph.D. fellowship from FCT (SFRH/BD/133192/2017)info:eu-repo/semantics/publishedVersio

Effects of transcranial direct current stimulation in dysphagic patients: Efeitos da estimulação transcraniana por corrente contínua em pacientes disfágicos

To determine the effects and effectiveness of transcranial direct current electrical stimulation in patients with complaints of gluttony. RESEARCH STRATEGIES: This is a systematic review and meta-analysis, qualitative and quantitative article. PubMed, ScienceDirect, and BVS Regional Portal were used as databases. They were only clinically controlled and/or randomized clinical trials from 2011 to 2020. SELECTION CRITERIA: Descriptors were used in a combined way: [(dysphagia AND tDCS) OR (dysphagia AND "transcranial stimulation") OR (tDCS AND swallowing)]. DATA ANALYSIS: Meta-analysis was performed using R statistical software version 4.0.2. When grouping effect sizes in Meta-analysis, two approaches were used: the Fixed Effects Model and the Random Effects model. RESULTS: After applying the selection criteria, 5 articles met the requirements for qualitative analysis and 3 for quantitative analysis (meta-analysis). The studies included had a mean of 5.2 years ± 2.38 years of publication and population obtained from patients with changes in gluttony after stroke. A stimulation modality chosen for intervention was the anodic type (n = 5; 100%), prioritizing a representation of the pharynx in the cortex engine, ranging from 4 to 30 combined tDCS. CONCLUSION: There was clinical improvement in the patients, with therapeutic advances being important in the medium term. It is noteworthy that the importance of conducting clinical studies with a greater number of participants is to carry out possible greater sedimentation of the technique in rehabilitating motor, sensory, and/or mixed swallowing genesis disorders

Factors influencing predator roadkills: the availability of prey in road verges

Road mortality is the most noticeable effect of roads on wildlife. Road verges may provide important refuges for small mammals and rabbits, particularly when roads cross intensive agricultural or grazed areas. In these circumstances, the increasing use of verges by prey species may attract predators to road surroundings increasing the risk of roadkill. The aim of this study was to quantify the role of prey availability (small mammals and rabbits) on predator road casualties, taking into account road and surrounding landscape characteristics. We analyzed this effect on different predator species, such as, snakes, owls and mammal carnivores. The study took place in a 10 km stretch of a National Road (EN4) in southern Portugal. Relationships among predator mortality and explanatory variables (prey abundance, landscape characteristics, and road verge features) were evaluated using Multivariate Redundancy Analysis (RDA) followed by a variation partitioning. Our results show that, although landscape features explained most of the mortality variation, the prey availability was also very important. Roadkills of Montpellier snake and Egyptian mongoose are strongly associated with wild rabbit abundance on verges, while mortality of stone marten, barn owl and tawny owl is related with wood mouse abundance, Mediterranean forest (montado) density, and verge shrub density. Implications for verge management and implementation of mitigation actions are discussed. We suggest vegetation removal in verges to decrease shelter and food availability for prey, and/or the promotion of habitat for prey in areas distant from roads

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

info:eu-repo/semantics/publishedVersio

Atualidades na assistência de enfermagem a portadores de úlcera venosa

Úlcera venosa é uma lesão cutânea que acomete o terço inferior das pernas. Está associada à insuficiência venosa crônica, sendo esta a principal causa de úlcera de membros inferiores. Pode interferir na qualidade de vida, pois gera repercussões negativas na esfera social e econômica. A decisão quanto ao tipo do tratamento e orientações para prevenção de feridas exige conhecimento técnico e científico de um enfermeiro. É fundamental para esses profissionais atualizarem os conhecimentos sobre esse assunto, pois a construção de pesquisas é dinâmica e, constantemente, novos conhecimentos são incorporados ou descartados quando ultrapassados. Os objetivos deste artigo de atualização são discorrer sobre o histórico e sintomas da úlcera venosa, assistência de enfermagem, opções de tratamento, prevenção e relação custo/benefício do tratamento tradicional e atual de feridas. O diagnóstico baseia-se em história clínica completa, exame físico com identificação dos sinais e sintomas e exame complementar para analisar estrutura e função do sistema venoso. O tratamento é direcionado para obter cicatrização da úlcera e evitar recidivas. Os avanços no conhecimento sobre o tratamento de feridas têm permitido a integralidade do cuidado, busca pela autonomia do portador de úlcera venosa e ênfase na qualidade da assistência para favorecer a relação custo/benefício