Sapientia
Repositório Científico da UAlg
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Effects and variability of decline in sea ice on marine primary production in the arctic
Publication . Walter, Charlotte; Relvas, Paulo; Samuelsen, Annette
The Arctic environment is rapidly changing and drastic declines in sea ice extent and thickness have been observed over the past decades. The thinning of the ice pack affects its dynamics and makes it more susceptible to form pressure-ridges and leads. Such features appear at a scale of meters to kilometers, and are thus usually not represented in common Earth system models. However, observations show that their presence influences polar phytoplankton communities and productivity, pointing at the importance of representing such sea ice features in biogeochemical ocean modeling. The following study investigates how Arctic primary production and carbon export simulated with the biogeochemical model HYCOM-ECOSMO are affected by different sea ice models. Two simulations are available; one coupled to the classical Los Alamos sea ice model (CICE) that simulates sea ice as a continuum that deforms in a viscous manner. In contrast, the second simulation was run with the next generation sea-ice model (neXtSIM) with a brittle rheology that better represents features such as leads and ridges. Climatologies, daily time series and maps of monthly mean values for relevant parameters were analyzed for three Arctic regions. Differences in sea ice concentration resulting from the different rheologies caused differences in light availability and primary production between simulations in all regions. The different influx volumes of melt water and resulting stratification of the upper ocean affected primary production in two of three regions, and might have caused differences in nutrient availability between simulations. These findings suggest that the choice of sea ice model affects primary production modeling in HYCOM-ECOSMO to a certain extent. The results of this study contribute to the evaluation of whether the better representation of mechanical damage in sea ice models with brittle rheology can improve primary production and carbon export predictions from Arctic Ocean biogeochemical models.
Development of IL-11 receptor targeting miniproteins
Publication . Komporday, Katalin Luca; Oroszlan, Gabor; Power, Deborah Mary
De novo protein design has emerged as a transformative approach for creating novel therapeutic molecules with highly specific functions and tailored structures. This thesis presents the design and development of miniproteins targeting the interleukin-11 receptor alpha (IL-11Rα), a key mediator in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). Miniproteins, small stable peptides with well-defined tertiary structures, offer advantages over traditional therapies by small molecules or antibodies through higher selectivity, improved tissue penetration, and lower risk of immunogenicity. Leveraging AI-driven bioinformatics tools, a library of 400 different miniprotein scaffolds was designed to selectively bind the IL-11Rα, competing with its natural ligand, IL-11 cytokine. The miniprotein library was synthesized as an oligonucleotide pool, cloned into phagemid vectors, and expressed on the pIII M13 bacteriophage surface for phage display-based selection. A biopanning campaign was used to enrich miniproteins with strong binding affinities for IL-11Rα across multiple screening rounds. Two lead candidates, DN226 and DN213 demonstrated high specificity and affinity confirmed by ELISA assays. However, DN226 showed a better affinity and competitiveness against the IL-11 cytokine for binding to the receptor compared to DN213. Since transient transfection expression of IL-11Rα in FreeStyle Human Embryonic Kidney (HEK293-F) cells faced yield and aggregation challenges, commercially sourced IL-11Rα was employed in downstream assays. The combination of computational design with classical biotechnological approaches enabled the rapid identification of functional miniproteins capable of binding the IL-11Rα. This work underscores the potential of AI-driven de novo protein design as a versatile technology for precise drug discovery and development. The identified miniproteins provide promising hit molecules for developing innovative, targeted anti-fibrotic therapies. Future work should focus on optimizing miniprotein candidates and evaluating their efficacy in cell-based and in vivo studies, paving the way for novel treatment approaches for fibrotic diseases, like IPF.
Evaluation of the therapeutic effect of human IPSC-derived neuroephitelial stem cells in an immunocompromised lentiviral-induced Machado Joseph Disease mouse model
Publication . Pires, Joana Gonçalo; Mendonça, Liliana Simões; Nóbrega, Clévio; Almeida, Luís Pereira de
Machado-Joseph Disease (MJD), or Spinocerebellar Ataxia Type 3 (SCA3), is a dominantly inherited neurodegenerative disorder caused by CAG repeat expansion in the ATXN3 gene, resulting in a polyglutamine-expanded ataxin-3 protein that forms toxic intranuclear aggregates. With no current disease-modifying therapies, novel approaches targeting the molecular and cellular basis of MJD are urgently needed. This study evaluated the therapeutic potential of neuroepithelial stem cells (Nesc) derived from human induced pluripotent stem cells (iPSCs), both CNT (not bearing the mutant ataxin-3) (CNT NESC) and MJD cells genetically engineered with allele-specific shRNAs targeting mutant ATXN3 RNA (Silenced MJD NESC), following striatal transplantation in NOD/SCID mice injected with lentivirus encoding for mutant ataxin-3 ( lentiviral-induced MJD mouse model). Our results demonstrate that both CNT and silenced MJD NESC are prone to survive up to eight weeks after transplantation into the striatum of NOD/SCID mice also injected with lentivirus encoding for mutant ataxin-3. Both cell types triggered a tendency reduction in the size of the inclusions. Western blot analysis showed a modest, non-significant decrease in high-molecular-weight ATXN3 aggregates in the silenced MJD NESC group. Additionally, no significant differences were observed between CNT mice and CNT and Silenced MJD NESC groups regarding microglia recruitment. RT-qPCR analysis revealed that the striatum of mice transplanted with CNT NESC and Silenced MJD NESC expressed higher Notch1 mRNA levels, and tendency increased for both Bdnf and Ngf mRNA levels. These results demonstrated the ability of NESC to trigger the bystander effects and enhance neurogenesis-related and neurotrophic factors levels after transplantation in the lentiviral-induced MJD mouse model. Collectively, these findings support the therapeutic promise of combining targeted gene silencing of MJD patients’ iPSC-derived NESC with NESC transplantation in MJD mouse models.
Diagnóstico, análise de tendências e contributos para a melhoria da gestão do desempenho das equipas: o caso de uma USF do modelo A
Publication . Abreu, Marisa Almeida de; Pescada, Susana; Vidal, João
A elevada pressão sentida ao nível dos sistemas de saúde e consequente aumento das necessidades de cuidados de saúde, obriga a uma maior e cada vez melhor gestão dos recursos existentes. Num cenário de imprevisibilidade, em que todos os futuros são possíveis, as equipas de saúde beneficiam em estar preparadas para decidir da melhor forma sobre a forma como devem fazer a sua própria gestão. Este estudo teve como propósito realizar um diagnóstico da situação atual de uma Unidade de Saúde Familiar (USF), a fim de identificar tendências e contributos para a melhoria da gestão do desempenho. Para tal, baseou-se na metodologia prospetiva, mais concretamente no Método dos Cenários proposto por Godet, em particular na Análise Estratégica de Atores. Numa fase inicial foi feita recolha e análise documental, incluindo uma análise SWOT, para melhor delimitação do sistema. Foi assim possível encontrar as variáveis-chave do sistema, bem como determinar quais os desafios e respetivos objetivos estratégicos, assim como os atores-chave. Toda a informação obtida nas entrevistas foi cuidadosamente analisada, recorrendo ao Método ACTores, Objetivos, Relações de força (MACTOR), uma ferramenta especifica da metodologia prospetiva, em particular do Método dos Cenários, que permite posicionar os atores em relação aos objetivos, hierarquizar os objetivos estratégicos e ainda estudar a relação de forças entre atores. A partir da análise estratégica de atores foi possível identificar um conjunto de recomendações estratégicas para a USF em estudo, com intuito de servirem de apoio à gestão interna da equipa e contribuir para a melhoria do seu desempenho.
O impacto das Práticas de RH no desempenho: O papel mediador do comprometimento organizacional e a moderação da satisfação profissional
Publication . Naendralal, Sofia Duro; Sousa, Cátia
Num contexto organizacional marcado pela crescente valorização do capital humano, torna-se essencial compreender de que forma as práticas de gestão de pessoas influenciam o comportamento dos trabalhadores. O presente estudo quantitativo teve como objetivo analisar a relação entre as perceções de práticas de recursos humanos (PRH) e o desempenho dos colaboradores, considerando o papel mediador do comprometimento organizacional e o efeito moderador da satisfação profissional. Pretendeu-se, assim, explorar não apenas relações diretas, mas também os mecanismos psicológicos e condições contextuais que explicam ou condicionam esta ligação. A investigação empírica baseou-se numa amostra de 193 participantes, maioritariamente do género feminino (70.5%), com idades entre os 18 e os 64 anos (M = 35.67; DP = 10.97), que responderam a um questionário online. As análises estatísticas incluíram testes de regressão, mediação e moderação. Os resultados indicam que perceções favoráveis das PRH se associam a maiores níveis de satisfação profissional e comprometimento organizacional, sendo este último, na sua dimensão afetiva, um mediador significativo da relação entre PRH e desempenho. Por outro lado, a satisfação profissional não moderou a ligação entre comprometimento e desempenho, apontando para o seu papel independente enquanto preditor. Estes resultados sublinham a relevância das práticas de recursos humanos na promoção de atitudes positivas e na melhoria do desempenho individual, quando sustentadas por vínculos afetivos fortes com a organização.