Browsing by Author "Silva, Ana"
Now showing 1 - 9 of 9
Results Per Page
Sort Options
- Activation of PI3K Is indispensable for Interleukin 7–mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cellsPublication . Barata, João T.; Silva, Ana; Brandao, Joana G.; Nadler, Lee M.; Cardoso, Angelo A.; Boussiotis, Vassiliki A.Interleukin (IL)-7 is essential for normal T cell development. Previously, we have shown that IL-7 increases viability and proliferation of T cell acute lymphoblastic leukemia (T-ALL) cells by up-regulating Bcl-2 and down-regulating the cyclin-dependent kinase inhibitor p27kip1. Here, we examined the signaling pathways via which IL-7 mediates these effects. We investigated mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (Erk) and phosphatidylinositol-3-kinase (PI3K)-Akt (protein kinase B) pathways, which have active roles in T cell expansion and have been implicated in tumorigenesis. IL-7 induced activation of the MEK-Erk pathway in T-ALL cells; however, inhibition of the MEK-Erk pathway by the use of the cell-permeable inhibitor PD98059, did not affect IL-7-mediated viability or cell cycle progression of leukemic cells. IL-7 induced PI3K-dependent phosphorylation of Akt and its downstream targets GSK-3, FOXO1, and FOXO3a. PI3K activation was mandatory for IL-7-mediated Bcl-2 up-regulation, p27kip1 down-regulation, Rb hyperphosphorylation, and consequent viability and cell cycle progression of T-ALL cells. PI3K signaling was also required for cell size increase, up-regulation of CD71, expression of the glucose transporter Glut1, uptake of glucose, and maintenance of mitochondrial integrity. Our results implicate PI3K as a major effector of IL-7-induced viability, metabolic activation, growth and proliferation of T-ALL cells, and suggest that PI3K and its downstream effectors may represent molecular targets for therapeutic intervention in T-ALL.
- Detection of the invasive mosquito species Aedes (Stegomyia) albopictus (Diptera: Culicidae) in PortugalPublication . Osório, Hugo; Zé-Zé, Líbia; Neto, Maria; Silva, Sílvia; Marques, Fátima; Silva, Ana; Alves, Maria JoãoThe Asian tiger mosquito Aedes albopictus is an invasive mosquito originating from the Asia-Pacific region. This species is of major concern to public and veterinary health because of its vector role in the transmission of several pathogens, such as chikungunya, dengue, and Zika viruses. In Portugal, a National Vector Surveillance Network (REde de VIgilância de VEctores—REVIVE) is responsible for the surveillance of autochthonous, but also invasive, mosquito species at points of entry, such as airports, ports, storage areas, and specific border regions with Spain. At these locations, networks of mosquito traps are set and maintained under surveillance throughout the year. In September 2017, Ae. albopictus was detected for the first time in a tyre company located in the North of Portugal. Molecular typing was performed, and a preliminary phylogenetic analysis indicated a high similarity with sequences of Ae. albopictus collected in Europe. A prompt surveillance response was locally implemented to determine its dispersal and abundance, and adult mosquitoes were screened for the presence of arboviral RNA. A total of 103 specimens, 52 immatures and 51 adults, were collected. No pathogenic viruses were detected. Despite the obtained results suggest low abundance of the population locally introduced, the risk of dispersal and potential establishment of Ae. albopictus in Portugal has raised concern for autochthonous mosquito-borne disease outbreaks.
- Intertidal pools as alternative nursery habitats for coastal fishesPublication . Dias, Marta; Roma, Joana; Fonseca, Catarina; Pinto, Maria; Cabral, Henrique; Silva, Ana; Vinagre, CatarinaFish were sampled monthly in four tidal pools, for two years, on the west Portuguese coast. Species diversity of transient fish was higher than that found in previous studies, in other parts of the world. The transient fish population comprised six species: the white seabream, Diplodus sargus, sand smelt, Atherina spp., the thinlip grey mullet, Liza ramada, the Baillon’s wrasse, Symphodus bailloni, the zebra seabream, Diplodus cervinus and the European pilchard, Sardina pilchardus. Abundance varied seasonally, yearly, and among pools, with peak numbers in spring and summer. The most abundant species in all pools, both as larvae and juveniles, was D. sargus. Diplodus sargus and Atherina spp. were present in most pools, from spring to autumn, while rare species were present mostly in the spring-summer period. Smaller mean sizes of larvae and juveniles were observed at the beginning of spring of 2011 (March–April) and at the end of spring/beginning of summer of 2012 (May–June). Mean size of larvae and juveniles often showed a continuous increase from spring to autumn in both years. The highest density peaks were due to the high number of post-larvae entering the pools in spring. In most pools, the overall condition (Fulton’s K) of D. sargus increased throughout the year, in both years. The species richness, the high densities of early stages, and their continuous growth observed in tidal pools strongly emphasize the importance of these environments for larvae and juveniles of several transient marine fishes.
- Molecular and functional evidence for activity of murine IL-7 on human lymphocytesPublication . Barata, João T.; Silva, Ana; Abecasis, Miguel; Carlesso, Nadia; Cumano, Ana; Cardoso, Angelo A.Although interleukin-7 (IL-7) is essential for human and murine lymphopoiesis and homeostasis, clear disparities between these species regarding the role of IL-7 during B-cell development suggest that other, subtler differences may exist. One basic unsolved issue of IL-7 biology concerns cross-species activity, because in contrast to the human ortholog, the ability of murine (m)IL-7 to stimulate human cells remains unresolved. Establishing whether two-way cross-species reactivity occurs is fundamental for evaluating the role of IL-7 in chimeric human-mouse models, which are the most versatile tools for studying human lymphoid development and disease in vivo. Here, we show that mIL-7 triggers the same signaling pathways as human (h)IL-7 in human T cells, promoting similar changes in viability, proliferation, size, and immunophenotype, even at low concentrations. This ability is not confined to T cells, because mIL-7 mediates cell growth and protects human B-cell precursors from dexamethasone-induced apoptosis. Importantly, endogenous mIL-7 produced in the mouse thymic microenvironment stimulates human T cells, because their expansion in chimeric fetal thymic organ cultures is inhibited by a mIL-7-specific neutralizing antibody. Our results demonstrate that mIL-7 affects human lymphocytes and indicate that mouse models of human lymphoid development and disease must integrate the biological effects of endogenous IL-7 on human cells.
- Overexpression of wild-type IL-7Rα promotes T-cell acute lymphoblastic leukemia/lymphomaPublication . Silva, Ana; Almeida, Afonso; Cachucho, Ana; Neto, João Luís; Demeyer, Sofie; Ramos De Matos, Mafalda; Hogan, Thea; Li, Yunlei; Meijerink, Jules; Cools, Jan; Grosso, Ana Rita; Seddon, Benedict; Barata, João T.Tight regulation of IL-7Rα expression is essential for normal T-cell development. IL-7Rα gain-of-function mutations are known drivers of T-cell acute lymphoblastic leukemia (T-ALL). Although a subset of patients with T-ALL display high IL7R messenger RNA levels and cases with IL7R gains have been reported, the impact of IL-7Rα overexpression, rather than mutational activation, during leukemogenesis remains unclear. In this study, overexpressed IL-7Rα in tetracycline-inducible Il7r transgenic and Rosa26 IL7R knockin mice drove potential thymocyte self-renewal, and thymus hyperplasia related to increased proliferation of T-cell precursors, which subsequently infiltrated lymph nodes, spleen, and bone marrow, ultimately leading to fatal leukemia. The tumors mimicked key features of human T-ALL, including heterogeneity in immunophenotype and genetic subtype between cases, frequent hyperactivation of the PI3K/Akt pathway paralleled by downregulation of p27Kip1 and upregulation of Bcl-2, and gene expression signatures evidencing activation of JAK/STAT, PI3K/Akt/mTOR and Notch signaling. Notably, we also found that established tumors may no longer require high levels of IL-7R expression upon secondary transplantation and progressed in the absence of IL-7, but remain sensitive to inhibitors of IL-7R-mediated signaling ruxolitinib (Jak1), AZD1208 (Pim), dactolisib (PI3K/mTOR), palbociclib (Cdk4/6), and venetoclax (Bcl-2). The relevance of these findings for human disease are highlighted by the fact that samples from patients with T-ALL with high wild-type IL7R expression display a transcriptional signature resembling that of IL-7-stimulated pro-T cells and, critically, of IL7R-mutant cases of T-ALL. Overall, our study demonstrates that high expression of IL-7Rα can promote T-cell tumorigenesis, even in the absence of IL-7Rα mutational activation.
- Plasmatic Klotho and FGF23 levels as biomarkers of CKD-associated cardiac disease in type 2 diabetic patientsPublication . Silva, Ana; Mendes, Filipa; Carias, Eduarda; Gonçalves, Rui; Fragoso, André; Dias, Carolina; Tavares, Nelson; Café, Hugo; Santos, Nélio; Rato, Fátima; Leão Neves, Pedro; Almeida, EdgarBackground: Research over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of cardiovascular disease CVD. The role of the interaction between fibroblast growth factor 23-(FGF-23)/Klotho in Klotho-mediated actions is still under debate. The main objective was to ascertain the potential use of plasmatic Klotho and FGF23 as markers for CKD-associated cardiac disease and mortality. Methods: This was a prospective analysis conducted in an outpatient diabetic nephropathy clinic, enrolling 107 diabetic patients with stage 2⁻3 CKD. Patients were divided into three groups according to their left ventricular mass index and relative wall thickness. Results: Multinomial regression analysis demonstrated that low Klotho and higher FGF-23 levels were linked to a greater risk of concentric hypertrophy. In the generalized linear model (GLM), Klotho, FGF-23 and cardiac geometry groups were statistically significant as independent variables of cardiovascular hospitalization (p = 0.007). According to the Cox regression model, fatal cardiovascular events were associated with the following cardiac geometric classifications; eccentric hypertrophy (p = 0.050); concentric hypertrophy (p = 0.041), and serum phosphate ≥ 3.6 mg/dL (p = 0.025), FGF-23 ≥ 168 (p = 0.0149), α-klotho < 313 (p = 0.044). Conclusions: In our population, Klotho and FGF23 are associated with cardiovascular risk in the early stages of CKD.
- Transições para a literacia dominante: perspectivas de coordenadores de centros de educação e formação de adultosPublication . Silva, Ana; Guimarães, Paula; Dionísio, Maria de LourdesO processo de Reconhecimento, Validação e Certificação de Competências (RVCC) é hoje considerado o maior movimento de requalificação da educação de adultos em Portugal. Tido como um importante dispositivo para a reconversão da sociedade e da economia portuguesas, pode dizer-se que o processo de RVCC, com lugar nos Centros de Novas Oportunidades (CNOs), tem a literacia2 como eixo essencial de ação, na medida em que, por um lado, o reconhecimento e validação de competências assentam maioritariamente em tarefas de leitura e escrita (histórias de vida, portefólios, etc.) e, por outro lado, as competências a reconhecer são, em última instância, relativas à compreensão e produção de textos (em Ciências, Matemática, Linguagem e Comunicação, etc...). Neste texto, coloca-se no centro da reflexão o modo como nove coordenadores de CNOs do distrito de Braga, Portugal, perspetivam mudanças nas relações dos sujeitos com as práticas de literacia, quando estes passam pelo processo de RVCC. Toma-se, assim, em consideração não só as configurações da literacia no âmbito da educação de adultos, como as conceções de leitura e de escrita que estão subjacentes às práticas pedagógicas de cada CNO, relatadas e descritas por cada coordenador. Entre as principais conclusões, destacam-se algumas (des)continuidades entre as orientações produzidas no âmbito do discurso oficial e as práticas especializadas no processo de RVCC; entre as conceções de literacia dos coordenadores e as mudanças por eles apontadas ao nível do relacionamento dos adultos com os textos.
- Use of rocky intertidal pools by shrimp species in a temperate areaPublication . Vinagre, Catarina; Dias, Marta; Fonseca, Catarina; Pinto, Maria; Cabral, Henrique; Silva, AnaRocky shores are among the most-intensively studied ecosystems, however, tidal pools remain relatively understudied. This study aims to investigate the habitat use and dynamics of the shrimp species that occur in tidal pools of a North-eastern Atlantic coast, the Portuguese coast, in particular species composition, abundance, seasonality and size structure. Shrimps were sampled monthly from six tidal pools for one year, in the west Portuguese coast. Species diversity was much higher than that found in previous studies, in other parts of the world. The shrimp population comprised 8 species: the European rock shrimp, Palaemon elegans, the common prawn, Palaemon serratus, the Atlantic ditch shrimp, Palaemon varians, the Baltic prawn, Palaemon adspersus, the Oriental shrimp, Palaemon macrodactylus and the relatively rare shrimps Eualus sollaudi, Eualus drachi and Caridion gordoni. Shrimp populations varied seasonally and among pools, with peak numbers in spring and summer. The most abundant species was P. elegans. P. elegans was present in all pools, throughout most of the year. Rare and exotic species were present mostly in spring-summer. Lower mean sizes of all shrimp were registered in the beginning of spring, most often in April or May, and gradually increased until winter. New-recruits of the most abundant species, P. elegans, generally entered the pools in spring and formed a high proportion of the population between April and August. They were responsible for the highest abundance peaks of shrimps occurring in the pools. The species richness and high numbers of juveniles occurring in tidal pools suggest that these environments may be nursery areas for coastal shrimp.
- What's in a tide pool? Just as much food web network complexity as in large open ecosystemsPublication . Mendonça, Vanessa; Madeira, Carolina; Dias, Marta; Vermandele, Fanny; Archambault, Philippe; Dissanayake, Awantha; Canning-Clode, João; Flores, Augusto A. V.; Silva, Ana; Vinagre, CatarinaUnderstanding the fundamental laws that govern complex food web networks over large ecosystems presents high costs and oftentimes unsurmountable logistical challenges. This way, it is crucial to find smaller systems that can be used as proxy food webs. Intertidal rock pool environments harbour particularly high biodiversity over small areas. This study aimed to analyse their food web networks to investigate their potential as proxies of larger ecosystems for food web networks research. Highly resolved food webs were compiled for 116 intertidal rock pools from cold, temperate, subtropical and tropical regions, to ensure a wide representation of environmental variability. The network properties of these food webs were compared to that of estuaries, lakes and rivers, as well as marine and terrestrial ecosystems (46 previously published complex food webs). The intertidal rock pool food webs analysed presented properties that were in the same range as the previously published food webs. The niche model predictive success was remarkably high (73-88%) and similar to that previously found for much larger marine and terrestrial food webs. By using a large-scale sampling effort covering 116 intertidal rock pools in several biogeographic regions, this study showed, for the first time, that intertidal rock pools encompass food webs that share fundamental organizational characteristics with food webs from markedly different, larger, open and abiotically stable ecosystems. As small, self-contained habitats, intertidal rock pools are particularly tractable systems and therefore a large number of food webs can be examined with relatively low sampling effort. This study shows, for the first time that they can be useful models for the understanding of universal processes that regulate the complex network organization of food webs, which are harder or impossible to investigate in larger, open ecosystems, due to high costs and logistical difficulties.