The Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA) (English: National Institute of Health Dr. Ricardo Jorge) is a public institution under the Portuguese Ministry of Health, with self scientific, technical, administrative, and financial autonomy.
Aspergillus fumigatus is the primary causative agent of aspergillosis. Cryptic species may exhibit variable pathogenic potential and antifungal resistance and, particularly those within the section Fumigati, have significant clinical and environmental relevance. However, the genomic and proteomic bases underlying these differences remain poorly understood. This study presents a comparative analysis of 42 genomes (including five newly sequenced genomes), together with their corresponding predicted proteomes, from A. fumigatus, and from four cryptic species: A. lentulus, A. udagawae, A. felis and A. hiratsukae. Notably, these represent the only genomes currently available for these cryptic species, allowing us to integrate antifungal resistance mechanisms, and virulence factors across the full existing genomic landscape. We showed that A. fumigatus retains a highly conserved core proteome, whereas A. felis and A. lentulus exhibit greater genomic plasticity. Our preliminary findings suggest that azole resistance is primarily driven by species-specific point mutations, which are not shared across the section Fumigati. Secondary metabolism pathways are the main difference observed among section Fumigati, with variations in biosynthetic gene clusters and mycotoxin production. Our findings emphasize the evolutionary balance between genomic conservation and evolutionary divergence in A. fumigatus sensu lato, determining azole resistance and pathogenicity-associated fitness.
The 2025/26 season was marked by co-circulation of influenza A subtypes, with the first detection of A(H3N2) subclade K in September 2025. In August 2025 in Portugal, 14.8% (95% CI: 12.2-17.8) of 886 persons tested had cross-protective antibodies against this subclade. The overall seroprevalence against circulating A(H1N1)pdm09 strains was 28.1% (95% CI: 24.4-32.0). These data highlight the presence of previous cross-reactive antibodies and the possible advantage of vaccination in the extent of detectable antibodies against influenza viruses.
Plasma membrane (PM) ion transport depends on tightly regulated trafficking and activation of ion channels. For the cystic fibrosis transmembrane conductance regulator (CFTR), dysregulation caused by tobacco smoke or chronic inflammation contributes to diseases such as chronic obstructive pulmonary disease (COPD). We previously showed that phosphorylation of CFTR at tyrosine 512 (Y512) by spleen tyrosine kinase promotes its internalization via the MAPK/SHC-1 pathway in CFBE airway cells. Here, we investigated whether this mechanism is conserved in other epithelial models and whether inhibition of SHC-1 increased CFTR abundance at the PM. CFTR surface levels were assessed in CFBE, 16HBE, and Caco-2 cells using biotinylation and immunoblotting after treatment with MEK inhibitor selumetinib, SHC-1 inhibitor idebenone (IDE), or its novel inhibitor 110#3. MAPK activity was evaluated by ERK phosphorylation. We found that MAPK/SHC-1-dependent CFTR internalization was conserved in 16HBE and Caco-2 cells. In CFBE cells, treatment with IDE or 110#3 increased PM CFTR levels, but also unrelated PM proteins (GLUT1 and E-cadherin). No significant effects were observed in 16HBE or Caco-2 cells. These findings suggest CFBE cells may not fully recapitulate endogenous CFTR trafficking and raise the possibility that selective SHC-1/pY512-CFTR inhibitors may modulate CFTR trafficking in COPD and other CFTR-related diseases.
The presence of endocrine-disrupting compounds (EDCs) in aquatic environments has raised significant concerns, particularly regarding their impact on marine biota. Among these compounds, 17α-ethinylestradiol (EE2), a synthetic estrogen widely used in oral contraceptives, is highly persistent and biologically active at very low concentrations. This study evaluated the effects of EE2 exposure on oxidative stress responses and endocrine disruption in Mytilus galloprovincialis, exposed for 28 days to three EE2 concentrations (10, 30, and 300 ng·L−1). Biomarkers of oxidative stress, including the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST), as well as Lipid Peroxidation (MDA levels), total ubiquitin (UBI) and the endocrine disruption marker, vitellogenin-like protein (VTG) were assessed. Results showed significant increase in GST and a decrease in CAT activities followed by an elevation at 300 ng·L−1, slightly higher than control values. Overall, results suggest an enhanced oxidative challenge. No significant changes were detected in MDA and UBI levels. VTG-like protein levels increased according to the EE2 concentrations tested, suggesting an effect on the mussel’s endocrine system. These results show the activation of detoxification and antioxidant defense mechanisms in exposed mussels as a response to mitigate oxidative stress damage. Furthermore, it highlights the importance of using biomarkers in pollution monitoring studies and environmental risk assessment.
