Browsing by Author "Mendes, Nuno"
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- Metabolic control of T cell immune response through glycans in inflammatory bowel diseasePublication . Dias, Ana M.; Correia, Alexandra; Pereira, Márcia S.; Almeida, Catarina R.; Alves, Inês; Pinto, Vanda; Catarino, Telmo A.; Mendes, Nuno; Leander, Magdalena; Oliva-Teles, MT; Maia, Luís; Delerue-Matos, Cristina; Taniguchi, Naoyuki; Lima, Margarida; Pedroto, Isabel; Marcos-Pinto, Ricardo; Lago, Paula; Reis, Celso A.; Vilanova, Manuel; Pinho, Salomé S.Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5−/−, MGAT5+/−) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.
- Methods and Challenges on the Out-Of-Plane Assessment of Existing Masonry BuildingsPublication . Lourenço, Paulo B.; Mendes, Nuno; Costa, Alexandre A.; Campos-Costa, AlfredoHistoric masonry buildings were built for many centuries taking into account mostly vertical static loads according to the experience of the builder, usually, without much seismic concern. The seismic behavior of ancient masonry buildings is particularly difficult to characterize and depends on several factors, namely the materials properties, geometry of the structure, connections between structural and non-structural elements, stiffness of the horizontal diaphragms, and building condition. However, the different masonry types present common features that lead to high seismic vulnerability of these buildings, such as high specific mass, low tensile strength, low to moderate shear strength, and low to moderate ductility.