http://hdl.handle.net/10174/29586 2026-04-03T23:37:35Z http://hdl.handle.net/10174/38623 Title: Chitosan- and chitosan-polaxamer 407 based nanoparticles: green nanotechnology tools for biomedical applications Authors: Carreiro, Elisabete; Antunes, Célia; Gastalho, C.; Craveiro, Alexandre Abstract: The chymotrypsin-like main protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for cleavage of two viral polyproteins into 16 nonstructural pro- teins. Its catalytic activity is critical for the life cycle of the SARS-CoV-2, since the inhibition of the 3CLpro can effectively block the whole replication of the virus. The 3CLpro has a bell- shaped activity-pH profile with a peak performance set at a value of approximately 7.4. Molecular dynamics and X-ray crystallog- raphy suggested that the enzyme undergoes some conformational changes due to the pH change of the environment. Our goal was to characterize the effects of pH on structure and dynamics of the 3CLpro in solution using nuclear magnetic resonance (NMR) spectroscopy. We obtained high quality NMR spectra recorded at pH between 5.2 and 8.5 for perdeuterated protein samples, selectively 1H, 13C-labelled on the methyl groups of Ile, Leu, Val and Met (ILVM) residues. Moreover, selective isotopic labelling of the histidine residues provided us with the residue specific pKa values for the individual imidazole moieties within this 66 kDa protein molecule. Since four out of seven histidines are located within the enzyme active site, these data allowed us to correlate the protonation states of the His side-chains with the proteolytic activity of the 3CLpro. Interestingly, we found that the proton- ation state of the histidines distant from the catalytic center also affects the 3CLpro proteolytic activity, leading to the discovery of the new allosteric pathway. Taken together, our results improve our understanding of the 3CLpro regulation and may facilitate the design of new potent inhibitors. 2024-01-06T00:00:00Z http://hdl.handle.net/10174/36131 Title: Prioritize Health Care in the Context of the Pandemic Authors: Araújo, Nuno; Fernandes, Filipe; Rosa, Álvaro; Borges, Ana; Vicente, Henrique; Neves, José Abstract: This work examines citizens’ attitudes towards Personal Priority Criteria according to their responses to questions that are part of questionnaires such as Priority Related Groups, Priorities Related to The General Population, and Priority in General, i.e., it shows that health condition severity, patient utility, and cost-effectiveness significantly influence people’s attitudes toward using personal criteria in setting those priorities. In thiswork such attitudes are highlighted by relating Social and Collective Intelligence (SCI), Logic Programming (LP) and The Laws of Thermodynamics (LoT) to a computer system where SCI aligns one with the methods and methodologies of problem solving; LP explains how theory improves practice, and LoT expresses the process of systems development in terms of increased/decreased of entropy. 2023-01-01T00:00:00Z http://hdl.handle.net/10174/34964 Title: N-1,2,3-Triazole-Isatin derivatives in lymphoma cell lines Authors: Gaudio, E.; Tarantelli, C.; Marques, C.S.; Ekeh, H.; Carmelo, M.; Burke, A.J.; Bertoni, F. Abstract: Molecular hybrid constructs are an interesting approach to merge individual pharmacophores with different mechanisms of action, potentially decreasing side effects. The 1,2,3-triazole unit is present in many bioactive compounds and it is characterized by its ability to be stable towards hydrolysis to increase the compounds lipophilicity. Hybrids containing this pharmacophore together with isatin and its analogues have shown a wide spectrum of potential therapeutic activities, also against cancer. Burke et al. have recently reported new N-1,2,3-triazole-isatin hybrids with in vitro anti- tumor activity in solid tumor cell lines (RSC Medicinal Chemistry 2022; EP3400938). Here, we present the in vitro anti-lymphoma activity and structure activity relationships (SAR) of 9 N-1,2,3-triazole-isatin hybrids. 2022-01-01T00:00:00Z http://hdl.handle.net/10174/30257 Title: An Assessment of Data Guidelines in Cryopreservation Laboratories Authors: Fernandes, Ana; Figueiredo, Margarida; Neves, José; Vicente, Henrique Abstract: On May 25, 2018, the General Data Protection Regulation (GDPR) entered into force in the European Union, which is of the utmost importance for monitoring its accomplishment by all organizations, especially those working in the health sector. However, it turns into a very difficult task, i.e., in order to meet this challenge, a practicable problem-solving methodology had to be developed and tested, that lead to a soft approach to computing using Artificial Neural Networks. On the other hand, the method chosen for data collection was the inquiry by questionnaire, in which 156 employees participated. The proposed system has an accuracy of about 90%, which can diagnose the fragility of the laboratory and encourage future improvements to ensure a high level of data protection. 2021-01-01T00:00:00Z