Sebastião Martins Mestre: da vitória na Guerra Peninsular à derrota nas Guerras Liberais

Sebastião Martins Mestre foi um militar e político algarvio que participou em dois acontecimentos decisivamente marcantes para a sociedade portuguesa do século XIX: as Invasões Francesas e as Guerras Liberais. Durante a juventude, Martins Mestre gloriou-se graças à intervenção nas invasões napoleónicas, mas quando decidiu enveredar pelo caminho da política, a sua imagem ficou para sempre ensombrada pela conduta. A presente dissertação tem como principal objetivo apresentar novos dados biográficos (relacionados com a família, atividade militar, atividade política, morte) que permitam compreender melhor a figura histórica de Sebastião Martins Mestre. O estudo inicia-se com o capítulo dedicado à família e funções militares, seguido do período referente às Invasões Francesas e, por último, será feita a análise à vida do biografado no âmbito das Guerras Liberais, onde centramos a nossa atenção no período em que foi governador de Vila Real de Santo António.Sebastião Martins Mestre was an algarvian military and politician who participated in two main events for Portuguese society in the 19th century: the French Invasions and the Liberal Wars. During his youth, Martins Mestre gloried due to his intervention in the Napoleonic invasions, but when he decided to take the path of politics, his image was forever overshadowed by his conduct. The main goal of this dissertation is to present new biographical data (family-related, military activity, political activity, death...) that will allow a better understading of the historical figure of Sebastião Martins Mestre. The study begins with a chapter dedicated to the family and military positions, followed by another alluding to the period of the French Invasions and a final chapter analyzes the life of the biographer in the context of the Liberal Wars, where we focus our attention on the period in which he was governor of Vila Real de Santo António

Enhancing functionalization of health care textiles with gold nanoparticle-loaded hydroxyapatite composites

Hospitals and nursing home wards are areas prone to the propagation of infections and are of particular concern regarding the spreading of dangerous viruses and multidrug-resistant bacteria (MDRB). MDRB infections comprise approximately 20% of cases in hospitals and nursing homes. Healthcare textiles, such as blankets, are ubiquitous in hospitals and nursing home wards and may be easily shared between patients/users without an adequate pre-cleaning process. Therefore, functionalizing these textiles with antimicrobial properties may considerably reduce the microbial load and prevent the propagation of infections, including MDRB. Blankets are mainly comprised of knitted cotton (CO), polyester (PES), and cotton-polyester (CO–PES). These fabrics were functionalized with novel gold-hydroxyapatite nanoparticles (AuNPs-HAp) that possess antimicrobial properties, due to the presence of the AuNPs’ amine and carboxyl groups, and low propensity to display toxicity. For optimal functionalization of the knitted fabrics, two pre-treatments, four different surfactants, and two incorporation processes were evaluated. Furthermore, exhaustion parameters (time and temperature) were subjected to a design of experiments (DoE) optimization. The concentration of AuNPs-HAp in the fabrics and their washing fastness were critical factors assessed through color difference (∆E). The best performing knitted fabric was half bleached CO, functionalized using a surfactant combination of Imerol® Jet-B (surfactant A) and Luprintol® Emulsifier PE New (surfactant D) through exhaustion at 70 ◦C for 10 min. This knitted CO displayed antibacterial properties even after 20 washing cycles, showing its potential to be used in comfort textiles within healthcare environments

Exploring a novel effect of lactoferrin on the plasma membrane towards the elucidation of the mechanisms of action: from yeast to human cells

Microbiotec'17 - Congress of Microbiology and Biotechnology 2017info:eu-repo/semantics/publishedVersio

Functional and sequence-based metagenomics to uncover carbohydrate-degrading enzymes from composting samples

The online version contains supplementary material available at: https://doi.org/10.1007/s00253-023-12627-9.The renewable, abundant, and low-cost nature of lignocellulosic biomass can play an important role in the sustainable production of bioenergy and several added-value bioproducts, thus providing alternative solutions to counteract the global energetic and industrial demands. The efficient conversion of lignocellulosic biomass greatly relies on the catalytic activity of carbohydrate-active enzymes (CAZymes). Finding novel and robust biocatalysts, capable of being active under harsh industrial conditions, is thus imperative to achieve an economically feasible process. In this study, thermophilic compost samples from three Portuguese companies were collected, and their metagenomic DNA was extracted and sequenced through shotgun sequencing. A novel multi-step bioinformatic pipeline was developed to find CAZymes and characterize the taxonomic and functional profiles of the microbial communities, using both reads and metagenome-assembled genomes (MAGs) as input. The samples' microbiome was dominated by bacteria, where the classes Gammaproteobacteria, Alphaproteobacteria, and Balneolia stood out for their higher abundance, indicating that the degradation of compost biomass is mainly driven by bacterial enzymatic activity. Furthermore, the functional studies revealed that our samples are a rich reservoir of glycoside hydrolases (GH), particularly of GH5 and GH9 cellulases, and GH3 oligosaccharide-degrading enzymes. We further constructed metagenomic fosmid libraries with the compost DNA and demonstrated that a great number of clones exhibited $\beta$-glucosidase activity. The comparison of our samples with others from the literature showed that, independently of the composition and process conditions, composting is an excellent source of lignocellulose-degrading enzymes. To the best of our knowledge, this is the first comparative study on the CAZyme abundance and taxonomic/functional profiles of Portuguese compost samples.Open access funding provided by FCT|FCCN (b-on). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit, the projects LIGNOZYMES—Metagenomics approach to unravel the potential of lignocellulosic residues towards the discovery of novel enzymes (POCI-01–0145-FEDER-029773), and B3iS—Biodiversity and Bioprospecting of Biosurfactants in Saline Environments (PTDC/BII-BIO/5554/2020); and by RNCA Advanced Computing Project MetaLignoZymes, metagenomic analysis of lignocellulosic residues towards the discovery of novel enzymes (CPCA/A0/408464/2021).info:eu-repo/semantics/publishedVersio

Lactoferrin perturbs lipid rafts and requires integrity of Pma1p-lipid rafts association to exert its antifungal activity against Saccharomyces cerevisiae

"Available online 07 January 2021"Lactoferrin (Lf) is a bioactive milk-derived protein with remarkable wide-spectrum antifungal activity. To deepen our understanding of the molecular mechanisms underlying Lf cytotoxicity, the role of plasma membrane ergosterol- and sphingolipid-rich lipid rafts and their association with the proton pump Pma1p was explored. Pma1p was previously identified as a Lf-binding protein. Results showed that bovine Lf (bLf) perturbs sterol-rich lipid rafts organization by inducing intracellular accumulation of ergosterol. Using yeast mutant strains lacking lipid rafts-associated proteins or enzymes involved in the synthesis of ergosterol and sphingolipids, we found that perturbations in the composition of these membrane domains increase resistance to bLf-induced yeast cell death. Also, when Pma1p-lipid rafts association is compromised in the Pma110 mutant and in the absence of the Pma1p-binding protein Ast1p, the bLf killing activity is impaired. Altogether, results showed that the perturbation of lipid rafts and the inhibition of both Pma1p and V-ATPase activities mediate the antifungal activity of bLf. Since it is suggested that the combination of conventional antifungals with lipid rafts-disrupting compounds is a powerful antifungal approach, our data will help to pave the way for the use of bLf alone or in combination for the treatment/eradication of clinically and agronomically relevant yeast pathogens/fungi.This work was supported by national funds through the Portuguese Foundation for Science and Technology (FCT I.P.) under the scope of the strategic funding of “Contrato-Programa” UIDB/04050/2020 and UIDB/ 04469/2020 unit; by the BioTecNorte operation (NORTE-01-0145- FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte; and by the Servicio para el Control de la Esterilización, Laboratorio de Microbiología Oral (CN-16-036). Cátia Santos-Pereira acknowledges the PhD fellowship PD/BD/128032/2016 funded by FCT under the scope of the doctoral programme in Applied and Environmental Microbiology (DP_AEM).info:eu-repo/semantics/publishedVersio

Deciphering the mechanisms underlying bovine milk lactoferrin anticancer activity using yeast and cancer cell lines as complementary models

Lactoferrin (Lf) is a milk derived iron-binding protein that exhibits a broad range of interesting biological activities, from which its anticancer and antifungal activities stand out. Our group has been elucidating the mechanisms and identifying the molecular targets underlying Lf anticancer/antifungal activities in order to improve its therapeutic efficacy and rational application. Indeed, we previously demonstrated that Lf triggers a mitochondrial and caspase-dependent regulated cell death in Saccharomyces cerevisiae (1). Moreover, we found that Lf selectively induces apoptosis in highly metastatic cell lines displaying the proton pump V-ATPase at the plasma membrane (2). However, much work is needed to further characterize Lf mechanisms of action. In the present work, we show how functional genomic approaches using yeast deletion mutants provided new insights on the activity of Lf against yeast that were then validated in human cancer cell lines. Results will be discussed in an integrated manner regarding their contribution towards understanding the molecular basis of Lf anticancer activity. In addition, this study highlights the great potential of yeast as a model to uncover mechanisms of action occurring in the more complex human cells. References (1) Acosta-Zaldívar M, Andrés MT, Rego A, Pereira CS, Fierro JF, Côrte-Real M. (2016) Human lactoferrin triggers a mitochondrial- and caspase-dependent regulated cell death in Saccharomyces cerevisiae. Apoptosis. 21(2):163-73. doi: 10.1007/s10495-015-1199-9. (2) Pereira CS, Guedes JP, Gonçalves M, Loureiro L, Castro L, Gerós H, Rodrigues LR, Côrte-Real M. (2016) Lactoferrin selectively triggers apoptosis in highly metastatic breast cancer cells through inhibition of plasmalemmal V-H+-ATPase. Oncotarget. 7(38):62144-62158. doi: 10.18632/oncotarget.11394.info:eu-repo/semantics/publishedVersio

Cymoxanil inhibits respiration through inhibition of mitochondrial complex IV

Cymoxanil is a synthetic acetamide fungicide, used against oomycetes. It was first introduced in 1977 and can be used against downy mildew diseases induced by Plasmopara viticola in grapevine cultures and late blight diseases caused by Phytophthora infestans, in tomatoes and potatoes cultures. This fungicide is used in mixed formulations and its higher solubility enables a relatively widespread occurrence in toxic concentrations in aquatic environments. Although it has been used over the years, its biochemical mode of action is not yet known. Some studies reported that cymoxanil affects growth, respiration, DNA, RNA and protein synthesis and RNA polymerase activity of Phytophthora infestans, and it was reported to inhibit cell growth and biomass production and decrease the respiration rate of S. cerevisiae. Using yeast S. cerevisiae as model, we further characterized its effect on mitochondria. We found that whole cells treated with cymoxanil present a higher inhibition of oxygen consumption after 3 h of treatment that remains over time. Using isolated mitochondria, we observe that cymoxanil inhibits respiratory rate of yeast cells by inhibiting oxidative phosphorylation, through inhibition of complex IV activity. Although other targets cannot be excluded, our data provide new information about mode of action of cymoxanil that can be instrumental to drive informed management regarding the use of this fungicide.info:eu-repo/semantics/publishedVersio

Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells

Available online 28 September 2023Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines was uncovered. Our data revealed that suppression of one of the central nodes of this signaling pathway, MEK1, affects proliferation, migration, and invasion of TNBC cells, that may be explained by the reversion of the epithelial-mesenchymal transition phenotype, which is facilitated by the MMP-2/MMP-9 downregulation. Moreover, an exosome-based system was successfully generated for the siRNA loading (iExoMEK1). Our data suggested absence of modification of the physical properties and general integrity of the iExoMEK1 comparatively to the unmodified counterparts. Such exosome-mediated downregulation of MEK1 led to a tumor regression accompanied by a decrease of angiogenesis using the chick chorioallantoic-membrane model. Our results highlight the potential of the targeting of MAPK/ERK cascade as a promising therapeutic approach against TNBC.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/ BIO/04469/2020 unit. CAM and immunohistochemistry experiments have been funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122); by National funds, through the Foundation for Science and Technology (FCT) - project UIDB/50026/ 2020 and UIDP/50026/2020 and by the project NORTE-01-0145- FEDER-000039, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Débora Ferreira is recipient of a fellowship supported by a doctoral advanced training (call NORTE-69-2015-15) funded by the European Social Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Débora Ferreira also acknowledges “Liga Portuguesa contra o cancro - Núcleo Regional do Norte (LPCC-NRN)” for her fellowship. The authors thank Diana Vilas Boas (CEB/University of Minho) for confocal microscopy technical support. Cátia Santos-Pereira acknowledges the PhD fellowship PD/BD/128032/2016 funded by FCT under the scope of the doctoral program in Applied and Environmental Microbiology (DP_AEM). Julieta Afonso acknowledges the Postdoctoral fellowship SFRH/BPD/116784/2016 funded by FCT. The work performed in the Kalluri Laboratory was supported by funds from UT MD Anderson Cancer Center and the Sid Richardson Foundation.info:eu-repo/semantics/publishedVersio

HERA - Environmental Risk Assessment of a contaminated estuarine environment: a case study

Sado River estuary is located in the west coast of Portugal. Previous environmental studies identified industrial contamination, non-point anthropogenic sources and contamination coming from the river, all promoting accumulation of polluted sediments with known impacts on the ecological system. Surrounding human populations have intense economic fishery activities. Together with agriculture, estuary fishing products are available to local residents. Food usage previously characterized through ethnographic studies suggests exposure to estuarine products, farming products, and water in daily activities, as potential routes of contamination. It is well established that long term exposure to heavy metals are associated with renal and neurological diseases, most heavy metals are classified as carcinogenic and teratogenic.Instituição Financiadora: FCT; Instituições participantes: IMAR -Instituto do Mar (coord.)e PRÓ-INSA, Associação para a Promoção da Investigação em Saúde, Instituto Nacional de Saúde Doutor Ricardo Jorg

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio