Browsing by Author "Vieira, Ana"
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- Characterization of the RofA regulon in the pandemic M1global and emergent M1UK lineages of Streptococcus pyogenesPublication . Zhi, Xiangyun; Vieira, Ana; Huse, Kristin K.; Martel, Paulo; Lobkowicz, Ludmila; Li, Ho Kwong; Croucher, Nick; Andrew, Ivan; Game, Laurence; Sriskandan, ShiraneeThe standalone regulator RofA is a positive regulator of the pilus locus in Streptococcus pyogenes. Found in only certain emm genotypes, RofA has been reported to regulate other virulence factors, although its role in the globally dominant emm1 S. pyogenes is unclear. Given the recent emergence of a new emm1 (M1 UK) toxigenic lineage that is distinguished by three non-synonymous SNPs in rofA, we characterized the rofA regulon in six emm1 strains that are representative of the two contemporary major emm1 lineages (M1 (global) and M1 (UK)) using RNAseq analysis, and then determined the specific role of the M1 (UK)-specific rofA SNPs. Deletion of rofA in three M1 (global) strains led to altered expression of 14 genes, including six non-pilus locus genes. In M1 (UK) strains, deletion of rofA led to altered expression of 16 genes, including nine genes that were unique to M1 (UK). Only the pilus locus genes were common to the RofA regulons of both lineages, while transcriptomic changes varied between strains even within the same lineage. Although introduction of the three SNPs into rofA did not impact gene expression in an M1 (global) strain, reversal of three SNPs in an M1 (UK) strain led to an unexpected number of transcriptomic changes that in part recapitulated transcriptomic changes seen when deleting RofA in the same strain. Computational analysis predicted that interactions with a key histidine residue in the PRD domain of RofA would differ between M1 (UK) and M1 (global). RofA is a positive regulator of the pilus locus in all emm1 strains but effects on other genes are strain- and lineage-specific, with no clear, common DNA binding motif. The SNPs in rofA that characterize M1 (UK) may impact regulation of RofA; whether they alter phosphorylation of the RofA PRD domain requires further investigation.
- Edible coatings enriched with essential oils on apples impair the survival of bacterial pathogens through a simulated gastrointestinal systemPublication . Vieira, Ana; Guerreiro, Adriana; Antunes, Maria Dulce; Miguel, Maria; Faleiro, Maria LeonorEdible coatings supplemented with essential oil components have been investigated to control spoilage microorganisms. In this study, the survival of Listeria monocytogenes and Salmonella enterica serovar Typhimurium on apples treated with edible coatings based on sodium alginate (2%) (ECs) and supplemented with essential oil components, namely eugenol (Eug) at 0.2% or in combination with 0.1% (v/v) of Eug and citral (Cit) at 0.15% was determined. Both bacterial pathogens were exposed on apples treated with ECs supplemented with Eug or Eug + Cit and challenged with gastrointestinal fluids and their survival was examined. Both pathogens were able to survive on the surface of 'Bravo de Esmolfe' apple. The use of ECs in fresh-cut fruits impaired the survival of both bacterial populations over 72 h at 4 °C. The exposure of the pathogens on apples with ECs supplemented with Eug and Cit and challenged with gastrointestinal fluids significantly reduced their survival. This study evidences that the use of alginate edible coating enriched with Eug or the combination of Eug and Cit can contribute to the safer consumption of minimally processed fruits.
- How many biomarker measurements are needed to predict prognosis in Crohn's disease patients under infliximab?—A prospective studyPublication . Magro, Fernando; Estevinho, Maria Manuela; Catalano, Gaia; Patita, Marta; Arroja, Bruno; Lago, Paula; Rosa, Isadora; Sousa, Helena Tavares; Ministro, Paula; Mocanu, Irina; Vieira, Ana; Castela, Joana; Moleiro, Joana; Roseira, Joana; Cancela, Eugénia; Sousa, Paula; Portela, Francisco; Correia, Luís; Moreira, Paula; Santiago, Mafalda; Dias, Sandra; Afonso, Joana; Danese, Silvio; Peyrin‐Biroulet, Laurent; Dias, Cláudia CamilaBackgroundTimely stratification of Crohn's disease (CD) is essential for patients' management. The use of noninvasive accurate biomarkers is key to monitor treatment and to pursue mucosal healing, the ultimate treatment endpoint in CD. ObjectiveWe aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression. MethodsData from 289 CD patients receiving infliximab (IFX) maintenance therapy for 2 years was collected; those patients were included in DIRECT, a prospective multicenter observational study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices. ResultsThe isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p <= 0.001] for composite outcomes 1 and 2, respectively) regardless of confounding factors. Isolated highly elevated C-reactive protein (CRP; >10.0 mg/L) and fecal calprotectin (FC; >500.0 mu g/g) in at least one visit were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 mu g/g) were only relevant when detected in at least two visits (consecutive or not). The combination of biomarkers in risk matrices had good ability to predict progression; patients simultaneously presenting anemia, highly elevated CRP and FC at least once had 42%-63% probability of achieving the composite outcomes. ConclusionThe combined evaluation of hemoglobin, CRP, and FC in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making.
- Influence of enhanced temperature on photosynthesis, photooxidative damage, and antioxidant strategies in Ceratonia siliqua L. seedlings subjected to water deficit and rewateringPublication . Osório, Maria Leonor; Osório, Júlio; Vieira, Ana; Gonçalves, Sandra; Romano, AnabelaPredicted future climatic changes for the Mediterranean region give additional importance to the study of photooxidative stress in local economic species subjected to combined drought and high-temperature conditions. Under this context, the impact of these stresses on photosynthesis, energy partitioning, and membrane lipids, as well as the potential ability to attenuate oxidative damage, were investigated in Ceratonia siliqua L. Two thermal regimes (LT: 25/18ºC; HT: 32/21ºC) and three soil water conditions (control, water stress, and rewetting) were considered. HT exacerbated the adverse effects of water shortage on photosynthetic rates (PN) and PSII function. The decrease in PN was 33% at LT whereas at HT it was 84%. In spite of this, the electron transport rate (ETR) was not affected, which points to an increased allocation of reductants to sinks other than CO2 assimilation. Under LT conditions, water stress had no significant effects on yield of PSII photochemistry (ΦPSII) and yields of regulated (ΦNPQ) and nonregulated (ΦNO) energy dissipation. Conversely, drought induced a significant decrease of ΦPSII and a concomitant increase of ΦNO in HT plants, thereby favouring the overproduction of reactive oxygen species (ROS). Moreover, signs of lipid peroxidation damage were detected in HT plants, in which drought caused an increase of 40% in malondialdehyde (MDA) content. Concurrently, a marked increase in proline content was observed, while the activities of catalase (CAT) and ascorbate peroxidase (APX) were unaffected. Despite the generation of a moderate oxidative stress response, C. siliqua revealed a great capability for photosynthetic recovery 36 h after rewatering, which suggests that the species can cope with predicted climate change.
- Methylation patterns in dysplasia in inflammatory bowel disease patientsPublication . Rosa, Isadora; Silva, Patricia; da Mata, Sara; Magro, Fernando; Carneiro, Fatima; Peixoto, Armando; Silva, Marco; Sousa, Helena Tavares; Roseira, Joana; Parra, Jose; Barosa, Rita; Vieira, Ana; Brito, Maria Jos; Lago, Paula; Coelho, Andre; Moleiro, Joana; da Silva, Joao Pereira; Fonseca, Ricardo; Albuquerque, Cristina; Dias Pereira, A.Background and aims:Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis. Methods:Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification. Results:Mean age at IBD diagnosis: 42 +/- 16 years;at dysplasia diagnosis: 56 +/- 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation ofIGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation ofMSH6, TIMP3was significantly associated to IBD-related dysplasia/cancer. Promoter methylation ofMSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1,BCL2genes was significantly associated to active IBD. Conclusions:Methylation analysis, namely ofMSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.
- Uma plataforma para a avaliação experimental de meta-heurísticasPublication . Vieira, Ana; Fonseca, C. M.
- Thiopurines have no impact on outcomes of Crohn's disease patients beyond 12 months of maintenance treatment with infliximabPublication . Sousa, Paula; Patita, Marta; Arroja, Bruno; Lago, Paula; Rosa, Isadora; Sousa, Helena Tavares; Ministro, Paula; Mocanu, Irina; Vieira, Ana; Castela, Joana; Moleiro, Joana; Cancela, Eugenia; Roseira, Joana; Portela, Francisco; Correia, Luis; Santiago, Mafalda; Dias, Sandra; Alves, Catarina; Afonso, Joana; Dias, Claudia Camila; Magro, FernandoThe emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines. Aims: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab. Methods: In this analysis of the 2 -year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C -reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug -related items was used to define treatment failure. Results: The study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub -analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021). Conclusion: In CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration.