Browsing by Issue Date, starting with "2023-03"
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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.
- Transparency, accountability, and governance: a literature review in the context of public hospitalsPublication . Nunes, Carlos; Gomes, Patrícia; Santana, JoaquimThis study develops a literature review based on bibliometric analysis on the theme of transparency and accountability within the scope of governance of public hospitals, seeking to identify research lines, theories, research methods, and existing gaps through the analysis of scientific publications until 2020. The investigation followed the theoretical lens of transparency and accountability in the public sector to understand its framework within the scope of the governance of hospitals. Using the Bibliometrix software, and after the consultation process of the articles published in the Scopus and WoS databases, a sample with 118 articles was selected. It was found that, in the period between 2017-2020, approximately 85% of the publications were qualitative, and there is a growing trend in the study of transparency and accountability within the scope of governance of public hospitals. Transparency often appears interconnected with the accountability of agents (accountability), external communication policies (public reports), internal communication policies, and their comprehensibility. The predominance of publications of North American and Chinese origin was also noted. The study also identifies the scarcity of research using quantitative models that explore dependency relationships between the dimensions studied, limiting the comprehensibility of the interdependence between transparency practices and organizations' internal and external attributes. The study contributes to the knowledge about the interactions between transparency, accountability, and reporting within the scope of governance of public hospitals.
- Structural modification of the Pseudomonas aeruginosa alkylquinoline cell–cell communication signal, HHQ, leads to benzofuranoquinolines with anti-virulence behaviour in ESKAPE pathogensPublication . ROSSETTO, VERONICA; Moore-Machacek, Ay'sha; Woods, David F.; Galvão, Helena M.; Shanahan, Rachel M.; Hickey, Aobha; O’Leary, Niall; O’Gara, Fergal; McGlacken, Gerard P.; Reen, F. JerryMicrobial populations have evolved intricate networks of negotiation and communication through which they can coexist in natural and host ecosystems. The nature of these systems can be complex and they are, for the most part, poorly understood at the polymicrobial level. The Pseudomonas Quinolone Signal (PQS) and its precursor 4- hydroxy- 2-heptylquinoline (HHQ) are signal molecules produced by the important nosocomial pathogen Pseudomonas aeruginosa. They are known to modulate the behaviour of co-colonizing bacterial and fungal pathogens such as Bacillus atropheaus, Candida albicans and Aspergillus fumigatus. While the structural basis for alkyl-quinolone signalling within P. aeruginosa has been studied extensively, less is known about how structural derivatives of these molecules can influ-ence multicellular behaviour and population- level decision-making in other co-colonizing organisms. In this study, we investigated a suite of small molecules derived initially from the HHQ framework, for anti-virulence activity against ESKAPE pathogens, at the species and strain levels. Somewhat surprisingly, with appropriate substitution, loss of the alkyl chain (present in HHQ and PQS) did not result in a loss of activity, presenting a more easily accessible synthetic framework for investigation. Virulence profiling uncovered significant levels of inter-strain variation among the responses of clinical and environmental isolates to small-molecule challenge. While several lead compounds were identified in this study, further work is needed to appreciate the extent of strain- level tolerance to small-molecule anti-infectives among pathogenic organisms.
- Antigenotoxic properties of the halophyte Polygonum maritimum L. highlight its potential to mitigate oxidative stress-related damagePublication . Oliveira, Daniela; Dias, Maria Inês; Barros, Lillian; Custódio, Luísa; Oliveira, RuiLong-term exposure to dietary xenobiotics can induce oxidative stress in the gastrointestinal tract, possibly causing DNA damage and contributing to the initiation of carcinogenesis. Halophytes are exposed to constant abiotic stresses, which are believed to promote the accumulation of antioxidant metabolites like polyphenols. The aim of this study was to evaluate the antioxidant and antigenotoxic properties of the ethanol extract of the aerial part of the halophyte Polygonum maritimum L. (PME), which can represent a dietary source of bioactive compounds with potential to attenuate oxidative stress-related damage. The PME exhibited a high antioxidant potential, revealed by the in vitro capacity to scavenge the free radical DPPH (IC50 = 2.29 +/- 0.10 mu g/mL) and the improved viability of the yeast Saccharomyces cerevisiae under oxidative stress (p < 0.001, 10 min). An antigenotoxic effect of PME against H2O2-induced oxidative stress was found in S. cerevisiae (p < 0.05) with the dominant deletion assay. In vitro colorimetric assays and LC-DAD-ESI/MSn analysis showed that PME is a polyphenol-rich extract composed of catechin, (epi)catechin dimer and trimers, quercetin and myricetin glycosides. Hence, P. maritimum is a source of antioxidant and antigenotoxic metabolites for application in industries that develop products to provide health benefits.
- The archaeological potential of the northern Luangwa Valley, Zambia: The Luwumbu basinPublication . Burke, A.; Bisson, M.; Schilt, Flora; Tolan, S.; Museba, J.; Drapeau, M. S. M.; Aleman, J. C.; Peros, M. C.The Luangwa Basin, Zambia, which forms part of the Zambezi drainage, is strategically located between the Central African plateau and the East African Rift system. The Luangwa River and major tributaries, such as the Luwumbu River, are perennial water sources supporting essential resources that sustain human communities and a rich and diverse fauna and flora. The archaeological record of Luangwa is relatively unknown, despite early archaeological exploration hinting at its potential. Recent research in the southern Luangwa valley, however, suggests that it preserves a long record of hominin occupation spanning the Early to Late Stone Age. The research described here details fieldwork carried out in northeastern Luangwa, in the Luwumbu Basin, that confirms that a relatively deep package of Quaternary deposits, containing evidence of the Stone Age occupation of the region persists in the upper piedmont zone.
- Six Algerian plants: Phenolic profile, antioxidant, antimicrobial activities associated with different simulated gastrointestinal digestion phases and antiproliferative propertiesPublication . Er Kemal, Mehtap; Bakchiche, Boulanouar; Kemal, Mehmet; Cheraif, Kadour; Kara, Yakup; Bardaweel, Sanaa K.; Miguel, Maria; Yildiz, Oktay; Ghareeb, Mosad A.Introduction: Mediterranean countries, including Algeria, have medicinal plants used in folk medicine, such as Artemisia campestris L., Artemisia herba-alba Asso, Juniperus phoenicea L., Juniperus oxycedrus L., Mentha pulegium L., and Lavandula angustifolia Mill. It is noteworthy that the bioaccessibility of their polyphenolic ingredients have not been critically evaluated before. Methods: The bioactive properties of the aqueous extracts of Artemisia campestris L., Artemisia herba-alba Asso, Juniperus phoenicea L., Juniperus oxycedrus L., Mentha pulegium L., and Lavandula angustifolia Mill. were investi-gated. They were subjected to a simulated gastrointestinal digestion to evaluate the antioxidant, antimicrobial activities and total polyphenol contents. Their antiproliferative activities against three human cancer cell lines (MCF-7, T47D, and Caco-2) were also performed using the aqueous extracts. The phenolic profile was also studied by reversed-phase high-performance liquid chromatography coupled to ultraviolet spectrometry detector (RP-HPLC-UV). Results: The results indicated that bioaccessibility of total phenolic compounds after the post-gastric, intestinal, and colon phases was in the ranges of 4.34-11.57 %, 0-0.55 %, and 3.92-9.24 %, respectively when compared with their aqueous extracts. Intestinal and colon phase samples collected from intestinal digestion of six plant extracts did not have any antioxidant activity. Juniperus spp. extracts had the highest antiproliferative activity compared to the results obtained from other tested species. Conclusions: The high antioxidant and cytotoxic activities of Juniperus samples may be attributed to the higher levels of total phenols, as well as the catechins, rutin and caffeic acid, whilst M. pulegium extract with the lowest phenolic content and lower amounts of these metabolites, having p-coumaric acid as a predominant phenolic compound, was shown to be less effective as an antioxidant and anticancer agent.
- Two probiotic candidates of the genus psychrobacter modulate the immune response and disease resistance after experimental infection in turbot (Scophthalmus maximus, Linnaeus 1758)Publication . Wuertz, Sven; Beça, Filipa; Kreuz, Eva; Wanka, Konrad M.; Azeredo, Rita; Machado, Marina; Costas, BenjaminProbiotic bacteria are a recognized alternative to classical methods of disease prophylaxis and therapy. We tested the effects of their application on the immune reaction in juvenile turbot. To prevent digestion of the probiotics, rectal administration was applied to maximise colonization, by-passing digestion in the stomach. The application of Psychrobacter nivimaris and Psychrobacter faecalis showed beneficial effects on the inflammatory response and disease resistance after infection with the common pathogen Tenacibaculum maritimum. Treatment with P. nivimaris and P. faecalis resulted in 0% and 8% mortalities post-infection, while in the treatment control, an elevated mortality of 20% was observed. In the challenge controls (no infection), no mortalities were observed during the entire experimental period. After an experimental infection, mRNA expression of selected immune markers (mhc II alpha, il-1 beta, tcr, tgf beta and tnf alpha) were determined by RT-QPCR at 0, 1 and 5 days post-infection (dpi). At 0 dpi, gene expression was comparable between the treatments and the treatment control, suggesting that probiotics did not act via immune stimulation of the host. At 1 dpi, all genes were up-regulated in the treatment control but not in the probiotic groups, indicating that the infection in probiotic-treated fish developed at a less severe level. At 5 dpi, mRNA expression returned to baseline levels. As a conclusion, the native probiotic candidates P. nivimaris and P. faecalis improved survival, whereas, in the control, mortality increased and expression of the immune markers was up-regulated post infection. This highlights a potential application of P. nivimaris and P. faecalis in disease prophylaxis, but further research is needed.
- Numerical analysis of the flow field and cross section design implications in a multifunctional artificial reefPublication . Maslov, Dmytro; Pereira, Eduardo; Duarte, Duarte; Miranda, Tiago; Ferreira, Vasco; Tieppo, Marcos; Cruz, Fábio; Johnson, JessicaNowadays, multifunctional artificial reefs are integrated in coastal areas all around the world. The design of such structures is currently complex and subjective. In this context, it is essential to improve overall design approaches to more effectively relate artificial reef geometry, function and optimal performance to specific deployment sites. Part of the solution to this challenge may lie in the use of in situ data to study the hydrodynamic performance of prospective artificial reefs. This research addresses this issue by performing a numerical investigation of the flow transformation of two similar artificial reef geometries, and the analysis of performance indicators based on (i) artificial reef assembly cross section, (ii) upwelling and (iii) wake regions evaluation, (iv) efficiency indices and (v) streamlines particles. Based on typical data related to wave action, a velocity inlet boundary condition was defined adopting the non-uniform velocity distribution, aimed at simulating the most realistic boundary con-dition at the chosen deployment location. The results showed that the multifunctional artificial reef assembly with the droplet shape cross section exhibited enhanced function performance when compared to a circular shape cross section by providing significantly higher values of the upwelling velocity, wake region and associated efficiency indices. In addition, the procedure presented in this study, which considers oceanographic data at the deployment site, the geometry of the artificial reef, in situ flow characteristics and boundary conditions, as well as the devised fluid flow performance indicators, can be used for the design of artificial reefs during the concept stage in an objective manner to consider the local design requirements.
- Evaluation of current antiemetic therapy response in patients undergoing MEC or HEC regimens in PortugalPublication . Araújo, António; Tavares, Nuno; Faria, Ana Luísa; Gomes, Rosa; Mendonça, Joana Carvalho; Parente, Bárbara; Capela, Andreia; Barata, Fernando; Macedo, AnaChemotherapy-induced nausea and vomiting (CINV) negatively impact cancer patients' quality of life and treatment outcomes. This study evaluated the achievement of complete response to CINV prophylaxis during the first five days after chemotherapy in adult outpatient cancer clinics with solid malignant tumours receiving Moderate or Highly Emetogenic Chemotherapy (MEC or HEC) in Portugal. During the study, patients completed three evaluations, and nausea severity and CINV impact on patients' daily life was assessed. A complete response (no emetic episodes, no use of rescue antiemetic medication, and no more than mild nausea) was observed in 72% of the cycles (N = 161) throughout the five days after chemotherapy. Amongst the patient population, 25% classified their CINV episodes as severe. Though more than half of the patients achieved a complete response, suggesting that a therapeutic effort is being made to minimise this side effect, the overall scenario is barely optimistic. Significantly, new CINV-control measures in MEC/HEC patients should be adopted, specifically avoiding the single use of dexamethasone and 5-HT3 and raising awareness of using NK1-RAs. Thus, it is critical to improve CINV prophylactic treatment and implement practical international antiemetic guidelines in Portuguese clinical practice, envisaging the improvement of supportive care for cancer patients.
- 5-Deazaalloxazine as photosensitizer of singlet oxygen and potential redox-sensitive agentPublication . Insińska-Rak, Małgorzata; Golczak, Anna; Gierszewski, Mateusz; Anwar, Zubair; Cherkas, Volodymyr; Kwiatek, Dorota; Sikorska, Ewa; Khmelinskii, Igor; Burdziński, Gotard; Cibulka, Radek; Mrówczyńska, Lucyna; Kolanowski, Jacek Lukasz; Sikorski, MarekFlavins are a unique class of compounds that combine the features of singlet oxygen generators and redox-dependent fluorophores. From a broad family of flavin derivatives, deazaalloxazines are significantly underdeveloped from the point of view of photophysical properties. Herein, we report photophysics of 5-deazaalloxazine (1a) in water, acetonitrile, and some other solvents. In particular, triplet excited states of 1ain water and in acetonitrile were investigated using ultraviolet-visible (UV-Vis) transient absorption spectroscopy. The measured triplet lifetimes for 1a were all on the microsecond time scale (approximate to 60 mu s) in deoxygenated solutions. The quantum yield of S-1 -> T-1 intersystem crossing for 1ain water was 0.43 based on T1 energy transfer from 1a to indicaxanthin (5) acting as acceptor and on comparative actinometric measurements using benzophenone (6). 1a was an efficient photosensitizer for singlet oxygen in aerated solutions, with quantum yields of singlet oxygen in methanol of about 0.76, compared to acetonitrile similar to 0.74, dichloromethane similar to 0.64 and 1,2-dichloroethane similar to 0.54. Significantly lower singlet oxygen quantum yields were obtained in water and deuterated water (Phi(Delta)similar to 0.42 and 0.44, respectively). Human red blood cells (RBC) were used as a cell model to study the antioxidant capacity in vitro and cytotoxic activity of 1a. Fluorescence-lifetime imaging microscopy (FLIM) data were analyzed by fluorescence lifetime parameters and distribution for different parts of the emission spectrum. Comparison of multidimensional fluorescent properties of RBC under physiological-like and oxidative-stress conditions in the presence and absence of 1a suggests its dual activity as probe and singlet-oxygen generator and opens up a pathway for using FLIM to analyze complex intracellular behavior of flavin-like compounds. These new data on structure-property relationship contribute to the body of information required for a rational design of flavin-based tools for future biological and biochemical applications.