116 research outputs found

    Plant aqueous extracts: antioxidant capacity via haemolysis and bacteriophage P22 protection

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    The bacteriophage P22/Salmonella Typhimurium system, as well as human erythrocytes have been used to assay for protection, against forced oxidation caused by hydrogen peroxide, brought about by several aqueous extracts of selected adventitious plants grown in Portugal. This study proved, for the first time, that the aforementioned bacteriophage-based system is a suitable method to assess the antioxidant activity of plant extracts; among the 12 plants tested, raspberry (Rubus idaeus), sage (Salvia sp.), savory (Satureja montana) and yarrow (Achillea millefolium) were found to effectively protect against oxidative damage caused by H2O2. Haemolysis was inhibited via pre-treatment with every plant extract tested, except heath at 0.1% (w/v). The two analytical methods produced different results – and for some plants, there was a dependence (either direct or inverse) of the quantitative protection effect on extract concentration, whereas for others no significant dependence was found at all. Savory yielded the most promising results, using either method. Therefore, the P22/Salmonella system can be used as a suitable in vivo assay, and human erythrocytes as a suitable in vitro assay to confirm (or not) the antioxidant capacity of plant extracts in biological matrices.info:eu-repo/semantics/acceptedVersio

    Aryl hydrocarbon receptor and cysteine redox dynamics underlie (Mal)adaptive mechanisms to chronic intermittent hypoxia in kidney cortex

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    Funding Information: Funding: This work was supported by Fundação para Ciência e Tecnologia [PTDC/MED-TOX/30418/2017] and iNOVA4Health [UID/Multi/04462/2013]. M.J.C., F.L.-C., N.R.C., C.G.-D. and J.M. are supported by FCT grants [SFRH/BD/131331/2017, PD/BD/128337/2017, PD/BD/114257/2016, and PD/BD/105892/2014, PTDC/MED-TOX/30418/2017 respectively]. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.We hypothesized that an interplay between aryl hydrocarbon receptor (AhR) and cysteine-related thiolome at the kidney cortex underlies the mechanisms of (mal)adaptation to chronic intermittent hypoxia (CIH), promoting arterial hypertension (HTN). Using a rat model of CIH-HTN, we investigated the impact of short-term (1 and 7 days), mid-term (14 and 21 days, pre-HTN), and long-term intermittent hypoxia (IH) (up to 60 days, established HTN) on Cyp1a1 protein level (a sensitive hallmark of AhR activation) and cysteine-related thiol pools. We found that acute and chronic IH had opposite effects on Cyp1a1 and the thiolome. While short-term IH decreased Cyp1a1 and increased protein-S-thiolation, long-term IH increased Cyp1a1 and free oxidized cysteine. In addition, an in vitro administration of cystine, but not cysteine, to human endothelial cells increased Cyp1a1 expression, supporting cystine as a putative AhR activator. This study supports Cyp1a1 as a biomarker of obstructive sleep apnea (OSA) severity and oxidized pools of cysteine as risk indicator of OSA-HTN. This work contributes to a better understanding of the mechanisms underlying the phenotype of OSA-HTN, mimicked by this model, which is in line with precision medicine challenges in OSA.publishersversionpublishe

    Embracing Nature-based Solutions to promote resilient marine and coastal ecosystems

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    The world is struggling to limit greenhouse gas emissions and reduce the human footprint on nature. We therefore urgently need to think about how to achieve more with actions to address mounting challenges for human health and wellbeing from biodiversity loss, climate change effects, and unsustainable economic and social development. Nature-based Solutions (NBS) have emerged as a systemic approach and an important component of the response to these challenges. In marine and coastal spaces, NBS can contribute to improved environmental health, climate change mitigation and adaptation, and a more sustainable blue economy, if implemented to a high standard. However, NBS have been largely studied for terrestrial – particularly urban – systems, with limited uptake thus far in marine and coastal areas, despite an abundance of opportunities. Here, we provide explanations for this lag and propose the following three research priorities to advance marine and coastal NBS: (1) Improve understanding of marine and coastal biodiversity-ecosystem services relationships to support NBS better designed for rebuilding system resilience and achieving desired ecological outcomes under climate change; (2) Provide scientific guidance on how and where to implement marine and coastal NBS and better coordinate strategies and projects to facilitate their design, effectiveness, and value through innovative synergistic actions; (3) Develop ways to enhance marine and coastal NBS communication, collaboration, ocean literacy and stewardship to raise awareness, co-create solutions with stakeholders, boost public and policy buy-in, and potentially drive a more sustained investment. Research effort in these three areas will help practitioners, policy-makers and society embrace NBS for managing marine and coastal ecosystems for tangible benefits to people and marine life.The study received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement MaCoBioS (contract no 869710), FutureMARES (contract no 869300) and REST-COAST (contract no 101037097).info:eu-repo/semantics/publishedVersio

    Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina

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    © 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Blood-vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs-sprouting angiogenesis and vascular remodeling-is established by a shift of collective front-to-rear polarity of endothelial cells in the mouse retina. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood-flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.Funding: European Research Council: C.A.F. (679368); X.T. (883739). European Commission: C.A.F. and M.O.B. (801423); X.T. and P.R.-C. (731957). H2020-MSCA-PF grants to M.G.-G. (797621) and M.O. (842498). Fondation LeDucq: C.A.F., A.E., and M.O.B. (17CVD03). EPSRC: M.O.B. (EP/T008806/1; EP/R029598/1). Fundação para a Ciência e Tecnologia: C.A.F. (PTDC/MED-PAT/31639/2017; PTDC/BIA-CEL/32180/2017; CEECIND/04251/2017). Spanish Ministry of Science and Innovation: P.R.-C. (PID2019-110298GB-I00); X.T. (PGC2018-099645-B-I00). Generalitat de Catalunya: X.T. and P.R.-C. (2017-SGR-1602). La Caixa Foundation: X.T. and P.R.-C. (LCF/PR/HR20/52400004). Fundació la Marató de TV3: X.T. (201903-30-31-32). EMBO: L.M.F. (ALTF 2-2018)info:eu-repo/semantics/publishedVersio

    Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes

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    Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242839/Anthrax is an infectious disease caused by Bacillus anthracis, a bioterrorism agent that develops resistance to clinically used antibiotics. Therefore, alternative mechanisms of action remain a challenge. Herein, we disclose deoxy glycosides responsible for specific carbohydrate-phospholipid interactions, causing phosphatidylethanolamine lamellar-to-inverted hexagonal phase transition and acting over B. anthracis and Bacillus cereus as potent and selective bactericides. Biological studies of the synthesized compound series differing in the anomeric atom, glycone configuration and deoxygenation pattern show that the latter is indeed a key modulator of efficacy and selectivity. Biomolecular simulations show no tendency to pore formation, whereas differential metabolomics and genomics rule out proteins as targets. Complete bacteria cell death in 10 min and cellular envelope disruption corroborate an effect over lipid polymorphism. Biophysical approaches show monolayer and bilayer reorganization with fast and high permeabilizing activity toward phosphatidylethanolamine membranes. Absence of bacterial resistance further supports this mechanism, triggering innovation on membrane-targeting antimicrobials.The European Union is gratefully acknowledged for the support of the project “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347. We thank the Management Authorities of the European Regional Development Fund and the National Strategic Reference Framework for the support of the Incentive System - Research and Technological Development Co-Promotion FACIB Project number 21457. Fundação para a Ciência e a Tecnologia is also acknowledged for the support of projects UID/Multi/00612/2013, FCT/UID/ Multi/04046/2013, IF/00808/2013/CP1159/CT0003, PTDC/BBBBQB/6071/2014, as well as for the post-doc grant SFRH/BPD/42567/2007 (A.M.), the Ph.D. grants SFRH/BDE/51998/2012 (C.D.), and SFRH/BDE/51957/2012 (J.P.P.), both co-sponsored by CIPAN, and also for the Ph.D. grant SFRH/BD/116614/2016 (R.N.).info:eu-repo/semantics/publishedVersio

    Translational molecular imaging in exocrine pancreatic cancer

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    Effective treatment for pancreatic cancer remains challenging, particularly the treatment of pancreatic ductal adenocarcinoma (PDAC), which makes up more than 95% of all pancreatic cancers. Late diagnosis and failure of chemotherapy and radiotherapy are all too common, and many patients die soon after diagnosis. Here, we make the case for the increased use of molecular imaging in PDAC preclinical research and in patient management

    Translational molecular imaging in exocrine pancreatic cancer

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    Effective treatment for pancreatic cancer remains challenging, particularly the treatment of pancreatic ductal adenocarcinoma (PDAC), which makes up more than 95% of all pancreatic cancers. Late diagnosis and failure of chemotherapy and radiotherapy are all too common, and many patients die soon after diagnosis. Here, we make the case for the increased use of molecular imaging in PDAC preclinical research and in patient management

    Biochars in soils : towards the required level of scientific understanding

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    Key priorities in biochar research for future guidance of sustainable policy development have been identified by expert assessment within the COST Action TD1107. The current level of scientific understanding (LOSU) regarding the consequences of biochar application to soil were explored. Five broad thematic areas of biochar research were addressed: soil biodiversity and ecotoxicology, soil organic matter and greenhouse gas (GHG) emissions, soil physical properties, nutrient cycles and crop production, and soil remediation. The highest future research priorities regarding biochar's effects in soils were: functional redundancy within soil microbial communities, bioavailability of biochar's contaminants to soil biota, soil organic matter stability, GHG emissions, soil formation, soil hydrology, nutrient cycling due to microbial priming as well as altered rhizosphere ecology, and soil pH buffering capacity. Methodological and other constraints to achieve the required LOSU are discussed and options for efficient progress of biochar research and sustainable application to soil are presented.Peer reviewe

    International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)

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    Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable

    Records of Mantodea (Insecta) collected with light trap at 45 meters height over an Amazon forest canopy, at ZF-2 nucleus, Manaus, Brazil

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    Insect collections were carried out monthly from January to December of 2004, during three nights of lunar transition third quarter moon/new moon from 18 p.m. to 6 a.m. They were collected over a vertical white sheet illuminated by a 250 watts mixed light and a 20 watts black light (BL) and black light bulb (BLB) lamps. The light trap was mounted at 45 meters height in a metallic tower of 50 meters height, in a "platô de terra firme", in the Cueiras River basin, in Manaus, Amazonas, Brazil. It was collected 23 species of Mantodea: Chaeteessidae (1 species); Mantoididae (2); Mantidae (15); Thespidae (2) and Acanthopidae (3). Six new species were registered and they will be described opportunely in the following genera: Cardioptera Burmeister, 1838; Phyllovates Kirby, 1904; Pseudovates Saussure, 1869; Stagmomantis Saussure, 1869; Stagmatoptera Burmeister, 1838 and Metilia Stal, 1877. Three species previously recorded to an indetermined Brazilian region are being recorded to Brazilian Amazon: Heterovates pardalina Saussure, 1872; Macromantis ovalifolia (Stoll, 1813) and Photina reticulata (Burmeister, 1838). Four records are new for the Amazonas state: Angela guianensis Rehn, 1906; Photina gracillis Giglio-Tos, 1915; Raptrix perspicua (Fabricius, 1787) and Vates festae Gigio-Tos, 1914. The specimens number collected monthly are presented for each species.Foram realizadas coletas mensais de insetos de janeiro a dezembro de 2004, durante três noites de transição lunar minguante/nova, das 18:00 às 06:00 horas. Os espécimes foram capturados em um lençol iluminado com lâmpada de 250 watts, luz mista de vapor de mercúrio e lâmpada de 20 watts black light (BL) e black light bulb (BLB). A armadilha foi montada a 45 metros de altura numa torre metálica de 50 metros, que ultrapassa a maioria das copas das árvores, num platô de terra firme, na bacia do rio Cuieiras, Manaus, Amazonas, Brasil. Foram coletados 23 espécies de Mantodea, sendo Chaeteessidae (1 espécie); Mantoididae (2); Mantidae (15); Thespidae (2) e Acanthopidae (3). Seis espécies são novas e serão descritas oportunamente nos seguintes gênerosCardioptera Burmeister, 1838, Phyllovates Kirby, 1904, Pseudovates Saussure, 1869, Stagmomantis Saussure, 1869, Stagmatoptera Burmeister, 1838 e Metilia Stal, 1877. Três espécies registradas para o Brasil sem uma região determinada estão sendo registradas para a Amazônia brasileiraHeterovates pardalina Saussure, 1872, Macromantis ovalifolia (Stoll, 1813) e Photina reticulata (Burmeister, 1838). Quatro registros são novos para o estado do AmazonasAngela guianensis Rehn, 1906, Photina gracillis Giglio-Tos, 1915, Raptrix perspicua (Fabricius, 1787) e Vates festae Gigio-Tos, 1914. Os números de indivíduos, em cada coleta mensal, são apresentados para cada espécie
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