15 research outputs found
Crosstalk between cGAS-STING signaling and cell death
No full textPublished online: 18 September 2020Cytosolic nucleic acid sensors have a critical role in detecting endogenous nucleic acids to initiate innate immune responses during microbial infections and/or cell death. Several seminal studies over the past decade have delineated the conserved mechanism of cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and the downstream signaling adapter stimulator of interferon genes (STING) in mediating innate immune signaling pathways as a host defense mechanism. Besides the predominant role in microbial infections and inflammatory diseases, there is an increased attention on alternative functional responses of cGAS-STING-mediated signaling. Here we review the complexity of interactions between the cGAS-STING signaling and cell death pathways. A better understanding of molecular mechanisms of this interplay is important with regard to the development of new therapeutics targeting cGAS-STING signaling in cancer, infectious, and chronic inflammatory diseases.Ambika M. V. Murthy, Nirmal Robinson and Sharad Kuma
Ammoniakfabriek volgens het A.M.V. proces van ICI
No full textDocument uit de collectie Chemische ProcestechnologieDelftChemTechApplied Science
Ozone-related acute excess mortality projected to increase in the absence of climate and air quality controls consistent with the Paris Agreement
No full textShort-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate. © 2024 Elsevier Inc.Funding text 1: We are grateful for the generous support that made this research possible. A.M.V.-C. acknowledges funding from the Swiss National Science Foundation ( TMSGI3_211626 ). K.C. acknowledges support from the Yale Planetary Solutions Project seed grant and the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R01HL169171 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health . A.G. and A.S. acknowledge funding from the European Union’s Horizon 2020 Project Exhaustion (grant ID: 820655 ). J.M. acknowledges support from the Fundação para a Ciência e a Tecnologia (reference: PTDC/CTA-AMB/3040/2021; https://doi.org/10.54499/PTDC/CTA-AMB/3040/2021 ). The funders were not involved in the research or preparation of the article. ; Funding text 2: We are grateful for the generous support that made this research possible. A.M.V.-C. acknowledges funding from the Swiss National Science Foundation (TMSGI3_211626). K.C. acknowledges support from the Yale Planetary Solutions Project seed grant and the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R01HL169171. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A.G. and A.S. acknowledge funding from the European Union's Horizon 2020 Project Exhaustion (grant ID: 820655). J.M. acknowledges support from the Fundação para a Ciência e a Tecnologia (reference: PTDC/CTA-AMB/3040/2021; https://doi.org/10.54499/PTDC/CTA-AMB/3040/2021). The funders were not involved in the research or preparation of the article. Conceptualization, K.C. A.S. and A.M.V.-C.; methodology, N.G.G.D. A.G. K.C. and A.M.V.-C.; formal analysis and visualization, N.G.G.D.; data curation: N.G.G.D. K.C. A.M.F. J.F.L. L.W. A.G. and A.M.V.-C.; writing – original draft, N.G.G.D. K.C.; writing – review and editing, A.M.F. J.F.L. P.L.K. L.W. A.G. S.B. E.L. J.M. P.M. S.N.P.S. C.F.S.N. J.K. Y.G. S.T. H.K. A.U. H.O. M.M. M.P. K.K. E.S. M. Scortichini, M. Stafoggia, M.H. B.A. M.H.D. C.D.C.V. N.S. R.M.G. H.K. W.L. A.T. C.I. B.F. C.Å. M.S.R. Y.L.G. S.C.P. V.C. M.B. A.Z. J.S. A.S. A.M.V.-C. and K.C.; supervision, A.S. A.M.V.-C. and K.C. The authors declare no competing interests. To improve the readability and clarity of the manuscript, the authors incorporated suggestions from the language models Chat GPT-3.5 and Bard. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication
Synergistic Effect of a Flavonoid-Rich Cocoa–Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats
No full textAuthor Contributions: Conceptualization, T.F.-M., L.V., M.A.M. and E.F.-M.; Data curation, P.G.-V., M.A.M., E.F.-M., T.F.-M., L.V., A.M.V. and S.R.; Formal Analysis, P.G.-V., M.A.M., E.F.-M., T.F.- M., L.V., A.M.V. and S.R.; Funding Acquisition, M.A.M., E.F.-M., T.F.-M., L.V., A.M.V. and S.R.; Methodology, P.G.-V., T.F.-M., L.V. and E.F.-M.; Project administration, M.A.M., T.F.-M., L.V. and S.R.: Writing—Original Draft P.G.-V., M.A.M. and E.F.-M.; Writing—Review and Editing P.G.-V., M.A.M., E.F.-M., T.F.-M., L.V., A.M.V. and S.R.; All authors have read and agreed to the published version of the manuscript.The loss of functional beta-cell mass in diabetes is directly linked to the development of diabetic complications. Although dietary flavonoids have demonstrated antidiabetic properties, their potential effects on pancreatic beta-cell preservation and their synergistic benefits with antidiabetic drugs remain underexplored. We have developed a potential functional food enriched in flavonoids by combining cocoa powder and carob flour (CCB), which has shown antidiabetic effects. Here, we investigated the ability of the CCB, alone or in combination with metformin, to preserve pancreatic beta cells in an established diabetic context and their potential synergistic effect. Zucker diabetic fatty rats (ZDF) were fed a CCB-rich diet or a control diet, with or without metformin, for 12 weeks. Markers of pancreatic oxidative stress and inflammation, as well as relative beta-cell mass and beta-cell apoptosis, were analyzed. Results demonstrated that CCB feeding counteracted pancreatic oxidative stress by enhancing the antioxidant defense and reducing reactive oxygen species. Moreover, the CCB suppressed islet inflammation by preventing macrophage infiltration into islets and overproduction of pro-inflammatory cytokines, along with the inactivation of nuclear factor kappa B (NFκB). As a result, the CCB supplementation prevented beta-cell apoptosis and the loss of beta cells in ZDF diabetic animals. The observed additive effect when combining the CCB with metformin underscores its potential as an adjuvant therapy to delay the progression of type 2 diabetes.Ministerio de Ciencia, Innovación y UniversidadesComunidad de MadridSección Deptal. de Bioquímica y Biología Molecular (Farmacia)Fac. de FarmaciaTRUEpu
Variation in hemolysin a expression between uropathogenic Escherichia coli isolates determines NLRP3-dependent vs. -independent macrophage cell death and host colonization
No full textUropathogenic Escherichia coli (UPEC) is the major cause of urinary tract infections (UTIs). The multidrug-resistant E. coli sequence type 131 (ST131) clone is a serious threat to human health, yet its effects on immune responses are not well understood. Here we screened a panel of ST131 isolates, finding that only strains expressing the toxin hemolysin A (HlyA) killed primary human macrophages and triggered maturation of the inflammasome-dependent cytokine IL-1β. Using a representative strain, the requirement for the hlyA gene in these responses was confirmed. We also observed considerable heterogeneity in levels of cell death initiated by different HlyA+ve ST131 isolates, and this correlated with secreted HlyA levels. Investigation into the biological significance of this variation revealed that an ST131 strain producing low levels of HlyA initiated cell death that was partly dependent on the nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, with this response being associated with a host-protective role in a mouse UTI model. When the same ST131 strain was engineered to overexpress high HlyA levels, macrophage cell death occurred even when NLRP3 function was abrogated, and bladder colonization was significantly increased. Thus, variation in HlyA expression in UPEC affects mechanisms by which macrophages die, as well as host susceptibility vs. resistance to colonization.-Murthy, A. M. V., Sullivan, M. J., Nhu, N. T. K., Lo, A. W., Phan, M.-D., Peters, K. M., Boucher, D., Schroder, K., Beatson, S. A., Ulett, G. C., Schembri, M. A., Sweet, M. J. Variation in hemolysin A expression between uropathogenic Escherichia coli isolates determines NLRP3-dependent vs. -independent macrophage cell death and host colonization
Structures of substrate- and nucleotide-bound propionate kinase from Salmonella typhimurium: substrate specificity and phosphate-transfer mechanism
No full textKinases are ubiquitous enzymes that are pivotal to many biochemical processes. There are contrasting views on the phosphoryl-transfer mechanism in propionate kinase, an enzyme that reversibly transfers a phosphoryl group from propionyl phosphate to ADP in the final step of non-oxidative catabolism of l-threonine to propionate. Here, X-ray crystal structures of propionate- and nucleotide-bound Salmonella typhimurium propionate kinase are reported at 1.8-2.0 Å resolution. Although the mode of nucleotide binding is comparable to those of other members of the ASKHA superfamily, propionate is bound at a distinct site deeper in the hydrophobic pocket defining the active site. The propionate carboxyl is at a distance of ∼5 Å from the γ-phosphate of the nucleotide, supporting a direct in-line transfer mechanism. The phosphoryl-transfer reaction is likely to occur via an associative SN2-like transition state that involves a pentagonal bipyramidal structure with the axial positions occupied by the nucleophile of the substrate and the O atom between the β- and the γ-phosphates, respectively. The proximity of the strictly conserved His175 and Arg236 to the carboxyl group of the propionate and the γ-phosphate of ATP suggests their involvement in catalysis. Moreover, ligand binding does not induce global domain movement as reported in some other members of the ASKHA superfamily. Instead, residues Arg86, Asp143 and Pro116-Leu117-His118 that define the active-site pocket move towards the substrate and expel water molecules from the active site. The role of Ala88, previously proposed to be the residue determining substrate specificity, was examined by determining the crystal structures of the propionate-bound Ala88 mutants A88V and A88G. Kinetic analysis and structural data are consistent with a significant role of Ala88 in substrate-specificity determination. The active-site pocket-defining residues Arg86, Asp143 and the Pro116-Leu117-His118 segment are also likely to contribute to substrate specificity
P62 inhibits IL-1β release during Salmonella Typhimurium infection of macrophages
No full textMacrophages are critical for the innate immune defense against the facultative intracellular Gram-negative bacterium Salmo\nella enterica serovar Typhimurium. Following phagocytosis by macrophages, S. Typhimurium activates cytoplasmic NLRC3 and NLRP4 inflammasomes, which share the adaptor ASC, resulting in the secretion of the pro-inflammatory cytokine IL-1β. To prevent excessive inflammation and tissue damage, inflammatory signaling pathways are tightly controlled. Recently, autophagy has been suggested to limit inflammation by targeting activated inflammasomes for autophagic degradation. However, the importance of the autophagic adaptor Sequestome-1 (hereafter, p62) for regulating inflammasome activation remains poorly understood. We report here that p62 restricts inflammasome availability and subsequent IL-1β secretion in macrophages infected with S. Typhimurium by targeting the inflammasome adaptor ASC for autophagic degradation. Importantly, loss of p62 resulted in impaired autophagy and increased IL-1β secretion, as well as IL-10 and IFN-β release. In summary, our results demonstrate a novel role for p62 in inducing autophagy and balancing major pro- and anti-inflammatory signaling pathways to prevent excessive inflammation during S. Typhimurium infection of macrophages.</jats:p
Regional variation in the role of humidity on city-level heat-related mortality
No full textThe rising humid heat is regarded as a severe threat to human survivability, but the proper integration of humid heat into heat-health alerts is still being explored. Using state-of-the-art epidemiological and climatological datasets, we examined the association between multiple heat stress indicators (HSIs) and daily human mortality in 739 cities worldwide. Notable differences were observed in the long-term trends and timing of heat events detected by HSIs. Air temperature (Tair) predicts heat-related mortality well in cities with a robust negative Tair-relative humidity correlation (CT-RH). However, in cities with near-zero or weak positive CT-RH, HSIs considering humidity provide enhanced predictive power compared to Tair. Furthermore, the magnitude and timing of heat-related mortality measured by HSIs could differ largely from those associated with Tair in many cities. Our findings provide important insights into specific regions where humans are vulnerable to humid heat and can facilitate the further enhancement of heat-health alert systems. © The Author(s) 2024.Q.G., M.H., and T.O. were supported by the Environment Research and Technology Development Fund (JPMEERF23S21120) of the Environmental Restoration and Conservation Agency provided by the Ministry of the Environment of Japan. Q.G. was supported by the Musha Shugyo international travel grants from the School of Engineering, The University of Tokyo. T.O. was supported by the Japan Society for the Promotion of Science (KAKENHI: 21H05002), and the Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency of Japan (JPMEERF23S21100). M.N.M. was supported by the European Commission (H2020-MSCA-IF-2020) under REA grant agreement no. 101022870. A.G. was supported by the Medical Research Council-UK (Grant ID: MR/V034162/1) and European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). J.K. was supported by the Czech Science Foundation, project 23-06749S. A.M.V.-C. supported by the Swiss National Science Foundation (TMSGI3_211626). V.H. was supported by the European Union’s Horizon 2020 research and innovation program (H2020-MSCA-IF-2020, Grant No.: 101032087). Y.S. was supported by Brain Pool Plus program funded by the Ministry of Science and ICT through the National Research Foundation of Korea (NRF-2021H1D3A2A03097768), and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2023R1A2C1004754)
A propagação vegetativa de plantas ornamentais na empresa Novo Sol Plantas: uma análise crítica de situações técnicas que condicionam o processo produtivo
No full textO autor deste Relatório, César José Vendinha Almeida Torres, formou-se em Engenharia Agrícola, ramo cientifico-tecnológico na Universidade de Évora em 2006. Em 2003 realizou em Évora, na herdade do Tojal, um “estágio” no âmbito do “Trabalho De Fim De Curso” com o tema “O efeito da sementeira directa sobre o escorrimento e a produção de sedimentos numa cultura de milho regada por rampa rotativa” o qual deu ainda origem a um seminário na Universidade de Évora em 2004 e a um artigo em acta de evento internacional com arbitragem científica:
Silva, L.L., Marques da Silva, J.R., Pisco, A.M.V., Torres, C.J.V. (2010) No-till and Basin tillage for reducing runoff and sediment yield on centre-pivot irrigated maize in a Mediterranean soil, in Proceedings of the EurAgeng 2010 Conference “Towards Environmental Technologies”, Clermont-Ferrand, França. ISBN 13:978-2-85362-684-2
Em 2004 começou a trabalhar na empresa Novo Sol Plantas, situada no conselho de Montijo e integrada no grupo multinacional Ball. A sua função na empresa é dirigir o sector de propagação vegetativa e endurecimento de todas as plantas com raiz. É responsável por controlar todos os Factores Ambientais (Temperatura, humidade relativa, ventilação, fotoperíodo e insolação); Fertirrigação (quantidade, frequência, nutrição, afinação e manutenção), Factores Nutritivos (equilíbrios nutricionais) e de qualidade (Reguladores de crescimento, carências, fototoxicidades, etc.). É também responsável pela gestão do espaço nos viveiros e endurecimentos, dimensionamento e controlo produtivo da mão-de-obra, aquisição e gestão dos stocks de factores de produção (tabuleiros, substratos, vasos).
A Novo Sol Plantas dedica-se à propagação vegetativa por estacaria de um grande número de plantas ornamentais, de onde se destacam fúchsias, verbenas e Polygala myrtifolia.
A Polygala myrtifolia é uma arbustiva cujo sucesso de enraizamento é baixo. Assim, um dos temas deste relatório é a tentativa de melhorar o sucesso do enraizamento por estaca desta espécie. Foram feitos ensaios onde se variou o tipo de estaca usada e a concentração de AIB (Acido Indol Butirico) no enraizamento. Foram obtidos melhores resultados com estacas vegetativas provenientes de crescimentos apicais algum tempo após manutenção das plantas mãe. Em relação ao IBA, 0,5% foi a concentração que originou melhores enraizamentos.
O segundo tema a ser desenvolvido neste relatório, prende-se com a produção de plantas com entre-nos curtos, de modo a que a planta fique compacta e dê posteriormente origem a um vaso compacto com uma forma “redonda” com muitas flores. Uma das técnicas mais utilizadas é a aplicação de reguladores de crescimento (PGR – Plant Growth Retardant).
Trata-se de produtos em que, pequenas variações na concentração utilizada e na forma de aplicação, podem ser catastróficas, levando frequentemente a resultados muito diferentes dos esperados. Para cada espécie, a dose certa, a forma de aplicação e o tempo em que esta deve ser feita, são críticos para o sucesso da técnica. É a experiência obtida no manuseamento deste tipo de produtos que aqui se relatará; ABSTRACT:This report’s author, César José Vendinha Almeida Torres graduated in Agricultural Engineering, at the University of Évora in 2006. In 2003 he started in Évora, (Tojal farm), an experimental work on the subject "The effect of direct seeding on runoff and sediment lost in a corn crop irrigated by center pivot" which also gave rise to a seminar at the University of Évora in 2004 and a peer review article resulting from a communication in an international event:
Silva, L.L., Marques da Silva, J.R., Pisco, A.M.V., Torres, C.J.V. (2010) No-till and Basin tillage for reducing runoff and sediment yield on centre-pivot irrigated maize in a Mediterranean soil, in Proceedings of the EurAgeng 2010 Conference “Towards Environmental Technologies”, Clermont-Ferrand, France. ISBN 13:978-2-85362-684-2
In 2004 he starts working in the company Novo Sol Plantas in Montijo’s region and integrated into the multinational group Ball. His job in the company is to manage the vegetative propagation sector and the hardening sector of all rooted plants. He must control all the environmental factors (temperature, moisture, ventilation, photoperiod and insolation); Irrigation (quantity, frequency, feed, calibration and maintenance), Nutritional factors (nutritional balances) and quality (growth regulators, feed needs, toxicities, etc.). He is also responsible for managing the space in the nursery, sizing and productivity control of labor, acquisition and management of stocks of inputs (tray’s, substrates, pots)
The Novo Sol Plantas main core business is the vegetative propagation by cuttings of a large number of ornamental plants, from which highlights species like fuchsias, verbenas and Polygala myrtifolia.
Polygala myrtifolia is a shrub whose rooting success by cuttings is low. So, one of this report topics is an attempt to improve the rooting success by cuttings of this specie. Tests were performed using different types of cuttings and different IBA (Indole Butyric Acid) concentrations on the rooting process. The best results were obtained with vegetative cuttings from apical growth of mother plants. Regarding IBA, 0.5% was the concentration that gave better rooting results.
The other topic being developed in this report, deals with the production of plants with short inter-nodal segments. The aim is to achieve compact plants which subsequently lead to a better-shaped flower pot. One of the most widely used techniques is the application of growth regulators (PGR - Plant Growth Retardant). These are products in which small variations in the concentration used and the application method can be disastrous, leading very often to product totally different from those expected. For each species, the right dosage, the application method and also the application time schedule, are critical to the success of the technique. It is the experience achieved in handling this type of products that we report here
The Eruption of 22 April 2021 as Observed by Solar Orbiter: Continuous Magnetic Reconnection and Heating After the Impulsive Phase
No full textsponsorship: Solar Orbiter is a space mission of international collaboration between ESA and NASA, operated by ESA. The EUI instrument was built by CSL, IAS, MPS, MSSL/UCL, PMOD/WRC, ROB, and LCF/IO with funding from the Belgian Federal Science Policy Office (BELPSO); the Centre National d'Etudes Spatiales (CNES); the UK Space Agency (UKSA); the Bundesministerium fuer Wirtschaft und Energie (BMWi) through the Deutsches Zentrum fuer Luft- und Raumfahrt (DLR); and the Swiss Space Office (SSO). Metis was built and operated with funding from the Italian Space Agency (ASI), under contracts to the National Institute of Astrophysics (INAF) and industrial partners. Metis was built with hardware contributions from Germany (Bundesministerium fuer Wirtschaft und Energie through DLR), from the Czech Republic (PRODEX), and from ESA. The STIX instrument is an international collaboration between Switzerland, Poland, France, Czech Republic, Germany, Austria, Ireland, and Italy. These results were also obtained in the framework of the projects C14/19/089 (C1 project Internal Funds KU Leuven), G.0D07.19N (FWO-Vlaanderen), SIDC Data Exploitation (ESA Prodex-12), and BelSPo projects BR/165/A2/CCSOM and B2/191/P1/SWiM. The ROB team thanks the Belgian Federal Science Policy Office (BELSPO) for the provision of financial support in the framework of the PRODEX Programme of the European Space Agency (ESA) under contract numbers 4000134088, 4000112292, 4000134474, and 4000136424. The work of F.S. was supported by DLR grant No. 50 OT 1904. O.P. is grateful to the German Leibniz Association. L.A.H. is supported by an ESA Research Fellowship. A.M.V and E.C.M.D acknowledge the Austrian Science Fund (FWF): I4555-N. P.M., M.P., and F.B. acknowledge the financial contribution from the agreement ASI-INAF n.2018-16-HH.0. C.M. was funded by the European Union. Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. The EUI dataset presented in this paper has been distributed as part of the EUI Data Release 5.0 and is freely accessible through DOI. (Belgian Federal Science Policy Office (BELPSO), Centre National d'Etudes Spatiales (CNES), UK Space Agency (UKSA), Bundesministerium fuer Wirtschaft und Energie (BMWi) through the Deutsches Zentrum fuer Luftund Raumfahrt (DLR), Swiss Space Office (SSO), Italian Space Agency (ASI), SIDC Data Exploitation (ESA Prodex-12), Germany (Bundesministerium fuer Wirtschaft und Energie through DLR), BelSPo projects|BR/165/A2/CCSOM, BelSPo projects|B2/191/P1/SWiM, KU Leuven, FWO-Vlaanderen, Belgian Federal Science Policy Office (BELSPO), ASI-INAF, DLR|50 OT 1904, German Leibniz Association, ESA Research Fellowship, Austrian Science Fund (FWF)|I4555-N, European Union, National Institute of Astrophysics (INAF), PRODEX Programme of the European Space Agency (ESA)|4000134088, PRODEX Programme of the European Space Agency (ESA)|4000112292, PRODEX Programme of the European Space Agency (ESA)|4000134474, PRODEX Programme of the European Space Agency (ESA)|4000136424)status: Publishe
