6,451 research outputs found

    Coordination between proteasome impairment and caspase activation leading to TAU pathology: neuroprotection by cAMP

    Full text link
    Neurofibrillary tangles (NFTs) are hallmarks of Alzheimer’s disease (AD). The main component of NFTs is TAU, a highly soluble microtubule-associated protein. However, when TAU is cleaved at Asp421 by caspases it becomes prone to aggregation leading to NFTs. What triggers caspase activation resulting in TAU cleavage remains unclear. We investigated in rat cortical neurons a potential coordination between proteasome impairment and caspase activation. We demonstrate that upon proteasome inhibition, the early accumulation of detergent-soluble ubiquitinated (SUb) proteins paves the way to caspase activation and TAU pathology. This occurs with two drugs that inhibit the proteasome by different means: the product of inflammation prostaglandin J2 (PGJ2) and epoxomicin. Our results pinpoint a critical early event, that is, the buildup of SUb proteins that contributes to caspase activation, TAU cleavage, TAU/Ub-protein aggregation and neuronal death. Furthermore, to our knowledge, we are the first to demonstrate that elevating cAMP in neurons with dibutyryl-cAMP (db-cAMP) or the lipophilic peptide PACAP27 prevents/ diminishes caspase activation, TAU cleavage and neuronal death induced by PGJ2, as long as these PGJ2-induced changes are moderate. db-cAMP also stimulated proteasomes, and mitigated proteasome inhibition induced by PGJ2. We propose that targeting cAMP/PKA to boost proteasome activity in a sustainable manner could offer an effective approach to avoid early accumulation of SUb proteins and later caspase activation, and TAU cleavage, possibly preventing/delaying AD neurodegeneration

    Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis

    Get PDF
    © 2022, Silva Pereira, De Niz et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.Trypanosoma congolense causes a syndrome of variable severity in animals in Africa. Cerebral trypanosomiasis is a severe form, but the mechanism underlying this severity remains unknown. We developed a mouse model of acute cerebral trypanosomiasis and characterized the cellular, behavioral, and physiological consequences of this infection. We show large parasite sequestration in the brain vasculature for long periods of time (up to 8 hr) and extensive neuropathology that associate with ICAM1-mediated recruitment and accumulation of T cells in the brain parenchyma. Antibody-mediated ICAM1 blocking and lymphocyte absence reduce parasite sequestration in the brain and prevent the onset of cerebral trypanosomiasis. Here, we establish a mouse model of acute cerebral trypanosomiasis and we propose a mechanism whereby parasite sequestration, host ICAM1, and CD4+ T cells play a pivotal role.This work was supported by European Union’s Horizon 2020 research and innovation program through a Marie Skłodowska-Curie Individual Standard European Fellowship to S.S.P., under grant agreement no. 839960, and from the European Research Council (ERC) (FatTryp, 771714) to L.M.F. M.D.N. was funded by Human Frontiers LT000047/2019 L (HFSP) and EMBO (ALTF 1048–2016). L.M.F., K.S., and C.A.F. are Investigators CEEC of the Fundação para a Ciência e a Tecnologia (CEECIND/03322/2018, CEECIND/00697/2018, CEECIND/04251/2017, respectively). C.A.F. was supported by a European Research Council starting grant (679368), the Fondation Leducq (17CVD03), and the Fundação para a Ciência e a Tecnologia (grants IF/00412/2012, EXPL/BEX- BCM/2258/2013, PRECISE-LISBOA-01–0145-FEDER-016394, PTDC/MED-PAT/31639/2017, PTDC/BIA-CEL/32180/2017).info:eu-repo/semantics/publishedVersio

    Pt-Ru Catalysts supported on mesoporous carbons for polymer electrolyte membrane fuel cells

    Get PDF
    Pt-Ru electrocatalysts supported on xerogels and CMK-3 ordered mesoporous carbons were synthesized by reduction with formate ions (SFM method). Some of the carbon supports were chemically treated with HNO3 in order to generate oxygen groups on the surface, while other supports were heat treated. Physical characterization of the catalyst was obtained using X-ray dispersive energy (EDX) and X-ray diffraction (XRD) techniques. Results showed that Pt-Ru catalysts with similar metal content (20%) and atomic ratios (Pt:Ru 1:1) were obtained. The electrochemical activity was studied by cyclic voltammetry and chronoamperometry. Higher methanol oxidation current densities were found for catalyst deposited on chemically treated supports. Electrode preparation and MEA assembly allowed an in-house built direct methanol fuel to be fitted with the synthesized catalysts and supports in order to assess their performance. Cell and reactants were conditioned by a direct methanol test station. Polarisation curves were measured and confirmed data obtained by voltammetry, regarding the effect of heat treatment of the carbon support. Normalised power curves per weight of catalyst are discussed in terms of the significant impact on noble metal loading and attained cell maximum power, in comparison with results obtained with a commercial catalyst

    Influence of catalyst support characteristics and functionalization on the catalytic activity of Pt-Ru for PEM fuel cells

    Get PDF
    Pt-Ru electrocatalysts supported on carbon xerogels and ordered mesoporous carbons were synthesized by reduction with formate ions (SFM method). Chemical and heat treatments were applied to modified the surface chemistry of original carbon supports. Physical characterization of the catalysts was performed using X-ray dispersive energy (EDX) and X-ray diffraction (XRD) techniques, while the electrochemical activity towards methanol oxidation was studied by cyclic voltammetry (CV). Pt-Ru catalysts with nominal metal content (20 wt.%) and atomic ratios (Pt:Ru 1:1) were successfully synthesized on the different supports. Higher methanol oxidation current densities were obtained for those supports with a higher content of surface oxygen groups. Gas diffusion electrode and membrane-electrode-assembly preparation allowed an in-house built of a direct methanol fuel monocell for the evaluation of the catalysts performance. Polarization curves were measured confirming the results obtained in a three electrodes electrochemical cell by CV. Normalized power curves per weight of Pt are discussed in terms of the significant impact on noble metal loading and attained cell maximum power, in comparison with results obtained with a commercial catalyst

    Biorecovery of Cr(VI) from wastewater and its catalytic reutilization

    Get PDF
    The performance of two zeolites with different structures and acidity properties was evaluated on the biosorption of Cr(VI) and catalytic oxidation of ethyl acetate. The starting zeolites, HY and HZSM5, were modified by ion exchange treatments in order to obtain zeolites with different acidity and sodium content. Arthrobacter viscosus supported on the different zeolites was used for Cr(VI) recovery from solution. The best removal efficiencies and uptake of chromium were achieved for the Y zeolites due to their higher ion exchange capacity. The Y and ZSM5 zeolites were characterized by ICP-AES, SEM, NH3 chemisorption, XRD and N2 adsorption. Y and ZSM5 zeolites obtained after biosorption of chromium were successfully reused as catalysts in the oxidation of ethyl acetate. The chromium-loaded ZSM5 zeolites were considerably more active and selective towards CO2 than chromium-loaded Y zeolites, essentially due to its different framework structure, textural and acidity properties

    Biological aspects of Eriopis connexa (Germar) (Coleoptera: Coccinellidae) fed on different insect pests of maize (Zea mays L.) and sorghum [Sorghum bicolor L. (Moench.)].

    Get PDF
    Eriopis connexa (Germar) (Coleoptera: Coccinellidae) occurs in several countries of South America and its mass rearing is important for biological control programmes. This work evaluated biological aspects of E. connexa larva fed on eggs of Anagasta kuehniella (Zeller) (Lepidoptera: Pyralidae) and Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) frozen for one day, fresh eggs of Diatraea saccharalis (Fabricius) (Lepidoptera: Pyralidae), S. frugiperda newly-hatched caterpillars, nymphs of Rhopalosiphum maidis (Fitch) and Schizaphis graminum (Rondani) (Hemiptera: Aphididae). Duration of larva, pupa and larva to adult stages differed among prey offered, whereas the prepupa stage was similar. Larva, pupa, prepupa and larva to adult viabilities were equal or major of 87.5% in all prey, except for larva fed on newly-hatched larvae of S. frugiperda. Eriopis connexa has good adaptation to different prey corroborating its polyphagous feeding habit, which evidences the potential of this natural enemy for controlling corn and sorghum pests

    Life-cycle greenhouse gas emissions of portuguese olive oil

    Get PDF
    The main goal of this paper was to assess the greenhouse gas (GHG) intensity of olive oil production in Portugal. A life-cycle model and inventory were implemented for the entire production process, including a comprehensive analysis of olive cultivation, olive oil extraction, packaging, and distribution. Data originates from five differently-sized Portuguese olive growers and from a total of six olive oil mills, representing the three extraction processes in use: three-phase extraction, two-phase extraction, and traditional pressing. The results show that the GHG intensity lies in the range 1.8-8.2 kg CO2eq/liter and that the main contributors were fertilizers (production and field emissions). Efficient use of fertilizers thus seems to be a key factor for mitigating the GHG intensity of olive oil production.This research was supported by project ECODEEP (Eco-efficiency and Eco-management in the Agro Industrial sector, FCOMP–05–0128–FEDER–018643) and the Portuguese Scienc
    • …
    corecore