23 research outputs found

    CPEB4 function in macrophages

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    [eng] As innate immune cells, macrophages sense endogenous and exogenous danger signals and respond orchestrating inflammatory processes. For the rapid induction and efficient resolution of inflammatory responses, macrophages induce the expression of pro- inflammatory and anti-inflammatory mediators, which cross-regulate each other through feedback loops. This process requires tightly controlled gene expression at multiple levels. Recently, the regulation of mRNA deadenylation has emerged as a key regulator of the strength and, critically, the duration of transient inflammatory responses. Cytoplasmic Polyadenylation Element Binding (CPEB1-4) family of RNA-binding proteins target mRNAs containing Cytoplasmic Polyadenylation Elements (CPEs) in their 3’UTR. CPEBs orchestrate the assembly of two types of ribonucleoprotein complexes (mRNPs) which can repress or stimulate the translation of target mRNAs by modulating the length of poly(A) tail. Several inflammatory mediators harbour CPEs in their 3’UTRs and are potential CPEB targets. Thus, we hypothesized that CPEBs could be an additional checkpoint to control inflammatory responses. We find that CPEB4 is a novel player in macrophage response to LPS. Upon LPS treatment, CPEB4 is upregulated and its polyadenylation function is activated, a process mediated by the MAPK p38α and ERK1/2 and two AU Rich Element Binding Proteins (ARE-BPs). Interestingly, the pattern of CPEB4 expression and activity suggests that it participates in late LPS-response, when the resolution of inflammation occurs. Indeed, myeloid-specific Cpeb4KO mice display increased sensitivity to LPS-induced endotoxic shock. We identify CPEB4 target mRNAs by RNA-Immunoprecipitation and Sequencing (RIP-Seq), uncovering that CPEB4 regulates the expression of negative regulators of MAPK signalling, thus creating the negative feedback loop needed the resolution of inflammation. Moreover, we also describe how the interplay between CPEB4, HuR and TTP defines mRNA behaviour during the different temporal windows of inflammatory responses.[spa] Como células del sistema inmune innato, los macrófagos detectan señales de peligro endógenas y exógenas y responden desencadenando procesos inflamatorios. Estas respuestas inflamatorias tienen que ser inducidas rápidamente pero a su vez, deben ser eficientemente resueltas. Para ello, los macrófagos inducen la expresión de mediadores pro- y anti- inflamatorios que controlan la expresión unos de otros mediante complejos circuitos regulatorios. Estos procesos requieren un estricto control de la expresión génica a distintos niveles. En los últimos años, se ha descrito que la regulación de los mRNAs por deadenilación es un elemento crucial para regular intensidad y sobretodo la duración de las respuestas inflamatorias. La família de proteínas de unión al RNA CPEBs (Cytoplasmic Polyadenylation Element Binding, CPEB1-4), unen mRNAs que contienen CPEs (Cytoplasmic Polyadenylation Elements) en su 3’UTR. Las CPEBs pueden reclutar dos tipos de complejos en los mRNAs que unen. Estos complejos modulan la longitud de la cola poly(A) y, por tanto, pueden reprimir o estimular su traducción. Los mRNAs de múltiples mediadores inflamatorios y son susceptibles de ser regulados por las CPEBs ya que contienen CPEs en sus 3’UTRs. Por tanto, las CPEBs podrían ser un nuevo mecanismo regulador del desarrollo de las respuestas inflamatorias. En este trabajo hemos descubierto que CPEB4 participa en la respuesta de los macrófagos frente a LPS. El tratamiento con LPS provoca un incremento en los niveles de CPEB4 y promueve que su función sea de polyadenylación. Este proceso es mediado por las MAPK p38α y ERK1/2 y dos proteínas que regulan mRNAs mediante la unión a AREs. El patrón de expresión de CPEB4 sugiere que esta proteína participa en la fase tardía de la respuesta a LPS, cuándo la respuesta inflamatoria es resuelta. Apoyando esta hipótesis, ratones KO para CPEB4 en las células mieloides son más sensibles al shock séptico inducido por LPS. Identificando los mRNAs que CPEB4 regula en este contexto, hemos descrito que CPEB4 regula la expresión de inhibidores de la señalización de la vía MAPK. De este modo, CPEB4 es necesaria para la resolución de la inflamación en respuesta a LPS. Además, hemos descrito como la regulación de mRNAs por CPEB4, HuR y TTP define diferentes patrones temporales de expresión durante el desarrollo de respuestas inflamatorias

    Study of the effect of microwave power coupled with hot air drying on orange peel by dielectric spectroscopy

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    [EN] Monitoring moisture and water activity during drying is crucial for process optimization, avoiding inadequate uses of energy. The main objective of this work was to study the dielectric properties of orange peel during hot air drying at 55 °C (HAD) and microwave power coupled with hot air drying at different power intensities (2 W/g, 4 W/g and 6 W/g). At 5, 15, 40, 60 and 120 min mass, aw, moisture, and permittivity were measured in fresh and dried samples. Results allowed developing a dielectric isotherm technique by adapting the GAB model to predict aw in dried orange peel by using ε'ε' (20 GHz). The physical meaning of the dielectric isotherm parameters (View the MathML sourceε0' and Cd) was studied. The value of View the MathML sourceε0' at 20 GHz (γ-dispersion) represents the induction effect of the minimum quantity of adsorbed water or the monomolecular moisture layer. The parameter Cd is related with isosteric heat, as well as the C parameter of the GAB model. The application of MW power produced an increase of isosteric heat or adsorption energy of the monomolecular layer, improving surface tension of samples and thus the hygroscopicity, explaining the reduction of the View the MathML sourceε0' independently of the quantity of the water molecules adsorbed.The authors would like to acknowledge the Basque Government for the financial support of the project (LasaiFood). The author Marta Castro-Giraldez wants to thanks to the UPV Postdoctoral Program (PAID-10-14) from Universidad Politecnica de Valencia for their support. The authors acknowledge the financial support from the Spanish Ministerio de Ciencia e Innovacion throughout the project AGL2011-30096.Talens Vila, C.; Castro Giraldez, M.; Fito Suñer, PJ. (2016). Study of the effect of microwave power coupled with hot air drying on orange peel by dielectric spectroscopy. LWT - Food Science and Technology. 66:622-628. https://doi.org/10.1016/j.lwt.2015.11.015S6226286

    Effect of Microwave Power Coupled with Hot Air Drying on Sorption Isotherms and Microstructure of Orange Pee

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    [EN] Drying is one of the most cost-effective methods of worthwhile by-product valorisation. This study had two main objectives. The first was to determine the effect of hot air drying (HAD) combined with microwave (MW) irradiation on the treatment kinetics and the macrostructural and microstructural properties of the dried product. The second aim was to develop engineering tools to predict the extent of dehydration. Drying was performed using hot air at 55 A degrees C and the combined (HAD + MW) treatment at different power intensities (2, 4, and 6 W/g). After 5, 15, 40, 60, and 120 min, the mass, surface, volume, water activity and moisture were measured in fresh and dried samples. Sorption isotherms were obtained and fitted to the GAB model, with high correlation coefficients. The macroscopic and microscopic analyses showed shrinkage and swelling in the peel tissue caused by the MW treatment. The HAD + MW methods not only resulted in increased moisture reduction but also induced microstructural changes that generated higher sorption capacity.The authors would like to thank the Basque Government for the financial support of the project (LasaiFood). They also acknowledge the financial support from the Spanish Ministerio de Economia, Industria y Competitividad, Programa Estatal de I+D+i orientada a los Retos de la Sociedad AGL2016-80643-R. This paper is contribution no. 777 from AZTI (Food Research Division). The authors would like to thank the Electronic Microscopy Service of the Universidad Politecnica de Valencia for its assistance in the use of Cryo-SEM.Talens Vila, C.; Castro Giraldez, M.; Fito Suñer, PJ. (2018). Effect of Microwave Power Coupled with Hot Air Drying on Sorption Isotherms and Microstructure of Orange Pee. Food and Bioprocess Technology. 11(4):723-734. https://doi.org/10.1007/s11947-017-2041-xS723734114Al-Muhtaseb, A. H., McMinn, W. A. M., & Magee, T. R. 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Development of a dielectric spectroscopy technique for the determination of apple (Granny Smith) maturity. Innovative Food Science & Emerging Technologies, 11(4), 749–754. https://doi.org/10.1016/j.ifset.2010.08.002 .Castro-Giráldez, M., Fito, P. J., Dalla Rosa, M., & Fito, P. (2011a). Application of microwaves dielectric spectroscopy for controlling osmotic dehydration of kiwifruit (Actinidia deliciosa cv Hayward). Innovative Food Science & Emerging Technologies, 12(4), 623–627. https://doi.org/10.1016/j.ifset.2011.06.013 .Castro-Giráldez, M., Fito, P. J., & Fito, P. (2011b). Application of microwaves dielectric spectroscopy for controlling long time osmotic dehydration of parenchymatic apple tissue. Journal of Food Engineering, 104(2), 227–233. https://doi.org/10.1016/j.jfoodeng.2010.10.034 .Demirel, Y., & Sandler, S. I. (2001). Linear-nonequilibrium thermodynamics theory for coupled heat and mass transport. 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    Effect of microwave power coupled with hot air drying on process efficiency and physico-chemical properties of a new dietary fibre ingredient obtained from orange peel

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    [EN] Orange by-products are an excellent source of dietary fibre. The main objective of this work was to compare the physico-chemical and technological properties of fibres obtained from orange by-products by applying two different drying methods: hot air (HAD) and hot air coupled with microwave drying (HAD + MW). Process efficiency was also compared. 92% reduction in processing time and 77% reduction in energy consumption was achieved with HAD + MW. The drying treatment did not affect the physico-chemical properties of the fibres; however, the shrinkage-swelling phenomena that occurred during drying changed the rehydration properties of the fibre. HAD mainly affected the mechanical energy whereas HAD + MW affected the surface tension. An increase in particle size due to an increase in porosity during HAD + MW improved the fibre swelling capacity. HAD + MW can reduce drying time resulting in a more efficient drying process that positively affects the orange fibre's technological properties.The authors would like to acknowledge the Basque Government for the financial support of the project (LasaiFood). The author Marta Castro-Giraldez wants to thanks to the UPV Postdoctoral Program (PAID-10-14) from Universidad Politecnica de Valencia for their support. The authors acknowledge the financial support from the Spanish Ministerio de Economia, Industria y Competitividad, Programa Estatal de I + D + i orientada a los Retos de la Sociedad AGL2016-80643-R. This paper is contribution no 738 from AZTI (New Foods).Talens Vila, C.; Arboleya, JC.; Castro Giráldez, M.; Fito Suñer, PJ. (2017). Effect of microwave power coupled with hot air drying on process efficiency and physico-chemical properties of a new dietary fibre ingredient obtained from orange peel. LWT - Food Science and Technology. 77:110-118. https://doi.org/10.1016/j.lwt.2016.11.036S1101187

    New technique of combined hot air and microwave drying to produce a new fiber ingredient from industrial by-products

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    [EN] The search for solutions to transform the by-products generated by the agri-food sector in high value-added ingredients is a priority. The aim of this research was to develop a microwave coupled with hot air drying technique allowing maximizing profits by reducing time and operational costs and to produce a dietary fiber ingredient with interesting technological properties for the development of healthy foods. The shrinkage-swelling phenomena occurred during drying changed the rehydration properties of the fibre ingredient obtained. An increase in particle size improved the fibre's swelling capacity when hydrated, allowing 50 % fat substitution in potato purees.Talens, C.; Castro Giráldez, M.; Fito Suñer, PJ. (2018). New technique of combined hot air and microwave drying to produce a new fiber ingredient from industrial by-products. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 49-56. https://doi.org/10.4995/IDS2018.2018.7875OCS495

    Association between two mass-gathering outdoor events and incidence of SARS-CoV-2 infections during the fifth wave of COVID-19 in north-east Spain : A population-based control-matched analysis

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    Many countries have resumed mass-gathering events like music festivals, despite the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading. In this study, we aimed to assess the effect of two mass-gathering outdoor events, held during a peak of SARS-CoV-2 transmission, on COVID-19 incidence. This was a retrospective, population-based control-matched analysis. The study population included attendees to two outdoor music festivals held in Catalonia (North-East Spain). The primary objective was to compare the incidence of COVID-19 within the 3-to-10 days following the event between attendees and a population-based control group. The analysis included 18,275 and 27,347 attendees to the first and second festivals, respectively, and their corresponding controls. The post-festival 7-day cumulative COVID-19 incidence among attendees and controls was 4.14% (95% CI 3.86-4.44) vs. 1.69% (1.51-1.88) for the first festival (RR 2.46; 2.16-2.80), and 2.42% (2.35-2.61) and 1.10% (0.99-1.2) for the second festival (RR 2.19; 1.92-2.51). COVID-19 incidence among immunized individuals was also two-fold higher in attendees than in controls. Previous COVID-19 infection, vaccination, and adequate mask-wearing were significantly associated with a lower risk of COVID-19 infection after the events. Despite the proven effectiveness of preventive measures such as Ag-RDT screening, mask-wearing and vaccination, caution should be taken when holding these events during a period of high community SARS-CoV-2 transmission. Crowdfunding campaign YoMeCorono () and the Generalitat de Catalunya

    Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection : a double-blind, placebo-controlled, randomised clinical trial

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    Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. registry: . 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19.

    Egocentric sexual network analysis among gay and bisexual men who have sex with men with and without mpox infection.

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    OBJECTIVES: Recent outbreaks of the mpox (monkeypox) virus have been detected in dense sexual networks of gay and bisexual men who have sex with men (GBMSM). The objective of this study is to describe and compare the epidemiological and behavioural characteristics, as well as the sexual networks, of GBMSM diagnosed with mild mpox in Spain. METHODS: A prospective case-control study was conducted in Spain from July 2022 to February 2023. The study targeted a key population of GBMSM aged 18 years or older. Study participants were categorised into cases, those who were diagnosed with mpox virus infection; and controls, those who were not diagnosed. We examined and compared the sexual network characteristics of the two groups-mpox-positive (mpox-P) and mpox-negative (mpox-N) egos-using χ2, t-test and Wilcoxon test to examine the differences between the two groups in each section. Finally, we conducted univariable and multivariable logistic regressions to determine the factors associated with mpox infection. RESULTS: Among the 105 participants, 35 (33.3%) were mpox-P. Compared with mpox-N, mpox-P respondents more frequently reported syphilis (mpox-P: 31.4%; mpox-N: 12.9%) and HIV (mpox-P: 45.7%; mpox-N: 18.6%), and mpox-P individuals to have had at least one sexual contact with a confirmed mpox case (mpox-P: 62.5%; mpox-N: 8.3%). In the egocentric network analysis, mpox-P respondents had a higher prevalence of group sex with alters (mpox-P: 18.5%; mpox-N: 8.9%) and one-time sexual partners (mpox-P: 46.1%; mpox-N: 31.7%). Multivariable logistic regressions showed that reporting stranger/client ties (adjusted OR (aOR)=10.3, 95% CI 1.39 to 76.6) with alters, being vaccinated for mpox (aOR=0.07, 95% CI 0.02 to 0.24) and tie strength heterogeneity (aOR=0.01, 95% CI 0.00 to 0.42) were associated with mpox infection. CONCLUSIONS: Our findings highlight the role of demographic, epidemiological and sexual network characteristics in the transmission of mpox virus during the outbreak in Spain. These findings have important implications for future prevention efforts

    A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19

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    Background: current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. Methods: we conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. Results: the analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. Conclusions: postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)

    A retrospective cohort study of risk factors for mortality among nursing homes exposed to COVID-19 in Spain

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    Long-term care (LTC) facilities have shown remarkably high mortality rates during the coronavirus disease 2019 (COVID-19) outbreak in many countries1, and different risk factors for mortality have been identified in this setting2–5. Using facilities as the unit of analysis, we investigated multiple variables covering facility characteristics and socioeconomic characteristics of the geographic location to identify risk factors for excess mortality from a comprehensive perspective. Furthermore, we used a clustering approach to detect patterns in datasets and generate hypotheses regarding potential relationships between types of nursing homes and mortality trends. Our retrospective analysis included 167 nursing homes providing LTC to 8,716 residents during the COVID-19 outbreak in Catalonia (northeast Spain). According to multiple regression analysis, COVID-19-related and overall mortality at the facility level were significantly associated with a higher percentage of patients with complex diseases, lower scores on pandemic preparedness measures and higher population incidence of COVID-19 in the surrounding population. When grouping nursing homes into eight clusters based on common features, we found higher mortality rates in four clusters, mainly characterized by a higher proportion of residents with complex chronic conditions or advanced diseases, lower scores on pandemic preparedness, being located in rural areas and larger capacity, respectively
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