A robust islanding detection method with zero-non-detection zone for distribution systems with DG

This paper proposes a strategy for detecting unintentional islanding operations (IOs) in distribution networks (DNs) with distributed generation (DG), which eliminating the non-detection zone (NDZ). This hybrid method achieves a zero-NDZ by taking advantage of both passive and active methodologies for an inverter-based DG scenario. The passive-based part of the proposed method considers settings with low thresholds and is activated whenever they are surpassed. The following step uses a three-phase static RC load. This load is connected to intentionally force the frequency and its derivative to exceed the established thresholds. Thus, the events with zero power imbalance can be identified. Unlike other existing methods, this technique does not degrade the power quality (PQ) and does not require DG output power curtailment. The evaluation of the proposed strategy has been carried out through an extensive set of scenarios considering both islanding and non-islanding events. The islanding detection capabilities of the proposed method have been explored considering a custom-made DN test system and the test system recommended by the IEEE 929-2000 standard. The proposed method has a simple implementation, requires a low level of computational complexity, provides a high degree of reliability, and assures fast islanding detection.Peer ReviewedObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No Contaminant::7.3 - Per a 2030, duplicar la taxa mundial de millora de l’eficiència energèticaObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No ContaminantObjectius de Desenvolupament Sostenible::11 - Ciutats i Comunitats SosteniblesPostprint (published version

Cellular vaccines in listeriosis: role of the Listeria antigen GAPDH

The use of live Listeria-based vaccines carries serious difficulties when administrated to immunocompromised individuals. However, cellular carriers have the advantage of inducing multivalent innate immunity as well as cell-mediated immune responses, constituting novel and secure vaccine strategies in listeriosis. Here, we compare the protective efficacy of dendritic cells (DCs) and macrophages and their safety. We examined the immune response of these vaccine vectors using two Listeria antigens, listeriolysin O (LLO) and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH), and several epitopes such as the LLO peptides, LLO189-201 and LLO91-99 and the GAPDH peptide, GAPDH1-22. We discarded macrophages as safe vaccine vectors because they show anti-Listeria protection but also high cytotoxicity. DCs loaded with GAPDH1-22 peptide conferred higher protection and security against listeriosis than the widely explored LLO91-99 peptide. Anti-Listeria protection was related to the changes in DC maturation caused by these epitopes, with high production of interleukin-12 as well as significant levels of other Th1 cytokines such as monocyte chemotactic protein-1, tumor necrosis factor-α, and interferon-γ, and with the induction of GAPDH1-22-specific CD4(+) and CD8(+) immune responses. This is believed to be the first study to explore the use of a novel GAPDH antigen as a potential DC-based vaccine candidate for listeriosis, whose efficiency appears to highlight the relevance of vaccine designs containing multiple CD4(+) and CD8(+) epitopes

Sensitive detection of SARS-CoV-2 seroconversion by flow cytometry reveals the presence of nucleoprotein-reactive antibodies in unexposed individuals

There is an ongoing need of developing sensitive and specific methods for the determination of SARS-CoV-2 seroconversion. For this purpose, we have developed a multiplexed flow cytometric bead array (C19BA) that allows the identification of IgG and IgM antibodies against three immunogenic proteins simultaneously: the spike receptor-binding domain (RBD), the spike protein subunit 1 (S1) and the nucleoprotein (N). Using different cohorts of samples collected before and after the pandemic, we show that this assay is more sensitive than ELISAs performed in our laboratory. The combination of three viral antigens allows for the interrogation of full seroconversion. Importantly, we have detected N-reactive antibodies in COVID-19-negative individuals. Here we present an immunoassay that can be easily implemented and has superior potential to detect low antibody titers compared to current gold standard serology methods.Acknowledgements: We thank Petros Tyrakis and Iván Martínez-Forero for critical reading and editing of the manuscript. Support was provided by the Severo Ochoa Excellence Accreditation from MCIU (SEV-2016-0644) and the SPRI I+D COVID-19 fund (Gobierno Vasco). Personal fellowships: A.A.-V. (La Caixa Inphinit LCF/BQ/DR20/11790022), A.B. (AECC Bizkaia), A.G.d.R (Bikaintek), A.P. (Ramón y Cajal), B.J.-L. (Gob. Vasco), and E.P.-F. (Juan de la Cierva-Formación). M.L.M.-C. acknowledges RTC2019-007125-1, DTS20/00138, SAF2017-87301-R, and BBVA UMBRELLA project. M.L.-H. acknowledges the ISCIII for grant COV20-0170 and the Government of Cantabria for grant 2020UIC22-PUB-0019. O.M., J.-M.M., and N.G.A.A. acknowledge the Agencia Estatal de Investigación (Spain) for grants CTQ2015-68756-R, RTI2018-101269-BI00, and RTI2018-095700-B-I00, respectively. A.P. has received grant funding from the European Research Council (ERC), grant agreement number 804236 (Horizon 2020), and the FERO Foundation

A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants

Vaccines against SARS-CoV-2 have alleviated infection rates, hospitalization and deaths associated with COVID-19. In order to monitor humoral immunity, several serology tests have been developed, but the recent emergence of variants of concern has revealed the need for assays that predict the neutralizing capacity of antibodies in a fast and adaptable manner. Sensitive and fast neutralization assays would allow a timely evaluation of immunity against emerging variants and support drug and vaccine discovery efforts. Here we describe a simple, fast, and cell-free multiplexed flow cytometry assay to interrogate the ability of antibodies to prevent the interaction of Angiotensin-converting enzyme 2 (ACE2) and the receptor binding domain (RBD) of the original Wuhan-1 SARS-CoV-2 strain and emerging variants simultaneously, as a surrogate neutralization assay. Using this method, we demonstrate that serum antibodies collected from representative individuals at different time-points during the pandemic present variable neutralizing activity against emerging variants, such as Omicron BA.1 and South African B.1.351. Importantly, antibodies present in samples collected during 2021, before the third dose of the vaccine was administered, do not confer complete neutralization against Omicron BA.1, as opposed to samples collected in 2022 which show significant neutralizing activity. The proposed approach has a comparable performance to other established surrogate methods such as cell-based assays using pseudotyped lentiviral particles expressing the spike of SARS-CoV-2, as demonstrated by the assessment of the blocking activity of therapeutic antibodies (i.e. Imdevimab) and serum samples. This method offers a scalable, cost effective and adaptable platform for the dynamic evaluation of antibody protection in affected populations against variants of SARS-CoV-2.Funding: This research was supported by the SPRI I+D COVID-19 fund (Basque Government, bG-COVID-19), BIOEF EITB Maratoia (BIO21/COV/037 to AP), the European Research Council (ERC) (ERC-2018-StG 804236-NEXTGEN-IO to AP), the Instituto de Salud Carlos iii (ISCiii, DTS21/00094 to AP and DTS20/00138 to MM-C), Ministerio de Ciencia, Innovación y Universidades (MICINN, PID2019-107956RA-I00 and TED2021-129433B-C21 to AP; PID2020-117116RB-I00 and RTC2019-007125-1 to MM-C) and the FERO Foundation to AP. Personal fellowships: EP-F (Juan de la Cierva-Formación, FJC2018-035449-I), ABo (AECC Bizkaia Scientific Foundation, PRDVZ19003BOSC), AG (Programa Bikaintek from the Basque Government, 48-AF-W1-2019-00012), AA-V (La Caixa Inphinit, LCF/BQ/DR20/11790022), BJ-L (Basque Government, PRE_2019_1_0320), ABl (AECC Bizkaia Scientific Foundation, PRDVZ21640DEBL), PV-B (Proyectos I +D+I, PRE2020-092342) and AP (Ramón y Cajal, RYC2018- 024183-I; and Ikerbasque Research Associate). Acknowledgments: The plasmids for the generation of pseudotyped lentiviral particles were kindly provided by Dr Jesse D. Bloom (Fred Hutchinson Cancer Research Center) and Dr Jean-Philippe Julien (The Hospital for Sick Children). HEK293T-ACE2 cells were kindly provided by Dr. June Ereño-Orbea (CIC bioGUNE) and Dr. Jean-Philippe Julien (The Hospital for Sick Children Research Institute, Toronto)

Presence of the Fungus B. dendrobatidis, but not B. salamandrivorans, in Wild Pyrenean Brook Newts (Calotriton asper) in Spain and France

International audienceIn the last 20 years, the emergence of chytridiomycosis due to the chytrid fungi Batrachochytrium dendrobatidis (Bd), and the more recently described Batrachochytrium salamandrivorans (Bsal), has caused severe amphibian population regressions across the planet (Bosch et al. 2001; Spitzen-van der Sluijs et al. 2016; Scheele et al. 2019). This has generated an increase in scientific interest to decipher the complex interaction between the environment, the fungus and amphibian hosts, and increased surveillance efforts in many localities (Canessa et al. 2020). Batrachochytrium spp. affect the vital function of the amphibian skin, leading to lethargy or skin discoloration, hyperkeratosis, erosions (even ulcerations in Bsal) of the epidermis, and eventually death (Berger et al. 1998; Weldon et al. 2004; Stuart et al. 2004; Wake and Vredenburg 2010; Martel et al. 2013). Bd is currently found on all continents where amphibians are present (Skerratt et al. 2007), affecting more than 700 species within the three orders of amphibians and has been considered a major threat to amphibian biodiversity worldwide (Crawford et al. 2010; Fisher et al. 2012; Olson et al. 2013; Olson and Ronnenberg 2014)

Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients

The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, generating a huge impact globally. This highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), along an exacerbated and uncontrolled systemic inflammation that in some cases induces a fatal cytokine storm. Although vaccines clearly have had a beneficial effect, there is still a high percentage of unprotected patients that develop the pathology, due to an ineffective immune response. Therefore, a thorough understanding of the modulatory mechanisms that regulate the response to SARS-CoV-2 is crucial to find effective therapeutic alternatives. Previous studies describe the relevance of Neddylation in the activation of the immune system and its implications in viral infection. In this context, the present study postulates Neddylation, a reversible ubiquitin-like post-translational modification of proteins that control their stability, localization and activity, as a key regulator in the immune response against SARS-CoV-2. For the first time, we describe an increase in global neddylation levels in COVID-19 in the serum of patients, which is particularly associated with the early response to infection. In addition, the results showed that overactivation of neddylation controls activation, proliferation, and response of peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Inhibition of neddylation, and the subsequent avoidance of activated PBMCs, reduces cytokine production, mainly IL-6 and MCP-1 and induce proteome modulation, being a critical mechanism and a potential approach to immunomodulate COVID-19 patients.Acknowledgements: This work was supported by the Ministry of Economy, Industry and Competitiveness PID2020-117116RB-I0, PID2019-107956RA-I00 integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación, cofinanciado con Fondos FEDER to (MLM-C, AP); Subprograma Retos Colaboración RTC2019-007125-1 to MLM-C; La Caixa Foundation Program HR17-00601 (to MLM-CH), Proyectos Investigacion en Salud DTS20/00138 (to MLM-CH) and DTS21/00094 (to AP), Departamento de Industria del Gobierno Vasco (to MLM-CH); Ciberehd_ISCIII_ is funded by the Instituto de Salud Carlos III. This work was partially supported by the Cantabrian Government (grant number 2020UIC22-PUB-001), and by Instituto de Salud Carlos III (grant number COV20/00170 to ML-H). ERC Starting grant 804236 NEXTGEN-IO (to AP), Ayuda RYC2018-024183-I financiada por MCIN/AEI416 /10.13039/501100011033 y por El FSE invierte en tu futuro (to AP). PhD fellowship from Asociación Española contra el Cáncer (PRDVZ172010SERR and PRDVZ19003BOSC) awarded to MS-M and AB. PhD fellowship from Gobierno Vasco awarded to NG-U, SL, and BJ-L (PRE_2020_2_0154). Finally, we would like to acknowledge Begoña Rodríguez Iruretagoyena for the technical support provided

Presence of the Fungus B. dendrobatidis, but not B. salamandrivorans, in Wild Pyrenean Brook Newts (Calotriton asper) in Spain and France

International audienceIn the last 20 years, the emergence of chytridiomycosis due to the chytrid fungi Batrachochytrium dendrobatidis (Bd), and the more recently described Batrachochytrium salamandrivorans (Bsal), has caused severe amphibian population regressions across the planet (Bosch et al. 2001; Spitzen-van der Sluijs et al. 2016; Scheele et al. 2019). This has generated an increase in scientific interest to decipher the complex interaction between the environment, the fungus and amphibian hosts, and increased surveillance efforts in many localities (Canessa et al. 2020). Batrachochytrium spp. affect the vital function of the amphibian skin, leading to lethargy or skin discoloration, hyperkeratosis, erosions (even ulcerations in Bsal) of the epidermis, and eventually death (Berger et al. 1998; Weldon et al. 2004; Stuart et al. 2004; Wake and Vredenburg 2010; Martel et al. 2013). Bd is currently found on all continents where amphibians are present (Skerratt et al. 2007), affecting more than 700 species within the three orders of amphibians and has been considered a major threat to amphibian biodiversity worldwide (Crawford et al. 2010; Fisher et al. 2012; Olson et al. 2013; Olson and Ronnenberg 2014)

Presence of the Fungus Batrachochytrium dendrobatidis, but not Batrachochytrium salamandrivorans, in Wild Pyrenean Brook Newts (Calotriton asper) in Spain and France

Este artículo contiene 6 páginas, 12 tabla, 2 figuras.This work was supported by the French Laboratory of Excellence project TULIP (ANR-10-LABX-41; ANR-11-IDEX-0002-02) by the INTERREG POCTEFA ECTOPYR (no. EFA031/15) and by the LIFE+ LIMNOPIRINEUS (LIFE13 NAT/ ES1210) projects.Peer reviewe

SARS-CoV-2 Infection Dysregulates the Metabolomic and Lipidomic Profiles of Serum.

COVID-19 is a systemic infection that exerts significant impact on the metabolism. Yet, there is little information on how SARS-CoV-2 affects metabolism. Using NMR spectroscopy, we measured the metabolomic and lipidomic serum profile from 263 (training cohort) + 135 (validation cohort) symptomatic patients hospitalized after positive PCR testing for SARS-CoV-2 infection. We also established the profiles of 280 persons collected before the coronavirus pandemic started. Principal-component analysis discriminated both cohorts, highlighting the impact that the infection has on overall metabolism. The lipidomic analysis unraveled a pathogenic redistribution of the lipoprotein particle size and composition to increase the atherosclerotic risk. In turn, metabolomic analysis reveals abnormally high levels of ketone bodies (acetoacetic acid, 3-hydroxybutyric acid, and acetone) and 2-hydroxybutyric acid, a readout of hepatic glutathione synthesis and marker of oxidative stress. Our results are consistent with a model in which SARS-CoV-2 infection induces liver damage associated with dyslipidemia and oxidative stress