Novel chimeric proteins mimicking SARS-CoV-2 spike epitopes with broad inhibitory activity.

SARS-CoV-2 spike (S) protein mediates virus attachment to the cells and fusion between viral and cell membranes. Membrane fusion is driven by mutual interaction between the highly conserved heptad-repeat regions 1 and 2 (HR1 and HR2) of the S2 subunit of the spike. For this reason, these S2 regions are interesting therapeutic targets for COVID-19. Although HR1 and HR2 have been described as transiently exposed during the fusion process, no significant antibody responses against these S2 regions have been reported. Here we designed chimeric proteins that imitate highly stable HR1 helical trimers and strongly bind to HR2. The proteins have broad inhibitory activity against WT B.1 and BA.1 viruses. Sera from COVID-19 convalescent donors showed significant levels of reactive antibodies (IgG and IgA) against the HR1 mimetic proteins, whereas these antibody responses were absent in sera from uninfected donors. Moreover, both inhibitory activity and antigenicity of the proteins correlate positively with their structural stability but not with the number of amino acid changes in their HR1 sequences, indicating a conformational and conserved nature of the involved epitopes. Our results reveal previously undetected spike epitopes that may guide the design of new robust COVID-19 vaccines and therapies.This work was supported by grants CV20.26565 from the Consejería de Economía y Conocimiento, Junta de Andalucía (Spain), PID2019.107515RB.C21 from the Spanish State Research Agency (SRA/10.13039/501100011033), and co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future. The work performed in C.M.’s laboratory was supported by grants from ANRS (Agence Nationale de Recherches sur le SIDA et les h´epatites virales), the Investissements d’Avenir program managed by the ANR under reference ANR-10-LABX-77 and EHVA (No. 681032, Horizon 2020). Work in S.B.’s laboratory was supported by grants from the Agence Nationale de la Recherche (ANR) (ANR-11-LABX-0070_TRANSPLANTEX), the INSERM (UMR_S1109), the Institut Universitaire de France (IUF), all the University of Strasbourg (IDEX UNISTRA), the European Regional Development Fund (European Union) INTERREG V program (project no. 3.2 TRIDIAG) and MSD-Avenir grant AUTOGEN

Electrodes based on nafion and epoxy-graphene composites for improving the performance and durability of open cathode fuel cells, prepared by electrospray deposition

Fabrication of electrodes for polymer electrolyte fuel cells is a intriguing process in which a balance between gas transport, electrical conductivity, proton transport and water managing must be optimized. In this work four different electrodes prepared by electrospray deposition have been studied using different catalytic inks, in which Nafion and epoxy doped with Graphene-Nanoplatelets were used as binders. After studying the behavior of those electrodes in a single open cathode fuel cell proton electrolyte membrane, it is clear that the addition of epoxy as binder doped with graphene, improves the performance of the fuel cell and increase the mechanical stability of the electrode avoiding the loose of catalyst during the electrode manipulation in the fuel cell assembly process and the durability of the fuel cell. To explain this behavior, an ex-situ study was carried out, in which properties such as its surface morphology, hydrophobicity and electrical and thermal conductivity of those electrodes were studied. From the results of this study, such improvement in the performance of the fuel cell was justified on the basis of the increase in the electrical conductivity, a diminution in its thermal conductivity and an enhancement of hydrophobicity (surface morphology) of the deposited catalyst layer, when an optimum quantity of epoxy is added to the catalytic ink that makes to improve the mechanical properties of those electrodesAJN and MAG are actually working on this project with a contract funded by the Comunidad Atonoma de la Región de Murcia, Conserjería de Desarrollo Económico, Turismo y Empleo, and the European Union, through the program RIS3- MUR, grant number 2I20SAE00079. This work has also been funded by the Spanish Ministry of Science and Innovation (AEI, Spain,PID2020-112744GB-I00/AEI/10.13039/501100011033 and RTI2018-095844-B-I00), Fundacion Seneca (Región de Murcia, Spain), grant number: 20985/PI/18 and Agencia estatal española de Investigación, grant number PID2019-104272RBC55/AEI/10.13039/501100011033. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper

Elementos de Matemáticas y aplicaciones

Material elaborado por profesores de la UCM para la asignatura de este nombre del grado en Ingeniería Matemáticas, el grado en Matemáticas y el grado en Matemáticas y Estadística. Contenidos: - Números enteros. Dígitos de control y criptografía. - Grupos de simetrías. Mosaicos. - Trigonometría plana y esférica. Aplicaciones (Navegación, Astronomía de posición, GPS). - Dinámica discreta. Aplicaciones (Finanzas, introducción al caos). - Teoría de grafos. Algoritmo de ordenación de Google

La química a través de la lente de la ciencia forense: validación de pruebas a la gota para la identificación presuntiva de sustancias controladas

Un químico forense es un profesional que analiza la evidencia que se obtiene de una escena de crimen y llega a una conclusión basada en su alto nivel de conocimiento analítico y su capacidad de manejo instrumental y de los respectivos métodos de validación. Desde el punto de vista didáctico, es posible aplicar principios químicos de una manera clara y accesible en el área forense e investigación criminal como medio del proceso enseñanza y aprendizaje. En este trabajo se presenta una propuesta para el desarrollo de protocolos experimentales para la identificación de drogas mediante pruebas a la gota, así mismo presenta una propuesta para validar la cuantificación de dichas pruebas utilizando el software SigmaScan®.A forensic chemist is a profesional analyzing the evidence obtained from a crime scene and reaches a conclusion based on its high level of analytical knowledge and ability to instrumental management and the respective validation methods. From the educational point of view, it is possible to apply chemical principles in a clear and accessible way in forensics and criminal investigation as a means of teaching and learning process. In this work aproposal for the development of experimental protocols for drug identification tests is presented and a proposal to validate the quantification of such tests using the software SigmaScan®

Ovine fertility by artificial insemination in the breeding season could be affected by intraseasonal variations in ram sperm proteomic profile

[EN] It is important to note that seasonality could affect ram reproductive parameters, and therefore, fertility results after artificial insemination. In this work, 1) we assessed fertility rates after cervical artificial insemination of 11,805 ewes at the beginning (June 21st to July 20th) and at the end (November 20th to December 21st) of the reproductive season in the Assaf breed for the last four years, and 2) we aimed to identify male factors influencing the different reproductive success obtained depending on the time at the mating season in which ovine artificial insemination was performed. For this purpose, we evaluated certain ram reproductive and ultrasonographical parameters as well as we performed a multiparametric and proteomic sperm analysis of 6–19 rams at two very distant points in the mating season (July as Early Breeding Season –EBS– and November as Late Breeding Season –LBS–). Rutinary assessments carried out in the ovine reproduction centers (testicular volume, libido, sperm production and mass motility) showed non-significant differences (P ≥ 0.05) between both studied times, as well as the ram ultrasonographic evaluation (Resistive and Pulsatility Index as Doppler parameters; and pixels mean gray level, and hypoechoic areas percentage and density as echotexture parameters). However, at level of sperm functionality, although sperm quality appeared non-significantly lower (P ≥ 0.05) in the EBS, we identified a significantly different (P 4, a P = 2.40e-07, and a q = 2.23e-06: Fibrous Sheath-Interacting Protein 2, Disintegrin and Metalloproteinase Domain-Containing Protein 20-like, Phosphoinositide-Specific Phospholipase C, Tektin 5, Armadillo Repeat-Containing Protein 12 Isoform X3, Solute Carrier Family 9B1, Radial Spoke Head Protein 3 Homolog, Pro-Interleukin-16, NADH Dehydrogenase [Ubiquinone] 1 Alpha Subcomplex Subunit 8, Testis, Prostate and Placenta-Expressed Protein, and Acyl Carrier Protein Mitochondrial. In conclusion, while our basic analyses on male and sperm quality showed similar results between the beginning and the end of the breeding season, on a proteomic level we detected a lower expression of sperm proteins linked to the energy metabolism, sperm-oocyte interactions, and flagellum structure in the EBS. Probably, this different protein expression could be related to the lower fertility rate of Assaf ewes after cervical artificial insemination at this time. More importantly, sperm proteins can be used as highly effective molecular markers in predicting sperm fertilization ability related to intraseasonal variations.S

Brief Research Report: Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients

Erratum for Brief Research Report: Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients. Tajuelo A, Carretero O, García-Ríos E, López-Siles M, Cano O, Vázquez M, Más V, Rodríguez-Goncer I, Lalueza A, López-Medrano F, Juan RS, Fernández-Ruiz M, Aguado JM, McConnell MJ, Pérez-Romero P. Front Immunol. 2022 Apr 25;13:878812. doi: 10.3389/fimmu.2022.878812. eCollection 2022. PMID: 35547738 Free PMC article.Introduction: There is robust evidence indicating that the SARS-CoV-2-specific humoral response is associated with protection against severe disease. However, relatively little data exist regarding how the humoral immune response at the time of hospital admission correlates with disease severity in unimmunized patients. Our goal was toidentify variables of the humoral response that could potentially serve as prognostic markers for COVID-19 progressionin unvaccinated SARS-CoV-2 patients. Methods: A prospective cross-sectional study was carried out in a cohort of 160 unimmunized, adult COVID-19 patients from the Hospital Universitario 12Octubre. Participants were classified into four clinical groups based on disease severity: non-survivors with respiratory failure (RF), RF survivors, patients requiring oxygen therapy and those not receiving oxygen therapy. Serum samples were taken on admission and IgM, IgG, IgG subclass antibody titers were determined by ELISA, and neutralizing antibody titersusing a surrogate neutralization assay. The differences in the antibody titers between groups and the association between the clinical and analytical characteristics of the patients and the antibody titers were analyzed. Results: Patients that developed RF and survived had IgM titers that were 2-fold higher than non-survivors (p = 0.001), higher levels of total IgG than those who developed RF and succumbed to infection (p< 0.001), and than patients who required oxygen therapy (p< 0.05), and had 5-fold higher IgG1 titers than RF non-survivors (p< 0.001) and those who needed oxygen therapy (p< 0.001), and 2-fold higher than patients that did not require oxygen therapy during admission (p< 0.05). In contrast, RF non-survivorshad the lowest neutralizing antibodylevels, which were significantly lower compared those with RF that survived (p = 0.03). A positive correlation was found between IgM, total IgG, IgG1 and IgG3 titers and neutralizing antibody titers in the total cohort (p ≤ 0.0036). Conclusions: We demonstrate that patients with RF that survived infection had significantly higher IgM, IgG, IgG1 and neutralizing titers compared to patients with RF that succumb to infection, suggesting that using humoral response variables could be used as a prognostic marker for guiding the clinical management of unimmunized patients admitted to the hospital for SARS-CoV-2 infection.This work was supported by Mutua Madrileña Foundation (2020/0056) “Plan Nacional de I+D+I” and Instituto de Salud Carlos III (COVID-19 Research Call COV20/00181 and COV20_00679), Subdirección General de Redes y Centros de Investigación Cooperativa, Spanish Ministry of Science and Innovation, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016) - co-financed by the European Development Regional Fund (EDRF) and the European Social Fund (ESF) "A way to achieve Europe- The ESF invests in your future". Red de Enfermedades Infecciosas (CIBERINFEC), CB21/13/00079. EG-R is supported by the Sara Borrell Program (CD18CIII/00007), MLS is supported by the Sara Borrell Program (CD17CIIII/00017), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades., and AT is supported by the Garantía Juvenil Program of the Comunidad Autonoma de Madrid. IRG holds a research training contract “Río Hortega” (CM19/00163) and MFR a research contract “Miguel Servet” (CP18/00073), both from the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation.S

Mapa de series, geoseries y geopermaseries de vegetación de España (Memoria del mapa de vegetación potencial de España). Parte II

Peer Reviewe

Demographic and clinical profile of idiopathic pulmonary fibrosis patients in Spain: the SEPAR National Registry

BackgroundLittle is known on the characteristics of patients diagnosed with idiopathic pulmonary fibrosis (IPF) in Spain. We aimed to characterize the demographic and clinical profile of IPF patients included in the IPF National Registry of the Spanish Respiratory Society (SEPAR).MethodsThis is a prospective, observational, multicentre and nationwide study that involved 608 IPF patients included in the SEPAR IPF Registry up to June 27th, 2017, and who received any treatment for their disease. IPF patients were predominantly males, ex-smokers, and aged in their 70s, similar to other registries.ResultsUpon inclusion, meanSD predicted forced vital capacity was 77.6%+/- 19.4, diffusing capacity for carbon monoxide was 48.5%+/- 17.7, and the 6-min walk distance was 423.5m +/- 110.4. The diagnosis was mainly established on results from the high-resolution computed tomography in the proper clinical context (55.0% of patients), while 21.2% of patients required invasive procedures (surgical lung biopsy) for definitive diagnosis. Anti-fibrotic treatment was prescribed in 69.4% of cases, 51.5% pirfenidone and 17.9% nintedanib, overall with a good safety profile.Conclusions The SEPAR IPF Registry should help to further characterize current characteristics and future trends of IPF patients in Spain and compare/pool them with other registries and cohorts