Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice

The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2

Las relaciones entre hermanos en la legislación de alcance territorial de la Castilla bajomedieval: de la protección al conflicto

Studies on the family in medieval Castile have not paid enough attention to relationships between family members. On the few occasions they have done so, the analysis has tended to focus on a vertical approach; consequently, little effort has been made to comprehend the ties between brothers and sisters in the Castilian Middle Ages. This paper aims to provide a closer look at this topic by means of an examination of Castilian royal legislation, trying to define the social content of brotherhood, as well as to reveal those fraternal liaisons concerning protection or conflict found in normative texts.Los estudios sobre la familia medieval en Castilla no han prestado especial atención a las relaciones intrafamiliares. Y cuando lo han hecho ha sido para analizarlas desde una perspectiva vertical, sin detenerse demasiado en comprender las que unieron a los hermanos y hermanas del medievo castellano. En este trabajo se propone una primera aproximación al tema analizando la legislación real castellana, tratando de delimitar el contenido social otorgado a la hermandad, así como las situaciones de protección o conflicto entre hermanos que se recogen en los textos normativos

Effects of Fabrication Methods on the Performance of Luminescent Solar Concentrators Based on Doped Polymer Optical Fibers.

In this work, we detail two types of fabrication processes of four polymer optical fibers doped with lumogen dyes. The fiber preforms have been manufactured with two different methods: extrusion and casting. We have compared the performance of the two types of fibers as luminescent solar concentrators by calculating their optical efficiencies and concentration factors. The obtained results show better performance for those fibers manufactured by the casting process. We have also studied the photostability of the two types of fibers doped with the dye lumogen red under solar light radiation. A high thermal stability of the doped fibers has been observed.This work was funded in part by the Fondo Europeo de Desarrollo Regional (FEDER), in partby the Ministerio de Ciencia, Innovación y Universidades under projects RTC2019-007194-4, RTI2018-094669-B-C31 and MAT2014-5742-R and in part by the GobiernoVasco/Eusko Jaurlaritza IT933-16,ELKARTEK KK-2019/00101 (μ4Indust), and ELKARTEK KK-2019/00051 (SMARTRESNA

Polymer optical fibers doped with organic materials as luminescent solar concentrator

This paper provides an analysis of the emission properties of different polymer optical fibers doped with organic materials with the aim of investigate their performance as luminescent solar concentrators. We present a study of the light propagation along the fibers, together with the experimental measurements of two different efficiencies: side illumination coupling efficiency and fluorescent fiber solar concentrator efficiency. The results obtained for all the fibers are compared and discussed.This work has been funded in part by the Fondo Europeo de Desarrollo Regional (FEDER); by the Ministerio de Economía y Competitividad under project TEC2015-638263-C03-1-R; by the Gobierno Vasco/Eusko Jaurlaritza under projects IT933-16 and ELKARTEK (KK-2016/0030 and KK-2016/0059); by the University of the Basque Country UPV/EHU under program UFI11/16; and by Ministerio de Economía y Competitividad under project MAT2014-57429- R. The work carried out by I. Parola has been funded by a research grant given by the Departamento de Educación, Política Lingüística y Cultura del Gobierno Vasco/Eusko Jaurlaritza for her PhD thesis.Peer Reviewe

No Evidence That Soluble TACI Induces Signalling via Membrane-Expressed BAFF and APRIL in Myeloid Cells.

Myeloid cells express the TNF family ligands BAFF/BLyS and APRIL, which exert their effects on B cells at different stages of differentiation via the receptors BAFFR, TACI (Transmembrane Activator and CAML-Interactor) and/or BCMA (B Cell Maturation Antigen). BAFF and APRIL are proteins expressed at the cell membrane, with both extracellular and intracellular domains. Therefore, receptor/ligand engagement may also result in signals in ligand-expressing cells via so-called "reverse signalling". In order to understand how TACI-Fc (atacicept) technically may mediate immune stimulation instead of suppression, we investigated its potential to activate reverse signalling through BAFF and APRIL. BAFFR-Fc and TACI-Fc, but not Fn14-Fc, reproducibly stimulated the ERK and other signalling pathways in bone marrow-derived mouse macrophages. However, these effects were independent of BAFF or APRIL since the same activation profile was observed with BAFF- or APRIL-deficient cells. Instead, cell activation correlated with the presence of high molecular mass forms of BAFFR-Fc and TACI-Fc and was strongly impaired in macrophages deficient for Fc receptor gamma chain. Moreover, a TACI-Fc defective for Fc receptor binding elicited no detectable signal. Although these results do not formally rule out the existence of BAFF or APRIL reverse signalling (via pathways not tested in this study), they provide no evidence in support of reverse signalling and point to the importance of using appropriate specificity controls when working with Fc receptor-expressing myeloid cells