Clinical and molecular characterization of a cardiac ryanodine receptor founder mutation causing catecholaminergic polymorphic ventricular tachycardia

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, including 36 SCDs during youth. Objectives We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation. Methods Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with β-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload–induced calcium release activity of the mutant channel in HEK293 cells. Results We identified the p.G357S_RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload–induced calcium release activity under conditions that mimic catecholaminergic stress. Conclusion Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S_RyR2 appear to depend on β-adrenergic stimulation

Cubic lead perovskite PbMoO3 with anomalous metallic behavior

A previously unreported Pb-based perovskite PbMoO$_3$ is obtained by high-pressure and high-temperature synthesis. This material crystallizes in the $Pm\bar{3}m$ cubic structure at room temperature, making it distinct from typical Pb-based perovskite oxides with a structural distortion. PbMoO$_3$ exhibits a metallic behavior down to 0.1 K with an unusual $T$-sub linear dependence of the electrical resistivity. Moreover, a large specific heat is observed at low temperatures accompanied by a peak in $C_P/T^3$ around 10 K, in marked contrast to the isostructural metallic system SrMoO$_3$. These transport and thermal properties for PbMoO$_3$, taking into account anomalously large Pb atomic displacements detected through diffraction experiments, are attributed to a low-energy vibrational mode, associated with incoherent off-centering of lone pair Pb$^{2+}$ cations. We discuss the unusual behavior of the electrical resistivity in terms of a polaron-like conduction, mediated by the strong coupling between conduction electrons and optical phonons of the local low-energy vibrational mode.Comment: 5 pages, 5 figure

Violation of Bell's inequality for Mathieu-Gauss vector modes

Vector beams display varying polarisation over planes transversal to their direction of propagation. The variation of polarisation implies that the electric field cannot be expressed as a product of a spatial mode and its polarisation. This non-separability has been analysed for particular vector beams in terms of non--quantum entanglement between the spatial and the polarisation-degrees of freedom, and equivalently, with respect to the degree of polarisation of light. Here we demonstrate theoretically and experimentally that Mathieu-Gauss vector modes violate a Bell-like inequality known as the Clauser-Horn-Shimony-Holt-Bell (CHSH-Bell) inequality. This demonstration provides new insights into that fact that a more general class of vector modes with elliptical symmetry also violate Bell inequalities.Comment: 8 pages, 6 figure

Two-Dimensional Numerical Simulation of Bed-Load Transport of a Finite-Depth Sediment Layer: Applications to Channel Flushing

Numerical modeling of bed-load transport in shallow flows, particularly oriented toward environmental flows, is an active field of research. Nevertheless, other possible applications exist. In particular, bed-load transport phenomena are relevant in urban drainage systems, including sewers. However, few applications of coupled two-dimensional (2D) shallow-water and bed-load transport models can be found, and their transfer from environmental applications-usually river and floodplain-into sewer applications requires some adaptation. Unlike to river systems, where there is a thick layer of sediment that constitutes a movable riverbed, sewer systems have thin layers of sediment that need to be removed, thus exposing a rigid, nonerodible surface. This problem requires careful numerical treatment to avoid generating errors and instability in the simulation. This paper deals with a numerical approach to tackle this issue in an efficient way that allows large-scale studies to be performed and provides empirical evidence that the proposed approach is accurate and applicable for sewage and channel-flushing problems. (C) 2017 American Society of Civil Engineers

How much biodiversity is concealed in the word ‘biodiversity’?

Non peer reviewe

In memoriam of Ricardo Flores: The career, achievements, and legacy of an inspirational plant virologist

[EN] Ricardo Flores (1947-2020) focused his research on the identification, replication, pathogenesis, and evolution of viroids, the minimal non-protein-coding circular RNAs (250-400 nt) able to replicate and incite diseases in plants that are remarkable for being at the lowest step of the biological scale. He and his collaborators initially identified and characterized additional group members, adding six new ones to the family Pospiviroidae, and expanding the Avsunviroidae from one to four members. They showed that members of the second family "encode" ribozymes, a property that, together with others, makes them candidates for being the most primitive replicons that emerged on our planet 3500 million years ago. He also made important contributions regarding how viroids replicate, providing relevant data on the templates, enzymes, and ribozymes that mediate this process and on the mutation rate, which turned out to be the highest reported for any biological entity. More recently, he concentrated on the role that RNA silencing could play on viroid-host interactions, describing details of this process. Ricardo also worked on citrus tristeza virus, a widely different type of subcellular pathogen, and made important contributions on the structure, localization and functions of its unique p23 protein. His research has produced 170 original articles and reviews, according to Web of Science. He encouraged the scientific careers of a large number of researchers, and collaborated with many others, some of whom have recapitulated his scientific legacy in this review and contributed with other chapters in this special issue.This work was supported by the Spanish Agencia Estatal de Investigaci ' on (AEI) and Fondo Europeo de Desarrollo Regional (FEDER), grant number PID2020-115571RB-100. We apologize to colleagues whose work was not cited in this review due to the page limit.Pallás Benet, V.; Hernandez Fort, C.; Marcos, JF.; Daròs, J.; Ambrós, S.; Navarro, B.; Navarro Bohigues, JA.... (2022). In memoriam of Ricardo Flores: The career, achievements, and legacy of an inspirational plant virologist. Virus Research. 312(198718):1-9. https://doi.org/10.1016/j.virusres.2022.1987181931219871