SARS-CoV-2 Point Mutation and Deletion Spectra and Their Association with Different Disease Outcomes

Mutant spectra of RNA viruses are important to understand viral pathogenesis and response to selective pressures. There is a need to characterize the complexity of mutant spectra in coronaviruses sampled from infected patients. In particular, the possible relationship between SARS-CoV-2 mutant spectrum complexity and disease associations has not been established. In the present study, we report an ultradeep sequencing (UDS) analysis of the mutant spectrum of amplicons from the nsp12 (polymerase)- and spike (S)- coding regions of 30 nasopharyngeal isolates (diagnostic samples) of SARS-CoV-2 of the first COVID-19 pandemic wave (Madrid, Spain, April 2020) classified according to the severity of ensuing COVID-19. Low-frequency mutations and deletions, counted relative to the consensus sequence of the corresponding isolate, were overwhelmingly abundant. We show that the average number of different point mutations, mutations per haplotype, and several diversity indices was significantly higher in SARS-CoV-2 isolated from patients who developed mild disease than in those associated with moderate or severe disease (exitus). No such bias was observed with RNA deletions. Location of amino acid substitutions in the three-dimensional structures of nsp12 (polymerase) and S suggest significant structural or functional effects. Thus, patients who develop mild symptoms may be a richer source of genetic variants of SARS-CoV-2 than patients with moderate or severe COVID-19. IMPORTANCE The study shows that mutant spectra of SARS-CoV-2 from diagnostic samples differ in point mutation abundance and complexity and that significantly larger values were observed in virus from patients who developed mild COVID-19 symptoms. Mutant spectrum complexity is not a uniform trait among isolates. The nature and location of low-frequency amino acid substitutions present in mutant spectra anticipate great potential for phenotypic diversification of SARS-CoV-2.post-print3280 K

SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations.

Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50- to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussed.post-print2277 K

Activation-Inhibition dynamics of the oscillatory bursts of the human EEG during resting state. The macroscopic temporal range of few seconds

The ubiquitous brain oscillations occur in bursts of oscillatory activity. The present report tries to define the statistical characteristics of electroencephalographical (EEG) bursts of oscillatory activity during resting state in humans to define (i) the statistical properties of amplitude and duration of oscillatory bursts, (ii) its possible correlation, (iii) its frequency content, and (iv) the presence or not of a fixed threshold to trigger an oscillatory burst. The open eyes EEG recordings of five subjects with no artifacts were selected from a sample of 40 subjects. The recordings were filtered in frequency ranges of 2 Hz wide from 1 to 99 Hz. The analytic Hilbert transform was computed to obtain the amplitude envelopes of oscillatory bursts. The criteria of thresholding and a minimum of three cycles to define an oscillatory burst were imposed. Amplitude and duration parameters were extracted and they showed durations between hundreds of milliseconds and a few seconds, and peak amplitudes showed a unimodal distribution. Both parameters were positively correlated and the oscillatory burst durations were explained by a linear model with the terms peak amplitude and peak amplitude of amplitude envelope time derivative. The frequency content of the amplitude envelope was contained in the 0–2 Hz range. The results suggest the presence of amplitude modulated continuous oscillations in the human EEG during the resting conditions in a broad frequency range, with durations in the range of few seconds and modulated positively by amplitude and negatively by the time derivative of the amplitude envelope suggesting activation-inhibition dynamics. This macroscopic oscillatory network behavior is less pronounced in the low-frequency range (1–3 Hz)

La formación general universitaria y la sustentabilidad a través del arte

El ser humano en el transcurso de la historia ha desarrollado una crisis ambiental, dañando el ecosistema de la tierra, disminuyendo su capacidad de sustentabilidad; por ello nuestro país enfrenta un gran deterioro en sus recursos naturales. Siendo la sustentabilidad, uno de los mayores retos que se enfrentan en la educación, se requiere que las nuevas generaciones desarrollen conocimientos, aptitudes, habilidades y valores q ue los lleven a lograr una mejor relación con los demás individuos y con la naturaleza, reconociendo la necesidad de sensibilizarlos ante las diferentes problemáticas ambientales que en la actualidad se presentan. El docente constantemente emplea métodos de enseñanza efectivos, atractivos y eficaces para transmitir a sus estudiantes conocimientos y provocar en ellos la inquietud de experimentar para construir saberes, reflexionar sobre lo aprendido, lo que está en su entorno cotidiano, al crear en algunas Unidades de Aprendizaje con material reciclado objetos con fines estéticos o de utilidad

Coordinated management of low voltage power networks with photovoltaic energy sources

Over the last decades, active power networks have reached great attention due to the incorporation of distributed energy resources into low voltage power systems. In this paper, a decentralized energy management strategy is proposed as an efficient way to minimize both active power losses and voltage profile deviation of an distribution power network with photovoltaic solar farms, and also at the same time, aims to improve the reliability and the security of supply. The coordinated energy management concept relies on a two-step optimization approach based on genetic algorithms (GA) and MINLP, in which a multi-objective function is used which takes into account reliability and operational technical constraints in its formulation. The suitability of the proposed methodology is tested on an existing low voltage power system, in which two aspects are considered: firstly, determining the optimal allocation of PV units and secondly, establishing the optimal reschedule of the active power of the generation units partic ipating in the energy mix and minimizing both the real power losses and voltage deviation of the entire power system.This work has been partly funded by the European Union seventh framework program FP7-SMARTCITIES-2013 under grant agreement 608860 IDE4L – Ideal grid for all

SARS-CoV-2 mutant spectra at different depth levels reveal an overwhelming abundance of low frequency mutations

Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50-to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussedThis work was supported by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 Research Call COV20/00181), and co-financed by European Development Regional Fund ‘A way to achieve Europe’. The work was also supported by grants CSIC-COV19-014 from Consejo Superior de Investigaciones Científicas (CSIC), project 525/C/2021 from Fundació La Marató de TV3, PID2020-113888RB-I00 from Ministerio de Ciencia e Innovación, BFU2017-91384-EXP from Ministerio de Ciencia, Innovación y Universidades (MCIU), PI18/00210 and PI21/00139 from Instituto de Salud Carlos III, and S2018/BAA-4370 (PLATESA2 from Comunidad de Madrid/FEDER). C.P., M.C., and P.M. are supported by the Miguel Servet programme of the Instituto de Salud Carlos III (CPII19/00001, CPII17/00006, and CP16/00116, respectively) cofinanced by the European Regional Development Fund (ERDF). CIBERehd (Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas) is funded by Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). B.M.-G. is supported by predoctoral contract PFIS FI19/00119 from Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo) cofinanced by Fondo Social Europeo (FSE). R.L.-V. is supported by predoctoral contract PEJD-2019-PRE/BMD-16414 from Comunidad de Madrid. C.G.-C. is supported by predoctoral contract PRE2018-083422 from MCIU. P.S. is supported by postdoctoral contract “Margarita Salas” CA1/RSUE/2021 from MCIU. B.S. was supported by a predoctoral research fellowship (Doctorados Industriales, DI-17-09134) from Spanish MINEC

Estudio del Ag/grafeno-TiO₂ en la fotocatálisis de colorantes

Síntesis y caracterización de nanopartículas de TiO₂ dopadas con grafeno/Ag y su actividad fotocatalítica en la degradación de Orange II y Black-5. Durante la degradación se utilizaron dos distintas fuentes de luz, luz UV y visible. En este trabajo se preparó titania por el método sol-gel y se dopó con grafeno y plata, posteriormente, fue caracterizada mediante rayos X, Raman y UV de sólidos. Los resultados mostraron que la titania sintetizada se encuentra en la fase cristalina anatasa, tanto en el sólido puro como dopado. Los resultados de las bandas prohibidas son cercanos al valor que presenta la fase anatasa. Los estudios confirman que existe muy poca actividad fotocatalítica cuando se utiliza la titania pura, en presencia de luz visible. Los resultados de las reacciones fotocatalíticas de la degradación del colorante Black 5 y Orange II indican que la degradación fotocatalítica mejora cuando se utiliza el TiO₂-grafeno-Ag con luz visible.Synthesis and characterization of graphene/Ag-TiO₂ nanoparticles and their photocatalytic activity in the degradation of Orange II and Black-5. During the degradation, two different light sources were used, UV and visible light. In this work, titania was prepared by the sol-gel method and it was doped with graphene and silver, later, it was characterized by X-rays, Raman and UV of solids. The results showed that the synthesized titania is found in the anatase crystalline phase, both in the pure and doped solid. The results of the forbidden bands are close to the value of the anatase phase. Studies confirm that there is very little photocatalytic activity when pure titania is used in the presence of visible light. The results of the photocatalytic degradation reactions of Black 5 and Orange II dye indicate that photocatalytic degradation improves when TiO₂-graphene-Ag is used with visible light