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

Vaccine breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota, and Omicron.

Replication of SARS-CoV-2 in the human population is defined by distributions of mutants that are present at different frequencies within the infected host and can be detected by ultra-deep sequencing techniques. In this study, we examined the SARS-CoV-2 mutant spectra of amplicons from the spike-coding (S-coding) region of 5 nasopharyngeal isolates derived from patients with vaccine breakthrough. Interestingly, all patients became infected with the Alpha variant, but amino acid substitutions that correspond to the Delta Plus, Iota, and Omicron variants were present in the mutant spectra of the resident virus. Deep sequencing analysis of SARS-CoV-2 from patients with vaccine breakthrough revealed a rich reservoir of mutant types and may also identify tolerated substitutions that can be represented in epidemiologically dominant variants.post-print656 K

El desarrollo de la comunicación sincrónica y asincrónica en el aula

Las Tecnologías de la Información y la Comunicación (TIC) son un conjunto de herramientas y dispositivos, que cada uno tiene características y posibilidades de formación específicas que se deben considerar al momento de crear los contenidos educativos y de programar las actividades formativas. En este trabajo se desarrolla el tema de la comunicación sincrónica y asincrónica mencionando como ayudan en el proceso enseñanza-aprendizaje y los retos que se presentan en el manejo de las mismas. Se analizan algunas de las herramientas más comunes que se pueden utilizar dentro y fuera del aula, tales como Facebook, Twitter o YouTube que inicialmente no fueron creadas con ese fin, pero que podemos aplicar tanto en el aula como fuera de ella, aumentando el aprovechamiento por parte de los alumnos

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)

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

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

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

The Social Perception of Sustainability in Teachers of The Faculty of Pedagogy Veracruz

El presente proyecto de investigación tiene como objetivo conocer la Percepción de Sustentabilidad en la Facultad de Pedagogía, región Veracruz de la Universidad Veracruzana. La muestra representativa fue aplicada a los docentes interinos por horas y utilizando como instrumento de recolección de información la encuesta, a través de un formulario en Google forms. Para ello, se delimitaron cuatro variables sujetas a análisis: concepto de sustentabilidad, normativa institucional, transversalidad curricular y vinculación. La perspectiva metodológica es cuantitativa y el tipo de investigación es exploratoria recolectando datos que permitan detectar patrones para dar explicación a fenómenos. En los resultados arrojados se encuentra que más de la mitad de los docentes (66.7%) están presentando dificultades para transversalizar la sustentabilidad al interior de sus Experiencias Educativas, aunque reconocen la gran importancia de una formación sustentable para una vida profesional, así como ver el papel que desempeña la sustentabilidad dentro de una máxima casa de estudios.This research project aims to know the Perception of Sustainability in the Faculty of Pedagogy, Veracruz region of the Universidad Veracruzana. The representative sample was applied to interim teachers by hours and using the survey as an information collection instrument, through a form in Google forms. To this end, four variables subject to analysis were delimited: concept of sustainability, institutional regulations, curricular transversality and linkage. The methodological perspective is quantitative and the type of research is exploratory collecting data to detect patterns to explain phenomena. In the results it is found that more than half of the teachers (66.7%) are presenting difficulties to mainstream sustainability within their Educational Experiences, although they recognize the great importance of sustainable training for a professional life, as well as seeing the role that sustainability plays within a maximum house of studies

Plan de mercadeo para el posicionamiento institucional de los productos distribuidos por el Instituto Misionero de San Pablo S.A. de C.V. ubicado en la ciudad de San Salvador, El Salvador, caso ilustrativo.

Librería San Pablo es una pequeña empresa dedicada a la venta de artículos religiosos, actualmente cuenta con dos sucursales en la ciudad de San Salvador, su casa matriz, ubicada en la 1ª Calle Poniente y 59 Avenida Norte # 3103 colonia escalón (San Salvador), y la segundad Sucursal se encuentra dentro del Centro Comercial Galerías Escalón local 358 Tel: 2245-0869. Con el propósito de construir una imagen de marca aún más sólida de Librería San Pablo, en la mente de los clientes actuales y potenciales, se ha encontrado la necesidad de la elaboración de un Plan de Mercadeo institucional, el cual pretende que la marca sea reconocida fácilmente en el mercado y al mismo tiempo esto contribuya a incrementar las ventas en la empresa. El trabajo está constituido por tres capítulos, en los cuales se establece una reseña histórica sobre la actividad que ejerce la pequeña empresa dedicada a la venta de artículos religiosos en la ciudad de San Salvador, en el desarrollo de la investigación la metodología utilizada fue recolectar información a través de los instrumentos estadísticos para conocer el nivel de aceptación por parte de los clientes actuales y potenciales que posee librería San Pablo, las técnicas utilizadas para la recolección de la información fueron la encuesta y la entrevista. Los instrumentos utilizados fueron el cuestionario y la guía de entrevista, una vez obtenidos los resultados se procedió a realizar la interpretación de los gráficos llegando a formular análisis que contribuyeron a realizar una propuesta adecuada a la necesidad que la empresa tenía. De acuerdo con la propuesta de un plan de mercadeo se incluyó; misión, visión, valores, políticas, objetivos y organigrama estructural. Una vez formulado el diagnostico se concluye que: 1. La pequeña empresa dedicada a la venta de artículos católicos no posee un plan de mercadeo que contribuya incrementar las ventas. 2. El reconocimiento sobre la existencia de Librería San Pablo que tiene la población de la ciudad de San Salvador es debido a que las personas visitan las sucursales que posee y no precisamente por invertir en publicidad en medios de comunicación para dar a conocer los productos que distribuye. Por lo que se recomendó a la pequeña empresa Instituto Misionero de San Pablo S.A de C.V. 1. Implementar un plan de mercadeo para que Librería San Pablo invierta en publicidad para así dar a conocer los productos que distribuye e incrementar el nivel de ventas de la empresa. Pero esto se podrá lograr uniendo esfuerzos de administradores y trabajadores para cubrir las necesidades amplias de los nuevos mercados. 2. Crear estrategias de mercadeo que contribuya a posicionar la marca de la empresa para alcanzar los niveles de ventas deseados