Co-option of an endogenous retrovirus envelope for host defense in hominid ancestors

Endogenous retroviral sequences provide a molecular fossil record of ancient infections whose analysis might illuminate mechanisms of viral extinction. A close relative of gammaretroviruses, HERV-T, circulated in primates for ~25 million years (MY) before apparent extinction within the past ~8 MY. Construction of a near-complete catalog of HERV-T fossils in primate genomes allowed us to estimate a ~32 MY old ancestral sequence and reconstruct a functional envelope protein (ancHTenv) that could support infection of a pseudotyped modern gammaretrovirus. Using ancHTenv, we identify monocarboxylate transporter-1 (MCT-1) as a receptor used by HERV-T for attachment and infection. A single HERV-T provirus in hominid genomes includes an env gene (hsaHTenv) that has been uniquely preserved. This apparently exapted HERV-T env could not support virion infection but could block ancHTenv mediated infection, by causing MCT-1 depletion from cell surfaces. Thus, hsaHTenv may have contributed to HERV-T extinction, and could also potentially regulate cellular metabolism

Paleovirological Analyses of Endogenous Retroviruses and Host Innate Immune Effectors

About 8 and 10 percent of the human and mouse genomes, respectively, are comprised of sequences of retroviral origin. Occasional infection of germ line can lead to integrated retroviral genomes being vertically inherited as host alleles. During thousands to millions of years, some of these sequences acquired inactivating mutations and were fixed in ancestral populations by genetic drift, while others became fixed by providing an evolutionary advantage to the host. Those inherited proviruses are termed endogenous retroviruses (ERVs) and have been identified in a variety of animal species representing an extensive viral “fossil” record of past retroviral infections. With the advent of whole genome sequencing projects and high throughput sequencing platforms, it became evident the wide diversity and the important role that these sequences have had in the evolution of their hosts. In the present study we developed a computational framework to identify ERVs in primate and murine genomes. The results of these genome screenings were used to identify suitable candidate sequences in which to perform paleovirological analyses that lead to the successful reconstruction of two ancient retroviruses. MuERV-L is an env-deficient highly abundant mouse specific ERV that has undergone two amplification bursts, being the more recent and prolific ~2 million years ago (MYA), probably through entirely intracellular mechanisms. MuERV-L is transcriptionally active at the two-cell stage of the mouse embryo and recent studies have implicated the co-option of its LTR as a promoter for totipotency genes. In the present work, we describe the analysis and reconstruction of an infectious ancestral MuERV-L (ancML) sequence through paleovirological analyses of MuERV-L elements in the mouse genome. The resulting ancML sequence was infectious in CHO cells and its replication was dependent on reverse transcription. We found that IFN-α could reduce ancML replication by ~20 fold. Additionally, we found that the expression of mouse APOBEC3 was able to restrict the replication of ancML. However, inspection of endogenous MuERV-L sequences suggested that the impact of APOBEC3 mediated hypermutation on MuERV-L evolution was limited. We discussed the possibility that type I IFN responses (maybe through restriction factors) might inhibit MuERV-L replication at the two-cell stage of the mouse embryo and have kept MuERV-L copy numbers under control. Although no extant human gammaretroviruses have been identified, HERV-T is a low copy primate ERV lineage that is closely related to the gammaretrovirus genus. Through phylogenetic and genomic analysis of HERV-T insertions we defined three distinct lineages. Two lineages (HERV-T1 and HERV-T2) entered the primate germline after the Old World monkey-ape split about ~32-30 MYA, whereas the other (HERV-T3) entered before this divergence ~40 MYA. Phylogenetic analysis of complete (LTR-gag-pol-env-LTR) proviral sequences showed that HERV-T2 was subjected to APOBEC3 mediated hypermutation, and subsequently expanded in apes, most likely through retrotransposon-like mechanisms. Phylogenetic and statistical analysis of HERV-T3 proviruses allowed us to estimate the sequence of their ~32 MY old ancestor, revealing that its unusually long leader sequence encoded a 855-nucleotide ORF separated from gag by 36 nucleotides. This pre-gag ORF of unknown function putatively codes for a protein that includes a transmembrane domain. Additional analysis of the HERV-T3 ancestral sequence allowed us to reconstruct the corresponding env sequence (ancHTenv). We found that a modern gammaretrovirus (MLV) could be pseudotyped with ancHTenv enabling it to infect a wide variety of primate cell lines with titers that are similar to MLV particles carrying the amphotropic MLV envelope. A single HERV-T proviral insertion in the genome of all great apes contains an env gene with full coding potential. Proteins encoded by the extant human HERV-T envelope gene (HsaHTenv) and one estimated to be encoded by the hominid ancestor were not able to generate infectious MLV pseudotyped particles, probably because HsaHTenv is not correctly processed into its mature and functional form. Statistical and phylogenetic analyses indicate that the env gene in this locus is evolving slower than the rest of the proviral sequences, and that selective pressures have acted on this locus to conserve its envelope sequence. Remarkably, we found that expression of the HsaHTenv was able to specifically block infection by MLV particles pseudotyped with the ancHTenv, but not particles pseudotyped with the amphotropic MLV envelope. Additionally, we identified MOT1 as the receptor used by ancHTenv. Further experiments are needed in order to test the hypothesis that HsaHTenv served as a restriction factor through interference with the receptor once used by HERV-T. As paleovirology also studies the evolution of the host defense mechanisms that have been shaped by past retroviral infections, we investigated the origins and evolution of tetherin, an orphan antiviral protein with no known homologs. We found that tetherin function is encoded by genes that exhibit no sequence homology and share only a common architecture and location in modern jawed vertebrate genomes, indicating an origin of ~450 MYA. Moreover, tetherin is part of a cluster of three potential sister genes that includes pv1 and a putative gene of unknown function, here referred as tm-cc(at), which encode proteins of similar architecture. Some variants of these proteins exhibit antiviral activity while others can be endowed with antiviral activity following a simple modification. Only in a slowly evolving species (coelacanths) does Tetherin exhibit homology to TMCC( aT). We suggest that neofunctionalization, drift and positive selection drove a near complete loss of sequence similarity among modern tetherin genes, and between tetherin and its sister genes. Scenarios by which this orphan gene may have arisen and evolved exemplify how protein modularity, evolvability and robustness can create new functions and preserve them, despite sequence divergence due to genetic conflict with past and present viruses

Development of a1 l2 learners’ literal reading comprehension of short online animated stories through vocabulary pre-reading activities

109 Páginas.​​Las habilidades de comprensión lectora juegan un papel importante en el proceso de aprendizaje de una lengua extranjera, tanto para aprendices jóvenes o adultos; es bien sabido que los buenos lectores tienen éxito en el desarrollo de otras habilidades de aprendizaje de la lengua. Sin embargo, no ha habido suficiente investigación en relación al uso de estrategias tradicionales como la enseñanza del vocabulario combinada con el uso de tecnologías multimodales para promover el desarrollo de comprensión lectora. El presente estudio se baso en el desarrollo de actividades de aprendizaje de vocabulario con el fin de lograr la comprensión lectora de historias animadas. Los niveles de comprensión de lectura fueron evaluados a través de tests de comprensión con formato de verdadero/ falso y seleccion multiple basados en el contenido de las historias. Una vez terminada la implementación, se aplicaron entrevistas a estudiantes y un cuestionario a los padres de familia para conocer sus percepciones sobre las actividades desarrolladas y el uso de tecnología. Luego de analizar los datos con la teoría fundamentada en datos, se encontró que las actividades realizadas con el vocabulario y los recursos multimodales contribuyeron al mejoramiento de su comprensión de lectura literal y además, generaron emociones positivas en los estudiantes. Estos resultados muestran que el uso de estrategias tradicionales como la pre-enseñanza de vocabulario en conjunto con la implementación de tecnologías multimodales deben ser mayormente consideradas por los actores de la enseñanza de Inglés como lengua extranjera en la educación básica primaria en Colombia.

Modeling of torsion stress giant magnetoimpedance in amorphous wires with negative magnetostriction

A model describing the influence of torsion stress on the giant magnetoimpedance in amorphous wires with negative magnetostriction is proposed. The wire impedance is found by means of the solution of Maxwell equations together with the Landau-Lifshitz equation, assuming a simplified spatial distribution of the magnetoelastic anisotropy induced by the torsion stress. The impedance is analyzed as a function of the external magnetic field, torsion stress and frequency. It is shown that the magnetoimpedance ratio torsion dependence has an asymmetric shape, with a sharp peak at some value of the torsion stress. The calculated field and stress dependences of the impedance are in qualitative agreement with results of the experimental study of the torsion stress giant magnetoimpedance in Co-based amorphous wires.Comment: 17 pages, 5 figure

Development of a1 l2 learners’ literal reading comprehension of short online animated stories through vocabulary pre-reading activities

109 Páginas.​​Las habilidades de comprensión lectora juegan un papel importante en el proceso de aprendizaje de una lengua extranjera, tanto para aprendices jóvenes o adultos; es bien sabido que los buenos lectores tienen éxito en el desarrollo de otras habilidades de aprendizaje de la lengua. Sin embargo, no ha habido suficiente investigación en relación al uso de estrategias tradicionales como la enseñanza del vocabulario combinada con el uso de tecnologías multimodales para promover el desarrollo de comprensión lectora. El presente estudio se baso en el desarrollo de actividades de aprendizaje de vocabulario con el fin de lograr la comprensión lectora de historias animadas. Los niveles de comprensión de lectura fueron evaluados a través de tests de comprensión con formato de verdadero/ falso y seleccion multiple basados en el contenido de las historias. Una vez terminada la implementación, se aplicaron entrevistas a estudiantes y un cuestionario a los padres de familia para conocer sus percepciones sobre las actividades desarrolladas y el uso de tecnología. Luego de analizar los datos con la teoría fundamentada en datos, se encontró que las actividades realizadas con el vocabulario y los recursos multimodales contribuyeron al mejoramiento de su comprensión de lectura literal y además, generaron emociones positivas en los estudiantes. Estos resultados muestran que el uso de estrategias tradicionales como la pre-enseñanza de vocabulario en conjunto con la implementación de tecnologías multimodales deben ser mayormente consideradas por los actores de la enseñanza de Inglés como lengua extranjera en la educación básica primaria en Colombia.

Determinación de crecientes extremas en las cuencas de alta montaña del Río Guadalupe y la Quebrada Piedras Blancas mediante la aplicación del Método Gradex

Ingeniero (a) CivilPregrad

Exercise Capacity in Children and Adolescents With Congenital Heart Disease: A Systematic Review and Meta-Analysis

Congenital heart disease (CHD) entails structural defects in the morphogenesis of the heart or its main vessels. Analyzing exercise capacity of children and adolescents with CHD is important to improve their functional condition and quality of life, since it can allow timely intervention on poor prognostic factors associated with higher risk of morbidity and mortality.To describe exercise capacity in children and adolescents with CHD compared with healthy controls.A systematic review was carried out. Randomized clinical trials and observational studies were included assessing exercise capacity through direct and indirect methods in children and adolescents between 5 and 17 years-old. A sensitive analysis was performed including studies with CHD repaired participants. Additionally, it was sub-analyzed by age range (< and ? 12 years old). Two independent reviewers analyzed the studies, extracted the data, and assessed the quality of the evidence.5619 articles were found and 21 were considered for the review. Eighteen articles used the direct exercise capacity measurement method by cardiopulmonary exercise test (CPET). The CHD group showed significant differences in peak oxygen consumption (VO2peak) with a value of -7.9 ml/Kg/min (95% CI: -9.9, -5.9, p = 0.00001), maximum workload (Wmax) -41.5 (95% CI: -57.9, -25.1 watts, p = 0.00001), ventilatory equivalent (VE/VCO2 ) slope 2.6 (95% CI: 0.3, 4.8), oxygen pulse (O2 pulse)-2.4 ml/beat (95% CI: -3.7, -1.1, p = 0.0003), and maximum heart rate (HRmax) -15 bpm (95% CI: -18, -12 bpm, p = 0.00001), compared with healthy controls. Adolescents (? 12 yrs) with CHD had a greater reduction in VO2peak (-10.0 ml/Kg/min (95% CI: -12.0, -5.3), p < 0.00001), Wmax (-45.5 watts (95% CI: -54.4, -36.7), p < 0.00001) and HRmax (-21 bpm (95% CI: -28, -14), p<0.00001).Suffering CHD in childhood and adolescence is associated with lower exercise capacity as shown by worse VO2peak, Wmax, VE/VCO2 slope, O2 pulse, and HRmax compared with matched healthy controls. The reduction in exercise capacity was greater in adolescents.www.crd.york.ac.uk/prospero/display_record.php?RecordID=208963, identifier: CRD42020208963.Copyright © 2022 Villaseca-Rojas, Varela-Melo, Torres-Castro, Vasconcello-Castillo, Mazzucco, Vilaró and Blanco

A new case of autosomal recessive agammaglobulinaemia with impaired pre-B cell differentiation due to a large deletion of the IGH locus

Males with X-linked agammaglobulinaemia (XLA) due to mutations in the Bruton tyrosine kinase gene constitute the major group of congenital hypogammaglobulinaemia with absence of peripheral B cells. In these cases, blockages between the pro-B and pre-B cell stage in the bone marrow are found. The remaining male and female cases clinically similar to XLA represent a genotypically heterogeneous group of diseases. In these patients, various autosomal recessive disorders have been identified such as mutations affecting IGHM, CD79A, IGLL1 genes involved in the composition of the pre-B cell receptor (pre-BCR) or the BLNK gene implicated in pre-BCR signal transduction. In this paper, we report on a young female patient characterised by a severe non-XLA agammaglobulinaemia that represents a new case of Igmu defect. We show that the B cell blockage at the pro-B to pre-B cell transition is due to a large homologous deletion in the IGH locus encompassing the IGHM gene leading to the inability to form a functional pre-BCR. The deletion extends from the beginning of the diversity (D) region to the IGHG2 gene, with all JH segments and IGHM, IGHD, IGHG3 and IGHG1 genes missing. CONCLUSION: alteration in Igmu expression seems to be relatively frequent and could account for most of the reported cases of autosomal recessive agammaglobulinaemia

The AMBRE Project: Stellar parameterisation of the ESO:FEROS archived spectra

The AMBRE Project is a collaboration between the European Southern Observatory (ESO) and the Observatoire de la Cote d'Azur (OCA) that has been established in order to carry out the determination of stellar atmospheric parameters for the archived spectra of four ESO spectrographs. The analysis of the FEROS archived spectra for their stellar parameters (effective temperatures, surface gravities, global metallicities, alpha element to iron ratios and radial velocities) has been completed in the first phase of the AMBRE Project. From the complete ESO:FEROS archive dataset that was received, a total of 21551 scientific spectra have been identified, covering the period 2005 to 2010. These spectra correspond to ~6285 stars. The determination of the stellar parameters was carried out using the stellar parameterisation algorithm, MATISSE (MATrix Inversion for Spectral SynthEsis), which has been developed at OCA to be used in the analysis of large scale spectroscopic studies in galactic archaeology. An analysis pipeline has been constructed that integrates spectral reduction and radial velocity correction procedures with MATISSE in order to automatically determine the stellar parameters of the FEROS spectra. Stellar atmospheric parameters (Teff, log g, [M/H] and [alpha/Fe]) were determined for 6508 (30.2%) of the FEROS archived spectra (~3087 stars). Radial velocities were determined for 11963 (56%) of the archived spectra. 2370 (11%) spectra could not be analysed within the pipeline. 12673 spectra (58.8%) were analysed in the pipeline but their parameters were discarded based on quality criteria and error analysis determined within the automated process. The majority of these rejected spectra were found to have broad spectral features indicating that they may be hot and/or fast rotating stars, which are not considered within the adopted reference synthetic spectra grid of FGKM stars.Comment: 28 pages, 28 figures, 9 table

Rotation velocities of hot horizontal branch stars in the globular clusters NGC 1904, NGC 2808, NGC 6093, and NGC 7078: the database

We present radial and rotation (v sini) velocity measurements, from UVES+VLT high resolution spectra of 61 stars in the blue horizontal branches (HB) of the Galactic globular clusters NGC 1904 (M79), NGC 2808, NGC 6093 (M80), and NGC 7078 (M15). The data reduction and the velocity determination, based on cross-correlation techniques, are discussed in detail. Most of this database has been used by Recio-Blanco et al. (2002) in their analysis of the rotation velocity properties of blue HB stars. Here we present additional data for NGC 2808. We confirm the results of the previous paper, in particular, a possible link between the HB jump and the abrupt change in the rotational velocity distribution around Teff ~ 11,500 K.Comment: 20 pages, 5 tables, 6 figures. Accepted for A&