Dissecting the basis for differential substrate specificity of ADAR1 and ADAR2.

Millions of adenosines are deaminated throughout the transcriptome by ADAR1 and/or ADAR2 at varying levels, raising the question of what are the determinants guiding substrate specificity and how these differ between the two enzymes. We monitor how secondary structure modulates ADAR2 vs ADAR1 substrate selectivity, on the basis of systematic probing of thousands of synthetic sequences transfected into cell lines expressing exclusively ADAR1 or ADAR2. Both enzymes induce symmetric, strand-specific editing, yet with distinct offsets with respect to structural disruptions: -26 nt for ADAR2 and -35 nt for ADAR1. We unravel the basis for these differences in offsets through mutants, domain-swaps, and ADAR homologs, and find it to be encoded by the differential RNA binding domain (RBD) architecture. Finally, we demonstrate that this offset-enhanced editing can allow an improved design of ADAR2-recruiting therapeutics, with proof-of-concept experiments demonstrating increased on-target and potentially decreased off-target editing.

Crucial contribution of the universities to SARS-CoV-2 surveillance in Ecuador: Lessons for developing countries.

COVID-19 pandemic has challenged public health systems worldwide, particularly affecting developing countries in Latin America like Ecuador. In this report, we exposed the fundamental role of the Ecuadorian universities to improve COVID-19 surveillance in the country, with an overall contribution over 15% of the total SARS-CoV-2 RT-PCR tests done. We highlight the role of our university during the first semester of the COVID-19 pandemic, contributing to a massive free SARS-CoV-2 testing up to almost 10% of the total diagnosis completed in the country, mainly focus on underserved urban, rural and indigenous communities. Finally, we described our contribution to a high quality and low-cost SARS-CoV-2 RT-PCR diagnostic in Ecuador.

Phylogeny and latitudinal biogeography of the Papillomaviridae family

Introduction: The latitudinal diversity gradient (LDG), a fundamental ecology pattern for higher organisms, has explained the increase of species diversity from the poles towards the tropics. Can we explain the biodiversity of Papillomaviruses based on this pattern? Objective: To analyse the phylogenetic diversity and phylogeography of most known genotypes and species belonging to Papillomaviridae Family isolated and molecularly characterized by distant latitudinal locations around the world. Methods: We collected 238 gene sequences encoding for the L1 and L2 viral capsid proteins from PaVE database. A geographical heat map based on the PV locations allowed to analyse the distribution and the number of PV species per country. Subsequently, a phylogenetic tree based on concatenated amino acid sequences L1 and L2 was constructed using a combination of Bayesian and Maximum Likelihood (ML) methods with Geneious version 11.2.1 and BEAST version 1.8.4. Statistical analysis with Principal Coordinate Analyses (PCA) using the Jaccard similarity index for presence-absence were carried out to test the similarity of the groups in the phylogenetic tree based on their viral species, the host and origin country lists. Distance-based redundancy analysis generated an ordination plot of the similarity of viral species list per group of the phylogenetic tree vs. host species per group, the country list per group and the number of samples per group. Finally, the significance of each model was tested by Analysis of variance (ANOVA). Results: A clear tendency of most of the papillomavirus (PV) species clustering in the Northern regions appeared. Our phylogenetic analyses largely support the taxonomic division into major papillomavirus genera (Alpha, Beta, Gamma, Delta, Lambda, Xi, Upsilon and Chi papillomaviruses), as reported in previous studies. Chelonid PV's, a papillomavirus in turtles, appeared as the oldest group for all papillomaviruses. Minor inconsistencies were found within some of the major taxonomic groups explained by the exhausted phylogenetic analyses. Due to the different sampling data efforts with little replication in certain groups, hosts and countries, numerical models did not fit to the proposed hypothesis. Conclusions: Phylogeographical analysis allowed determining the global distribution of papillomaviruses species diversity per latitudinal location. As most of the papillomavirus (PV) species were clustered in the Northern regions, this may clearly represent a statistical bias because larger efforts in PV studies have historically been done in the US and Europe. The biogeographical trend of a latitudinal diversity gradient does not apply for papillomaviruses. Even though no support to the phylogeographical pattern of LDG for PV was obtained, our results may only be the product of a socio-economical-scientific artefact and not a natural phenomenon.

Introducción: El gradiente de diversidad latitudinal, un patrón ecológico fundamental para los organismos superiores ha servido para explicar el incremento de la diversidad de especies desde los polos hacia los trópicos. ¿Podemos entonces explicar la biodiversidad de papilomavirus (PV) basado en este patrón? Objetivo: Analizar la diversidad filogenética y la filogeografía de los genotipos y especies más conocidas que pertenecen a la Familia Papillomaviridae aislados y molecularmente caracterizados por sus locaciones latitudinales distantes alrededor del mundo. Métodos: Recolectamos 238 secuencias de genes que codifican las proteínas de la cápside viral L1 y L2 a partir de la base de datos PaVE. Un mapa de calor geográfico basado en la ubicación de PV permitió analizar la distribución y el número de especies de PV por país. Posteriormente, un árbol filogenético basado en secuencias de aminoácidos concatenadas L1 y L2 se construyó utilizando una combinación de métodos Bayesianos y de Máxima Verosimilitud con Geneious versión 11.2.1 y BEAST versión 1.8.4. Con respecto al análisis estadístico, se realizaron tres análisis de componentes principales utilizando el índice de similitud de Jaccard para presencia-ausencia, a fin de evaluar la similitud de los grupos en el árbol filogenético en función de sus especies virales, el huésped o las listas de países. El análisis de redundancia basado en la distancia generó una gráfica de ordenación de la similitud de la lista de especies virales por grupo del árbol filogenético vs las especies hospedadoras por grupo, la lista de países por grupo y el número de muestras por grupo. Finalmente, la significancia de cada modelo se evaluó mediante análisis de varianza (ANOVA). Resultados: Existió una tendencia clara de la mayoría de las especies de papilomavirus agrupadas en regiones del norte. Nuestro análisis sustenta en gran medida la división taxonómica en los principales géneros de virus del papiloma (Alfa, Beta, Gama, Delta, Lamda, Xi, Ípsilon y Ji), como se informó en estudios anteriores. Los PV de los quelonios, papilomavirus en tortugas, apareció como el grupo más antiguo para todos los papilomavirus. Inconsistencias menores fueron encontrados dentro de algunos de los principales grupos taxonómicos explicadas por los análisis filogenéticos. Además, una serie de análisis estadísticos fueron realizados para determinar la significancia en la diversidad de especies correlacionada con la locación geográfica. Debido a diferentes esfuerzos en el muestreo de datos con poca replicación en ciertos grupos, hospedadores, y países, los modelos no se ajustaron a la hipótesis propuesta. Conclusiones: Los análisis filogeográficos permitieron determinar la distribución global de la diversidad de especies de PV por locación latitudinal. Como en la mayoría de las especies de PV fueron agrupados en las regiones del norte, esto claramente podría representar un sesgo estadístico porque esfuerzos más grandes en los estudios de PV históricamente han sido realizados en Estados Unidos de América y Europa. La tendencia biogeográfica del gradiente latitudinal de especies no aplica para los virus del papiloma. A pesar de que no se obtuvo apoyo para el patrón filogeográfico de LDG para PV, nuestros resultados podrían ser solo el producto de un artefacto social, económico y científico y no un fenómeno natural.

Peptide Phage Display: Molecular Principles and Biomedical Applications.

Phage display (PD) is a technology based on the presentation of functional exogenous peptides on the capsid surface of bacteriophages. PD is performed by introducing a DNA sequence of interest at a specific position within a functional viral gene. In addition, peptide phage libraries are powerful tools for expressing a wide range of random peptides and for specific peptide screening. Specifically, PD applications include the analysis of binding and interactions between proteins, the identification of bioactive peptides that bind to receptors, the identification of disease-associated antigens, and the identification of cell-specific peptides. Since its emergence, PD technology has revolutionized several fields in the biological sciences, such as oncology, cell biology, and pharmacology, the innumerable applications for which will be described throughout this review.

Human genetics and genomics research in Ecuador: historical survey, current state, and future directions.

BACKGROUND: In South America, the history of human genetics is extensive and its beginnings go back to the onset of the twentieth century. In Ecuador, the historical record of human genetics and genomics research is limited. In this context, our work analyzes the current status and historical panorama of these fields, based on bibliographic searches in Scopus, Google Scholar, PubMed, and Web of Science. RESULTS: Our results determined that the oldest paper in human genetics coauthored by an Ecuadorian institution originates from the Central University of Ecuador in 1978. From a historical standpoint, the number of articles has increased since the 1990s. This growth has intensified and it is reflected in 137 manuscripts recorded from 2010 to 2019. Areas such as human population genetics, phylogeography, and forensic sciences are the core of genetics and genomics-associated research in Ecuador. Important advances have been made in the understanding of the bases of cancer, some genetic diseases, and congenital disorders. Fields such as pharmacogenetics and pharmacogenomics have begun to be explored during the last years. CONCLUSIONS: This work paints a comprehensive picture and provides additional insights into the future panorama of human genetic and genomic research in Ecuador as an example of an emerging, resource-limited country with interesting phylogeographic characteristics and public health implications.