The multi-reference contrast method: facilitating set enrichment analysis

Set enrichment analysis (SEA) is used to identify enriched biological categories/terms within high-throughput differential expression experiments. This is done by evaluating the proportion of differentially expressed genes against a background reference (BR). However, the choice of the "appropriate" BR is a perplexing problem and results will depend on it. Here, a visualization procedure that integrates results from several BRs and a stability analysis of enriched terms is presented as a tool to aid SEA. The multi-reference contrast method (MRCM) combines results from multiple BRs in a unique picture. The application of the proposed method was illustrated in one proteomic and three microarray experiments. The MRCM facilitates the exploration task involved in ontology analysis on proteomic/genomic experiments, where consensus terms were found to validate main experimental hypothesis. The use of more than one reference may provide new biological insights. The tool automatically highlights non-consensus terms assisting SEA.S

Encuesta de anticuerpos de enfermedad de Marek en aves de vida libre de la provincia de Buenos Aires

La enfermedad de Marek (EM) es un linfoma de células T inducido en pollos por el virus de la EM (VEM) que es altamente asociado a células. Las lesiones de EM consisten en linfomas de células T CD4 + que afectan a un número de órganos y tejidos, incluyendo iris, la piel y vísceras, junto con infiltración de células linfoides en los nervios periféricos que resultan en síntomas de parálisis. La enfermedad, causada por un herpesvirus, y se puede distinguir etiológicamente de otras neoplasias linfoides de aves. EM es y ha sido controlado desde principios de los años 1970 mediante el uso de las vacunas. Durante las últimas cuatro décadas, la investigación sobre EM ha proporcionado una mayor comprensión de los mecanismos moleculares de la enfermedad y los factores que afectan a la resistencia genética. Sin embargo, a pesar del uso generalizado de vacunas y el desarrollo de nuevos métodos de vacunación, la EM sigue siendo un reto importante para la salud de las aves comerciales, en particular por el continuo aumento de la virulencia de las cepas del VEM. Es evidente que, en ausencia de medidas de control, incluyendo “fallas de vacunas”, la EM es capaz de causar pérdidas devastadoras. Como una enfermedad que ocurre en todo el mundo, con los informes de las fallas de vacunación y la aparición probable de patotipos más virulentos, la EM plantea graves amenazas para la industria avícola, y desarrollar estrategias para su control sigue siendo uno de los grandes retos. Además, la incidencia de EM en otras especies de aves tales como pavos y gansos demuestra la gama de huéspedes y el aumento de importancia económica. Sin embargo, el papel de EM en aves de vida libre nunca ha sido estudiado profundamente. Se evaluará Una encuesta preliminar de anticuerpos en las aves de vida libre.Facultad de Ciencias Veterinaria

Brucellosis Vaccines: Assessment of Brucella melitensis Lipopolysaccharide Rough Mutants Defective in Core and O-Polysaccharide Synthesis and Export

Background: The brucellae are facultative intracellular bacteria that cause brucellosis, one of the major neglected zoonoses. In endemic areas, vaccination is the only effective way to control this disease. Brucella melitensis Rev 1 is a vaccine effective against the brucellosis of sheep and goat caused by B. melitensis, the commonest source of human infection. However, Rev 1 carries a smooth lipopolysaccharide with an O-polysaccharide that elicits antibodies interfering in serodiagnosis, a major problem in eradication campaigns. Because of this, rough Brucella mutants lacking the O-polysaccharide have been proposed as vaccines. Methodology/Principal Findings: To examine the possibilities of rough vaccines, we screened B. melitensis for lipopolysaccharide genes and obtained mutants representing all main rough phenotypes with regard to core oligosaccharide and O-polysaccharide synthesis and export. Using the mouse model, mutants were classified into four attenuation patterns according to their multiplication and persistence in spleens at different doses. In macrophages, mutants belonging to three of these attenuation patterns reached the Brucella characteristic intracellular niche and multiplied intracellularly, suggesting that they could be suitable vaccine candidates. Virulence patterns, intracellular behavior and lipopolysaccharide defects roughly correlated with the degree of protection afforded by the mutants upon intraperitoneal vaccination of mice. However, when vaccination was applied by the subcutaneous route, only two mutants matched the protection obtained with Rev 1 albeit at doses one thousand fold higher than this reference vaccine. These mutants, which were blocked in O-polysaccharide export and accumulated internal O-polysaccharides, stimulated weak anti-smooth lipopolysaccharide antibodies. Conclusions/Significance: The results demonstrate that no rough mutant is equal to Rev 1 in laboratory models and question the notion that rough vaccines are suitable for the control of brucellosis in endemic areas.This work was funded by the European Commission (Research Contract QLK2-CT-2002-00918) and the Ministerio de Ciencia y Tecnología of Spain (Proyecto AGL2004-01162/GAN)

The Caldera. No. 18

En las tres primeras semanas de agosto, concretamente los días 4, 14 y 18, nuestra querida Institución, recibió 132 jóvenes oradores, de quince Colegios de Bucaramanga y del área metropolitana, interesados en participar en la segunda versión del Concurso de Oratoria; el área de Lengua Castellana quiere resaltar la, cada vez más positiva, acogida a este magno evento, cuyo objetivo central se enfoca en posibilitar un espacio significativo para los jóvenes educandos de los grados noveno, décimo y undécimo, con el fin de poner en práctica sus habilidades comunicativas, el planteamiento de sus ideas y el desarrollo del pensamiento crítico, a través de la palabra; este año los discursos se centraron en la relación que los jóvenes pueden establecer entre paz, literatura y medios de comunicación; es interesante y gratificante ver cómo los jóvenes, aceptaron este reto y, para las eliminatorias de este año, se presentaron casi el triple de los participantes del año anterior (47, asistieron en el año 2014); se seleccionaron 17 finalistas, que se disputaron los tres primeros lugares en la gran final, el 28 de Agosto, en el marco de Ulibro 2015. Este año el primer lugar fue para la oradora del Colegio San Pedro, la estudiante Andrea Juliana Sepúlveda, de noveno grado, quien descolló entre los participantes.Trabajo por proyectos en el Instituto Caldas; Por: Gisela Afanador Díaz…04 Por: Gisela Afanador Díaz; Por: Juliana García Pérez…09 Reloj Solar 2015; Por: Silvia Peñuela Suárez…11 II Concurso Inter Colegiado de Oratoria; Por: Camila Briceño…12 Expresiones Caldistas…15 Primer Encuentro Inter Colegiado por la Convivencia Pacífica; Por: Carlos Alirio Castillo Portilla…27 Galería de Imágenes…28In the first three weeks of August, specifically on the 4th, 14th and 18th, our beloved Institution received 132 young speakers, from fifteen schools in Bucaramanga and the metropolitan area, interested in participating in the second version of the Speech Contest; The area of ​​Spanish Language wants to highlight the increasingly positive reception of this great event, whose central objective is focused on providing a meaningful space for young students of the ninth, tenth and eleventh grades, in order to put into practice their communication skills, the approach of their ideas and the development of critical thinking, through the word; This year the speeches focused on the relationship that young people can establish between peace, literature and the media; It is interesting and gratifying to see how the young people accepted this challenge and, for this year's qualifying rounds, almost three times the number of participants from the previous year showed up (47, attended in 2014); 17 finalists were selected, who competed for the first three places in the grand final, on August 28, within the framework of Ulibro 2015. This year the first place went to the speaker from Colegio San Pedro, student Andrea Juliana Sepúlveda, from ninth grade, who stood out among the participants

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries