An overview of bioinformatics tools for epitope prediction: Implications on vaccine development

AbstractExploitation of recombinant DNA and sequencing technologies has led to a new concept in vaccination in which isolated epitopes, capable of stimulating a specific immune response, have been identified and used to achieve advanced vaccine formulations; replacing those constituted by whole pathogen-formulations. In this context, bioinformatics approaches play a critical role on analyzing multiple genomes to select the protective epitopes in silico. It is conceived that cocktails of defined epitopes or chimeric protein arrangements, including the target epitopes, may provide a rationale design capable to elicit convenient humoral or cellular immune responses. This review presents a comprehensive compilation of the most advantageous online immunological software and searchable, in order to facilitate the design and development of vaccines. An outlook on how these tools are supporting vaccine development is presented. HIV and influenza have been taken as examples of promising developments on vaccination against hypervariable viruses. Perspectives in this field are also envisioned

An additional set of phages to characterize epidemic methicillin-resistant Staphylococcus aureus strains from Spain (1989-92).

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) isolates in Spain have increased dramatically; in 1986 there were only 1.2% MRSA amongst all nosocomial Staphylococcus aureus (SA) isolates, by 1989 this percentage had risen to 44% in some hospital causing a very serious epidemic situation in the country. We have characterized these isolates by direct, reverse and Fisk phage typing and we have also looked for an additional local set of phages to help us to differentiate these strains. We have been able to differentiate an epidemic strain from other MRSA strains which cause sporadic hospital outbreaks, and we have also distinguished between some variants of the epidemic strain.This research has been supported by a grant from the Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS), Ministerio de Sanidad y Consumo, Spain; No. 93/0144.S

Redox and Catalytic Properties of Promoted NiO Catalysts for the Oxidative Dehydrogenation of Ethane

[EN] NiO and metal-promoted NiO catalysts (M-NiO, with a M/(M+Ni) atomic ratio of 0.08, with M = Nb, Sn, or La) have been prepared, tested in the oxidative dehydrogenation (ODH) of ethane, and characterized by means of XRD, TPR, HRTEM, Raman, XPS, and in situ XAS (using H-2/He, air or C2H6/He mixtures). The selectivity to ethylene during the ODH of ethane decreases according to the following trend: Nb NiO Sn NiO > La NiO > NiO, whereas the catalyst reducibility (determined by both TPR and XAS using H-2/He mixtures) shows the opposite trend. However, different reducibility and catalytic behavior in the absence of oxygen (ethane/He mixtures) have been observed, especially when comparing Nb- and Sn-promoted NiO samples. These differences can be ascribed mainly to a different phase distribution of the promoter. The results presented here are discussed in terms of the nature of active and selective sites for ODH of ethane in selective and unselective catalysts, but also the role of promoters and the importance of their phase distribution.The authors would like to acknowledge the DGICYT in Spain CTQ2012-37925-C03-2, CTQ2015-68951-C3-1-R, and CTQ2015-68951-C3-3-R. Authors thank European Synchrotron Radiation Facility, ESRF (Project CH-4512; BM25-SpLine Beamlime). Authors from ITQ also thank Project SEV-2016-0683 for financial support. D.D. thanks MINECO and Severo Ochoa Excellence Program for his fellowship (SVP-2014-068669). B.S. also thanks UV-INV-AE16-484416. Finally, the authors thank the Electron Microscopy Service of Universitat Politecnica de Valencia for their support.Delgado-Muñoz, D.; Solsona Espriu, BE.; Ykrelef, A.; Rodriguez-Gomez, A.; Caballero, A.; Rodríguez-Aguado, E.; Rodriguez-Castellón, E.... (2017). Redox and Catalytic Properties of Promoted NiO Catalysts for the Oxidative Dehydrogenation of Ethane. The Journal of Physical Chemistry C. 121(45):25132-25142. https://doi.org/10.1021/acs.jpcc.7b07066S25132251421214

Ecais study: inadvertent cardiovascular adverse events in sepsis

Objetivo Describir la incidencia de eventos cardiovasculares adversos en pacientes con diagnóstico de sepsis en sus diferentes estadios. Diseño Estudio observacional, descriptivo, longitudinal. Ámbito Unidades de cuidados intensivos de tipo mixto de dos hospitales universitarios en la ciudad de Bogotá. Participantes Se incluyeron una serie de pacientes mayores de edad, que ingresan a UCI con diagnostico de sepsis, sin evidencia de lesión miocárdica isquémica previa. Intervenciones Registros electrocardiográficos continuos de 12 derivaciones durante 48 horas con monitoría Holter Variables de interés Isquemia, arritmia cardiaca, variabilidad de la frecuencia cardiaca. Resultados Se analizaron 100 pacientes, 62% de los cuales se estadificó como choque séptico. El 3% presentó evento cardiovascular adverso de tipo isquémico detectado por Holter y desapercibido por monitoreo convencional. El 46% presentaron un evento de tipo arrítmico por Holter, comparado con solo un 6% detectado por monitoreo convencional. La mortalidad cruda fue de 40%. El 100% presentó pérdida de la variabilidad de la frecuencia cardiaca. Conclusión La sepsis en esta experiencia mostró una baja incidencia de eventos cardiovasculares isquémicos. Los eventos arrítmicos, sin embargo, mostraron una incidencia alta. El monitoreo convencional falló en detectar la totalidad de los eventos isquémicos y en mayor proporción los eventos arrítmicos. En esta serie, los eventos cardiovasculares generados por descarga adrenérgica no impactan en la mortalidad.Objective To describe the incidence of cardiovascular adverse events in patients with sepsis in its various stages. Design A longitudinal, descriptive, observational study was carried out. Setting Intensive care units of two university hospitals in Bogotá (Colombia). Patients A number of patients consecutively admitted to the adult ICU with a diagnosis of sepsis, and no evidence of previous ischemic myocardial injury. Interventions Forty-eight hours of electrocardiographic record using Holter technology. Main variables Ischemia, cardiac arrhythmia, heart rate variability. Results A total of 100 patients were analyzed, 62% being staged as presenting septic shock. Three percent suffered ischemic events detected by Holter and unnoticed through conventional monitoring. Forty-six percent suffered an arrhythmic event detected by Holter, compared with only 6% as detected by conventional monitoring. Mortality was 40%. All patients showed loss of heart rate variability. Conclusion In this study patients with sepsis showed a low incidence of cardiovascular ischemic events. In contrast, arrhythmic events showed a high incidence. Conventional monitoring failed to detect any of the ischemic events and most arrhythmic events. In this study, cardiovascular events generated by adrenergic discharge had no impact upon mortality

Purification of retinal ganglion cells using low-pressure flow cytometry

Purified Retinal Ganglion Cells (RGCs) for in vitro study have been a valuable tool in the study of neural regeneration and in the development of therapies to treat glaucoma. Traditionally, RGCs have been isolated from early postnatal rats and mice, and more recently from human in vitro derived retinal organoids using a two-step immunopanning technique based upon the expression of Thy-1. This technique, however, limits the time periods from which RGCs can be isolated, missing the earliest born RGCs at which time the greatest stage of axon growth occurs, as well as being limited in its use with models of retinal degeneration as Thy-1 is downregulated following injury. While fluorescence associated cell sorting (FACS) in combination with new optogenetically labeled RGCs would be able to overcome this limitation, the use of traditional FACS sorters has been limited to genomic and proteomic studies, as RGCs have little to no survival post-sorting. Here we describe a new method for RGC isolation utilizing a combined immunopanning-fluorescence associated cell sorting (IP-FACS) protocol that initially depletes macrophages and photoreceptors, using immunopanning to enrich for RGCs before using low-pressure FACS to isolate these cells. We demonstrate that RGCs isolated via IP-FACS when compared to RGCs isolated via immunopanning at the same age have similar purity as measured by antibody staining and qRT-PCR; survival as measured by live dead staining; neurite outgrowth; and electrophysiological properties as measured by calcium release response to glutamate. Finally, we demonstrate the ability to isolate RGCs from early embryonic mice prior to the expression of Thy-1 using Brn3b-eGFP optogenetically labeled cells. This method provides a new approach for the isolation of RGCs for the study of early developed RGCs, the study of RGC subtypes and the isolation of RGCs for cell transplantation studies

Node overlap removal by growing a tree

Node overlap removal is a necessary step in many scenarios including laying out a graph, or visualizing a tag cloud. Our contribution is a new overlap removal algorithm that iteratively builds a Minimum Spanning Tree on a Delaunay triangulation of the node centers and removes the node overlaps by ”growing” the tree. The algorithm is simple to implement yet produces high quality layouts. According to our experiments it runs several times faster than the current state-of-the-art methods

The Pioneer anomaly in the context of the braneworld scenario

We examine the Pioneer anomaly - a reported anomalous acceleration affecting the Pioneer 10/11, Galileo and Ulysses spacecrafts - in the context of a braneworld scenario. We show that effects due to the radion field cannot account for the anomaly, but that a scalar field with an appropriate potential is able to explain the phenomena. Implications and features of our solution are analyzed.Comment: Final version to appear at Classical & Quantum Gravity. Plainlatex 19 page

Comparison of flipped learning and traditional lecture method for teaching digestive system diseases in undergraduate medicine: A prospective non-randomized controlled trial

Introduction: This study examined the effects of a large-scale flipped learning (FL) approach in an undergraduate course of Digestive System Diseases. Methods: This prospective non-randomized trial recruited 404 students over three academic years. In 2016, the course was taught entirely in a Traditional Lecture (TL) style, in 2017 half of the course (Medical topics) was replaced by FL while the remaining half (Surgical topics) was taught by TL and in 2018, the whole course was taught entirely by FL. Academic performance, class attendance and student’s satisfaction surveys were compared between cohorts. Results: Test scores were higher in the FL module (Medical) than in the TL module (Surgical) in the 2017 cohort but were not different when both components were taught entirely by TL (2016) or by FL (2018). Also, FL increased the probability of reaching superior grades (scores >7.0) and improved class attendance and students’ satisfaction. Conclusion: The holistic FL model is more effective for teaching undergraduate clinical gastroenterology compared to traditional teaching methods and has a positive impact on classroom attendances

Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice

Even though the idea that amyloid beta peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein processing and tau alterations in this type of dementia remains controversial. We further investigated the role of beta-amyloid production/deposition in tau pathology and neuronal cell death in the mouse brain by crossing Tg2576 and VLW lines expressing human mutant amyloid precursor protein and human mutant tau, respectively. The resulting double transgenic mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain limbic areas. These findings challenge the idea that tau pathology in Alzheimer's disease is merely a downstream effect of amyloid production/deposition and suggest that reciprocal interactions between beta-amyloid and tau alterations may take place in vivo

Search for coherent charged pion production in neutrino-carbon interactions

We report the result from a search for charged-current coherent pion production induced by muon neutrinos with a mean energy of 1.3 GeV. The data are collected with a fully active scintillator detector in the K2K long-baseline neutrino oscillation experiment. No evidence for coherent pion production is observed and an upper limit of $0.60 \times 10^{-2}$ is set on the cross section ratio of coherent pion production to the total charged-current interaction at 90% confidence level. This is the first experimental limit for coherent charged pion production in the energy region of a few GeV.Comment: 5 pages, 4 figure