Extracellular vesicles in parasitic diseases

Parasitic diseases affect billions of people and are considered a major public health issue. Close to 400 species are estimated to parasitize humans, of which around 90 are responsible for great clinical burden and mortality rates. Unfortunately, they are largely neglected as they are mainly endemic to poor regions. Of relevance to this review, there is accumulating evidence of the release of extracellular vesicles (EVs) in parasitic diseases, acting both in parasite–parasite inter-communication as well as in parasite–host interactions. EVs participate in the dissemination of the pathogen and play a role in the regulation of the host immune systems. Production of EVs from parasites or parasitized cells has been described for a number of parasitic infections. In this review, we provide the most relevant findings of the involvement of EVs in intercellular communication, modulation of immune responses, involvement in pathology, and their potential as new diagnostic tools and therapeutic agents in some of the major human parasitic pathogens

Spleen-Dependent Immune Protection Elicited by CpG Adjuvanted Reticulocyte-Derived Exosomes from Malaria Infection Is Associated with Changes in T cell Subsets' Distribution

Added corrigendum published in 2017-01-17 https://doi.org/10.3389/fcell.2016.00153Reticulocyte-derived exosomes (rex) are 30-100 nm membrane vesicles of endocytic origin released during the maturation of reticulocytes to erythrocytes upon fusion of multivesicular bodies with the plasma membrane. Combination of CpG-ODN with rex obtained from BALB/c mice infected with the reticulocyte-prone non-lethal P. yoelii 17X malaria strain (rexPy), had been shown to induce survival and long lasting protection. Here, we show that splenectomized mice are not protected upon rexPy+CpG inmunizations and that protection is restored upon passive transfer of splenocytes obtained from animals immunized with rexPy+CpG. Notably, rexPy immunization of mice induced changes in PD1- memory T cells with effector phenotype. Proteomics analysis of rexPy confirmed their reticulocyte origin and demonstrated the presence of parasite antigens. Our studies thus prove, for what we believe is the first time, that rex from reticulocyte-prone malarial infections are associated with splenic long-lasting memory responses. To try extrapolating these data to human infections, in vitro experiments with spleen cells of human transplantation donors were performed. Plasma-derived exosomes from vivax malaria patients (exPv) were actively uptaken by human splenocytes and stimulated spleen cells leading to changes in T cell subsets

Proteomics study of human cord blood reticulocyte-derived exosomes

Reticulocyte-derived exosomes (Rex), extracellular vesicles of endocytic origin, were initially discovered as a cargo-disposal mechanism of obsolete proteins in the maturation of reticulocytes into erythrocytes. In this work, we present the first mass spectrometry-based proteomics of human Rex (HuRex). HuRex were isolated from cultures of human reticulocyte-enriched cord blood using different culture conditions and exosome isolation methods. The newly described proteome consists of 367 proteins, most of them related to exosomes as revealed by gene ontology over-representation analysis and include multiple transporters as well as proteins involved in exosome biogenesis and erythrocytic disorders. Immunoelectron microscopy validated the presence of the transferrin receptor. Moreover, functional assays demonstrated active capture of HuRex by mature dendritic cells. As only seven proteins have been previously associated with HuRex, this resource will facilitate studies on the role of human reticulocyte-derived exosomes in normal and pathological conditions affecting erythropoiesis

Plasmodium vivax gametocytes in the bone marrow of an acute malaria patient and changes in the erythroid miRNA profile

Plasmodium vivax is the most widely distributed human malaria parasite and responsible for large amounts of disease and burden [1]. The presence of P. vivax in the bone marrow was first noticed in the late 19th century [2], and examinations of sternal bone marrow aspirates were performed as an accessory to examinations of peripheral blood in malaria, including P. vivax [3]. Since then, little progress has been made in studying P. vivax infections in this tissue. One report explored accumulation of dyserythropoietic cells in anaemic infected patients [4]. In addition, two case studies reported P. vivax infections after autologous bone marrow transplantation [5][6], and a third one documented an accidental P. vivax infection due to bone marrow transplantation between a malaria-infected donor and a malaria-free receptor [7]. In Brazil, one patient with persistent thrombocytopaenia and an enlarged spleen was diagnosed with chronic P. vivax malaria after the finding of schizonts in the bone marrow aspirate [8]. In all these reports and case studies, however, parasite loads and life stages found in the bone marrow were not investigated, and no molecular tools were available to rule out mixed infections or to characterize specific parasite stages

Factores que influyen en el proceso de enseñanza-aprendizaje de las operaciones con fracciones, en los estudiantes de séptimo grado de cinco Centros Escolares del municipio de Cojutepeque, Departamento de Cuscatlán.

El estudio que se llevó a cabo posee como propósito investigar los factores que influyen en el proceso de enseñanza- aprendizaje de las operaciones con fracciones, en los estudiantes de séptimo grado de cinco Centros Escolares del Municipio de Cojutepeque del departamento de Cuscatlán. Se utilizó el método de muestreo probabilístico (de tipo estratificado y el aleatorio simple) y no probabilístico. Para los estudiantes se aplicó el probabilístico, ya que toda la población tiene igual posibilidad de ser encuestados; para los docentes y directores se utilizó el no probabilístico ya que se decide antes a quien encuestar y entrevistar. Con los resultados que se obtengan, se pretende conocer si la mayoría de los estudiantes comprenden y resuelven con facilidad los ejercicios que se les explica en la clase, si los padres colaboran al resolver tareas, el docente muestra disposición para aclarar dudas. También si se aplica un diagnóstico al inicio del año escolar para realizar las adecuaciones curriculares, si se trabajan con metodología ESMATE, se capacitan constantemente, también para retroalimentar los temas de mayor dificultad utilizan estrategias como resolver guías de ejercicios, tutoriales y otros. En cuanto a los directores, asignan las materias por especialidad, tienen conocimiento, sobre los avances o dificultades que presentan los estudiantes en las operaciones con fracciones, existen acuerdos de mejora de las competencias en resolución de fracciones, entre el director y docente. También si hay falta de recursos para realizar juegos lúdicos durante el proceso de la clase, según metodología ESMATE y existe constantemente comunicación con los padres de familia. The purpose of the study was to investigate the factors that influence the teaching-learning process of operations with fractions in seventh grade students in five schools in the municipality of Cojutepeque in the department of Cuscatlán. The method used was probabilistic (stratified and simple random) and non-probabilistic sampling. For the students, the probabilistic method was applied, since the entire population has an equal chance of being surveyed; for the teachers and directors, the non-probabilistic method was used since it is decided beforehand who to survey and interview. With the results that are obtained, it is intended to know if the majority of the students understand and solve easily the exercises that are explained to them in class, if the parents collaborate when solving tasks, the teacher shows disposition to clarify doubts. Also if a diagnosis is applied at the beginning of the school year to make the curricular adjustments, if they work with ESMATE methodology, they are constantly trained, also to give feedback to the most difficult subjects they use strategies like solving exercise guides, tutorials and others. As for the directors, they assign the subjects by specialty, they have knowledge, about the advances or difficulties that the students present in the operations with fractions, there are agreements of improvement of the competences in resolution of fractions, between the director and the teacher, also if there is lack of resources to carry out playful games during the process of the class, according to methodology ESMATE and there is constant communication with the parents

Responsabilidad social y universidad

182 p.En esta colección se centra en la responsabilidad social que corresponde a las instituciones de educación superior. Así mismo , aporta al compromiso misional de la universidad de inculturar la doctrina social católica y el estudio, análisis, sensibilización y propuestas frente a las realidades culturales, políticas, económicas y sociales de Colombia. Esta obra está destinada a las comunidades académicas que orientan sus reflexiones a la proyección social de sus entes educativos.Prólogo Responsabilidad social universitaria 1· Humanizar el hábitat. Un ejemplo de responsabilidad social William Fernando Puentes González 2. Una introducción a la idea de justicia. Un debate contemporáneo ¿qué es una sociedad justa? Armando Rojas Claros 3. Acercamiento al personalismo de Emmanuel Mounier como propuesta ante la problemática de la sociedad actual Alexander Aldana Piñeros 4. La cortesía, expresión de la responsabilidad social Edilberto Cruz Espejo 5. Construcción de ciudadanía y de ciudadano: la formación del profesional incluyente Edgar Javier Garzón P. 6. Evaluación e impacto de un programa de formación humanística en instituciones educativas de la ciudad de Bogotá Katherin Hurtado Morales, Humberto Grimaldo Durán, Floralba Barrero Rivera y Alba Lucía Meneses Báez 7. Caritas in veritate: verdad y acción, un paso a la responsabilidad social en el mundo globalizado Elizabeth Duvanca Reyes 8. Doctrina Social de la Iglesia y desarrollo humano: ejemplo de responsabilidad social Giovanni Reyes Ortiz 9. La responsabilidad social universitaria desde el paradigma de la psicología comunitaria Nelly Ayala Rodríguez María Constanza del Portillo Obando María Victoria Neira Roa 10. Informática comunitaria y acciones de mejoramiento para la proyección social Jorge Fernando Bejarano Lobo 11. Responsabilidad social en la educación matemática Jacinto Eloy Puig Portal 12. Responsabilidad social. Recuento de experiencias Doris Carda de Bernal Bibliografí

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Search for diboson resonances in hadronic final states in 139 fb −1 of pp collisions at s = 13 TeV with the ATLAS detector

Abstract: Narrow resonances decaying into W W, W Z or ZZ boson pairs are searched for in 139 fb−1 of proton-proton collision data at a centre-of-mass energy of s = 13 TeV recorded with the ATLAS detector at the Large Hadron Collider from 2015 to 2018. The diboson system is reconstructed using pairs of high transverse momentum, large-radius jets. These jets are built from a combination of calorimeter- and tracker-inputs compatible with the hadronic decay of a boosted W or Z boson, using jet mass and substructure properties. The search is performed for diboson resonances with masses greater than 1.3 TeV. No significant deviations from the background expectations are observed. Exclusion limits at the 95% confidence level are set on the production cross-section times branching ratio into dibosons for resonances in a range of theories beyond the Standard Model, with the highest excluded mass of a new gauge boson at 3.8 TeV in the context of mass-degenerate resonances that couple predominantly to gauge bosons

Measurement of the azimuthal anisotropy of charged-particle production in Xe+Xe collisions at sNN =5.44 TeV with the ATLAS detector

This paper describes the measurements of flow harmonics v2-v6 in 3μb-1 of Xe+Xe collisions at sNN=5.44 TeV performed using the ATLAS detector at the Large Hadron Collider (LHC). Measurements of the centrality, multiplicity, and pT dependence of the vn obtained using two-particle correlations and the scalar product technique are presented. The measurements are also performed using a template-fit procedure, which was developed to remove nonflow correlations in small collision systems. This nonflow removal is shown to have a significant influence on the measured vn at high pT, especially in peripheral events. Comparisons of the measured vn with measurements in Pb+Pb collisions and p+Pb collisions at sNN=5.02 TeV are also presented. The vn values in Xe+Xe collisions are observed to be larger than those in Pb+Pb collisions for n=2, 3, and 4 in the most central events. However, with decreasing centrality or increasing harmonic order n, the vn values in Xe+Xe collisions become smaller than those in Pb+Pb collisions. The vn in Xe+Xe and Pb+Pb collisions are also compared as a function of the mean number of participating nucleons, (Npart), and the measured charged-particle multiplicity in the detector. The v3 values in Xe+Xe and Pb+Pb collisions are observed to be similar at the same (Npart) or multiplicity, but the other harmonics are significantly different. The ratios of the measured vn in Xe+Xe and Pb+Pb collisions, as a function of centrality, are also compared to theoretical calculations