A DIVA vaccine strain lacking RpoS and the secondary messenger c-di-GMP for protection against salmonellosis in pigs

International audienceAbstractSalmonellosis is the second most common food-borne zoonosis in the European Union, with pigs being a major reservoir of this pathogen. Salmonella control in pig production requires multiple measures amongst which vaccination may be used to reduce subclinical carriage and shedding of prevalent serovars, such as Salmonella enterica serovar Typhimurium. Live attenuated vaccine strains offer advantages in terms of enhancing cell mediated immunity and allowing inoculation by the oral route. However, main failures of these vaccines are the limited cross-protection achieved against heterologous serovars and interference with serological monitoring for infection. We have recently shown that an attenuated S. Enteritidis strain (ΔXIII) is protective against S. Typhimurium in a murine infection model. ΔXIII strain harbours 13 chromosomal deletions that make it unable to produce the sigma factor RpoS and synthesize cyclic-di-GMP (c-di-GMP). In this study, our objectives were to test the protective effects of ΔXIII strain in swine and to investigate if the use of ΔXIII permits the discrimination of vaccinated from infected pigs. Results show that oral vaccination of pre-weaned piglets with ΔXIII cross-protected against a challenge with S. Typhimurium by reducing faecal shedding and ileocaecal lymph nodes colonization, both at the time of weaning and slaughter. Vaccinated pigs showed neither faecal shedding nor tissue persistence of the vaccine strain at weaning, ensuring the absence of ΔXIII strain by the time of slaughter. Moreover, lack of the SEN4316 protein in ΔXIII strain allowed the development of a serological test that enabled the differentiation of infected from vaccinated animals (DIVA)

Evaluation of a Salmonella strain lacking the secondary messenger C-di-GMP and RpoS as a live oral vaccine

Salmonellosis is one of the most important bacterial zoonotic diseases transmitted through the consumption of contaminated food, with chicken and pig related products being key reservoirs of infection. Although numerous studies on animal vaccination have been performed in order to reduce Salmonella prevalence, there is still a need for an ideal vaccine. Here, with the aim of constructing a novel live attenuated Salmonella vaccine candidate, we firstly analyzed the impact of the absence of cyclic-di-GMP (c-di-GMP) in Salmonella virulence. Cdi- GMP is an intracellular second messenger that controls a wide range of bacterial processes, including biofilm formation and synthesis of virulence factors, and also modulates the host innate immune response. Our results showed that a Salmonella multiple mutant in the twelve genes encoding diguanylate cyclase proteins that, as a consequence, cannot synthesize c-di-GMP, presents a moderate attenuation in a systemic murine infection model. An additional mutation of the rpoS gene resulted in a synergic attenuating effect that led to a highly attenuated strain, referred to as ΔXIII, immunogenic enough to protect mice against a lethal oral challenge of a S. Typhimurium virulent strain. ΔXIII immunogenicity relied on activation of both antibody and cell mediated immune responses characterized by the production of opsonizing antibodies and the induction of significant levels of IFN-γ, TNF-α, IL-2, IL-17 and IL-10. ΔXIII was unable to form a biofilm and did not survive under desiccation conditions, indicating that it could be easily eliminated from the environment. Moreover, ΔXIII shows DIVA features that allow differentiation of infected and vaccinated animals. Altogether, these results show ΔXIII as a safe and effective live DIVA vaccine.SB is a predoctoral fellow from the Public University of Navarra. CG and BG are recipients of a postdoctoral contract under Grants IIM 13329.RI1 and BIO2011-30503-C02-02, respectively. This work was supported by grant IIM 13329.RI1 from the Departamento de Innovación, Empresa y Empleo, Government of Navarra and grants BIO2011-30503-C02-02 and BIO2014-53530-R from the Spanish Ministry of Economy and Competitiveness.Peer Reviewe

Impregnación de bórax y ácido bórico en caña Guadua angustifolia Kunth por el método de inmersión

La caña Guadua angustifolia Kunth es un material con un gran potencial de industrialización que no ha sido objeto de estudio en el ámbito de la preservación por lo que se carece de una guía técnica sobre este procedimiento. El objetivo de esta investigación fue cuantificar niveles de impregnación del preservante elaborado con sales de boro aplicado por el método de inmersión en caña Guadua angustifolia Kunth. Para ello se utilizaron probetas de caña fresca en etapa madura que fueron secadas al horno y sumergidas durante diferentes períodos de tiempo de preservación en una solución de bórax y ácido bórico al 4%. Para al análisis cualitativo, las probetas se cortaron a la mitad transversalmente y los segmentos se expusieron a sustancias reveladoras elaboradas a partir de Cúrcuma longa y ácido clorhídrico. Adicionalmente, la dimensión de la coloración obtenida tras esta reacción química fue evaluada a través del análisis cuantitativo mediante el uso de fórmulas. Los principales resultados demostraron que para obtener niveles de absorción superiores a los 200 kg/m3 es necesario que las muestras se encuentren con un contenido de humedad inferior al 15% previo a la preservación; además, se estableció que un tiempo de inmersión de al menos 72 horas garantiza alcanzar un nivel tóxico de retención efectiva de 0,40 a 0,50 kg/m3 de producto activo

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Análisis de una cepa avirulenta de Salmonella enteritidis para su uso como vacuna viva atenuada

Salmonella enterica subs. enterica ser. Enteritidis es un importante patógeno zoonótico con capacidad de infectar a un amplio rango de huéspedes. Actualmente representa un importante problema de salud pública dado que en el año 2010 se declararon en Europa 100.000 casos de enterocolitis por esta bacteria (de los cuales 2500 casos fueron declarados en España), asociados principalmente al consumo de carne de origen porcino. Para reducir la prevalencia de Salmonella en las granjas, la Directiva (CE) 2160/2003 de la Unión Europea propone exigir la vacunación de toda la cabaña ganadera avícola y porcina. Para responder a esta necesidad, en este estudio hemos valorado la capacidad de una cepa atenuada de S. Enteritidis para el desarrollo de una vacuna capaz de inducir una respuesta inmune que disminuya la colonización de órganos y liberación de Salmonella en heces en explotaciones intensivas de ganado porcino. La cepa de Salmonella candidata para el desarrollo de la vacuna ha sido, S. Enteritidis 3934ΔXII*, que tiene delecionado los genes que codifican las 12 proteínas de la familia GGDEF. Esta cepa es avirulenta, tiene muy disminuida su capacidad para sobrevivir en el ambiente y como no contiene DNA exógeno no estaría catalogada como OGM. Ensayos de inmunización por vía oral utilizando un modelo de infección murino, revelaron que la inmunización con una sola dosis de 107ufc de esta cepa es capaz de inducir una respuesta inmune protectora frente a una infección por Salmonella, indicando que dicha cepa puede ser un candidato idóneo para su uso como vacuna viva atenuada.Salmonella enterica subsp. Enterica ser. Enteritidis is an important zoonotic pathogen capable of infecting a wide range of hosts. Nowadays it represents an important problem of public health provided that in the year 2010 there were declared 100.000 Enterocolitis's cases caused by this bacterium in Europe (of which 2500 cases were declared in Spain), associated mainly with the consumption of meat of porcine origin. To reduce the prevalence of Salmonella, the Directive 2160/2003 of the European Union proposes to demand the vaccination of the whole poultry and porcine cattle for the year 2015. Given this requirement, in this study we have evaluated the ability of an attenuated strain of S. Enteritidis for the development of a vaccine capable of inducing an immune response that diminishes the colonization and Salmonella's liberation in feces of pigs in intensive piggeries. The Salmonella strain evaluated for vaccine development has been, S. Enteritidis 3934ΔXII*, in which the genes coding for the 12 GGDEF proteins had been deleted. This strain is avirulent, it has strongly diminished the capacity to survive in the environment and, given that it does not contain exogenous DNA, it would not be catalogued as GMO. Trials of oral immunization using a murine infection model revealed that immunization with a single dose of 107ufc of this strain is capable of inducing a protective immune response against Salmonella infection, indicating that this strain can be a suitable candidate for the development of Salmonella attenuated life vaccine.Máster Universitario en AgrobiotecnologíaUnibertsitate Masterra Agrobioteknologia

Evaluación de guantes de protección para la poda con tijeras neumáticas y eléctricas

Ingeniería Técnica AgrícolaNekazaritza Ingeniaritza Tekniko

Testing source confusion and identification capability in Cherenkov telescope array data

The Cherenkov Telescope Array will provide the deepest survey of the Galactic Plane performed at very-high-energy gamma-rays. Consequently, this survey will unavoidably face the challenge of source confusion, i.e. the non-unique attribution of signal to a source due to multiple overlapping sources. Among the known populations of Galactic gamma-ray sources and given their extension and number, pulsar wind nebulae (PWNe, and PWN TeV haloes) will be the most affected. We aim to probe source confusion of TeV PWNe in forthcoming CTA data. For this purpose, we performed and analysed simulations of artificially confused PWNe with CTA. As a basis for our simulations, we applied our study to TeV data collected from the H.E.S.S. Galactic Plane Survey for ten extended and two point-like firmly identified PWNe, probing various configurations of source confusion involving different projected separations, relative orientations, flux levels, and extensions among sources. Source confusion, defined here to appear when the sum of the Gaussian width of two sources is larger than the separation between their centroids, occurred in ∼30 per cent of the simulations. For this sample and 0.5° of average separation between sources, we found that CTA can likely resolve up to 60 per cent of those confused sources above 500 GeV. Finally, we also considered simulations of isolated extended sources to see how well they could be matched to a library of morphological templates. The outcome of the simulations indicates a remarkable capability (more than 95 per cent of the cases studied) to match a simulation with the correct input template in its proper orientation

A bibliometric analysis of the Intelligent transportation systems based on science mapping

In this paper we highlight the conceptual structure of the Intelligent Transportation Systems (ITS) research field in the period 1992-2011. To do that, an automatic approach for detecting and visualizing hidden themes and their evolution across a consecutive span of years is applied. This automatic approach, based on co-word analysis, combines performance analysis and science mapping. To show the conceptual evolution of ITS, three consecutive periods have been defined: 1992-2001, 2002-2006, 2007-2011. We have identified that the ITS research has been focused on six main thematic areas: VEHICLE-AND-ROAD-TRACKING, DRIVER-BEHAVIORAND-SAFETY, SCENARIOS-SIMULATION, TRAFFIC-FLOWAND-TRAFFIC-MANAGEMENT, VEHICLE-CONTROL and VEHICLE-NAVIGATION