The humoral immune response to BCG vaccination

Bacillus Calmette Guérin (BCG) is the only currently available vaccine against tuberculosis (TB), but it confers incomplete and variable protection against pulmonary TB in humans and bovine TB (bTB) in cattle. Insights into the immune response induced by BCG offer an underexploited opportunity to gain knowledge that may inform the design of a more efficacious vaccine, which is urgently needed to control these major global epidemics. Humoral immunity in TB and bTB has been neglected, but recent studies supporting a role for antibodies in protection against TB has driven a growing interest in determining their relevance to vaccine development. In this manuscript we review what is known about the humoral immune response to BCG vaccination and re-vaccination across species, including evidence for the induction of specific B cells and antibodies; and how these may relate to protection from TB or bTB. We discuss potential explanations for often conflicting findings and consider how factors such as BCG strain, manufacturing methodology and route of administration influence the humoral response. As novel vaccination strategies include BCG prime-boost regimens, the literature regarding off-target immunomodulatory effects of BCG vaccination on non-specific humoral immunity is also reviewed. Overall, reported outcomes to date are inconsistent, but indicate that humoral responses are heterogeneous and may play different roles in different species, populations, or individual hosts. Further study is warranted to determine whether a new TB vaccine could benefit from the targeting of humoral as well as cell-mediated immunity

A mycobacterial growth inhibition assay (MGIA) for bovine TB vaccine development

Human tuberculosis remains a significant cause of mortality and morbidity throughout the world. The global economic impact of bovine TB is considerable. An effective vaccine would be the most cost-effective way to control both epidemics, particularly in emerging economies. TB vaccine research would benefit from the identification of an immune correlate of protection with which vaccines could be gated at both preclinical and clinical levels. In-vitro mycobacterial growth inhibition assays (MGIA) are functional assays that include most aspects of the complex host immune response to mycobacteria, and they may serve as functional immune correlates for vaccine development. We applied to cattle an MGIA that was developed for use with human and murine samples. Several technical difficulties were encountered while transferring it to the cattle model. However, our data demonstrate that the assay was not discriminatory in cattle and further work is needed before using it for bovine TB vaccine development

Educational Curatorship of Visual Arts: Building Parameters for the Final Years of Middle and High School

This article discusses the educational curatorship of visual arts based on the analysis of a cyclical process of creation, application in the classroom and evaluation of the educational material Violência & heroísmo. Produced and tested within the scope of the teaching, research, and extension project “Mediação da experiência estética na escola”, from the Universidade do Estado de Minas Gerais, this material is based on a series of conceptual and methodological premises that seek to integrate aesthetic and ethical education. Considering the experience acquired in the project and references found in the literature on art education, eight parameters are proposed for educational curatorship focused on middle school, which includes 6th to 9th grades, and high school.Este artículo discute la curaduría educativa de artes visuales basada en el análisis de un proceso cíclico de creación, aplicación en el aula y evaluación del material educativo Violência e heroísmo. Producido y probado en el marco del proyecto de enseñanza, investigación y extensión “Mediação da experiência estética na escola”, de la Universidade do Estado de Minas Gerais, este material se basa en una serie de premisas conceptuales y metodológicas que buscan integrar la educación estética y ética. Considerando la experiencia adquirida en el proyecto y las referencias encontradas en la literatura de enseñanza de arte, se proponen ocho parámetros para la curaduría educativa dirigida a la educación primaria II, que abarca desde el 6º hasta el 9º año, y para la educación secundaria.Este artigo discute a curadoria educativa de artes visuais com base na análise de um processo cíclico de criação, aplicação em sala de aula e avaliação do material educativo Violência & heroísmo. Produzido e testado no âmbito do projeto de ensino, pesquisa e extensão “Mediação da experiência estética na escola”, da Universidade do Estado de Minas Gerais, esse material se sustenta em uma série de premissas conceituais e metodológicas que busca integrar educação estética e ética. Considerando a experiência adquirida no projeto e referências encontradas na literatura de ensino de arte, são propostos oito parâmetros para a curadoria educativa voltada para o ensino fundamental II, que compreende do 6º ao 9º ano, e para o ensino médio

SYBR Green-based Real-Time PCR targeting kinetoplast DNA can be used to discriminate between the main etiologic agents of Brazilian cutaneous and visceral leishmaniases

<p>Abstract</p> <p>Background</p> <p>Leishmaniases control has been hampered by the unavailability of rapid detection methods and the lack of suitable therapeutic and prophylactic measures. Accurate diagnosis, which can distinguish between <it>Leishmania </it>isolates, is essential for conducting appropriate prognosis, therapy and epidemiology. Molecular methods are currently being employed to detect <it>Leishmania </it>infection and categorize the parasites up to genus, complex or species level. Real-time PCR offers several advantages over traditional PCR, including faster processing time, higher sensitivity and decreased contamination risk.</p> <p>Results</p> <p>A SYBR Green real-time PCR targeting the conserved region of kinetoplast DNA minicircles was able to differentiate between <it>Leishmania </it>subgenera. A panel of reference strains representing subgenera <it>Leishmania </it>and <it>Viannia </it>was evaluated by the derivative dissociation curve analyses of the amplified fragment. Distinct values for the average melting temperature were observed, being 78.95°C ± 0.01 and 77.36°C ± 0.02 for <it>Leishmania </it>and <it>Viannia</it>, respectively (p < 0.05). Using the Neighbor-Joining method and Kimura 2-parameters, the alignment of 12 sequences from the amplified conserved minicircles segment grouped together <it>L</it>. (<it>V</it>.) <it>braziliensis </it>and <it>L</it>. (<it>V</it>.) <it>shawii </it>with a bootstrap value of 100%; while for <it>L</it>. (<it>L</it>.) <it>infantum </it>and <it>L</it>. (<it>L</it>.) <it>amazonensis</it>, two groups were formed with bootstrap values of 100% and 62%, respectively. The lower dissociation temperature observed for the subgenus <it>Viannia </it>amplicons could be due to a lower proportion of guanine/cytosine sites (43.6%) when compared to species from subgenus <it>Leishmania </it>(average of 48.4%). The method was validated with 30 clinical specimens from visceral or cutaneous leishmaniases patients living in Brazil and also with DNA samples from naturally infected <it>Lutzomyia </it>spp. captured in two Brazilian localities.</p> <p>Conclusions</p> <p>For all tested samples, a characteristic amplicon melting profile was evidenced for each <it>Leishmania </it>subgenus, corroborating the data from reference strains. Therefore, the analysis of thermal dissociation curves targeting the conserved kinetoplast DNA minicircles region is able to provide a rapid and reliable method to identify the main etiologic agents of cutaneous and visceral leishmaniases in endemic regions of Brazil.</p

To pass or not to pass:modeling the movement and affordance dynamics of a pick and place task

Humans commonly engage in tasks that require or are made more efficient by coordinating with other humans. In this paper we introduce a task dynamics approach for modeling multi-agent interaction and decision making in a pick and place task where an agent must move an object from one location to another and decide whether to act alone or with a partner. Our aims were to identify and model (1) the affordance related dynamics that define an actor's choice to move an object alone or to pass it to their co-actor and (2) the trajectory dynamics of an actor's hand movements when moving to grasp, relocate, or pass the object. Using a virtual reality pick and place task, we demonstrate that both the decision to pass or not pass an object and the movement trajectories of the participants can be characterized in terms of a behavioral dynamics model. Simulations suggest that the proposed behavioral dynamics model exhibits features observed in human participants including hysteresis in decision making, non-straight line trajectories, and non-constant velocity profiles. The proposed model highlights how the same low-dimensional behavioral dynamics can operate to constrain multiple (and often nested) levels of human activity and suggests that knowledge of what, when, where and how to move or act during pick and place behavior may be defined by these low dimensional task dynamics and, thus, can emerge spontaneously and in real-time with little a priori planning

The Influence of Dentin Age and the Presence of Cracks in Removal of the Root Filling Material

Introduction: This study evaluated the removal of the filling material during endodontic retreatment considering the presence of cracks and the dentin age. Methods and Materials: A total of 20 freshly extracted single-rooted teeth were categorized into the following two groups according to the age of the patients: Group Young (Y; aged 18-30 years) and Group Old (O; aged ≥60 years). Each tooth specimen was scanned by microcomputed tomography (micro-CT) subsequently after endodontic retreatment with the Reciproc instruments (REC). The images were analyzed for differences in the volume of dentin cracks and the presence of the filling material in the middle and apical thirds of the teeth among the groups, according to the dentin age. Results: The micro-CT images showed that after retreatment, there were more cracks in the old root dentin than those in the young root dentin, although the difference was not statistically significant (P&gt;0.05). The greatest reduction in the filling material was achieved when the old root dentin with cracks was retreated when compared with that of the young root dentin with cracks, but the difference was not statistically significant (P&gt;0.05). Conclusion: The dentinal age and the presence of cracks were not found to be relevant factors for the removal of the filling material.Keywords: Dentin; Microcomputed Tomography; Retreatmen

Analysis of Genetic Variation in the Bovine SLC11A1 Gene, Its Influence on the Expression of NRAMP1 and Potential Association With Resistance to Bovine Tuberculosis

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a chronic zoonotic disease where host genetics is thought to contribute to susceptibility or resistance. One of the genes implicated is the SLC11A1 gene, that encodes for the natural resistance-associated macrophage protein 1 (NRAMP1). The aim of this study was to identify SLC11A1 polymorphisms and to investigate any resulting functional differences in NRAMP1 expression that might be correlated with resistance/susceptibility to M. bovis infection. Sequencing of the SLC11A1 gene in cDNA isolated from Brown Swiss, Holstein Friesian, and Sahiwal cattle identified five single nucleotide polymorphisms (SNPs) in the coding region, but only one of these (SNP4, c.1066C>G, rs109453173) was present in all three cattle breeds and therefore warranted further investigation. Additionally, variations of 10, 11, and 12 GT repeats were identified in a microsatellite (MS1) in the SLC11A1 3′UTR. Measurement of NRAMP1 expression in bovine macrophages by ELISA showed no differences between cells generated from the different breeds. Furthermore, variations in the length of the MS1 microsatellite did not impact on NRAMP1 protein expression as analyzed by luciferase reporter assay. However, further analysis of the ELISA data identified that the presence of the alternative G allele at SNP4 was associated with increased expression of NRAMP1 in bovine macrophages. Since NRAMP1 has been shown to influence the survival of intracellular pathogens such as M. bovis through the sequestering of iron, it is possible that cattle expressing the alternative G allele might have an increased resistance to bTB through increased NRAMP1 expression in their macrophages

Limiting global-mean temperature increase to 1.5-2°C could reduce the incidence and spatial spread of dengue fever in Latin America

The Paris Climate Agreement aims to hold global-mean temperature well below 2°C and to pursue efforts to limit it to 1.5°C above preindustrial levels. Whilst it is recognized that there are benefits for human health in limiting global warming to 1.5°C, the magnitude with which those societal benefits will be accrued remains unquantified. Crucial to public health preparedness and response is the understanding and quantification of such impacts at different levels of warming. Using dengue in Latin America as a study case, a climatedriven dengue generalized additive mixed model was developed to predict global warming impacts using five different global circulation models, all scaled to represent multiple global-mean temperature assumptions. We show that policies to limit global warming to 2°C could reduce dengue cases by about 2.8 (0.8–7.4) million cases per year by the end of the century compared with a no-policy scenario that warms by 3.7°C. Limiting warming further to 1.5°C, produces an additional drop in cases of about 0.5 (0.2–1.1) million per year. Furthermore, we found that by limiting global warming we can limit the expansion of the disease towards areas where incidence is currently low. We anticipate our study to be a starting point for more comprehensive studies incorporating socioeconomic scenarios and how they may further impact dengue incidence. Our results demonstrate that although future climate change may amplify dengue transmission in the region, impacts may be avoided by constraining the level of warming