Comparison of the effect of autoclaved and non-autoclaved live soil exposure on the mouse immune system : Effect of soil exposure on immune system.

BACKGROUND: . Lack of exposure to the natural microbial diversity of the environment has been linked to dysregulation of the immune system and numerous noncommunicable diseases, such as allergies and autoimmune disorders. Our previous studies suggest that contact with soil material, rich in naturally occurring microbes, could have a beneficial immunoregulatory impact on the immune system in mice and humans. However, differences in the immunomodulatory properties of autoclaved, sterile soil material and non-autoclaved, live soil material have not been compared earlier. RESULTS: . In this study, we exposed C57BL/6 mice to autoclaved and live soil powders that had the same rich microbiota before autoclaving. We studied the effect of the soil powders on the mouse immune system by analyzing different immune cell populations, gene expression in the gut, mesenteric lymph nodes and lung, and serum cytokines. Both autoclaved and live soil exposure were associated with changes in the immune system. The exposure to autoclaved soil resulted in higher levels of Rorγt, Inos and Foxp3 expression in the colon. The exposure to live soil was associated with elevated IFN-γ concentration in the serum. In the mesenteric lymph node, exposure to live soil reduced Gata3 and Foxp3 expression, increased the percentage of CD8 + T cells and the expression of activation marker CD80 in XCR1+SIRPα- migratory conventional dendritic cell 1 subset. CONCLUSIONS: . Our results indicate that exposure to the live and autoclaved soil powders is not toxic for mice. Exposure to live soil powder slightly skews the immune system towards type 1 direction which might be beneficial for inhibiting type 2-related inflammation. Further studies are warranted to quantify the impact of this exposure in experimental type 2 inflammation.

Low IL-13Rα1 expression on mast cells tunes them unresponsive to IL-13.

Cytokine-mediated mast cell regulation enables precise optimization of their own proinflammatory cytokine production. During allergic inflammation, interleukin (IL)-4 regulates mast cell functions, tissue homing, and proliferation, but the direct role of closely related IL-13 for mast cell activation remains unclear. Previous work has shown that mast cells are potent IL-13 producers, but here we show that mouse mast cells do not directly respond to IL-13 by Stat6 activation, as they do not express measurable amount of IL-13 receptor α1 (IL-4Rα1) messenger RNA. Consequently, IL-4 responses are mediated via type I IL-4R (IL-4/IL4Rα/γC), and IL-4-induced Stat6 activation is abolished in γC-deficient mast cells. Type II IL-4R deficiency (IL-13Rα1 knockout) has no effect on IL-4-induced Stat6 activation. In basophils, both IL-4 and IL-13 induce Stat6 activation in wild-type and γC-deficient cells, while in type II IL-4R-deficient basophils, IL-4 signaling is impaired at low ligand concentration. Thus, mast cell and basophil sensitivity to IL-4/IL-13 is different, and in mast cells, lack of IL-13Rα1 expression likely explains their unresponsiveness to IL-13.

How does serif vs sans serif typeface impact the usability of e-commerce websites?

This study tries to find evidence that points towards the best typeface to use in e-commerce websites to maximize usability, trust, loyalty, appearance and overall user satisfaction. We tested the difference between serif and sans serif inside the same font family. A total of 246 volunteers participating in the experiment were asked to complete a set of tasks and a questionnaire on an e-commerce website prototype. We measured task completion time, reading speed and reading comprehension. From the results, using multiple linear regression, we deduced that only gender determines user preferences. Females tend to prefer the serif version of the typeface under study. Although most e-commerce websites use sans serif typefaces, we could not find evidence supporting this decision. The serif and sans serif characteristic inside the same font family does not affect usability on a website, as it was found that it has no impact on reading speed and user preference.

Hacia una herramienta de cribado temprano del trastorno del espectro del autismo (TEA) / Towards an Early Screening Tool for AutismSpectrum Disorder (ASD)

En los últimos años el empleo de la metodología del eye tracking ha sido objeto de estudio de diferentes investigaciones en torno a esta técnica como posible medida objetiva para la detección temprana de indicadores de Trastorno del Espectro Autista (TEA). En el presente estudio se ha elaborado un total de 15 vídeos estímulo divididos en cuatro bloques con el objeto de diseñar una prueba objetiva de sencilla y rápida aplicación, mediante un dispositivo eye tracker, que permita realizar una detección objetiva y muy temprana de indicadores de riesgo de desarrollar TEA; para ello se cuenta con una muestra formada por 148 sujetos, 74 sujetos con indicadores clínicos de TEA y 74 sujetos con desarrollo típico. Los resultados confirman que es posible configurar un software que, tras analizar los registros de mirada de un bebé obtenidos con un dispositivo eye tracker, nos proporcione automáticamente su probabilidad de presentar un “patrón de mirada de máxima atención al objeto (riego de TEA) o un patrón de mirada de recogida de información social (no TEA)”. Con las tareas aquí presentadas, tras analizar la sensibilidad de cada vídeo y cada variable, se han obtenido resultados estadísticamente significativos en cada uno de los vídeos estímulo, por lo que se concluye que la metodología del eye tracking con el empleo de los estímulos aquí diseñados puede operar como método de detección objetivo y eficaz de indicadores de alarma de TEA. (AU)

In recent years, eye-tracking methodology technique has been the objectof study used in different investigations as a potential objective measure of the diagnosis ofASD. In the present study, a total of 15 stimulus videos have been prepared. These are divided into four blocks to design an objective test with simple and rapid application, by using an eye-tracker device, which allows an early diagnosis of ASD. To do so, we measured a sample made up of 148 subjects, 74 subjects with ASD and 74 with typical development. The results confirm that it is possible to configure a software that, after analysing the gaze records of a baby obtained with an eye-tracker device, automatically provides us with its probability of presenting an “ASD or no ASD Gaze Pattern”. With the tasks presented here, after analysing the sensitivity of each video and each variable, statistically significant results have been obtained in each of the stimulus videos. Based on that output, it can be concluded that the eye-tracking methodology with the use of the stimuli designed here can be used as an objective and effective diagnostic method for ASD. (AU)

Effect of inactivated nature-derived microbial composition on mouse immune system.

INTRODUCTION: The hygiene hypothesis suggests that decrease in early life infections due to increased societal-level hygiene standards subjects one to allergic and autoimmune diseases. In this report, we have studied the effect of sterilized forest soil and plant-based material on mouse immune system and gut microbiome. METHODS: Inbred C57Bl/6 mice maintained in normal sterile environment were subjected to autoclaved forest soil-derived powder in their bedding for 1 h a day for 3 weeks. Immune response was measured by immune cell flow cytometry, serum cytokine enzyme-linked immunoassay (ELISA) and quantitative polymerase chain reaction (qPCR) analysis. Furthermore, the mouse gut microbiome was analyzed by sequencing. RESULTS: When compared to control mice, mice treated with soil-derived powder had decreased level of pro-inflammatory cytokines namely interleukin (IL)-17F and IL-21 in the serum. Furthermore, splenocytes from mice treated with soil-derived powder expressed less IL-1b, IL-5, IL-6, IL-13, and tumor necrosis factor (TNF) upon cell activation. Gut microbiome appeared to be stabilized by the treatment. CONCLUSIONS: These results provide insights on the effect of biodiversity on murine immune system in sterile environment. Subjecting mice to soil-based plant and microbe structures appears to elicit immune response that could be beneficial, for example, in type 2 inflammation-related diseases, that is, allergic diseases.

IL-13Rα1 Suppresses Tumor Progression in Two-Stage Skin Carcinogenesis Model by Regulating Regulatory T Cells.

Type 2 inflammation‒related cytokine IL-13 plays a protective role in experimental papilloma induction in mice. To understand the mechanisms by which IL-13 contributes to papilloma formation, we utilized Il13rα1-knockout (KO) mice in a widely used 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoyl phorbol-13-acetate two-stage skin carcinogenesis protocol that mimics the development of squamous cell carcinoma. KO mice developed more papillomas and significantly faster than wild-type mice. Papilloma development reduced regulatory T cells in wild-type mice but substantially less in KO mice. In line with this, IL-2 and IL-10 levels decreased in wild-type mice but not in KO mice. Furthermore, systemic IL-5 and TSLP levels were elevated, whereas IL-22 was decreased during papilloma formation in the skin of KO mice. Polymorphonuclear myeloid‒derived suppressor cells were decreased in the KO mice at the early phase of papilloma induction. We show that IL-13Rα1 protects from papilloma development in chemically induced skin carcinogenesis, and our results provide further insights into the protective role of functional IL-4 and IL-13 signaling through type II IL-4 receptor in tumor development.

Implicit detection of user handedness in touchscreen devices through interaction analysis.

Mobile devices now rival desktop computers as the most popular devices for web surfing and E-commerce. As screen sizes of mobile devices continue to get larger, operating smartphones with a single-hand becomes increasingly difficult. Automatic operating hand detection would enable E-commerce applications to adapt their interfaces to better suit their user's handedness interaction requirements. This paper addresses the problem of identifying the operative hand by avoiding the use of mobile sensors that may pose a problem in terms of battery consumption or distortion due to different calibrations, improving the accuracy of user categorization through an evaluation of different classification strategies. A supervised classifier based on machine learning was constructed to label the operating hand as left or right. The classifier uses features extracted from touch traces such as scrolls and button clicks on a data-set of 174 users. The approach proposed by this paper is not platform-specific and does not rely on access to gyroscopes or accelerometers, widening its applicability to any device with a touchscreen.

A PBMC-Based System to Assess Human T Cell Responses to Influenza Vaccine Candidates In Vitro.

Vaccine development is an expensive and time-consuming process that heavily relies on animal models. Yet, vaccine candidates that have previously succeeded in animal experiments often fail in clinical trials questioning the predictive value of animal models. Alternative assay systems that can add to the screening and evaluation of functional characteristics of vaccines in a human context before embarking on costly clinical trials are therefore urgently needed. In this study, we have established an in vitro system consisting of long-term cultures of unfractionated peripheral blood mononuclear cells (PBMCs) from healthy volunteers to assess (recall) T cell responses to vaccine candidates. We observed that different types of influenza vaccines (whole inactivated virus (WIV), split, and peptide vaccines) were all able to stimulate CD4 and CD8 T cell responses but to different extents in line with their reported in vivo properties. In-depth analyses of different T cell subsets revealed that the tested vaccines evoked mainly recall responses as indicated by the fact that the vast majority of the responding T cells had a memory phenotype. Furthermore, we observed vaccine-induced activation of T follicular helper cells, which are associated with the induction of humoral immune responses. Our results demonstrate the suitability of the established PBMC-based system for the in vitro evaluation of memory T cell responses to vaccines and the comparison of vaccine candidates in a human immune cell context. As such, it can help to bridge the gap between animal experiments and clinical trials and assist in the selection of promising vaccine candidates, at least for recall antigens.

The epithelial barrier-protecting properties of a soy hydrolysate.

Enhancing the epithelial barrier function could be a possible strategy to prevent food allergy or reduce its symptoms. Soy hydrolysates containing bioactive peptides could be instrumental in this. In this study, the protective effects of pretreatment with 6 soy hydrolysates on calcium ionophore A23187-induced TEER reduction were studied in T84 cells. The effects of the most potent soy hydrolysate on tight junction gene expression were studied. In order to identify the underlying pathways involved, the barrier disruptor specificity of the effect was studied by comparing the protective effects on TEER and Lucifer Yellow flux after the exposure to barrier disruptors that work via different intracellular pathways, i.e. the disruptors A23187, mellitin, and deoxynivalenol (DON). Preincubation with one of the six hydrolysates protected the epithelial cells from a decrease in TEER induced by A23187 (restored to 105% of the starting point, while A23187 alone decreased to 53% of the starting value) and mellitin (restored to 11% of the starting point, while mellitin alone decreased to 3.8% of the starting value). This soy hydrolysate was found to increase claudin-1 and decrease claudin-2 expression. The protective effect of the hydrolysate on TEER was specific for the barrier disruptors A23187 and mellitin, but was not observed for DON. This observation suggests that the soy hydrolysate may act via PKC isoforms, which are known to lead to changes in the expression of claudin-1 and 2. Our data suggest that specific soy hydrolysates may be designed to strengthen the epithelial barrier which might be instrumental in the management of the barrier function in individuals at risk of developing food allergy.