Dysbiosis in a canine model of human fistulizing Crohn's disease

Crohn's disease (CD) is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance toward the commensal microbiota. On average, 29.5% and 42.7% CD patients experience perianal complications at 10 and 20 y after diagnosis, respectively. Perianal CD (pCD) result in high disease burden, diminished quality of life, and elevated health-care costs. Overall pCD are predictors of poor long-term outcomes. Animal models of gut inflammation have failed to fully recapitulate the human manifestations of fistulizing CD. Here, we evaluated dogs with spontaneous canine anal furunculosis (CAF), a disease with clinical similarities to pCD, as a surrogate model for understanding the microbial contribution of human pCD pathophysiology. By comparing the gut microbiomes between dogs suffering from CAF (CAF dogs) and healthy dogs, we show CAF-dog microbiomes are either very dissimilar (dysbiotic) or similar (healthy-like), yet unique, to healthy dog's microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance of Bacteroides vulgatus and Escherichia coli and a decreased abundance of Megamonas species and Prevotella copri. Our results mirror what have been reported in previous microbiome studies of patients with CD; particularly, CAF dogs exhibited two distinct microbiome composition: dysbiotic and healthy-like, with determinant bacterial taxa such as E. coli and P. copri that overlap what it has been found on their human counterpart. Thus, our results support the use of CAF dogs as a surrogate model to advance our understanding of microbial dynamics in pCD

Brote de gastroenteritis por agua potable de suministro público

Introducción: La potabilidad del agua induce a descartar el posible origen hídrico de los brotes. El objetivo fue investigar un brote de gastroenteritis por agua potable de suministro público. Métodos: Después de la notificación de un brote de gastroenteritis en el municipio de Baqueira (Valle de Arán) se diseñó un estudio epidemiológico de cohortes retrospectivo. Mediante un muestreo sistemático se eligió a 87 personas hospedadas en los hoteles y a 62 alojadas en diferentes apartamentos. Se recogió información sobre 4 factores (consumo de agua de la red, bocadillos, agua y alimentos en las pistas de esquí) y presencia de síntomas. Se determinó la existencia de cloro, se analizó el agua de la red y se realizó un coprocultivo a 4 enfermos. La implicación de cada factor se determinó con el riesgo relativo (RR) y su intervalo de confianza (IC) del 95%. Resultados: La incidencia de gastroenteritis fue del 51,0% (76/149). Los porcentajes de los síntomas fueron los siguientes: fiebre, 27,0%; diarrea, 87,5%; náuseas, 50,7%; vómitos, 30,3%, y dolor abdominal, 80,0%. El único factor que presentó un riesgo estadísticamente significativo fue el consumo de agua de la red (RR = 11,0; IC del 95%, 1,6-74,7). La calificación sanitaria del agua fue de potabilidad. Se observó un defecto de situación del clorador en el depósito, que fue corregido. Se recomendó incrementar aún más las concentraciones de cloro, lo cual se acompañó de una disminución de los casos. Los coprocultivos de los 4 enfermos fueron negativos para las enterobacterias investigadas. Conclusiones: El estudio demuestra la posibilidad de presentación de brotes hídricos por agua cualificada como potable y sugiere la necesidad de mejorar la investigación microbiológica (determinación de protozoos y virus) en este tipo de brotes

Rendering and interactive virtual prototyping

Application of virtual reality techniques to architectural design allows to decrease the conception cost by virtual prototyping . In order to make the prototype usable for the decision process, an accurate lighting simulation must be done . The important need of interactivity in the manipulation of the prototype, for virtual walk-through or for modifying the prototype, implies a time efficient lighting simulation in the virtual world . Generaly, lighting simulation used in this type of application used empirical models whose only advantage is the real-time simulation . Texture mapping is a technique widely used to increase the quality of the simulation but without reaching the needed accuracy for architectural design . The radiosity model, based on the radiative transfers theory, allows to determine the lighting of a scene in a view-independent way. This model's limitation is its complexity. Also, its use in a virtual prototyping application needs the definition of adapted evaluation method . In this paper we propose a software environment, organised around two simulation kernels - Visualisation-interaction and Lighting simulation - that allows the use of the radiosity model during the design of an architectural environment. We present more precisely the design and the implementation of the lighting simulation module, called Eclairagiste, which objective is to ensure the maximum lighting accuracy at each instant . The Eclairagiste module, defined as an entity of the virtual reality programming environment VIPER, uses a multi-resolution representation of the radiosity function and relie on resolution method derived from hierarchical radiosity.L'application des techniques de réalité virtuelle à l'architecture permet de diminuer les coûts de conception du projet par prototypage virtuel. Afin de rendre le prototype développé exploitable pour la prise de décision, une simulation convenable de l'éclairage doit être effectuée. Le besoin important d'interactivité dans la manipulation du prototype, soit pour des déplacements de l'utilisateur dans le monde virtuel, soit pour des modifications géométriques apportées à ce monde, nécessite un éclairage très rapide de la scène. Actuellement, les modèles d'éclairage utilisés, dans ce type d'application, sont des approximations empiriques des modèles physiques dont le seul avantage est la rapidité d'évaluation. Les textures sont largement utilisées pour augmenter le réalisme des scènes virtuelles mais le niveau de simulation de l'éclairage reste grossier. Le modèle de radiosité, modèle physique fondé sur l'évaluation des transferts radiatifs dans une scène, permet de déterminer, de façon indépendante du point de vue, la valeur du signal lumineux en tout point de la scène, en tenant compte de toute la scène (illumination globale). Le principal inconvénient de ce modèle étant le temps de calcul nécessaire à sa résolution, son utilisation dans une application de prototypage passe par la définition de techniques de résolution adaptées. Nous proposons dans cet article une plate-forme logicielle, organisée autour de deux noyaux de simulation - Visualisation-Interaction et Simulation de l'éclairage -, permettant d'utiliser le modèle de radiosité lors de la conception par prototypage virtuel d'environnements architecturaux. Nous présentons plus particulièrement la conception et l'implantation d'un module de simulation de l'éclairage, appelé éclairagiste, dont l'objectif est d'assurer le réalisme maximum à chaque instant. Le module éclairagiste, définit comme une entité de l'environnement de programmation d'applications de réalité virtuelle VIPER, utilise une modélisation multi-échelle de la radiosité et repose sur une méthode de résolution dérivée de la radiosité hiérarchique

CosmoHub: Interactive exploration and distribution of astronomical data on Hadoop

We present CosmoHub (https://cosmohub.pic.es), a web application based on Hadoop to perform interactive exploration and distribution of massive cosmological datasets. Recent Cosmology seeks to unveil the nature of both dark matter and dark energy mapping the large-scale structure of the Universe, through the analysis of massive amounts of astronomical data, progressively increasing during the last (and future) decades with the digitization and automation of the experimental techniques. CosmoHub, hosted and developed at the Port d'Informació Científica (PIC), provides support to a worldwide community of scientists, without requiring the end user to know any Structured Query Language (SQL). It is serving data of several large international collaborations such as the Euclid space mission, the Dark Energy Survey (DES), the Physics of the Accelerating Universe Survey (PAUS) and the Marenostrum Institut de Ciències de l'Espai (MICE) numerical simulations. While originally developed as a PostgreSQL relational database web frontend, this work describes the current version of CosmoHub, built on top of Apache Hive, which facilitates scalable reading, writing and managing huge datasets. As CosmoHub's datasets are seldomly modified, Hive it is a better fit. Over 60 TiB of cataloged information and 50×10 astronomical objects can be interactively explored using an integrated visualization tool which includes 1D histogram and 2D heatmap plots. In our current implementation, online exploration of datasets of 10 objects can be done in a timescale of tens of seconds. Users can also download customized subsets of data in standard formats generated in few minutes.CosmoHub has been partially funded through projects of the Spanish national program “Programa Estatal de I + D + i” of the Spanish government. The support of the ERDF fund is gratefully acknowledged

Brote de gastroenteritis por agua potable de suministro público

ResumenIntroducciónLa potabilidad del agua induce a descartar el posible origen hídrico de los brotes. El objetivo fue investigar un brote de gastroenteritis por agua potable de suministro público.MétodosDespués de la notificación de un brote de gastroenteritis en el municipio de Baqueira (Valle de Arán) se diseñó un estudio epidemiológico de cohortes retrospectivo. Mediante un muestreo sistemático se eligió a 87 personas hospedadas en los hoteles y a 62 alojadas en diferentes apartamentos. Se recogió información sobre 4 factores (consumo de agua de la red, bocadillos, agua y alimentos en las pistas de esquí) y presencia de síntomas. Se determinó la existencia de cloro, se analizó el agua de la red y se realizó un coprocultivo a 4 enfermos. La implicación de cada factor se determinó con el riesgo relativo (RR) y su intervalo de confianza (IC) del 95%.ResultadosLa incidencia de gastroenteritis fue del 51,0% (76/149). Los porcentajes de los síntomas fueron los siguientes: fiebre, 27,0%; diarrea, 87,5%; náuseas, 50,7%; vómitos, 30,3%, y dolor abdominal, 80,0%. El único factor que presentó un riesgo estadísticamente significativo fue el consumo de agua de la red (RR = 11,0; IC del 95%, 1,6-74,7). La calificación sanitaria del agua fue de potabilidad. Se observó un defecto de situación del clorador en el depósito, que fue corregido. Se recomendó incrementar aún más las concentraciones de cloro, lo cual se acompañó de una disminución de los casos. Los coprocultivos de los 4 enfermos fueron negativos para las enterobacterias investigadas.ConclusionesEl estudio demuestra la posibilidad de presentación de brotes hídricos por agua cualificada como potable y sugiere la necesidad de mejorar la investigación microbiológica (determinación de protozoos y virus) en este tipo de brotes.AbstractIntroductionThe chlorination of public water supplies has led researchers to largely discard drinking water as a potential source of gastroenteritis outbreaks. The aim of this study was to investigate an outbreak of waterborne disease associated with drinking water from public supplies.MethodsA historical cohort study was carried out following notification of a gastroenteritis outbreak in Baqueira (Valle de Arán, Spain). We used systematic sampling to select 87 individuals staying at hotels and 67 staying in apartments in the target area.Information was gathered on four factors (consumption of water from the public water supply, sandwiches, water and food in the ski resorts) as well as on symptoms. We assessed residual chlorine in drinking water, analyzed samples of drinking water, and studied stool cultures from 4 patients. The risk associated with each water source and food type was assessed by means of relative risk (RR) and 95% confidence intervals (CI).ResultsThe overall attack rate was 51.0% (76/149). The main symptoms were diarrhea 87.5%, abdominal pain 80.0%, nausea 50.7%, vomiting 30.3%, and fever 27.0%. The only factor associated with a statistically significant risk of disease was consumption of drinking water (RR = 11.0; 95% CI, 1.6-74.7). No residual chlorine was detected in the drinking water, which was judged acceptable. A problem associated with the location of the chlorinator was observed and corrected. We also recommended an increase in chlorine levels, which was followed by a reduction in the number of cases. The results of stool cultures of the four patients were negative for enterobacteria.ConclusionsThis study highlights the potential importance of waterborne outbreaks of gastroenteritis transmitted through drinking water considered acceptable and suggests the need to improve microbiological research into these outbreaks (viruses and protozoa detection)

Recent advances in food allergy

Food allergy is a public health issue that has significantly increased worldwide in the past decade, affecting consumers’ quality of life and making increasing demands on health service resources. Despite recent advances in many areas of diagnosis and treatment, our general knowledge of the basic mechanisms of the disease remain limited i.e., not at pace with the exponential number of new cases and the explosion of new technologies. Many important key questions remain: What defines a major allergen? Why do some individuals develop food allergies and others do not? Which are the environmental factors? Could the environmental factors be monitored through epigenetics or modified by changes in the microbiome? Can tolerance to food be induced? Why are some foods more likely to trigger allergies than others? Does the route and timing of exposure have any role on sensitization? These and many other related questions remain unanswered. In this short review some of these topics are addressed in the light of recent advances in the area

Vital function of PRELI and essential requirement of its LEA motif

Proteins containing the late embryogenesis abundant (LEA) motif comprise a conserved family, postulated to act as cell protectors. However, their function and mechanisms of action remain unclear. Here we show that PRELI, a mammalian LEA-containing homolog of yeast Ups1p, can associate with dynamin-like GTPase Optic Atrophy-1 (OPA1) and contribute to the maintenance of mitochondrial morphology. Accordingly, PRELI can uphold mitochondrial membrane potential (ΔΨm) and enhance respiratory chain (RC) function, shown by its capacity to induce complex-I/NADH dehydrogenase and ATP synthase expression, increase oxygen consumption and reduce reactive oxygen species (ROS) production. PRELI can also inhibit cell death induced by STS, TNF-α or UV irradiation. Moreover, in vitro and in vivo dominant-negative overexpression of mutant PRELI/LEA− (lacking the LEA motif) and transient in vitro PRELI-specific knockdown can render lymphocytes vulnerable to apoptosis, cause mouse embryo lethality and revert the resistance of lymphoma cells to induced death. Collectively, these data support the long-presumed notion of LEA protein-dependent mechanisms of cytoprotection and suggest that PRELI interacts with OPA1 to maintain mitochondria structures intact, sustain balanced ion−/proton+ gradients, promote oxidative phosphorylation reactions, regulate pro- and antiapoptotic protein traffic and enable cell responses to induced death. These findings may help to understand how bioenergetics is mechanistically connected with cell survival cues

Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (<it>KLK7</it>/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells.</p> <p>Methods</p> <p>The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using <it>in vitro </it>degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2.</p> <p>Results</p> <p>The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells.</p> <p>Conclusion</p> <p>A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using <it>in vitro </it>degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion.</p