Interleukin 18 maintains a long-standing inflammation in coeliac disease patients

Producción CientíficaDietary gluten induces an early response in the intestine of coeliac disease patients (CD), within a few hours, and this is driven by high levels of proinflammatory cytokines, including IFNg and IL-15, as has been thoroughly shown by gluten stimulation of biopsy explants. Our aim was to identify the immune mediators involved in the long-standing inflammation in untreated CD patients at diagnosis. mRNA and protein levels of TNFa, IL-12(p35), IL-12(p40), IL-15, IL-18 and IL-23(p19) were quantified in biopsies from active CD patients, CD patients on a gluten-free diet (GFD), healthy controls, and patients with non-CD inflammation and mild histological changes in the intestine. Biopsies from CD patients on a GFD were also stimulated in vitro with gliadin, and protein expression of IL-15 and IL-18 was analysed. Levels of IL-12 and IL-23 mRNA are nearly absent, and TNFa levels remain unchanged among different groups. Both the active and inactive forms of IL-18 protein have been found in all samples from active CD, and protein expression was only localized within the crypts. Levels of IL-15 mRNA remain unchanged, and protein expression, localized within the lamina propria, is found in a small number of samples. In vitro stimulation with gluten induces the expression of IL-15 and IL-18. In active CD, the early response following gluten intake characterized by high IFNg levels is driven by IL-18, and probably IL-15, and this alternates with periods of long-standing inflammation with moderate IFNg levels, maintained by IL-18 alone

Wildfire-Induced Changes in Flood Risk in Recreational Canyoning Areas: Lessons from the 2017 Jerte Canyons Disaster

Few studies identify potential hazards affecting canyoning. This activity has an increasing number of practitioners, and hence, a greater number of people are affected by potential natural hazards. Mountain rivers are located in places subject to several hydrological hazards; the risks are mostly connected with floods produced by intense storms or dam operation, but changes in hydrological factors may alter the usual basin behavior given even moderate or less severe storms. Data about flood events and the peak discharge of the 2017 flood in the two studied canyons were collected by means of a quick field survey of water levels after the flood, hydrological modeling, and soil analysis. The present research shows the dramatic consequences of a two-year return period storm affecting a guided group of canyoneers. A previous wildfire changed the soil, leading to hydrophobic conditions and increasing the flood effects. Peak discharge increased from 2 m3 s−1 in normal conditions to 12 m3 s−1 under a hydrophobic regime related to wildfire occurrence; moreover, a reduction in the time of concentration also occurred, pointing to a more powerful and dangerous flood event. In this paper, some hydrological recommendations are highlighted that will be helpful in recreational canyoning management, leading to safer practice

Torrential floods in ephemeral streams: wadies and alluvial fans

Los sistemas torrenciales se caracterizan por corrientes efímeras pero súbitas, que alcanzan rápidamente su caudal punta e incorporan abundante carga sólida que depositan también de forma brusca al desvanecerse la crecida. Se manifiestan desde formas métricas de ladera o cabecera (cárcavas y barrancos) hasta kilométricas, como ramblas y grandes abanicos aluviales. Pero su morfología y dinámica son equiparables: cuenca de recepción muy activa, corto canal de transferencia y zona de producción, generalmente abanico. Estas tres zonas se repiten a diferentes escalas dentro de la misma línea de drenaje, generando depósitos sobre los que el cauce se vuelve a encajar o que abandona migrando a zonas más deprimidas. Esta dinámica esporádica y cambiante, su capacidad erosiva, así como los altos caudales líquidos y sólidos, confieren a estos sistemas una gran peligrosidadThe torrential stream dynamics is characterized by ephemeral but sudden streamflows (flashfloods) that quickly reach their peak flow, entraining abundant load that also deposits abruptly when the flood vanishes. They offer wide range morphologies, from metric forms (gullies) on headwaters and slopes, to kilometric ones like ramblas (arroyos) and large alluvial fans. But their morphology and dynamics are similar: very active reception basin, short transference channel and widespread production area, commonly an alluvial fan. These three zones may be recurring at different scales within the same drainage line, generating deposits on which the channel either entrenches or abandons, migrating towards more depressed areas. This erratic and changing dynamics, the erosive capacity, as well as the high load and discharge, confer to these systems a great hazardDepto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu

High-pressure synthesis, structural and complex magnetic properties of the ordered double perovskite Pb2NiReO6

The ordered double perovskite Pb2NiReO6 has been prepared at 6 GPa and temperatures ranging from 1273 to 1373 K. Its crystal structure determined by X-ray powder diffraction and selected area electron diffraction shows monoclinic symmetry with centrosymmetric space group I2/m (a = 5.6021(1) Å, b = 5.6235(1) Å, c = 7.9286(1) Å and β = 90.284°(1)). High angle annular dark field microscopy studies reveal the existence of compositional microdomains. The compound displays a re-entrant spin-glass transition from a ferrimagnetic ordering below TN 37 K between the Re+5 and Ni+3 (high spin configuration) magnetic sublattices to a spin-glass configuration. Magnetic field dependent magnetization measurements revealed wasp-waisted hysteresis loops at 5 K. These shaped features originate from the antiferromagnetic/ferromagnetic (AFM/FM) competing interactions

Tachyphylaxis to β2-agonists in Spanish asthmatic patients could be modulated by β2-adrenoceptor gene polymorphisms

Producción CientíficaThe study of determinants of asthma is a subject of much interest currently, especially the pharmacogenetic aspects of asthma management. Genetic polymorphisms affecting amino-acids at positions 16 and 27 within β2-adrenoceptor (β2AR) gene have been implicated in the asthma phenotypes and influence on the variability observed in response to use of bronchodilator agents used in the treatment of asthma. Whether these polymorphisms alter the bronchoprotection response to -agonist treatment in Spanish asthmatic population is unknown. The aim of this study was to investigate whether genetic polymorphisms within β2AR gene modulate the clinical outcomes of the individual response to β2-agonist therapy and the development of desensitization in Spanish asthmatic patients.Fondo de Investigación Sanitaria y Ministerio de Sanidad, Consumo y Bienestar Social (FIS00648 and 02/3068)Junta de Castilla y León (VA032/04

Concrete lining of the core-foundation interface to prevent internal erosion: An efficiency assessment

The core-foundation interface of the embankment dams requires particular attention during design and construction, and specific surveillance during operation. A deficient treatment of this area may facilitate seepage along the interface and erosion of the core-base which, in turn, could lead to a major internal erosion process. Several dam incidents and failures were initiated following this mechanism. For instance, an imperfect core-foundation treatment was one of the causes of the Teton Dam collapse in 1976. Therefore, it is clear that this surface requires specific study and treatment. Stripping, cleaning, removing unsuitable materials and shaping, are considered the minimum operations for preparing it. In addition to this, a gallery beneath the core-base could be used. This gallery is an excellent safety element, as it provides a direct access to foundation, facilitating inspection and grouting during operation. Hence, despite its construction cost, is a usual arrange on impervious core dams. However, depending on the specific lithology and stratification, this option could be replaced by a concrete lining of the core-foundation interface. An option that could be advantageous when the following circumstances concur: the foundation is not erodible and no additional grouting treatment is predictable; and the excavation of the trench which houses the gallery would damage or decompress the rock, deteriorating the foundation conditions. The risk of contact erosion at the core-foundation interface increases in those sites where the bed?s strike is orthogonal to the dam axis. In such case seepage may flow along the joints eroding the clay particles of the core-base . Internal erosion through the contact when these adverse geological conditions appear could be prevented by placing a concrete lining . This concrete protection works as a barrier, separating the core particles from the beds and joints. This measure, that could be a cost-effective alternative to galleries, was used to prevent internal erosion on Andévalo dam. It is a rockfill dam with a thin clay core, 80 m high and 1862 m long, with one of the largest Spanish reservoirs (1025 hm3). Its construction was completed in 2002 and its first filling has been finished in 2013. This paper presents that experience, describing the foundation characteristics, the design features and the performance assessment of the lining during the impoundment

Interleukin 18 maintains a long-standing inflammation in coeliac disease patients

Producción CientíficaDietary gluten induces an early response in the intestine of coeliac disease patients (CD), within a few hours, and this is driven by high levels of proinflammatory cytokines, including IFNg and IL-15, as has been thoroughly shown by gluten stimulation of biopsy explants. Our aim was to identify the immune mediators involved in the long-standing inflammation in untreated CD patients at diagnosis. mRNA and protein levels of TNFa, IL-12(p35), IL-12(p40), IL-15, IL-18 and IL-23(p19) were quantified in biopsies from active CD patients, CD patients on a gluten-free diet (GFD), healthy controls, and patients with non-CD inflammation and mild histological changes in the intestine. Biopsies from CD patients on a GFD were also stimulated in vitro with gliadin, and protein expression of IL-15 and IL-18 was analysed. Levels of IL-12 and IL-23 mRNA are nearly absent, and TNFa levels remain unchanged among different groups. Both the active and inactive forms of IL-18 protein have been found in all samples from active CD, and protein expression was only localized within the crypts. Levels of IL-15 mRNA remain unchanged, and protein expression, localized within the lamina propria, is found in a small number of samples. In vitro stimulation with gluten induces the expression of IL-15 and IL-18. In active CD, the early response following gluten intake characterized by high IFNg levels is driven by IL-18, and probably IL-15, and this alternates with periods of long-standing inflammation with moderate IFNg levels, maintained by IL-18 alone

Is it true coeliacs do not digest gliadin ?. Degradation pattern of gliadin in coeliac disease small intestinal mucosa

Prolyl-endopeptidase supplementation has been proposed to favour gliadin degradation as an alternative treatment for coeliac disease (CD), although the real usefulness of this therapy in vivo is still under discussion. 1 However, our data point to alternative treatments aiming to modify the intestinal microbiota in patients with CD by the use of probiotics and/or prebiotics. We propose that the induction of gliadin proteolysis in the human gut might not be the solution but the origin of CD

Human corneal fibroblast migration and ECM synthesis during stromal repair: Role played by PDGF-BB, bFGF, and TGFβ1 (HCFs migration and ECM synthesis during stromal repair: GFs effects)

Producción CientíficaThe development of treatments that modulate corneal wound healing to avoid fibrosis during tissue repair is important for the restoration of corneal transparency after an injury. To date, few studies have studied the influence of growth factors (GFs) on human corneal fibroblast (HCF) expression of extracellular matrix (ECM) proteins such as collagen types I and III, proteoglycans such as perlecan, or proteins implicated in cellular migration such as α5β1-integrin and syndecan-4. Using in vitro HCFs, we developed a mechanical wound model to study the influence of the GFs basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-BB), and transforming growth factor beta 1 (TGFβ1) on ECM protein production and cellular migration. Our results show that mechanical wounding provokes the autocrine release of bFGF and TGFβ1 at different time points during the wound closure. The HCF response to PDGF-BB was a rapid closure due to fast cellular migration associated with a high focal adhesion replacement and a high expression of collagen and proteoglycans, producing a non-fibrotic healing. bFGF stimulated non-fibrotic ECM production and limited the migration process. Finally, TGFβ1 induced expression of the fibrotic markers collagen type III and α5β1 integrin, and it inhibited cellular migration due to the formation of focal adhesions with a low turnover rate. The novel in vitro HCF mechanical wound model can be used to understand the role played by GFs in human corneal repair. The model can also be used to test the effects of different treatments aimed at improving the healing process

Human colon-derived soluble factors modulate gut microbiota composition

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).-- et al.The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune - IL-15-and microbiota - LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition.BS and AH were recipients of a Ramón y Cajal postdoctoral contract and a FPI grant, respectively, from the Spanish Ministry of Economy and Competitiveness. The authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC). This research was funded by the BBSRC Institute Strategic Programme for Gut Health and Food Safety BB/J004529/1. This research was also funded by Grants AGL2010-14952 and AGL2013-44039-R from the Spanish “Plan Estatal de I + D + i,” and by Grant EM2014/046 from the “Plan galego de investigación, innovación e crecemento 2011-2015.”Peer Reviewe