Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor γ activity

Colitis involves immune cell–mediated tissue injuries, but the contribution of epithelial cells remains largely unclear. Vanin-1 is an epithelial ectoenzyme with a pantetheinase activity that provides cysteamine/cystamine to tissue. Using the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis model we show here that Vanin-1 deficiency protects from colitis. This protection is reversible by administration of cystamine or bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor (PPAR)γ antagonist. We further demonstrate that Vanin-1, by antagonizing PPARγ, licenses the production of inflammatory mediators by intestinal epithelial cells. We propose that Vanin-1 is an epithelial sensor of stress that exerts a dominant control over innate immune responses in tissue. Thus, the Vanin-1/pantetheinase activity might be a new target for therapeutic intervention in inflammatory bowel disease

Palaeontological data about the climatic trends from Chattian to present along the Northeastern Atlantic frontage

Climatic changes that affected the Northeastern Atlantic frontage are analyzed on the basis of the evolution of faunas and floras from the late Oligocene onwards. The study deals with calcareous nannoplankton, marine micro- and macrofaunas, some terrestrial vertebrates and vegetal assemblages. The climate, first tropical, underwent a progressive cooling (North-South thermic gradient). Notable climatic deteriorations (withdrawal towards the South or disappearance of taxa indicative of warm climate and appearance of "cold" taxa) are evidenced mainly during the Middle Miocene and the late Pliocene. Faunas and floras of modern pattern have regained, after the Pleistocene glaciations, a new climatic ranging of a temperate type in the northern part

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner

Uncovering the Oppenheimer Siddur: using scientific analysis to reveal the production process of a medieval illuminated Hebrew manuscript

The aim of this research was to use non-invasive scientifc analysis to uncover evidence of the planning process and relationship between pigments used in text copying and artwork production in the Oppenheimer Siddur (Oxford Bodleian Library MS Opp. 776), an illuminated 15th-century Hebrew prayer book. In many medieval Hebrew illuminated manuscripts, the authorship of the artwork is unknown. This manuscript’s colophon states that it was copied by its scribe-owner for personal family use but does not confrm who was responsible for the artwork. Prior deductive analysis suggested that the scribe-owner may also have been the manuscript’s artist, based on common motifs and an apparent shared colour palette appearing in both texts and artwork. Visual examination using high resolution digital images also identifed points of contact between pigments used in the manuscript’s texts and artwork, raising questions about the pigment application sequence, and concurrent versus sequential text copying and artwork production. An in-house developed remote spectral imaging system (PRISMS) with 10 flters spanning the spectral range from 400 to 880 nm was modifed for close-range application to image two of the folios to examine the sequence of production, identify the pigments and compare the materials used for the illumination and the text. Optical microscopy and Fourier Transform Infrared spectroscopy in the attenuated total refection mode (FTIR-ATR) were used directly on the folios to complement the spectral imaging data in binding media and pigment identifcation. The results revealed close matches in refectance spectra for the colorants and inks used in both text copying and illuminations, suggesting that the same mixture of colorants and inks have been used. The spectral imaging in the near infrared bands revealed a hidden underdrawing, indicating a design change during production of the manuscript, and the outlining of letters prior to coloured pigment being applied. The pigment use, the variation in the binder for diferent pigments and some elements of its production were found to be consistent with those described in historical sources. The evidence from this study supports the hypothesis that the scribe applied pigments for the manuscript’s artwork at the same time he did some of the scribal work which has implications for understandings of Jewish medieval visual cultures

Effect of hot calendering on physical properties and water vapor transfer resistance of bacterial cellulose films

This work investigates the effect of hot calendering on bacterial cellulose (BC) films properties, aiming the achievement of good transparency and barrier property. A comparison was made using vegetal cellulose (VC) films on a similar basis weight of around 40 g.m-2. The optical-structural, mechanical and barrier property of BC films were studied and compared with those of highly beaten VC films. The Youngs moduli and tensile index of the BC films are much higher than those obtained for VC (14.5 16.2 GPa vs 10.8 8.7 GPa and 146.7 64.8 N.m.g-1 vs 82.8 40.5 N.m.g-1), respectively. Calendering increased significantly the transparency of BC films from 53.0 % to 73.0 %. The effect of BC ozonation was also studied. Oxidation with ozone somewhat enhanced the brightness and transparency of the BC films, but at the expenses of slightly lower mechanical properties. BC films exhibited a low water vapor transfer rate, when compared to VC films and this property decreased by around 70 % following calendering, for all films tested. These results show that calendering could be used as a process to obtain films suitable for food packaging applications, where transparency, good mechanical performance and barrier properties are important. The BC films obtained herein are valuable products that could be a good alternative to the highly used plastics in this industry.The authors thank FCT (Fundação para a Ciência e Tecnologia) and FEDER (Fundo Europeu de Desenvolvimento Regional) for the financial support of the project FCT PTDC/AGR-FOR/3090/2012— FCOMP-01-0124-FEDER-027948 and the awarding of a research grant for Vera Costa

Bio++: Efficient Extensible Libraries and Tools for Computational Molecular Evolution

Efficient algorithms and programs for the analysis of the ever-growing amount of biological sequence data are strongly needed in the genomics era. The pace at which new data and methodologies are generated calls for the use of pre-existing, optimized—yet extensible—code, typically distributed as libraries or packages. This motivated the Bio++ project, aiming at developing a set of C++ libraries for sequence analysis, phylogenetics, population genetics, and molecular evolution. The main attractiveness of Bio++ is the extensibility and reusability of its components through its object-oriented design, without compromising the computer-efficiency of the underlying methods. We present here the second major release of the libraries, which provides an extended set of classes and methods. These extensions notably provide built-in access to sequence databases and new data structures for handling and manipulating sequences from the omics era, such as multiple genome alignments and sequencing reads libraries. More complex models of sequence evolution, such as mixture models and generic n-tuples alphabets, are also included

Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2β1 Integrin Collagen Receptor

Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex) is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders. In this study, we determined whether Sb could accelerate enterocyte migration. Cell migration was determined in Sb force-fed C57BL6J mice and in an in vitro wound model. The impact on α2β1 integrin activity was assessed using adhesion assays and the analysis of α2β1 mediated signaling pathways both in vitro and in vivo. We demonstrated that Sb secretes compounds that enhance the migration of enterocytes independently of cell proliferation. This enhanced migration was associated with the ability of Sb to favor cell-extracellular matrix interaction. Indeed, the yeast activates α2β1 integrin collagen receptors. This leads to an increase in tyrosine phosphorylation of cytoplasmic molecules, including focal adhesion kinase and paxillin, involved in the integrin signaling pathway. These changes are associated with the reorganization of focal adhesion structures. In conclusion Sb secretes motogenic factors that enhance cell restitution through the dynamic regulation of α2β1 integrin activity. This could be of major importance in the development of novel therapies targeting diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases

Vanin-1 Pantetheinase Drives Smooth Muscle Cell Activation in Post-Arterial Injury Neointimal Hyperplasia

The pantetheinase vanin-1 generates cysteamine, which inhibits reduced glutathione (GSH) synthesis. Vanin-1 promotes inflammation and tissue injury partly by inducing oxidative stress, and partly by peroxisome proliferator-activated receptor gamma (PPARγ) expression. Vascular smooth muscle cells (SMCs) contribute to neointimal hyperplasia in response to injury, by multiple mechanisms including modulation of oxidative stress and PPARγ. Therefore, we tested the hypothesis that vanin-1 drives SMC activation and neointimal hyperplasia. We studied reactive oxygen species (ROS) generation and functional responses to platelet-derived growth factor (PDGF) and the pro-oxidant diamide in cultured mouse aortic SMCs, and also assessed neointima formation after carotid artery ligation in vanin-1 deficiency. Vnn1−/− SMCs demonstrated decreased oxidative stress, proliferation, migration, and matrix metalloproteinase 9 (MMP-9) activity in response to PDGF and/or diamide, with the effects on proliferation linked, in these studies, to both increased GSH levels and PPARγ expression. Vnn1−/− mice displayed markedly decreased neointima formation in response to carotid artery ligation, including decreased intima:media ratio and cross-sectional area of the neointima. We conclude that vanin-1, via dual modulation of GSH and PPARγ, critically regulates the activation of cultured SMCs and development of neointimal hyperplasia in response to carotid artery ligation. Vanin-1 is a novel potential therapeutic target for neointimal hyperplasia following revascularization

Diffusion coefficient in a semi-dilute solution measured by concentration gradient technique and compared to quasielastic light scattering results

We show experimentally that the translational diffusion coefficient of a semi-dilute solution does not depend on the time scale over which the measurement is made. As a consequence isothermal and adiabatic compressibilities are identical in semi-dilute solutions, and this diffusion coefficient can be viewed either as a cooperative diffusion coefficient in the pseudo-gel model, or as a diffusion coefficient of a coil without hydrodynamic interactions between its elements.Nous montrons expérimentalement, que le coefficient de diffusion translationnel d'une solution semidiluée est indépendant de l'échelle de temps sur laquelle s'effectue la mesure, Ceci impose que, dans ce cas, les compressibilités isotherme et adiabatique soient identiques, et l'on peut interpréter le coefficient de diffusion — soit comme résultant d'un mouvement coopératif d'un pseudogel — soit comme résultant du déplacement d'une chaine sans interaction hydrodynamique entre ses éléments