Environmental Degradation, Climate Change and Migration: from Research to Policy-Making. IES Policy Brief Issue 2013/08/September 2013

Summary. In recent months, the migratory impacts of environmental degradation and climate change have gained increased worldwide attention. In response to the publication of the EC Staff Working Document on Climate Change, Environmental Degradation and Migration, this policy brief critically outlines current themes and issues that surround this global phenomenon, specifically the findings of current international research which frame the discussions on terminology and current legal, political and institutional conceptual debates. Several proposals were put forward during a Policy Forum in January 2013. Firstly, there is a need for tailored and actionable research outputs that take into account political pressures and realities on the ground. Secondly, migration and climate policies would be clearly boosted through the elaboration of a common policy-oriented research agenda of which elements were put forward at the event. Finally, efficient communication tools and channels could be developed to transfer research findings to policy-makers

Par2 Inactivation Inhibits Early Production of TSLP, but Not Cutaneous Inflammation, in Netherton Syndrome Adult Mouse Model

Netherton syndrome (NS) is a severe genodermatosis characterized by abnormal scaling and constant atopic manifestations. NS is caused by mutations in SPINK5 (Serine Protease INhibitor Kazal-type 5), which encodes LEKTI (LymphoEpithelial Kazal Type-related Inhibitor). Lack of LEKTI causes stratum corneum detachment secondary to epidermal proteases hyperactivity. Whereas a skin barrier defect is generally regarded as a major cause for atopy, we previously identified a cell-autonomous signaling cascade that triggers pro-Th2 cytokine thymic stromal lymphopoietin (TSLP) production in LEKTI-deficient epidermis. This signaling is initiated by unrestricted kallikrein 5 (KLK5) activity, which directly activates proteinase-activated receptor 2 (PAR2)-mediated expression of TSLP and favors a cutaneous proallergic microenvironment independently of the environment and of the adaptive immune system. To further confirm these results in vivo, we generated Spink5/Par2 double knockout (DKO) mice. At embryonic day 19.5, these mice display a dramatic decrease in TSLP expression, although stratum corneum detachment persists, confirming the role of the KLK5–PAR2 cascade in TSLP-mediated early proallergic signaling. However, deletion of Par2 in adult DKO-grafted skin does not rescue the inflammatory phenotype probably resulting from stratum corneum detachment. We conclude that several mechanisms trigger and maintain the inflammatory phenotype in NS. These include skin barrier impairment, mechanical stress secondary to stratum corneum detachment, as well as protease-induced proinflammatory and proallergic pathways, including PAR2-mediated overexpression of TSLP

Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

<p>Abstract</p> <p>Background</p> <p>A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red) and analyzed 2 time points (3 and 24 hours) for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality) was calculated.</p> <p>Results</p> <p>The use of MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive experimental design to assess the cytotoxic effect of one nanoparticle. With this experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate toxicity, and no toxicity was observed for Tungsten Carbide. No correlation between cytotoxicity and equivalent spherical diameter or specific surface area was found.</p> <p>Conclusion</p> <p>Our study clearly highlights the difference of sensitivity between cell types and cytotoxicity assays that has to be carefully taken into account when assessing nanoparticles toxicity.</p

Uptake and Fate of Fluorescently Labeled DNA Nanostructures in Cellular Environments: A Cautionary Tale

Fluorescent dye labeling of DNA oligonucleotides and nanostructures is one of the most used techniques to track their fate and cellular localization inside cells. Here, we report that intracellular fluorescence, and even FRET signals, cannot be correlated with the cellular uptake of intact DNA structures. Live cell imaging revealed high colocalization of cyanine-labeled DNA oligos and nanostructures with phosphorylated small-molecule cyanine dyes, one of the degradation products from these DNA compounds. Nuclease degradation of the strands outside and inside the cell results in a misleading intracellular fluorescent signal. The signal is saturated by the fluorescence of the degradation product (phosphorylated dye). To test our hypothesis, we synthesized a range of DNA structures, including Cy3-and Cy5-labeled DNA cubes and DNA tetrahedra, and oligonucleotides with different stabilities toward nucleases. All give fluorescence signals within the mitochondria after cellular uptake and strongly colocalize with a free phosphorylated dye control. Kinetics experiments revealed that uptake of stable DNA structures is delayed. We also studied several parameters influencing fluorescent data: stability of the DNA strand, fixation methods that can wash away the signal, position of the dye on the DNA strand, and design of FRET experiments. DNA nanostructures hold tremendous potential for biomedical applications and biotechnology because of their biocompatibility, programmability, and easy synthesis. However, few examples of successful DNA machines in vivo have been reported. We believe this contribution can be used as a guide to design better cellular uptake experiments when using fluorescent dyes, in order to further propel the biological development, and application of DNA nanostructures

Évaluation des interventions du pharmacien dans trois secteurs cliniques différents (cardiologie, pneumologie et médecine interne) selon le modèle traditionnel et le modèle décrit dans la nouvelle offre de soins pharmaceutiques de l’IUCPQ-UL

oai:pharmactuel.journals.sfu.ca:article/1224Résumé Objectifs : Un nouveau modèle d’offre de soins pharmaceutiques basé sur une hiérarchisation des patients a été mis en place récemment à Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval. Cette étude visait à établir une comparaison de ce modèle avec le modèle traditionnel (sans égard à un ordre de priorité des usagers) et à déterminer les interventions pharmaceutiques qui n’auraient pas été faites pour ces mêmes patients selon le nouveau modèle.Méthode : Des soins pharmaceutiques selon le modèle traditionnel ont été dispensés au cours de l’étude pendant huit à dix jours dans trois unités de soins (15 à 25 lits ciblés par unité) en présence d’un seul pharmacien. Les interventions réalisées ont été relevées, puis catégorisées selon leur impact clinique et leur inclusion ou non dans la nouvelle offre de soins.Résultats : Les pharmaciens ont réalisé 200 interventions. Le nouveau modèle aurait permis de déceler près de 100 % (16/17) des interventions dont l’impact était majeur et 43 % (43/99) dont l’impact était significatif. L’impact de 84 interventions sur les 200 réalisées a été jugé mineur et 73 % de ces interventions (61/84) auraient été omises avec le nouveau modèle. Conclusion : Le nouveau modèle d’offre de soins pharmaceutiques sous sa forme actuelle cible adéquatement les interventions qui ont un impact clinique majeur et une partie des interventions qui ont un impact clinique significatif. Des ajustements sont à prévoir pour englober davantage d’interventions dont l’impact est significatif. Ce nouveau modèle fournit de solides assises pour une utilisation judicieuse des services du pharmacien qui dispense des soins pharmaceutiques dans un contexte de nécessité d’optimisation des ressources.AbstractObjectives: A new, patient prioritization-based model for pharmaceutical care was recently instituted at the IUCPQ-UL. This study was aimed at comparing this model with the conventional model (in which patient priority ranking is not a consideration) and identifying the pharmaceutical interventions that would not be performed for these patients in the new model.Method: Pharmaceutical care under the conventional model was dispensed during the study for 8 to 10 days in three care units (15 to 25 beds targeted per unit) in the presence of a single pharmacist. The interventions performed were recorded and then categorized according to their clinical impact and according to whether or not they are included in the new offer of care.Results: The pharmacists performed 200 interventions. Close to 100 % (16/17) of those with a major impact and 43% (43/99) of those with a significant impact were identified in the new model. Eighty-four of the 200 interventions performed were considered to have had a minor impact, and 73 % of these interventions (61/84) were not included in the new model. Conclusion: The current version of the new model of offering pharmaceutical care appropriately targets interventions with a major clinical impact and some of the interventions with a significant clinical impact. Adjustments will be needed to include more of the latter. It provides a solid basis for judicious pharmacist utilization in the provision of pharmaceutical care in a context where resource optimization is necessary

Glycerol Supplementation Enhances L. reuteri’s Protective Effect against S. Typhimurium Colonization in a 3-D Model of Colonic Epithelium

The probiotic effects of Lactobacillus reuteri have been speculated to partly depend on its capacity to produce the antimicrobial substance reuterin during the reduction of glycerol in the gut. In this study, the potential of this process to protect human intestinal epithelial cells against infection with Salmonella enterica serovar Typhimurium was investigated. We used a three-dimensional (3-D) organotypic model of human colonic epithelium that was previously validated and applied to study interactions between S. Typhimurium and the intestinal epithelium that lead to enteric salmonellosis. Using this model system, we show that L. reuteri protects the intestinal cells against the early stages of Salmonella infection and that this effect is significantly increased when L. reuteri is stimulated to produce reuterin from glycerol. More specifically, the reuterin-containing ferment of L. reuteri caused a reduction in Salmonella adherence and invasion (1 log unit), and intracellular survival (2 log units). In contrast, the L. reuteri ferment without reuterin stimulated growth of the intracellular Salmonella population with 1 log unit. The short-term exposure to reuterin or the reuterin-containing ferment had no observed negative impact on intestinal epithelial cell health. However, long-term exposure (24 h) induced a complete loss of cell-cell contact within the epithelial aggregates and compromised cell viability. Collectively, these results shed light on a potential role for reuterin in inhibiting Salmonella-induced intestinal infections and may support the combined application of glycerol and L. reuteri. While future in vitro and in vivo studies of reuterin on intestinal health should fine-tune our understanding of the mechanistic effects, in particular in the presence of a complex gut microbiota, this the first report of a reuterin effect on the enteric infection process in any mammalian cell type

Nose-only inhalations of high-dose alumina nanoparticles/hydrogen chloride gas mixtures induce strong pulmonary pro-inflammatory response: a pilot study

Objective Solid composite propellants combustion, in aerospace and defense fields, can lead to complex aerosols emission containing high concentrations of alumina nanoparticles (Al2O3 NPs) and hydrogen chloride gas (HClg). Exposure to these mixtures by inhalation is thus possible but literature data toward their pulmonary toxicity are missing. To specify hazards resulting from these combustion aerosols, a pilot study was implemented. Materials and methods Male Wistar rats were nose-only exposed to Al2O3 NPs (primary size 13 nm, 10 g/L suspension leading to 20.0–22.1 mg/m3 aerosol) and/or to HClg aerosols (5 ppm target concentration) following two exposure scenarios (single exposures (SE) or repeated exposures (RE)). Bronchoalveolar lavage fluids (BALF) content and lungs histopathology were analyzed 24 h after exposures. Results Repeated co-exposures increased total proteins and LDH concentrations in BALF indicating alveolar–capillary barrier permeabilization and cytolysis. Early pulmonary inflammation was induced after RE to Al2O3 NPs ± HClg resulting in PMN, TNF-α, IL-1β, and GRO/KC increases in BALF. Both exposure scenarios resulted in pulmonary histopathological lesions (vascular congestions, bronchial pre-exfoliations, vascular and interalveolar septum edemas). Lung oxidative damages were observed in situ following SE. Conclusion Observed biological effects are dependent on both aerosol content and exposure scenario. Results showed an important pro-inflammatory effect of Al2O3 NPs/HClg mixtures on the lungs of rat 24 h after exposure. This pilot study raises concerns toward potential long-term pulmonary toxicity of combustion aerosols and highlights the importance for further studies to be led in order to define dose limitations and exposure thresholds for risk management at the work place

TranscriptomeBrowser: A Powerful and Flexible Toolbox to Explore Productively the Transcriptional Landscape of the Gene Expression Omnibus Database

International audienceAs public microarray repositories are constantly growing, we are facing the challenge of designing strategies to provide productive access to the available data.\ We used a modified version of the Markov clustering algorithm to systematically extract clusters of co-regulated genes from hundreds of microarray datasets stored in the Gene Expression Omnibus database (n = 1,484). This approach led to the definition of 18,250 transcriptional signatures (TS) that were tested for functional enrichment using the DAVID knowledgebase. Over-representation of functional terms was found in a large proportion of these TS (84%). We developed a JAVA application, TBrowser that comes with an open plug-in architecture and whose interface implements a highly sophisticated search engine supporting several Boolean operators (http://tagc.univ-mrs.fr/tbrowser/). User can search and analyze TS containing a list of identifiers (gene symbols or AffyIDs) or associated with a set of functional terms.\ As proof of principle, TBrowser was used to define breast cancer cell specific genes and to detect chromosomal abnormalities in tumors. Finally, taking advantage of our large collection of transcriptional signatures, we constructed a comprehensive map that summarizes gene-gene co-regulations observed through all the experiments performed on HGU133A Affymetrix platform. We provide evidences that this map can extend our knowledge of cellular signaling pathways