Analyse protéomique différentielle des cellules endothéliales de la barrière hémato-encéphalique (identification de protéines induites par les cellules gliales)

En contrôlant le passage para- et transcellulaire des composés du sang vers le cerveau (et inversement), la barrière hémato-encéphalique (BHE) constitue la gardienne du compartiment cérébral. Bien que relativement connu dans son aspect physiologique, le phénotype BHE des cellules endothéliales des capillaires cérébraux (BCECs) reste mal compris au regard des mécanismes moléculaires qui gouvernent son établissement et son maintien. Dans cette optique, à l aide du modèle in vitro de BHE développé au laboratoire (co-culture de BCECs bovines et de cellules gliales de rats), nous avons réalisé deux études protéomiques comparatives afin d identifier les protéines cytoplasmiques potentiellement impliquées dans l induction et le maintien de ce phénotype: d une part une approche qualitative sans marquage (label free) et d autre part une approche quantitative grâce à un marquage isotopique préalable des protéines (isotope-coded protein label, ICPL). Les deux approches, label free et ICPL se sont révélées complémentaires et ont permis, respectivement, l identification de 447 et de 412 protéines (dont 290 quantifiées). Quatre protéines d un intérêt particulier dans le domaine de la BHE (phosphatase alcaline tissu-non spécifique, TNAP ; protéine 1 possédant un domaine d homologie à Eps15, EHD1 ; superoxyde dismutase, SODC et homologue 7 de la protéine de la maladie de Parkinson PARK7, DJ-1) ont fait l objet de caractérisations biochimiques approfondies et ouvrent des pistes d investigation sur des potentielles voies cellulaires induites par les cellules gliales et impliquées dans le phénotype BHE.The blood-brain barrier (BBB) controls the para- and transcellular crossing of compounds from blood to brain (and inversely) and establishes the gatekeepers of the brain. The major part of therapeutic drugs developed to fight the brain diseases is deemed inefficient in vivo due to the presence of the BBB that they are unable to cross. Although relatively well known in its physiological aspect, the BBB phenotype of brain capillary endothelial cells (BCECs) remains largely under known and misunderstood in regards of the molecular mechanisms that govern its establishment and its maintenance. To this goal, using the in vitro BBB model developed in the laboratory (co-culture of bovine BCECs with rat glial cells), we performed two differential proteomic studies to identify the main cytoplasmic proteins involved in the establishment and maintenance of this phenotype: a qualitative label free approach and a quantitative isotope-coded protein labeling (ICPL) approach.The two different approaches, label free and ICPL, are complementary and led to the identification of 447 and 412 proteins, respectively. Four proteins of particular interest for BBB (tissue-non specific alkaline phosphatase, TNAP; Eps15 homology domain containing protein 1, EHD1; superoxide dismutase, SODC and Parkinson disease protein 7 homolog PARK7, DJ-1) have been more deeply studied and they open new discovery prospects related to cellular pathways induced by glial cells and involved in the BBB phenotype.ARRAS-Bib.electronique (620419901) / SudocSudocFranceF

Water Purification in Micromagnetofluidic Devices: Mixing in MHD Micromixers

AbstractThis contribution addresses a possible solution for water purification from heavy metals by magnetic nanoparticles in microfluidic water flow systems. In this technique, the most important component is the micromixer while efficient mixing and particle driving is achieved by external magnetic fields. For the simulation of water flow and nanoparticles, Computational Fluid Dynamics methods are used. The 2D and 3D Navier-Stokes equations are solved for the flow field while trajectories of the magnetic nanoparticles are simulated by the use of a Lagrangian method. Compared to traditional techniques, this method is expected to succeed chemical speed and increased water purification times

CFRP Reinforcement and Repair of Steel Pipe Elbows Subjected to Severe Cyclic Loading

In order to ensure safe operation and structural integrity of pipelines and piping systems subjected to extreme loading conditions, it is often necessary to strengthen critical pipe components. One method to strengthen pipe components is the use of composite materials. The present study is aimed at investigating the mechanical response of pipe elbows, wrapped with carbon fiber-reinforced plastic (CFRP) material, and subjected to severe cyclic loading that leads to low-cycle fatigue (LCF). In the first part of the paper, a set of LCF experiments on reinforced and nonreinforced pipe bend specimens are described focusing on the effects of CFRP reinforcement on the number of cycles to failure. The experimental work is supported by finite element analysis presented in the second part of the paper, in an attempt to elucidate the failure mechanism. For describing the material nonlinearities of the steel pipe, an efficient cyclic-plasticity material model is employed, capable of describing both the initial yield plateau of the stress–strain curve and the Bauschinger effect characterizing reverse plastic loading conditions. The results from the numerical models are compared with the experimental data, showing an overall good comparison. Furthermore, a parametric numerical analysis is conducted to examine the effect of internal pressure on the structural behavior of nonreinforced and reinforced elbows, subjected to severe cyclic loading.</jats:p

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Analyse protéomique de cellules endothéliales de capillaires cérébraux ayant acquis le phénotype de barrière hémato-encéphalique

LENS-BU Sciences (624982102) / SudocSudocFranceF

Aortic Arch Floating Thrombus Complicated by Distal Embolization in a Patient with Malignancy

Free floating thrombus of aortic arch in a minimally atherosclerotic or nonaneurysmal aorta is a rare disease entity which carries a potential risk of distal embolization with catastrophic consequences. We present the case of a 52-years-old patient with ovarian cancer and aortic arch floating thrombus who initially managed with low molecular weight heparin and eventually undergone surgical thrombectomy of left external iliac and common femoral artery due to acute ischemia of left lower leg

Polymer Free Amphilimus Drug Eluting Stent for Infrapopliteal Arterial Disease in Patients with Critical Limb Ischemia: A New Device in the Armamentarium

Background and Objectives: Endovascular technologies have significantly improved the outcome of patients with critical limb ischemia (CLI). Drug eluting stents (DES) have documented their efficacy against percutaneous transluminal angioplasty (PTA) and bare metal stents (BMS) in infrapopliteal arterial occlusive disease. However, late in-stent neoatherosclerosis may lead to vascular lumen loss and eventually thrombosis. Polymer free DES constitute a new technology aiming to improve long term patency which their action is still under investigation. The purpose of this study is to report the mechanism of action and to provide a literature review of a novel polymer free amphilimus eluting stent (Cre8, Alvimedica, Instabul, Turkey) in infrapopliteal arterial disease. Methods: Publications listed in electronic databases, European Union Drug Regulating Authorities Clinical Trials Database, as well as scientific programmes of recent interventional vascular conferences were searched. Three studies were included. We analyzed primary and secondary patency, major amputation rate, freedom from CD-TLR, and mortality. Results: Cre8 was implanted in 79 patients with CLI. Most of the patients (n = 65) were Rutherford class 5–6 (82.3%), and diabetes mellitus (DM) was present in 66 patients (83.5%). Mean primary patency was 82.5% at 12 months. Mean lesion stented length was 20 mm and 35 mm in two studies. Mean limb salvage was 91.3% at 12 months. Freedom from CD-TLR was reported in two out of the three studies and was 96% and 83.8%. Mortality was 15% and 23.8% in the same studies, whilst it was not reported in one study. Conclusion: Stenting of infrapopliteal arteries with Cre8 is safe and feasible in patients with CLI and diabetes. All studies have shown very good primary patency and freedom from CD-TLR at 12 and 24 months. Larger observational prospective studies and randomized trials are necessary to establish long term effectiveness and clinical outcomes using the non-polymer Cre8 DES