A large-scale electrophoresis- and chromatography-based determination of gene expression profiles in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties

<p>Abstract</p> <p>Background</p> <p>Brain capillary endothelial cells (BCECs) form the physiological basis of the blood-brain barrier (BBB). The barrier function is (at least in part) due to well-known proteins such as transporters, tight junctions and metabolic barrier proteins (e.g. monoamine oxidase, gamma glutamyltranspeptidase and P-glycoprotein). Our previous 2-dimensional gel proteome analysis had identified a large number of proteins and revealed the major role of dynamic cytoskeletal remodelling in the differentiation of bovine BCECs. The aim of the present study was to elaborate a reference proteome of Triton X-100-soluble species from bovine BCECs cultured in the well-established <it>in vitro </it>BBB model developed in our laboratory.</p> <p>Results</p> <p>A total of 215 protein spots (corresponding to 130 distinct proteins) were identified by 2-dimensional gel electrophoresis, whereas over 350 proteins were identified by a shotgun approach. We classified around 430 distinct proteins expressed by bovine BCECs. Our large-scale gene expression analysis enabled the correction of mistakes referenced into protein databases (e.g. bovine vinculin) and constitutes valuable evidence for predictions based on genome annotation.</p> <p>Conclusions</p> <p>Elaboration of a reference proteome constitutes the first step in creating a gene expression database dedicated to capillary endothelial cells displaying BBB characteristics. It improves of our knowledge of the BBB and the key proteins in cell structures, cytoskeleton organization, metabolism, detoxification and drug resistance. Moreover, our results emphasize the need for both appropriate experimental design and correct interpretation of proteome datasets.</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

Studying Molecular Aspects of the Blood-Brain Barrier Using an in Vitro Model: Contribution of a Global Proteomics Strategy

International audienceA global proteomics strategy was initiated to decipher molecular mechanisms associated with the blood-brain barrier (BBB) phenotype of the brain capillary endothelial cells. The different methods implemented were shown complementarily. The main results obtained using an in vitro BBB model allowed highlighting the role of several protein actors of cytoskeleton remodelling, the involvement of the asymmetric dimethylarginine pathway in regulating endothelial function and the role of tissue non-specific alkaline phosphatase in the regulation of endothelial permeability

Proteomics and the blood–brain barrier: how recent findings help drug development

International audienceThe drug discovery and development processes are divided into different stages separated by milestones to indicate that significant progress has been made and that certain criteria for target validation, hits, leads and candidate drugs have been met. Proteomics is a promising approach for the identification of protein targets and biochemical pathways involved in disease process and thus plays an important role in several stages of the drug development. The blood-brain barrier is considered as a major bottleneck when trying to target new compounds to treat neurodegenerative diseases. Based on the survey of recent findings and with a projection on expected improvements, this report attempt to address how proteomics participates in drug development

Progresser avec le co-apprentissage

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Mise en œuvre d'une unité d'enseignement sur la prévention des risques basée sur le concept "être autonome en respectant les consignes"

International audienceDans l’enseignement portant sur la prévention des risques adressé aux étudiants de deuxième année de licence de Sciences de la Vie, les apprentissages se font à travers des mini-projets réalisés en équipes de quatre étudiants, dans des groupes constitués de six équipes qui sont encadrées par un membre de l’équipe pédagogique. Les interactions se font en présentiel et à travers la plateforme de formation à distance (forums dédiés, conception d’un glossaire sur les bases de la prévention, ressources pédagogiques, rapports intermédiaires et final...). Le tempo est donné par une fiche de suivi, avec les cibles à réaliser, des indicateurs d’avancement pour chaque activité et qui permet l’autoévaluation. La restitution finale permet de s’enrichir des thèmes abordés par les 6 équipes du groupe. Les résultats des évaluations et les productions des étudiants valident le bien-fondé de l’approche d’hybridation utilisée pour les apprentissages

De-N-glycosylation activities are found in every part of the tomato plant

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Understanding the blood-brain barrier using gene and protein expression profiling technologies

International audienceThe blood-brain barrier (BBB) contributes to the brain homeostasis by regulating the passage of endogenous and exogenous compounds. This function is in part due to well-known proteins such as tight junction proteins, plasmamembrane transportersandmetabolic barrier proteins. Over the last decade, genomics and proteomics have emerged as supplementary tools for BBB research. The development of genomic and proteomic technologies has provided several means to extend the BBB knowledge and to investigate additional routes for the bypass of this barrier. These profiling technologies have been used on BBB models to decipher the physiological characteristics and, under stress conditions, to understand the molecular mechanisms of brain diseases. In this review, we will report and discuss the genomic and proteomic studies recently carried out to enhance the understanding of BBB features