Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism.

This review is respectfully dedicated to the memory of Michel Ollivon, Research Director at CNRS (Châtenay-Malabry, France), outstanding physico-chemist specialist of lipid organization, recipient of the Hilditch Memorial Lecture award, who was the initiator of the network RMT LISTRAL. We are also sadly paying tribute to Jean-Luc Vendeuvre, Food Engineer at the French Pork and Pig Institute (IFIP, Maisons-Alfort, France), outstanding expert in meat products who participated actively in RMT LISTRAL and provided unpublished data for figures in the present review, who passed away during review submission. RMT LISTRAL: Mixed Technological Network combining academic and industrial partners, devoted to the enhancement and divulgation of knowledge regarding structured dietary lipids.International audienceOn a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Implication de l'activité lectinique des HSP70 dans la protection des protéines O-GlcNAc vis-à-vis de la dégradation protéasomale

La O-GlcNAc, une modification post-traductionnelle dynamique, semble intervenir dans la dégradation protéasomale. Le système ubiquitine-protéasome permet la dégradation régulée de protéines ubiquitinées. Les protéines de choc thermique Hsp70 jouent un rôle fondamental dans cette régulation. Elles empêchent l'agrégation des protéines lors d'un stress, tentent de les remettre en conformation et le cas échéant, induisent leur ubiquitination et leur dégradation. Nous avons mis en évidence l'activité lectinique des Hsp70 vis-à-vis des résidus de GlcNAc. Cette activité est modulable en fonction de nombreux stress et est particulièrement induite lors d'un stress thermique ou nutritionnel. Nous avons alors émis l'hypothèse d'une protection des protéines O-GIcNAc vis-àvis de la dégradation protéasomale par les Hsp70. Ceci nous a conduit à étudier la relation entre O-GlcNAc et ubiquitine. La mise en évidence de la glycosylation de E1, enzyme impliquée dans le processus d'ubiquitination, suggère que cette enzyme pourrait être le dénominateur commun entre les deux modifications. L'identification de deux acides aminés potentiellement impliqués dans le site lectinique par des expériences de "docking" ont permis l'élaboration d'un mutant dont les capacités de fixation de la GlcNAc sont partiellement abolies. En conclusion, l'ensemble de ces résultats suggère que la O-GIcNAc puisse être un signal de sauvegarde des protéines en cas de stress, via l'interaction lectinique des hsp70, permettant ainsi leur remise en conformation. Ce système pourrait constituer l'homologue cytosolique du cycle gluco/dégluco du réticulum endoplasmique.LILLE1-BU (590092102) / SudocSudocFranceF

The mass spectrometric analysis of glycoproteins and their glycan structures

One of the most common post-translational modifications of proteins involves the covalent attachment of N- or O-linked carbohydrates to the protein. Glycan moieties are involved in a wide variety of intracellular, cell-cell and cell-matrix recognition events. The study of glycoprotein-linked carbohydrates remains one of the most challenging tasks given to biochemists and bioanalysts as these molecules can exhibit complex branched structures that can differ in linkage and the level of branching. This is why understanding how glycosylation affects the activities and functions of proteins in health and disease represents a major challenge. Mass spectrometry, is one of the most powerful and versatile techniques for the structural analysis of glycoconjugates. This review summarizes the state of knowledge for the mass spectrometric analysis of glycoproteins and their glycan structures