Soft adsorption of densely packed layers of DNA-plasmid * 1,3-diaminopropane complexes onto highly oriented pyrolytic graphite designed to erode in water

International audienceIn this Article, we report a simple and effective method to build up self-assembled and well-calibrated layers of plasmid DNA*1,3-diaminopropane complexes onto highly oriented pyrolitic graphite (HOPG). The method is based on the self-assembly of the poly electrolytes onto HOPG in an excess of positively charged protonated diamines (Dap2+) in comparison to the negatively charged phosphate moieties of the DNA backbone in solution. Although short distortions in the helical parameters of DNA (maximum 12% hypochromicity) are revealed by UV-vis absorption spectrometry, the native B form of the plasmids is conserved. By fixing the excess of positive charges arising from Dap2+ cations, it is possible to construct assemblies of a well-defined thickness ranging typically from 1 monolayer (ML) of DNA to 10 ML; 1 ML has a thickness of 2.2 ± 0.5 nm. Adding TRIS-EDTA (TE) buffer lowers considerably the damage rate observed when plasmids are mixed with Dap2+ in pure water. The thickness of the first dense monolayer matches well the DNA cross-sectional dimensions, indicating that this layer is strongly anchored to the surface; it is insoluble in water. Conversely, thicker layers can be released in aqueous media, and the plasmids do not undergo dramatic damage. In the presence of TE buffer, condensation of the plasmids on the HOPG surface and a further release of the deposits in water yields a loss of supercoiling that ranges typically from 10% to 20% when the layer thickness varies from 22 to 12 nm. Such densely packed and releasable DNA plasmid layers with a very well-characterized and constant thickness constitute a substantial progress for biochemical and radiochemical experiments

N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.

APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition

An extension of the core product model for the maturity management of the digital mock up: use of graph and knowledge to describe mechanical parts

International audienceReverse engineering (RE) of mechanical parts consists in creating a 3D virtual model using data that are often gathered by 3D measurement systems like laser scanners. The resulting point cloud is then transformed into a geometrical model. The purpose of RE activity is to make maintenance or redesign operations easier. The boundary of the literature is the component, isolated from its product assembly. Because of unreported on-field maintenance, a long time running in-use product may not reflect its digital mock-up (DMU) anymore. In order to maintain an efficient lifecycle, the changes made have to be considered. This paper focuses on the development of a knowledge-based RE methodology to support the DMU maturity management: to identify the maturity defaults, which correspond to unreported changes, in the CAD assembly model in order to make it matching the real product. That approach is supported by a core product model data model extension

From Behavior of Water on Hydrophobic Graphene Surfaces to Ultra-Confinement of Water in Carbon Nanotubes

In recent years and with the achievement of nanotechnologies, the development of experiments based on carbon nanotubes has allowed to increase the ionic permeability and/or selectivity in nanodevices. However, this new technology opens the way to many questionable observations, to which theoretical work can answer using several approximations. One of them concerns the appearance of a negative charge on the carbon surface, when the latter is apparently neutral. Using first-principles density functional theory combined with molecular dynamics, we develop here several simulations on different systems in order to understand the reactivity of the carbon surface in low or ultra-high confinement. According to our calculations, there is high affinity of the carbon atom to the hydrogen ion in every situation, and to a lesser extent for the hydroxyl ion. The latter can only occur when the first hydrogen attack has been achieved. As a consequence, the functionalization of the carbon surface in the presence of an aqueous medium is activated by its protonation, then allowing the reactivity of the anion

A potential solution to avoid overdose of mixed drugs in the event of Covid-19: Nanomedicine at the heart of the Covid-19 pandemic

International audienceSince 2020, the world is facing the first global pandemic of 21st century. Among all the solutions proposed to treat this new strain of coronavirus, named SARS-CoV-2, the vaccine seems a promising way but the delays are too long to be implemented quickly. In the emergency, a dual therapy has shown its effectiveness but has also provoked a set of debates around the dangerousness of a particular molecule, hydroxychloroquine. In particular, the doses to be delivered, according to the studies, were well beyond the acceptable doses to support the treatment without side effects. We propose here to use all the advantages of nanovectorization to address this question of concentration. Using quantum and classical simulations we will show in particular that drug transport on boron nitrogen oxide nanosheets increases the effectiveness of the action of these drugs. This will definitely allow to decrease the drug quantity needing to face the disease

From Behavior of Water on Hydrophobic Graphene Surfaces to Ultra-Confinement of Water in Carbon Nanotubes

In recent years and with the achievement of nanotechnologies, the development of experiments based on carbon nanotubes has allowed to increase the ionic permeability and/or selectivity in nanodevices. However, this new technology opens the way to many questionable observations, to which theoretical work can answer using several approximations. One of them concerns the appearance of a negative charge on the carbon surface, when the latter is apparently neutral. Using first-principles density functional theory combined with molecular dynamics, we develop here several simulations on different systems in order to understand the reactivity of the carbon surface in low or ultra-high confinement. According to our calculations, there is high affinity of the carbon atom to the hydrogen ion in every situation, and to a lesser extent for the hydroxyl ion. The latter can only occur when the first hydrogen attack has been achieved. As a consequence, the functionalization of the carbon surface in the presence of an aqueous medium is activated by its protonation, then allowing the reactivity of the anion

Enhanced DR5 binding capacity of nanovectorized TRAIL compared to its cytotoxic version by affinity chromatography and molecular docking studies

IF 2.091International audienceTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of cancer cells when bound to its cognate receptors, TRAIL-R1 and TRAIL-R2 (DR4 and DR5), without being toxic to healthy cells. Nanovectorized TRAIL (abbreviated as NPT) is 10 to 20 times more efficient than one of the most potent soluble TRAIL used in preclinical studies (His-TRAIL). To determine whether differences in affinity may account for NPT superiority, a thermodynamic study was undertaken to evaluate NPT versus TRAIL binding affinity to DR5. Docking calculations showed that TRAIL in homotrimer configuration was more stable than in heterotrimer, because of the presence of one Zn ion in its structure. Indeed, TRAIL trimers can have head-to-tail orientations when Zn is missing. Altogether these data suggest that TRAIL homotrimer structures are predominant in solution and then are grafted on NPT. When docked to DR5, NPT carrying TRAIL homotrimer leads to a more stable complex than TRAIL monomer-based NPT. To comfort these observations, the extracellular domain of DR5 was immobilized on a chromatographic support using an in situ immobilization technique. The determination of the thermodynamic data (enthalpy H degrees and entropy S degrees*) of TRAIL and NPT binding to DR5 showed that the binding mechanism was pH dependent. The affinity of NPT to DR5 increased with pH, and the ionized energy was more important for NPT than for soluble TRAIL. Moreover, because of negative values of H degrees and S degrees* quantities, we demonstrated that van der Waals and hydrogen bonds governed the strong NPT-DR5 association for pH>7.4 (as for TRAIL alone). Copyright (c) 2016 John Wiley & Sons, Ltd

ePTFE ‐based biomedical devices: An overview of surgical efficiency

International audiencePolytetrafluoroethylene (PTFE) is a ubiquitous material used for implants and medical devices in general because of its high biocompatibility and inertness: blood vessel, heart, table jawbone, nose, eyes, or abdominal wall can benefit from its properties in case of disease or injury. Its expanded version, ePTFE is an improved version of PTFE with better mechanical properties, which extends its medical applications. A material as frequently used as ePTFE with these exceptional properties deserves a review of its main uses, developments, and possibility of improvements. In this systematic review, we examined clinical trials related to ePTFE-based medical devices from the literature. Then, we excluded all trials using ePTFE as a control to test other devices. ePTFE-coated stents, hemodialysis and bypass grafts, guided bone and tissue regeneration membranes, hernia and heart repair and other devices are reviewed. The rates of success using these devices and their efficiency compared to other materials used for the same purposes are reported. ePTFE appears to be more or just as efficient compared to them. Some success rates remain low, suggesting the need of improvement ePTFE for medical applications

A Reverse Engineering Method for DMU Maturity Management: Use of a Functional Reeb Graph

Part 8: PLM Maturity and Improvement ConceptsInternational audienceIn a development process, Digital Mock-Up (DMU) is the referential view of the developed product, all along the product states (“as-design”, “as-manufactured”, etc.). In case of long lifetime products, such as boats or planes, each released product has its own DMU. During the use, maintenance operations are made. Some of the modifications are made “on field” and are not always reported to the DMU which is no longer mature. The product lifecycle is impacted and not efficient anymore. This paper focuses on a systematized methodology for checking the maturity level of a DMU by confronting it to the real product it is intended to represent. DMU inconsistencies correspond to unreported product components modifications. The first step of the process is a global comparison between the DMU and a digitization of the in-use product using the Reeb graph. The used comparison criterion is the topology. The second step is to identify the kept DMU components in the digitized dataset and thus deduce inconsistencies. That step implies a new shape descriptor combining topological and functional descriptions of a mechanical part: the Functional Reeb Graph