The Expression of Myeloproliferative Neoplasm-Associated Calreticulin Variants Depends on the Functionality of ER-Associated Degradation

BACKGROUND: Mutations in CALR observed in myeloproliferative neoplasms (MPN) were recently shown to be pathogenic via their interaction with MPL and the subsequent activation of the Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) pathway. However, little is known on the impact of those variant CALR proteins on endoplasmic reticulum (ER) homeostasis. METHODS: The impact of the expression of Wild Type (WT) or mutant CALR on ER homeostasis was assessed by quantifying the expression level of Unfolded Protein Response (UPR) target genes, splicing of X-box Binding Protein 1 (XBP1), and the expression level of endogenous lectins. Pharmacological and molecular (siRNA) screens were used to identify mechanisms involved in CALR mutant proteins degradation. Coimmunoprecipitations were performed to define more precisely actors involved in CALR proteins disposal. RESULTS: We showed that the expression of CALR mutants alters neither ER homeostasis nor the sensitivity of hematopoietic cells towards ER stress-induced apoptosis. In contrast, the expression of CALR variants is generally low because of a combination of secretion and protein degradation mechanisms mostly mediated through the ER-Associated Degradation (ERAD)-proteasome pathway. Moreover, we identified a specific ERAD network involved in the degradation of CALR variants. CONCLUSIONS: We propose that this ERAD network could be considered as a potential therapeutic target for selectively inhibiting CALR mutant-dependent proliferation associated with MPN, and therefore attenuate the associated pathogenic outcomes

Ordre local dans de nouvelles formes de NiPS_3 obtenues par chimie douce et par intercalation de lithium

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Isolation céramique pour câbles supraconducteurs en Nb3Sn

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Elaboration de silices mésoporeuses MSU-X (applications en chromatographie HPLC et membranes d'ultrafiltration)

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Harnessing the power of latex solutions based on titania particles - using si-ATRP towards larger surface modification for applications in gas separation membranes

Membranes are vital and touch every aspect of our daily lives. For instance, they ensure that clean or pure drinking water can be produced, or they can purify our air. However, there is no one-membrane material that can perform all these objectives, and they must be catered for each specific application. As more traditional membrane materials are either polymer based or inorganic/ceramic based, each application will require a different material that can use one or both of these components. Currently, much research is dedicated to combining both polymer and inorganic based materials to form hybrid membranes that could "have the best of both worlds". The most common form of hybrid membranes are mixed matrix membranes, or MMM. However, their synthesis normally involves the direct addition of inorganic particles into an existing polymeric solution, leading to composite materials without strong interaction between organic and inorganic moieties. In this work, we explore the reversal of this process; that is, the formation of the polymeric component directly from the surface of these particles using surface-initiated atom-transfer radical polymerization, or si-ATRP. Such a method intends to provide a high intimacy between polymers and ceramics, and strong interconnection via covalent bonds. Using a latex based solution of these functionalized titania particles, we present two pathways, known as "Coating Onto" and "Grafting From" pathways, in which these latexes can be applied to larger, tubular membrane coatings. These latexes were first analyzed by TGA to determine their functionalization densities and degree of polymerization. SEM was then employed to visually assess the membrane surfaces to determine the final optimal conditions used for preliminary gas separation tests. (C) 2016 Elsevier B.V. All rights reserved

Organic-inorganic hybrid materials designed by controlled radical polymerization and mediated using commercial dual functional organophosphorous coupling agents

Hybrid materials that are composed of a polymeric material interfaced with an inorganic, metal oxide material have been a rapidly expanding research area in the last few decades. However, interfacial regions remain an important area of focus, and as such hybrid materials do not always possess a very robust or stable interface. Tailor-made interfacial molecules have been successfully reported but material scientists wishing to develop composite interfacial materials would favorably use commercial solutions. Our study shows how we can leverage a commercially available organophosphonic acid group that is coupled with a 2-bromo isobutyrate initiator for surface initiated atom transfer radical polymerization (SI-ATRP) for use as a strong interfacial molecule. We illustrate this mechanism with both nanoparticles of titania and flat titania substrates used as the grafting support and polymerization anchoring points. We demonstrate that the size of the organophosphonic acid initiator, specifically the carbon spacer between the reactive groups, controls the stability of the molecule. The actual covalent linkage between the phosphonic acid group and the titania surface while also leaving the ATRP initiating group able to start the polymerization, is confirmed via P-31 solid state NMR spectroscopy, liquid H-1 NMR spectroscopy XPS, DLS and SEM

The formation and study of poly(ethylene oxide)-poly(norbornene) block-copolymers on the surface of titanium-dioxide particles: a novel approach towards application of si-ROMP to larger surface modification

Ring-opening metathesis polymerization, or ROMP, has been known in the world of polymers as a success story. With its discovery in the middle of the 20th century, the study and understanding of this reaction led to its adoption in a multitude of areas in both academic and industrial domains. However, with the general shift towards hybrid materials and better material integration, surface-initiated polymerization (SIP) has been an area of great interest that ROMP has only tapped into at the very end of the 20th century. With this point in mind, we demonstrate another pathway towards SIP using the si-ROMP approach to form block-copolymers of poly(ethylene-oxide)-poly(norbornene) (PEO-PNB) brushes on particles of titania. In this study, particle modification was first performed and studied, which was then applied towards coating larger, curved tubes to assess their ability for surface modification. In the case of particles, each step was analyzed by XPS to ensure that the expected elements appeared. TGA was then implemented to determine the general grafting density of the PEO chains on the surface, which was found to be 2.7 molecules per nm(2). TGA could also determine the degree of polymerization (DP) of the polynorbornene chain, which was 12 500. Finally, SEM was used to image the final products, both film formation using particles, and after use of these particles as a surface coating to cover larger surface areas for surface modification. The functionalized titania particles are determined to be an interesting candidate material for a "seed" layer, which can be used for larger surface modification