Water-mediated structuring of bone apatite

International audienceIt is well known that organic molecules from the vertebrate extracellular matrix of calcifying tissues are essential in structuring the apatite mineral. Here, we show that water also plays a structuring role. By using solid-state nuclear magnetic resonance, wide-angle X-ray scattering and cryogenic transmission electron microscopy to characterize the structure and organization of crystalline and biomimetic apatite nanoparticles as well as intact bone samples, we demonstrate that water orients apatite crystals through an amorphous calcium phosphate-like layer that coats the crystalline core of bone apatite. This disordered layer is reminiscent of those found around the crystalline core of calcified biominerals in various natural composite materials in vivo. This work provides an extended local model of bone biomineralization

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasingly investigated, aiming to identify recurrent genetic events involved in myelomagenesis. Whole exome and whole genome sequencing studies have shown that MM is a genetically heterogeneous disease that evolves through accumulation of both clonal and subclonal driver mutations [3] and identified recurrently somatically mutated genes, including KRAS, NRAS, FAM46C, TP53, DIS3, BRAF, TRAF3, CYLD, RB1 and PRDM1 [3,4,5]. Despite the fact that family-based studies have provided data consistent with an inherited genetic susceptibility to MM compatible with Mendelian transmission [6], the molecular basis of inherited MM predisposition is only partly understood. Genome-Wide Association (GWAS) studies have identified and validated 23 loci significantly associated with an increased risk of developing MM that explain ~16% of heritability [7] and only a subset of familial cases are thought to have a polygenic background [8]. Recent studies have identified rare germline variants predisposing to MM in KDM1A [9], ARID1A and USP45 [10], and the implementation of next-generation sequencing technology will allow the characterization of more such rare variants. [...]French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organizatio

Analyse de l'impact du bruit de commutation sur les blocs digitaux des circuits intégrés CMOS

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Comportement transitoire des diodes lors d événements transitoires rapides de type ESD (Outils de Caractérisation et Physique du semi-conducteur et modélisation CMOS)

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Bone mineral: new insights into its chemical composition

International audienceSome compositional and structural features of mature bone mineral particles remain unclear. They have been described as calcium-deficient and hydroxyl-deficient carbonated hydroxyapatite particles in which a fraction of the po 4 3− lattice sites are occupied by HPO 4 2− ions. The time has come to revise this description since it has now been proven that the surface of mature bone mineral particles is not in the form of hydroxyapatite but rather in the form of hydrated amorphous calcium phosphate. Using a combination of dedicated solid-state nuclear magnetic resonance techniques, the hydrogen-bearing species present in bone mineral and especially the HPO 4 2− ions were closely scrutinized. We show that these HPO 4 2− ions are concentrated at the surface of bone mineral particles in the so-called amorphous surface layer whose thickness was estimated here to be about 0.8 nm for a 4-nm thick particle. We also show that their molar proportion is much higher than previously estimated since they stand for about half of the overall amount of inorganic phosphate ions that compose bone mineral. As such, the mineral-mineral and mineral-biomolecule interfaces in bone tissue must be driven by metastable hydrated amorphous environments rich in HPO 4 2− ions rather than by stable crystalline environments of hydroxyapatite structure

Solid-state NMR characterization of drug-model molecules encapsulated in MCM-41 silica

International audienceIn this contribution, we present a solid-state NMR approach to characterize drugmodel molecules as ibuprofen, benzoic acid, and lauric acid, encapsulated in MCM-41 silica and submitted to strong confinement effects. In particular, we show that by a careful choice of the solid-state NMR sequences, it is possible to efficiently characterize these highly mobile molecules and their interactions with the pore surface. Thus, we demonstrate that 13C NMR spectroscopy is a powerful tool to characterize and even quantify entrapped and non-entrapped species by using either single-pulse excitation (SPE) or cross-polarization (CP). Whereas the standard {1H}-13C CP experiment is of poor efficiency for mobile species, we show that 13C signal-to-noise (S/N) ratio can be significantly improved through 1H-13C cross-relaxation (namely, nuclear Overhauser effect, nOe) by using a 1H power-gated technique. The long transversal relaxation times [T2(1H) up to 22 ms] observed allow the setup of J-coupling-based experiments such as 2D {1H}-13C heteronuclear multiple-quantum coherence (HMQC) in order to fully characterize the encapsulated molecules. Thus, we demonstrate that the use of sequences derived from solution-state NMR such as these two latter experiments is highly efficient to characterize highly mobile organic molecules trapped in mesopores. Finally, we show that 1H spin diffusion-based experiments can give useful information on the proximities between trapped molecules and the silica surfac

On-chip Generation of Sine-wave Summing Digital Signals: an Analytic Study Considering Implementation Constraints

In the context of biosensor as much as Built-In-Self Test (BIST), on-chip sine-wave signal generation is a recurring research topic. Considering the implementation constraints, it implies a trade-off between the amount of resources and the signal quality. An attractive solution consists in combining several digital signals to build this analog sine-wave. The objective of this paper is to give an analytic study of various potential digital-based solutions. Thanks to this study, we prove that the technique consisting in setting the phase shifts and various amplitude values of the square-wave signals is the most efficient approach. This study allows the selection of the optimal square-wave signal parameters to cancel low-order harmonics of the generated signal. We proposed a solution for specification-oriented definition of the architectur

Probing the mobility of ibuprofen confined in MCM-41 materials using MAS-PFG NMR and hyperpolarised-Xe-129 NMR spectroscopy

International audienceThe continuous-flow hyperpolarised (HP)-Xe-129 NMR and magic angle spinning-pulsed field gradient (MAS-PFG) NMR techniques have been used for the first time to study the distribution and the dynamics of ibuprofen encapsulated in MCM-41 with two different pore diameters

Investigation of the Interface in Silica-Encapsulated Liposomes by Combining Solid State NMR and First Principles Calculations

In the context of nanomedicine, liposils (liposomes and silica) have a strong potential for drug storage and release schemes: such materials combine the intrinsic properties of liposome (encapsulation) and silica (increased rigidity, protective coating, pH degradability). In this work, an original approach combining solid state NMR, molecular dynamics, first principles geometry optimization, and NMR parameters calculation allows the building of a precise representation of the organic/inorganic interface in liposils. H-1-Si-29H-1 and H-1-P-31H-1 Double Cross-Polarization (CP) MAS NMR experiments were implemented in order to explore the proton chemical environments around the silica and the phospholipids, respectively. Using VASP (Vienna Ab Initio Simulation Package), DFT calculations including molecular dynamics, and geometry optimization lead to the determination of energetically favorable configurations of a DPPC (dipalmitoylphosphatidylcholine) headgroup adsorbed onto a hydroxylated silica surface that corresponds to a realistic model of an amorphous silica slab. These data combined with first principles NMR parameters calculations by GIPAW (Gauge Included Projected Augmented Wave) show that the phosphate moieties are not directly interacting with silanols. The stabilization of the interface is achieved through the presence of water molecules located in-between the head groups of the phospholipids and the silica surface forming an interfacial H-bonded water layer. A detailed study of the P-31 chemical shift anisotropy (CSA) parameters allows us to interpret the local dynamics of DPPC in liposils. Finally, the VASP/solid state NMR/GIPAW combined approach can be extended to a large variety of organic-inorganic hybrid interfaces