Semi-synthesis of a HGF/SF kringle one (K1) domain scaffold generates a potent in vivo MET receptor agonist

The development of MET receptor agonists is an important goal in regenerative medicine, but is limited by the complexity and incomplete understanding of its interaction with HGF/SF (Hepatocyte Growth Factor/Scatter Factor). NK1 is a natural occurring agonist comprising the N-terminal (N) and the first kringle (K1) domains of HGF/SF. In the presence of heparin, NK1 can self-associate into a “head to tail” dimer which is considered as the minimal structural module able to trigger MET dimerization and activation whereas isolated K1 and N domains showed a weak or a complete lack of agonistic activity respectively. Starting from these structural and biological observations, we investigated whether it was possible to recapitulate the biological properties of NK1 using a new molecular architecture of isolated N or K1 domains. Therefore, we engineered multivalent N or K1 scaffolds by combining synthetic and homogeneous site-specifically biotinylated N and K1 domains (NB and K1B) and streptavidin (S). NB alone or in complex failed to activate MET signaling and to trigger cellular phenotypes. Importantly and to the contrary of K1B alone, the semi-synthetic K1B/S complex mimicked NK1 MET agonist activity in cell scattering, morphogenesis and survival phenotypic assays. Impressively, K1B/S complex stimulated in vivo angiogenesis and, when injected in mice, protected the liver against fulminant hepatitis in a MET dependent manner whereas NK1 and HGF were substantially less potent. These data reveal that without N domain, proper multimerization of K1 domain is a promising strategy for the rational design of powerful MET agonists.     

Green–Lazarsfeld's conjecture for generic curves of large gonality

We use Green's canonical syzygy conjecture for generic curves to prove that the Green–Lazarsfeld gonality conjecture holds for generic curves of genus g, and gonality d, if g/3<d<[g/2]+2. To cite this article: M. Aprodu, C. Voisin, C. R. Acad. Sci. Paris, Ser. I 336 (2003).     

In situ evaluation of interfacial affinity in CeO2 based hybrid nanoparticles by pulsed field gradient NMR

Complexation affinity of laurate ligands (C(12)H(23)O(2)) grafted onto the surface of cerium(IV) oxide nanoparticles can be probed and quantified in situ, by pulsed field gradient (1)H NMR through the dependence of the diffusion coefficient on the size of a species.     

(13)C/(12)C isotope labelling to study leaf carbon respiration and allocation in twigs of field-grown beech trees

In situ (13)C/(12)C isotopic labelling was conducted in field-grown beech (Fagus sylvatica) twigs to study carbon respiration and allocation. This was achieved with a portable gas-exchange open system coupled to an external chamber. This method allowed us to subject leafy twigs to CO(2) with a constant carbon isotope composition (delta(13)C of -51.2 per thousand) in an open system in the field. The labelling was done during the whole light period at two different dates (in June 2002 and October 2003). The delta(13)C values of respiratory metabolites and CO(2) that is subsequently respired during the night were measured. It was found that night-respired CO(2) is not completely labelled (only ca. 58% and 27% of new carbon is found in respired CO(2) immediately after the labelling in June 2002 and October 2003, respectively) and the labelling level progressively disappeared during the next day. It is concluded that the carbon respired by beech leaves after illumination was supplied by a mixture of carbon sources in which current carbohydrates were not the only contributors. In addition, as has been found in herbaceous plants, isotopic data before labelling showed that carbon isotope discrimination favoring the (13)C isotope occurred during the night respiration of beech leaves.     

Bright Infrared-to-Ultraviolet/Visible Upconversion in Small Alkaline Earth-Based Nanoparticles with Biocompatible CaF2 Shells

Upconverting nanoparticles (UCNPs) are promising candidates for photon-driven reactions, including light-triggered drug delivery, photodynamic therapy, and photocatalysis. Herein, we investigate the NIR-to-UV/visible emission of sub-15 nm alkaline-earth rare-earth fluoride UCNPs (M_1−xLn_xF_2+x, MLnF) with a CaF₂ shell. We synthesize 8 alkaline-earth host materials doped with Yb³⁺ and Tm³⁺, with alkaline-earth (M) spanning Ca, Sr, and Ba, MgSr, CaSr, CaBa, SrBa, and CaSrBa. We explore UCNP composition, size, and lanthanide doping-dependent emission, focusing on upconversion quantum yield (UCQY) and UV emission. UCQY values of 2.46 % at 250 W cm⁻² are achieved with 14.5 nm SrLuF@CaF₂ particles, with 7.3 % of total emission in the UV. In 10.9 nm SrYbF:1 %Tm³⁺@CaF₂ particles, UV emission increased to 9.9 % with UCQY at 1.14 %. We demonstrate dye degradation under NIR illumination using SrYbF:1 %Tm³⁺@CaF₂, highlighting the efficiency of these UCNPs and their ability to trigger photoprocesses.     

Aluminium Mediated Glycosaminoglycan/Amyloid-β Association Mechanism

In Alzheimer’s disease, it has been proposed that glycosaminoglycans facilitate amyloid fibril formation and/or stabilize the plaque aggregates. Chondroitin sulfates are sulfated glycosaminoglycans represented an ideal distribution of charge for amyloid-β (Aβ) interactions. Recent studies have suggested a possible link between the neurotoxicity of aluminum and the pathogenesis of Alzheimer’s disease. In this paper, the interaction of Aβ with chondroitin sulfates immobilized on a chromatographic column and the role of aluminum had been studied using a biochromatographic approach (molecular chromatography). A novel biochromatographic column was developed in our laboratory for studying this interaction. This study demonstrated that the aluminum interacted with Aβ and played a role in the Aβ/chondroitin sulfates association. For a Al³⁺ concentration (x) in the medium less than 30 μmM, the Aβ/chondroitin sulfates binding decreased with x due to a decrease of the charge–charge interactions between Aβ and its chondroitin sulfates binding site. Above 30 μmM of Al³⁺ in the medium, the affinity of Aβ to chondroitin sulfates increased slightly with x because the net number of ions (n) (Al³⁺ or Cl^?) released or bound upon complex formation is low. As well, it was clearly demonstrated, that above 30 μmM the n value depend on the Al³⁺ concentration in the bulk solvent. This dependence was due to a gradual and conformational change of the Aβ which around 80 μmM adopted a less flexible structure; its binding site was thus less accessible to Aβ and Aβ/chondroitin sulfates association decreased slightly.     

Solvents for ring-closing metathesis reactions

A study of the influence of eight diverse solvents on a Grubbs II-catalysed ring-closing metathesis (RCM) reaction reveals a complex dependence of the different reaction steps on the solvent and suggests acetic acid as a useful solvent for RCM reactions.     

Molecular Gears: From Solution to Surfaces

This review highlights the major efforts devoted to the development of molecular gears over the past 40 years, from pioneering covalent bis-triptycyl systems undergoing intramolecular correlated rotation in solution, to the most recent examples of gearing systems anchored on a surface, which allow intermolecular transmission of mechanical power. Emphasis is laid on the different strategies devised progressively to control the architectures of molecular bevel and spur gears, as intramolecular systems in solution or intermolecular systems on surfaces, while aiming at increased efficiency, complexity and functionality.     

Thermally stable potassium N-heterocyclic carbene complexes with alkoxide ligands, and a polymeric crystal structure with distorted, bridging carbenes

Alkoxide-functionalized N-heterocyclic carbenes (NHCs) stabilise the potassium-imidazole-2-ylidene fragment against 1,2 alkyl rearrangement reactions; this allows the first structural characterisation of a potassium NHC complex, which reveals distorted and unusual bonding interactions between the imidazole ring and the potassium cation.