Solution Structure of Human p8 MTCP1 , a Cysteine-rich Protein Encoded by the MTCP1 Oncogene, Reveals a New a a a-Helical Assembly Motif

International audienceMature-T-Cell Proliferation) is the ®rst gene unequivocally identi®ed in the group of uncommon leukemias with a mature phenotype. The three-dimensional solution structure of the human p8 MTCP1 protein encoded by the MTCP1 oncogene was determined by homonuc-lear proton two-dimensional NMR methods at 600 MHz. After sequence speci®c assignments, a total of 931 distance restraints and 57 dihedral restraints were collected. The location of the three previously unassigned disul®de bridges was determined from preliminary DIANA structures, using a statistical analysis of intercystinyl distances. The solution structure of p8 MTCP1 is presented as a set of 30 DIANA structures, further re®ned by restrained molecular dynamics using a simulated annealing protocol with the AMBER force ®eld. The r.m.s.d. values with respect to the mean structure for the backbone and all heavy atoms for a family of 30 structures are 0.73(AE0.28) and 1.17(AE0.23) A Ê , when the structured core of the protein (residues 5 to 63) is considered. The solution structure of p8 MTCP1 reveals an original scaffold consisting of three a helices, associated with a new cysteine motif. Two of the helices are covalently paired by two disul®de bridges, forming an a-hairpin which resembles an antiparallel coiled-coil. The third helix is oriented roughly parallel to the plane de®ned by the a-antiparallel motif and its axis forms an angle of %60 with respect to the main axis of this motif

Indium(III) halides as exceptionally active, water-tolerant catalysts for cationic polymerization of styrenics

International audienceThe (co)polymerization of styrenes, α-methylstyrene, and indene is efficiently promoted by InBr3 or InCl3, in combination with an alkyl halide. This convenient route employs unpurified (wet) monomers, proceeds at slightly higher than room temperatures, and uses amounts as low as 20 ppm of indium pre-catalyst

Water-tolerant Catalyst Systems for the Bulk Cationic Polymerization of para-Methylstyrene and Indene

International audienceWater-tolerant catalyst systems have been investigated for the cationic oligomerization of technical-grade p-methylstyrene and indene, for the production of industrially relevant aromatic resins. Systems based on 1-p-tolylethanol and 1-indanol (ROH) as initiators, in association with Cu(OTf)2, Bi(OTf)3 (OTf = triflate) and B(C6F5)3 as co-initiators/catalysts, show interesting productivities at 60 °C under air, with as low as 0.2-1.0 mol% catalyst loading. Most of the reactions are not controlled in terms of molecular weights of the products, except for indene oligomerization by the borane catalyst where experimental Mn values match well the theoretical values, as determined by the amount of added initiator over a 5-fold range (with 2-10 mol% vs. monomer). The ROH/tris(pentafluorophenyl)borane system offers the best compromise in terms of productivity and control over the molecular weights of the oligomers, which can be manipulated by the amount of initiator and reaction temperature

Hexahydrofarnesyl as an original bio-sourced alkyl chain for the preparation of glycosides surfactants with enhanced physicochemical properties

International audienceFive new bio-based surfactants have been synthetized by coupling hexahydrofarnesol with mono and di-saccharides. Hexahydrofarnesol (3,7,11-trimethyl-dodecan-1-ol) is a by-product of the industrial production of farnesane, a sustainable aviation fuel obtained by a fermentation process from sugar feedstocks. Using hexahydrofarnesol as the lipophilic starting material allows obtaining 100% bio-based surfactants while valorizing an industrial by-product. Moreover, the C15-branched alkyl chain brings unique properties to the surfactants. This paper presents a physicochemical characterization of these new surfactants including their behaviors in water (water solubility, critical micellar concentration and surface tension) and in oil/water systems (interfacial tension against model oil and ternary phase behavior). Their hydrophilicities have been determined thanks to the PIT-slope method and compared to the ones of standard surfactants with linear alkyl chains, in order to distinguish the contributions of the sugar polar heads and of the branched hexahydrofarnesyl lipophilic chain. This novel class of surfactants combines the properties of sugar-based surfactants (low sensitivity to temperature and salinity, ability to form Winsor III microemulsion systems over a wide range of salinity), along with specificities linked to the branched alkyl chain (lower Krafft temperature, low surface tension)

Biomasse : les enjeux pour l’avenir de la chimie du carbone

International audienceThis article follows "Biomass: the future of carbon chemistry?" published in June-July 2016 issue, and deals more specifically with biomass resources, functions of the primary biorefinery, ways of overcoming the "recalcitrance" of cellulose, lignin applications, chemical conversions of fatty acids, microbial technologies for obtaining oils, and with the terpenes value chain. The driving forces for the development of bio-based products and the major challenges of the sector are also presented.Cet article fait suite à celui paru en 2016, « Biomasse : l'avenir de la chimie du carbone ? », et traite plus spécifique-ment des ressources en biomasse, des fonctions de la bioraffinerie primaire, des manières de vaincre la « récal-citrance » de la cellulose, d'applications de la lignine, de conversions chimiques des acides gras, des technologies microbiennes d'obtention des huiles et de la filière terpénique. Les éléments moteurs de développement des produits biosourcés et les grands défis de la filière sont également présentés

Mesoporous thin film WO ₃ photoanode for photoelectrochemical water splitting: a sol–gel dip coating approach

International audienceA facile and cost-efficient method to fabricate a mesoporous structured WO3 photoanode was implemented for use in a tandem dual water splitting photoelectrochemical cell. Semi-transparent thin films of tungsten trioxide were fabricated by sol-gel process, incorporating a block co-polymer to induce a template-directed mesoporous structure. These thin films are deposited by dip coating onto transparent conducting oxide substrates and crystallized at a low temperature of 400°C in air. These thin film photoanodes exhibit a photocurrent of up to 0.6 mA/cm² in potassium phosphate buffers of pH 2, 4, and 6 at 1.23 V vs. RHE under 300 mW/cm² visible (400 – 900 nm) light irradiation with a faradic efficiency of up to 75%. Furthermore, we have demonstrated that corrosion occurs in electrolytes of pH > 4. The faradic efficiencies in varying pH solutions however suggest that parasitic redox reactions occurs in acidic conditions, limiting the O2 production and demonstrating the need for stable surface co-catalysts to increase faradic efficiencies. In neutral conditions, protective layers and/or co-catalysts are needed for increasing WO3 photoanode stability

Solution structure of the recombinant human oncoprotein p13 MTCP1

International audienceThe human oncoprotein p13 MTCP1 is coded by the MTCP1 gene, a gene involved in chromosomal translocations associated with T-cell prolymphocytic leukemia, a rare form of human leukemia with a mature T-cell phenotype. The primary sequence of p13 MTCP1 is highly and only homologous to that of p14 TCL1 , a product coded by the gene TCL1 which is also involved in T-cell prolymphocytic leukemia. These two proteins probably represent the first members of a new family of oncogenic proteins. We present the three-dimensional solution structure of the recombinant p13 MTCP1 determined by homonuclear proton two-dimensional NMR methods at 600 MHz. After proton resonance assignments, a total of 1253 distance restraints and 64 dihedral restraints were collected. The solution structure of p13 MTCP1 is presented as a set of 20 DYANA structures. The rmsd values with respect to the mean structure for the backbone and all heavy atoms for the conformer family are 1.07 ± 0.19 and 1.71 ± 0.17 Å, when the structured core of the protein (residues 11-103) is considered. The solution structure of p13 MTCP1 consists of an orthogonal β-barrel, composed of eight antiparallel β-strands which present an original arrangement. The two β-pleated loops which emerge from this barrel might constitute the interaction surface with a potential molecular partner. Abbreviations: t(X;14)(q28;q11), indicates a translocation between the q28 band of chromosome X and the q11 band of chromosome 14; inv(14;14)(q11;q32), indicates an inversion between the q11 and q32 bands of chromosome 14; V(D)J, variability (diversity

Elucidating transfer hydrogenation mechanisms in non-catalytic lignin depolymerization

Lignin undergoes catalytic depolymerization in the presence of a variety of transfer hydrogenation agents, however the mechanisms for non-catalytic depolymerization of lignin via transfer hydrogenation are not well understood; this makes process optimization difficult. Herein, for the first time a mechanism for this process is proposed. For the purposes of understanding the mechanisms involved in these non-catalytic lignin depolymerization processes, this study investigates the equilibrium system of formic acid, methyl formate and carbon monoxide, as agents for the depolymerization of lignin, in the presence of either water or methanol as solvents. In the methyl formate/water (at 300 °C) system, 73 wt% oil was produced which contained a significant amount of low molecular weight alkylphenols, with less than 1 wt% char produced. In aqueous media, the results showed that methyl formate maintains an equilibrium with formic acid which is itself in equilibrium with carbon monoxide. It was found that using either formic acid or methyl formate for non-catalytic transfer hydrogenation of lignin can produce high amounts of oil, and can be described as a two-stage mechanism. After 10 min of reaction at 300 °C, around a quarter of the formic acid is consumed via hydride transfer of the formate proton, preventing the condensation of lignin fragments. At the same time, approximately three quarters of the formic acid decomposes to carbon dioxide and carbon monoxide. Once the formic acid is consumed, the carbon monoxide was identified as the precursor to a reactive reductive reagent and was able to activate the proton of the water molecule preventing further condensation of the lignin fragments. It has been previously thought that transfer hydrogenation in lignin using formic acid occurs via the production of molecular hydrogen. Here it is demonstrated that formic acid reacts directly with the lignin, without this hydrogen formation. Therefore the key parameters for efficient transfer hydrogenation of the lignin to maximize bio-oil yield appear to involve controlling the reactions between lignin and formic acid, methyl formate or carbon monoxide under aqueous conditions, thereby reducing the reagent cost and loading while maintaining efficient lignin conversion

ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity

Resistances to immunotherapies remains a major hurdle towards a cure for melanoma in numerous patients. An increase in the mesenchymal phenotype and a loss of differentiation have been clearly associated with resistance to targeted therapies. Similar phenotypes have been more recently also linked to resistance to immune checkpoint therapies. We demonstrated here that the loss of MIcrophthalmia associated Transcription Factor (MITF), a pivotal player in melanocyte differentiation, favors the escape of melanoma cells from the immune system. We identified Integrin beta-like protein 1 (ITGBL1), a secreted protein, upregulated in anti-PD1 resistant patients and in MITFlow melanoma cells, as the key immunomodulator. ITGBL1 inhibited immune cell cytotoxicity against melanoma cells by inhibiting NK cells cytotoxicity and counteracting beneficial effects of anti-PD1 treatment, both in vitro and in vivo. Mechanistically, MITF inhibited RUNX2, an activator of ITGBL1 transcription. Interestingly, VitaminD3, an inhibitor of RUNX2, improved melanoma cells to death by immune cells. In conclusion, our data suggest that inhibition of ITGBL1 might improve melanoma response to immunotherapies