72 research outputs found

    Acid/base-triggered switching of circularly polarized luminescence and electronic circular dichroism in organic and organometallic helicenes.

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    Electronic circular dichroism and circularly polarized luminescence acid/base switching activity has been demonstrated in helicene-bipyridine proligand 1 a and in its “rollover” cycloplatinated derivative 2 a. Whereas proligand 1 a displays a strong bathochromic shift (>160 nm) of the nonpolarized and circularly polarized luminescence upon protonation, complex 2 a displays slightly stronger emission. This strikingly different behavior between singlet emission in the organic helicene and triplet emission in the organometallic derivative has been rationalized by using quantum-chemical calculations. The very large bathochromic shift of the emission observed upon protonation of azahelicene-bipyridine 1 a has been attributed to the decrease in aromaticity (promoting a charge-transfer-type transition rather than a π–π* transition) as well as an increase in the HOMO–LUMO character of the transition and stabilization of the LUMO level upon protonation

    Effective Gene Therapy in a Mouse Model of Prion Diseases

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    Classical drug therapies against prion diseases have encountered serious difficulties. It has become urgent to develop radically different therapeutic strategies. Previously, we showed that VSV-G pseudotyped FIV derived vectors carrying dominant negative mutants of the PrP gene are efficient to inhibit prion replication in chronically prion-infected cells. Besides, they can transduce neurons and cells of the lymphoreticular system, highlighting their potential use in gene therapy approaches. Here, we used lentiviral gene transfer to deliver PrPQ167R virions possessing anti-prion properties to analyse their efficiency in vivo. Since treatment for prion diseases is initiated belatedly in human patients, we focused on the development of a curative therapeutic protocol targeting the late stage of the disease, either at 35 or 105 days post-infection (d.p.i.) with prions. We observed a prolongation in the lifespan of the treated mice that prompted us to develop a system of cannula implantation into the brain of prion-infected mice. Chronic injections of PrPQ167R virions were done at 80 and 95 d.p.i. After only two injections, survival of the treated mice was extended by 30 days (20%), accompanied by substantial improvement in behaviour. This delay was correlated with: (i) a strong reduction of spongiosis in the ipsilateral side of the brain by comparison with the contralateral side; and (ii) a remarkable decrease in astrocytic gliosis in the whole brain. These results suggest that chronic injections of dominant negative lentiviral vectors into the brain, may be a promising approach for a curative treatment of prion diseases

    Protective effect of thrombospondin-4 expressing mesenchymal stem cells in osteoarthritis

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    Bonding and substituent effects in electron-rich mononuclear ruthenium sigma-arylacetylides of the formula [(eta(2)-dppe)(eta(5)-C5Me5)Ru(C C)-1,4-(C6H4)X][PF6](n) (n = 0, 1; X = NO2, CN, F, H, OMe, NH2)

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    Frédéric Paul, Benjamin G. Ellis, Michael I. Bruce, Loic Toupet, Thierry Roisnel, Karine Costuas, Jean-François Halet, and Claude Lapint
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