57 research outputs found

    Azacytidine Enhances Regulatory T-Cells In Vivo and Prevents Experimental Xenogeneic Graft-Versus-Host Disease

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    Background The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Tregs). Objective We investigated the impact of AZA on xenogeneic graft-versus-host disease (xGVHD) in a humanized murine model of transplantation, and described the impact of the drug on human T cells in vivo. Methods In order to induce xGVHD, human peripheral blood mononuclear cells (huPBMC) were administered intravenously in NOD-scid IL-2Rγnull (NSG) mice. Results AZA successfully improved both survival (p<0.0001) and xGVHD scores (p<0.0001). Further, AZA significantly decreased human T-cell proliferation as well as INF-γ and TNF-α serum levels, and reduced the expression of GRANZYME B and PERFORIN 1 by cytotoxic T cells. In addition, AZA administration significantly increased the function, proliferation and frequency of Tregs through demethylation of FOXP3i1 and higher secretion of IL-2 by conventional T cells due to IL2 gene promoter site 1 demethylation. Interestingly, among AZA-treated mice surviving the acute phase of xGVHD, there was an inverse correlation between the presence of Tregs and signs of chronic GVHD. Finally, Tregs harvested from the spleen of AZA-treated mice were suppressive and stable over time since they persisted at high frequency in secondary transplant experiments. Conclusion These findings emphasize a potential role for AZA as prevention or treatment of GVHD

    Le chemostat : moyen d'investigation des facteurs de croissance en milieu oligotrophe

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    La présente étude a trait à des expériences de croissance effectuées au moyen d'une culture continue en chémostat d'une souche bactérienne, Pseudomonas putida, susceptible de donner lieu à des reviviscences dans les eaux de distribution. L'incorporation de carbone s'avère possible tant au départ de sources organiques telles que l'acétate de sodium que de sources inorganiques comme le bicarbonate. Il ressort de cette étude que les eaux potables oligotrophes ne contiennent pas qu'un seul substrat limitant spécifique mais bien plusieurs, de sorte que le taux de dilution n'est pas nécessairement équivalent au taux de croissance, contrairement à ce qu'on rencontre en culture continue où ce taux est limité par un seul substrat. De par ses possibilités de simulation, il s'avère que la technique par chémostat permet d'approcher au mieux les conditions de développement bactérien dans les installations et réseaux de distribution

    Biological filtration for drinking water production of Tailfer

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    Perspectives de l'utilisation du bioxyde de chlore dans la désinfection des eaux - effets du chlorite résiduel

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    Le bioxyde de chlore employé dans les traitements d'oxydation et de désinfection des eaux se retrouve largement sous forme de chlorite résiduel. Selon les conditions de la pratique, les concentrations varient entre 40 et 80% par rapport au bioxyde engagé. Cette étude envisage les propriétés de l'ion chlorite résiduel. Le pouvoir bactéricide du chlorite est faible, cependant il montre un effet ralentisseur considérable sur la croissance des germes de reviviscence, cet effet est illustré sur Pseudomonas putida. Le chlorite exerce un effet léthal sur Asellus aquaticus probablement par action sur l'hémocyanine. Cet effet est très favorable pour le maintien de la qualité générale des eaux dans les réseaux de distribution

    A structural, infrared, and Mossbauer spectral study of rosemaryite, NaMnFe3+Al(PO4)(3)

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    Rosemaryite, ideally NaMnFe(3+)AI(PO4)(3), has been collected in the Buranga pegmatite, Rwanda. A single-crystal structure refinement was performed to R-1 = 4.01 %, in the P2(1)/n space group, with a = 12.001(2), b = 12.396(1), c = 6.329(1) angstrom, beta 114.48(1)degrees, Vol. = 856.9(2) angstrom(3), Z = 4. The crystal structure and cation distributions are similar to those of ferrorosemaryite, NaFe2+Fe3+Al(PO4)(3), and qingheiite, Na2MnMgAl(PO4)(3), but aluminium predominantly occurs in the M(2a) site, not in the M(2b) site as observed in ferrowyllieite, Na2Fe22+Al(PO4)(3). The topologies of the X(1a) and X(1b) crystallographic sites are identical to those found in ferrorosemaryite, and correspond to a distorted octahedron and to a distorted cube, respectively. The [7+1]-coordinated X(2) site is a very distorted gable disphenoid, similar to the A(2)' site of the alluaudite structure. Mossbauer spectra have been obtained from 4.2 to 295 K, and fitted with a model including two Fe3+ and two Fe2+ doublets. The Fe2+ component corresponding to 2/3 of the Fe2+ spectral area and having a smaller quadrupole splitting of 2.63 mm/s at 15 K, is assigned to the Fe2+ on the M(2a) site, and the Fe2+ component with the larger quadrupole splitting of 3.17 mm/s at 15 K, is assigned to the Fe2+ on the M(1) site. Fe3+ is located only at the M(2a) and M(2b) sites, and the Fe3+ component corresponding to 3/4 of the Fe3+ and exhibiting the larger quadrupole spitting of 0.77 mm/s at 15 K, is most likely associated with Fe3+ on the M(2b) site. The infrared spectrum of rosemaryite shows absorption bands at 3450 and 1624 cm(-1), bands that arise from the vibrational modes of H2O and confirm the presence of water in the channels of the wyllieite structure. A comparison of both the Mossbauer spectra and structural data of rosemaryite with those of other phosphates of the alluaudite and wyllieite groups, is also presented

    A structural, magnetic, and Mossbauer spectral study of several Na-Mn-Fe-bearing alluaudites

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    The synthesis and the chemical, structural, magnetic, and Mossbauer spectral characterization of three synthetic alluaudites, Na2Mn2Fe(PO4)(3), NaMn Fe-2(PO4)(3) and (Na2MnFeFeIII)-Fe-II(PO4)(3), and a natural sample with the nominal composition of NaMn Fe-2(PO4)(3), collected in the Buranga pegmatite, Rwanda, are reported. All four compounds have the expected alluaudite monoclinic C2/c structure with the general formula [A(2)A(2)'][A(1)A(1)'A(1)(2)'']M(1)M(2)(2)(PO4)(3) in which manganese(II) is on the M(1) site and manganese(II), iron(III) and, in some cases, iron(II) on the M(2) site. The X-ray structure of Na2Mn2Fe(PO4)(3) also indicates a partially disordered distribution of Na-I and Mn-II on the M(1) and A(1) crystallographic sites. All four compounds are paramagnetic above 40 K and antiferromagnetically ordered below. Above 40 K the effective magnetic moments of NaMnFe2(PO4)(3) and Na2MnFeII Fe-III(PO4)(3) are those expected of high-spin manganese(II) and iron(III) with the (6)A(1g) electronic ground state and high-spin iron(II) with the T-5(2g) electronic ground state. In contrast, the effective magnetic moment of Na2Mn2Fe(PO4)(3) is lower than expected as a result of enhanced antiferromagnetic exchange coupling by the manganese(II) on the M(2) site. The Mossbauer spectra of all four compounds have been measured from 4.2 to 295 K and have been found to be magnetically ordered below 40 K for Na2Mn2Fe(PO4)(3) and similar to35 K for the remaining compounds. The Mossbauer spectra of Na2Mn2Fe(PO4)(3) exhibit the two expected iron(III) quadrupole doublets and/or magnetic sextets expected for a random distribution of manganese(II) and iron(III) ions on the M(2) site. Further, the Mossbauer spectra of (Na2MnFeFeIII)-Fe-II(PO4)(3) exhibit the two iron(II) and two iron(III) quadrupole doublets and/or magnetic sextets expected for a random distribution of iron(II) and iron(III) on the M(2) site. Surprisingly, the synthetic and natural samples of NaMnFe2(PO4)(3) have 19 and 10% of iron(II) on the M(2) site; apparently the presence of some iron(II) stabilizes the alluaudite structure through the reduction of iron(III)-iron(III) repulsion. The temperature dependence of the iron(II) quadrupole splitting yields a 440 to 600 cm(-1) low-symmetry component to the octahedral crystal field splitting at the M(2) site. The iron(II) and iron(III) hyperfine fields observed at 4.2 K are consistent with the presence of antiferromagnetic ordering at low temperatures in all four compounds
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