A Functional Variant in ERAP1 Predisposes to Multiple Sclerosis

The ERAP1 gene encodes an aminopeptidase involved in antigen processing. A functional polymorphism in the gene (rs30187, Arg528Lys) associates with susceptibility to ankylosying spondylitis (AS), whereas a SNP in the interacting ERAP2 gene increases susceptibility to another inflammatory autoimmune disorder, Crohn's disease (CD). We analysed rs30187 in 572 Italian patients with CD and in 517 subjects suffering from multiple sclerosis (MS); for each cohort, an independent sex- and age-matched control group was genotyped. The frequency of the 528Arg allele was significantly higher in both disease cohorts compared to the respective control population (for CD, OR = 1.20 95%CI: 1.01–1.43, p = 0.036; for RRMS, OR = 1.26; 95%CI: 1.04–1.51, p = 0.01). Meta-analysis with the Wellcome Trust Cases Control Consortium GWAS data confirmed the association with MS (pmeta = 0.005), but not with CD. In AS, the rs30187 variant has a predisposing effect only in an HLA-B27 allelic background. It remains to be evaluated whether interaction between ERAP1 and distinct HLA class I alleles also affects the predisposition to MS, and explains the failure to provide definitive evidence for a role of rs30187 in CD. Results herein support the emerging concept that a subset of master-regulatory genes underlay the pathogenesis of autoimmunity

Structural and Spectroscopic Investigation of Novel 2D and 3D Uranium Oxo-Silicates/Germanates and Some Statistical Aspects of Uranyl Coordination in Oxo-Salts

Synthesis, structural and spectroscopic characterization, and topological analysis of five novel uranyl-based silicates and germanates have been performed. The open-framework K4(UO2)2Si8O20·4H2O has been synthesized under hydrothermal conditions and is based upon [USi6] heptamers interconnected via edge-sharing. Its structure is composed of sechser silicate layers with 4-, 8-, and 16-membered rings. The largest 16-membered rings have an average dimension of ∼8.93 × 9.42 Å2. β-K2(UO2)Si4O10 has been obtained by the high-temperature flux growth method. Its 3D framework contains a loop-branched sechser single layer with 4- and 8-membered rings and consists of the same [USi6] heptamers as observed in K4(UO2)2Si8O20·4H2O. Na6(UO2)3(Si2O7)2 has also been synthesized from melted fluxes and represents a 2D layer structure composed by [USi4] pentamers. Two iso-structural compounds A+(UO2)(HGeO4)·H2O (A+ = Rb+, Cs+) were synthesized via the hydrothermal method, and their structures are of the α-uranophane type. The 2D layers consist of [U2Ge2] tetramer secondary building units (SBUs). The Raman spectra of all novel phases were collected, and bands were assigned according to the existing oxo-silicate rings and oxo-germanium units. Additionally, we performed a statistical investigation of the local coordination of uranyl ions in all known inorganic structures with different oxo-anions (TOx, T = B3+, Si/Ge4+, P/As5+, S/Se/Te6+, Cr/Mo/W6+, P/As3+, and Se/Te4+). We found a direct correlation between the ionic potential of the central cations T in oxo-anions in their higher oxidation states and the coordination number of uranyl groups

Formation of Open Framework Uranium Germanates: The Influence of Mixed Molten Flux and Charge Density Dependence in U-Silicate and U-Germanate Families

Seven novel open-framework uranyl germanates, K2(UO2)GeO4, K6(UO2)3Ge8O22, α-Cs2(UO2)Ge2O6, β-Cs2(UO2)Ge2O6, Cs2(UO2)GeO4, and A(UO2)3(Ge2O7)2 (A = [NaK6Cl]6+, [Na2Cs6Cl2]6+), were grown from different mixed molten fluxes. The three-dimensional (3D) structure of K2(UO2)GeO4 with 8-ring channels can be built upon [UGe4] pentamer secondary building units (SBUs). The 3D framework of K6(UO2)3Ge8O22 with trapezoid (Ge8O22)12– clusters consists of two types of [UGe4] pentamers. The 3D framework of α-Cs2(UO2)Ge2O6 with 10-ring channels, crystallizing in the P21/n space group, is constructed by [UGe4] pentamers. The structure of β-Cs2(UO2)Ge2O6 contains achter (eight) single germanate chains and is composed of [UGe6] heptamers and [UGe4] pentamers. The structure of Cs2(UO2)GeO4 with hexagonal 10-ring channels is composed of [U3Ge4] heptamers and twisting five-fold GeO4 tetrahedra in four-membered Ge4O12 rings occur. 3D frameworks of NaK6Cl(UO2)3(Ge2O7)2 (space group Pnnm) and Na2Cs6Cl2(UO2)3(Ge2O7)2 (P21/c) can be constructed from the same SBUs [UGe4] pentamers. Thermal stability of salt-inclusions was studied by TG and PXRD analysis. Analysis of charge density for the U–Si–O system indicates that the polymerization of silicate units reduces the cross-links of the 3D frameworks. The concept of SBUs combined with the cutting and gluing strategy was applied to understand and analyze the distinct 8-, 10-, 12-, and 14- membered channels for the uranyl germanate family. The charge density of all known 3D U–Si/Ge–O frameworks has been investigated, which shows strong correlations with chemical composition of corresponding phases. The increase of Si/O (Ge/O) ratios in silicate units results in the decrease of negative charge density. Moreover, the charge density increases with decreasing countercation size within the same Si/O ratio. The correlations can be used to predict inclusion phase formation within U–Si/Ge–O families. Raman spectra of the studied uranyl germanates were measured, and bands were assigned on the basis of structural features

The Role of Acidity in the Synthesis of Novel Uranyl Selenate and Selenite Compounds and Their Structures

Herein, the novel uranyl selenate and selenite compounds Rb2[(UO2)2(SeO4)3], Rb2[(UO2)3(SeO3)2O2], Rb2[UO2(SeO4)2(H2O)]·2H2O, and (UO2)2(HSeO3)2(H2SeO3)2Se2O5 have been synthesized using either slow evaporation or hydrothermal methods under acidic conditions and their structures were refined using single crystal X-ray diffraction. Rb2[(UO2)2(SeO4)3] synthesized hydrothermally adopts a layered 2D tetragonal structure in space group P42/ncm with a = 9.8312(4) Å, c = 15.4924(9) Å, and V = 1497.38(15) Å, where it consists of UO7 polyhedra coordinated via SeO4 units to create units UO2(SeO4)58− moieties which interlink to create layers in which Rb+ cations reside in the interspace. Rb2[(UO2)3(SeO3)2O2] synthesized hydrothermally adopts a layered 2D triclinic structure in space group P1¯ with a = 7.0116(6) Å, b = 7.0646(6) Å, c = 8.1793(7) Å, α = 103.318(7)°, β = 105.968(7)°, γ = 100.642(7)° and V = 365.48(6) Å3, where it consists of edge sharing UO7, UO8 and SeO3 polyhedra that form [(UO2)3(SeO3)2O2] layers in which Rb+ cations are found in the interlayer space. Rb2[UO2(SeO4)2(H2O)]·2H2O synthesized hydrothermally adopts a chain 1D orthorhombic structure in space group Pmn21 with a = 13.041(3) Å, b = 8.579(2) Å, c = 11.583(2) Å, and V = 1295.9(5) Å3, consisting of UO7 polyhedra that corner share with one H2O and four SeO42− ligands, creating infinite chains. (UO2)2(HSeO3)2(H2SeO3)2Se2O5 synthesized under slow evaporation conditions adopts a 0D orthorhombic structure in space group Cmc21 with a = 28.4752(12) Å, b = 6.3410(3) Å, c = 10.8575(6) Å, and V = 1960.45(16) Å3, consisting of discrete rings of [(UO2)2(HSeO3)2(H2SeO3)2Se2O5]2. (UO2)2(HSeO3)2(H2SeO3)2Se2O5 is apparently only the second example of a uranyl diselenite compound to be reported. A combination of single crystal X-ray diffraction and bond valance sums calculations are used to characterise all samples obtained in this investigation. The structures uncovered in this investigation are discussed together with the broader family of uranyl selenates and selenites, particularly in the context of the role acidity plays during synthesis in coercing specific structure, functional group, and topology formation

Unexpected Behavior of Np in Oxo-selenate/Oxo-selenite Systems

A study of neptunium (Np) chemistry in the complex oxo-selenium system has been performed. Hereby, two sets of precipitation experiments were conducted, investigating the influence of the initial oxidation state of selenium using SeIVO2 and H2SeVIO4 with NpV in alkali nitrate solution, keeping the ratio of Np:Se constant. Surprising results were observed. Five novel neptunium and selenium bearing compounds have been obtained by slow evaporation from aqueous solution. The novel NpIV phase K4-x[Np(SeO3)4-x(HSeO3)x]•(H2O)1.5 (1) crystallizes in green colored plate shaped crystals and was obtained by adding SeO2 and ANO3 to a NpV stock solution. Single-crystal X-ray diffraction reveals one-dimensional chain structures composed of square antiprismatic NpO8 polyhedra linked via four trigonal pyramidal SeO3 and HSeO3 units. Raman spectral analysis supports the presence of both selenite and hydroselenite due to the presence of corresponding modes within the spectra. The addition of selenic acid to a NpV stock solution resulted in the precipitation of elongated rose prisms of K2[(NpO2)2(SeO4)3(H2O)2]•(H2O)1.5 (2), Rb2[(NpO2)2(SeO4)3(H2O)2]•(H2O)2 (3) and K9[(NpO2)9(SeO4)13.5(H2O)6]•(H2O)12 (4) as well as light red plates of Cs2[(NpO2)2(SeO4)3] (5). To our knowledge, this is the first report of NpVI selenates. All four structures show two-dimensional layered structures with alkali cations acting as charge balancing counter cations. Hereby the layers of compounds 2 and 3 are found to be orientational geometric isomers. Distinctly different phenomena are made responsible for the phase formation within these systems. The kinetically driven process of NpV disproportionation led to the formation of the NpIV selenites in the SeIV based system whereas the oxidation of NpV by reduction of nitrate in acidic conditions is made responsible for the formation of the NpVI sel-enates in the SeVI system. The influence of air oxygen is also discussed for the latter reaction.JRC.G.I.5-Advanced Nuclear Knowledg

Achieving and Stabilizing Uranyl Bending via Physical Pressure

Applying physical pressure in the uranyl–sulfate system has resulted in the formation of the first purely inorganic uranyl oxo-salt phase with a considerable uranyl bend: Na4[(UO2)(SO4)3]. In addition to a strong bend of the typically almost linear O═U═O, the typically equatorial plane is broken up by two out-of-plane oxygen positions. Computational investigations show the origin of the bending to lie in the applied physical pressure and not in the electronic influence or steric hindrance. The increase in pressure onto the system has been shown to increase uranyl bending. Furthermore, the phase formation is compared with a reference phase of a similar structure without uranyl bending, and a transition pressure of 2.5 GPa is predicted, which is well in agreement with the experimental results