Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins

Background Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAc alpha 2-3Gal). less thanbrgreater than less thanbrgreater thanPurpose The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of beta-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis. less thanbrgreater than less thanbrgreater thanMethods Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA. less thanbrgreater than less thanbrgreater thanResults Analysis of similar to 100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to similar to 100 controls, consistent with the known loss of galactosylation. A subgroup of similar to 15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA andlt;0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease. less thanbrgreater than less thanbrgreater thanConclusion This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.Funding Agencies|Swedish Research Council (Vetenskapsradet)|2008-3356|Swedish Foundation for Swedish Research|FFL4|Swedish Healthcare System (ALF)||Region Skane||</p

Ubiquitin-specific protease 5 is required for the efficient repair of DNA double-strand breaks

During the DNA damage response (DDR), ubiquitination plays an important role in the recruitment and regulation of repair proteins. However, little is known about elimination of the ubiquitination signal after repair is completed. Here we show that the ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, is involved in the elimination of the ubiquitin signal from damaged sites and is required for efficient DNA double-strand break (DSB) repair. Depletion of USP5 sensitizes cells to DNA damaging agents, produces DSBs, causes delayed disappearance of γH2AX foci after Bleocin treatment, and influences DSB repair efficiency in the homologous recombination pathway but not in the non-homologous end joining pathway. USP5 co-localizes to DSBs induced by laser micro-irradiation in a RAD18-dependent manner. Importantly, polyubiquitin chains at sites of DNA damage remained for longer periods in USP5-depleted cells. Our results show that disassembly of polyubiquitin chains by USP5 at sites of damage is important for efficient DSB repair. © 2014 Nakajima et al

Hydrogen absorption characteristics of oxygen-stabilized rare-earth iron intermetallic compounds

Le comportement thermique des systèmes hydrogène-composés stabilisés par l'oxygène, R3Fe8Ox (R = Y, Dy, Ho) a été étudié par gravimétrie et analyse thermique. Les résultats sont comparés à ceux obtenus sur les composés binaires RFe2 et RFe3.The thermal behavior of oxygen-stabilized R3Fe8Ox-hydrogen (R = Y, Dy, Ho) systems was studied by means TGA-DTA techniques. The results were compared to those obtained on binary RFe2 and RFe3 compounds

MAGNETISM AND HYPERFINE INTERACTIONS IN (Np1-xUx)6Fe

Des études Mössbauer de la transition à 59,5 keV du 237Np et de la transition à 14,4 keV du 57Fe ainsi que des mesures de susceptibilité magnétique ont été faites sur le système (Np1-xUx)6Fe. La susceptibilité magnétique ainsi que les résultats Mössbauer montrent que les actinides et le fer ne possèdent pas de moment magnétique localisé. Les échantillons ne s'ordonnent pas magnétiquement à aussi basse température que 1,9 K. Le spectre du 57Fe comporte un doublet quadrupolaire, eqQ = 16(2) Mc/s et un déplacement isomérique de - 0,29(6) mm/s par rapport au Fe métallique. Les spectres Mössbauer du 237Np, à toutes les températures et pour toutes les valeurs de x (T < 77 K, x = 0 ; 0,5 ; 0,8 ; 0,9) sont composés de deux sous-spectres purement quadrupolaires non-axiaux et ayant une intensité relative de 2 : 1. Pour le Np6Fe, eq1Q = 4450(50) Mc/s, η = 0,46(2) et eq2Q = 900(100) Mc/s, η = 0,9(1). Ces résultats sont en excellent accord avec la structure cristalline connue (tétragonale 41/mcm) où les ions de Np se trouvent dans deux sites de faible symétrie. Le déplacement isomérique des deux sous-spectres (-16(1) mm/s et -21(2) mm/s par rapport au NpAl2) correspond au neptunium pentavalent. Les ions Np5+ ne sont pas des ions Kramers et, puisqu'ils sont situés dans des champs cristallins de faible symétrie, leur manque de magnétisme n'est pas surprenant. D'autre part, pour le fer, ce phénomène est beaucoup moins courant dans les composés intermétalliques.Magnetic susceptibility and Mössbauer studies of the 59.5 keV transition of 237Np and the 14.4 keV transition of 57Fe in (Np1-xUx)6Fe were performed. The susceptibility and the Mössbauer experimental results prove that the actinides and the iron do not carry a localized magnetic moment. The samples do not order magnetically down to 1.9 K. The 57Fe spectrum consists of a quadrupole doublet, eqQ = 16(2) Mc/s, and isomer shift - 0.29(6) mm/s, relative to Fe metal. The 237Np Mössbauer spectra, for all temperatures and x values (T < 77 K, x = 0, 0.5, 0.8, 0.9) are composed of two pure non-axial quadrupole subspectra of relative intensities 2:1. In Np6Fe, eq1Q = 4450(50) Mc/s, η = 0.46(2) and eq2Q = 900(100) Mc/s, η = 0.9(1). These results agree very well with the known crystal structure (tetragonal 41/mcm) which contains Np ions in two low symmetry sites. The isomer shift of the two subspectra (-16(1) mm/s and -21(2) mm/s relative to NpAl2) corresponds to pentavalent neptunium. Np5+ are non Kramers ions and since they are located in very low symmetry crystalline fields, their being nonmagnetic is not surprising. On the other hand, the phenomenon that iron in an inter-metallic compound is nonmagnetic is not that common

Magnetic and hyperfine properties of NpFe2-xCoxSi2 tetragonal systems

Des mesures d'aimantation, d'effet Mössbauer et de diffraction neutronique ont été effectuées sur les composés intermétalliques NpFe2-xCoxSi2 (où x = 0 ; 1 ; 1,5 ; 2). Les études Mössbauer de 237Np permettent de mettre en évidence, pour les diverses valeurs de x, un ordre magnétique en dessous de 87(3), 15(3), 37(3) et 42(3) K respectivement, ainsi que des champs hyperfins de 2 535(50), 1 600(50), 2 210(50) et 2 600(50) MHz et des déplacements isomériques (relatifs à NpAl2) de - 2,3(3) ; + 7,6(3) ; 0(3) et - 2,9 mm/s. On a observé une très faible aimantation de caractère non saturé (à 4,2 K et 20 kOe). Un échantillon polycristallin de NpCo2Si2 a été étudié par diffraction neutronique entre 2 et 160 K. En dessous de 44 K on a observé cinq lignes de surstructure compatibles avec une structure antiferromagnétique de type I du sous-réseau Np(2 a ), pour laquelle TN = 44(3) K. Les intensités observées s'expliquent en attribuant un moment de 1,5 µB à l'ion Np et aucun moment localisé sur l'ion Co. Une corrélation directe entre déplacement isomérique, champ hyperfin et température d'ordre est mise en évidence pour la première fois. Une telle corrélation ne peut s'expliquer qu'en supposant une importante hybridation f-d et f-s.Magnetization, 237Np Mössbauer effect and neutron diffraction studies of the tetragonal NpFe2-x CoxSi2 (x = 0, 1, 1.5, 2) intermetallic compounds were performed. The Mössbauer studies of the 237Np show a magnetic order below 87(3), 15(3), 37(3), 42(3) K, hyperfine fields of 2 535(50), 1 600(50), 2 210(50), 2 600(50) MHz and isomeric shifts of - 2.3(3), + 7.6(3), 0(3), - 2.9 mm/s (relative to NpAl2 respectively. An extremely low magnetization of non-saturated character (at 4.2 K, 20 kOe) is observed. A polycrystalline ingot sample of NpCo2Si2 was studied by neutron diffraction at temperatures from 2 to 160 K. Five superlattice lines were observed at temperatures below 44 K and are consistent with an antiferromagnetic structure of the Np(2 a) sublattice of type I with TN = 44(3) K. The Np ion magnetic moment consistent with the diffracted intensities is 1.5(2) µB with no localized moment on the Co ion. A direct correlation between the isomer shift, hyperfine field and ordering temperature is reported for the first time. This unusual correlation can be explained only if strong f-d, f-s hybridization are assumed