Genetics of immunoglobulin-A vasculitis (Henoch-Schönlein purpura): An updated review

Immunoglobulin-A vasculitis (IgAV) is classically a childhood small-sized blood vessel vasculitis with predominant involvement of the skin. Gastrointestinal and joint manifestations are common in patients diagnosed with this condition. Nephritis, which is more severe in adults, constitutes the most feared complication of this vasculitis. The molecular bases underlying the origin of IgAV have not been completely elucidated. Nevertheless, several pieces of evidence support the claim that genes play a crucial role in the pathogenesis of this disease. The human leukocyte antigen (HLA) region is, until now, the main genetic factor associated with IgAV pathogenesis. Besides a strong association with HLA class II alleles, specifically HLA-DRB1 alleles, HLA class I alleles also seem to influence on the predisposition of this disease. Other gene polymorphisms located outside the HLA region, including those coding cytokines, chemokines, adhesion molecules as well as those related to T-cells, aberrant glycosylation of IgA1, nitric oxide production, neoangiogenesis, renin-angiotensin system and lipid, Pyrin and homocysteine metabolism, may be implicated not only in the predisposition to IgAV but also in its severity. An update of the current knowledge of the genetic component associated with the pathogenesis of IgAV is detailed in this review.Acknowledgements: RL-Mis supported by the Miguel Servet I programme of the Spanish Ministry of Economy and Competitiveness through the grant CP16/ 00033. FG is recipient of a Sara Borrell postdoctoral fellowship from the “Instituto Carlos III de Salud” at the Spanish Ministry of Health (Spain) (CD15/00095). SR-M is supported by funds from the RETICS Program (RIER) (RD16/0012/0009). FDC is supported by the Ramón y Cajal programme of the Spanish Ministry of Economy and Competitiveness through the grant RYC-2014-16458

Phase transition in LiVO2 studied by near-edge x-ray-absorption spectroscopy

We present temperature-dependent V-2p and O-1s x-ray-absorption spectra of LiVO2. The aim of this study is to monitor changes in electronic structure on going through the phase transition. The spectral changes turn out to be very small: the V-3d-O-2p hybridization does not change considerably, and the symmetry of the V-ion ground state (high-spin T-3(1)) is retained. To explain our results, together with the anomalously low magnetic susceptibility below the transition temperature, we propose a model in which a three-orbital sublattice is formed in the V (111) planes, which results in a total singlet state.</p

OXYGEN-1S AND COBALT-2P X-RAY ABSORPTION OF COBALT OXIDES

The oxygen ls and cobalt 2p x-ray absorption spectra of CoO, Li-doped CoO and LiCoO2 have been measured with 0.1 eV resolution. The cobalt 2p spectra are analysed with a ligand-field multiplet model and the inclusion of charge-transfer effects is discussed. The oxygen ls spectra are interpreted as transitions to empty oxygen p states and it is concluded that the effects of correlations in the 3d band possibly are too small to be detectable. The symmetries and the electronic configurations of the cobalt ions in the oxides are determined. It is concluded that, in contrast to for example NiO and La2CuO4, the doping-induced states are possibly of 1A1 symmetry, which would imply that the quasi-particles have spin 3/2 and are most likely trapped

PARP1 is overexpressed in nasopharyngeal carcinoma and its inhibition enhances radiotherapy

Nasopharyngeal carcinoma is a rare but highly invasive cancer. As options of agents for effectivecombination chemoradiotherapy for advanced nasopharyngeal carcinoma are limited, novel therapeutic approaches are desperately needed. The ubiquitin ligase CHFR is known to target PARP1 for degradation and is epigenetically inactivated in nasopharyngeal carcinoma. We present evidence that PARP1 protein is indeed overexpressed in nasopharyngeal carcinoma cells in comparison with immortalized normal nasopharyngeal epithelial cells. Tissue microarray analysis also indicated thatPARP1protein is significantly elevated in primary nasopharyngeal carcinoma tissues, with strong correlation with all stages of nasopharyngeal carcinoma development. We found that the PARP inhibitor AZD2281 (olaparib) increased DNA damage, cell-cycle arrest, and apoptosis in nasopharyngeal carcinoma cells challenged with ionizing radiation or temozolomide. Isobologram analysis confirmed that the cytotoxicity triggered by AZD2281 and DNAdamaging agents was synergistic. Finally, AZD2281 also enhanced the tumor-inhibitory effects of ionizing radiation in animal xenograft models. These observations implicate that PARP1 overexpression is an early event in nasopharyngeal carcinoma development and provide a molecular basis of using PARP inhibitors to potentiate treatment of nasopharyngeal carcinoma with radio- and chemotherapy. Mol Cancer Ther; 12(11); 2517-28. © 2013 AACR