6 research outputs found

    Age-dependent deamidation of αB-crystallin

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    AbstractBovine and human αB-crystallin undergo deamidation upon aging in the lens. In bovine αB-crystallin, the specific site of dearnidation has been identified by peptide mapping after tryptic digestion. Asn-146 was found to be subject to deamidation, whereas the only other asparagine residue, at position 78, is not affected. Asn-146 is flanked at the carboxylic side by a glyeyl residue. Yet, the rate of in vivo deamidation is low. In vitro studies reveal that the deamidation is accompanied by significant racemization, indicating that the deamidation proceeds via formation of a succinimide intermediate

    New insights into the genetic etiology of Alzheimer's disease and related dementias

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    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele

    Genome-wide association study of circulating interleukin 6 levels identifies novel loci

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    Altres ajuts: Novo Nordisk Foundation (NNF18OC0052457).Interleukin 6 (IL-6) is a multifunctional cytokine with both pro-A nd anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology

    Characteristics, management, and outcomes of patients with left‐sided infective endocarditis complicated by heart failure: a substudy of the ESC‐EORP EURO‐ENDO (European infective endocarditis) registry

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