Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults

Activation of inflammatory pathways measured by serum inflammatory markers such as interleukin-18 (IL-18) and interleukin-1 receptor antagonist (IL-1ra) is strongly associated with the progression of chronic disease states in older adults. Given that these serum cytokine levels are in part a heritable trait, genetic variation may predict increased serum levels. Using the Cardiovascular Health Study and InCHIANTI cohorts, a genome-wide association study was performed to identify genetic variants that influence IL18 and IL-1ra serum levels among older adults. Multiple linear regression models characterized the association between each SNP and log-transformed cytokine values. Tests for multiple independent signals within statistically significant loci were performed using haplotype analysis and regression models conditional on lead SNP in each region. Multiple SNPs were associated with these cytokines with genome-wide significance, including SNPs in the IL18-BCO gene region of chromosome 2 for IL-18 (top SNP rs2250417, P = 1.9×10−32) and in the IL1 gene family region of chromosome 2 for IL-1ra (rs6743376, P = 2.3×10−26). Haplotype tests and conditional linear regression models showed evidence of multiple independent signals in these regions. Serum IL-18 levels were also associated with a region on chromosome 2 containing the NLRC4 gene (rs12989936, P = 2.7×10−19). These data characterize multiple robust genetic signals that influence IL-18 and IL-1ra cytokine production. In particular, the signal for serum IL-18 located on chromosome two is novel and potentially important in inflammasome triggered chronic activation of inflammation in older adults. Replication in independent cohorts is an important next step, as well as molecular studies to better understand the role of NLRC4

Solar Wind Turbulence and the Role of Ion Instabilities

International audienc

GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium

Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10−8) and 39 suggestive (P-value< 5 × 10−5) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10−10). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength

Valutazione dei fenomeni di corrosione di bronzi dorati in diverse condizioni espositive: il caso della Porta del Paradiso di Lorenzo Ghiberti

Nella fase finale del restauro, tuttora in corso, la Porta del Paradiso di Lorenzo Ghiberti, importante opera scultorea in bronzo dorato del Rinascimento verrà rimontata per essere nuovamente esposta al pubblico. I prodotti di corrosione che si sono formati tra il bronzo e la doratura sono instabili e tuttora estremamente sensibili alle variazioni microclimatiche. È dunque necessario identificare le migliori condizioni di esposizione museale in modo da inibire ogni ulteriore procedere del degrado e allo stesso tempo garantire una adeguata fruizione da parte del pubblico. L’Opificio delle Pietre Dure ha promosso un progetto di monitoraggio al fine di studiare e proporre soluzioni sostenibili al problema. Sono state prese in considerazione tre possibili alternative: 1) una teca saturata con azoto; 2) una teca a umidità relativa bassa e controllata; 3) una lamina dinamica di aria secca soffiata verticalmente per separare la superficie dorata della Porta dal resto dell’ambiente. Al fine di effettuare una scelta consapevole e ponderata è necessario verificare da un punto di vista conservativo, mediante dati qualitativi e quantitativi, quali possono essere gli effetti delle tre metodologie espositive individuate. A questo scopo due elementi della Porta del Paradiso sono stati esposti nelle due teche, monitorando i cambiamenti della superficie nel tempo mediante analisi del colore e della composizione dei prodotti di corrosione che si dovessero eventualmente formare. La lamina d’aria secca invece è ancora in fase di realizzazione. Inoltre, al fine di avere una misura quantitativa dell’efficacia delle diverse condizioni di esposizione, è stato messo a punto un sistema di sensori “galvanici” in bronzo patinato e dorato che simulano la composizione e la stratigrafia delle formelle della Porta. Tali sensori sono stati posizionati vicino agli elementi in bronzo dorato in modo da poter effettuare misure in continuo della velocità di corrosione, e studiare l’impatto del microambiente nelle diverse condizioni di esposizione

Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults

Activation of inflammatory pathways measured by serum inflammatory markers such as interleukin-18 (IL-18) and interleukin-1 receptor antagonist (IL-1ra) is strongly associated with the progression of chronic disease states in older adults. Given that these serum cytokine levels are in part a heritable trait, genetic variation may predict increased serum levels. Using the Cardiovascular Health Study and InCHIANTI cohorts, a genome-wide association study was performed to identify genetic variants that influence IL18 and IL-1ra serum levels among older adults. Multiple linear regression models characterized the association between each SNP and log-transformed cytokine values. Tests for multiple independent signals within statistically significant loci were performed using haplotype analysis and regression models conditional on lead SNP in each region. Multiple SNPs were associated with these cytokines with genome-wide significance, including SNPs in the IL18-BCO gene region of chromosome 2 for IL-18 (top SNP rs2250417, P = 1.9×10(−32)) and in the IL1 gene family region of chromosome 2 for IL-1ra (rs6743376, P = 2.3×10(−26)). Haplotype tests and conditional linear regression models showed evidence of multiple independent signals in these regions. Serum IL-18 levels were also associated with a region on chromosome 2 containing the NLRC4 gene (rs12989936, P = 2.7×10(−19)). These data characterize multiple robust genetic signals that influence IL-18 and IL-1ra cytokine production. In particular, the signal for serum IL-18 located on chromosome two is novel and potentially important in inflammasome triggered chronic activation of inflammation in older adults. Replication in independent cohorts is an important next step, as well as molecular studies to better understand the role of NLRC4