Astronomical Observations

OBJECTIVE: To investigate the role of Fcg receptor (FcgR) genes in susceptibility to rheumatoid arthritis (RA) using family based studies, to examine possible interactions between FcgR genotypes and the shared epitope (SE), and to assess linkage disequilibrium between FcgR loci. METHODS: Association studies were performed in 95 Caucasian, single-case, nuclear Caucasian families with both parents alive using haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) statistics. Three FcgR polymorphisms (FcgRIIA-131H/R, FcgRIIIA-158V/F, and FcgRIIIB-NA1/NA2) were genotyped using polymerase chain reaction methods. Linkage analysis was performed using 3 microsatellite markers (D1S498, D1S2844, D1S2762) flanking the FcgR region in an independent set of 90 Caucasian, multiple-case families. Potential effects of disease heterogeneity, including sex and the presence of rheumatoid factor, SE, and erosive or nodular disease, were taken into account in the analysis. Logistic regression analysis was performed to determine whether FcgR alleles are independent risk factors for the susceptibility to and/or severity of RA. Linkage disequilibrium was calculated using pairwise linkage disequilibrium statistics. RESULTS: HHRR and TDT analysis showed no evidence of preferential transmission of any FcgR alleles studied, and there were no important associations with any given disease phenotype. Moreover, neither linkage to microsatellite markers close to the FcgR genes on chromosome 1 nor linkage disequilibrium between FcgR loci was present in our population. The distribution of inherited genotypes provided evidence for an interaction between the SE and the FcgRIIIA-158V allele and between the SE and the FcgRIIIA-158V-FcgRIIA-131H 2-locus haplotype since the combined presence of these factors increased the susceptibility to RA (OR 4.13, 95% CI 1.6-10.62 and OR 2.83, 95% CI 1.25-6.38, respectively). However, regression analysis showed that neither the 158V allele nor the 158V-131H haplotype contributed as independent factors to susceptibility or severity of RA. CONCLUSION: Isolated FcgR genes do not play a major independent role in susceptibility to RA. To a limited extent, the presence of high-binding alleles at the FcgRIIIA locus or at the FcgRIIIA-FcgRIIA haplotype might predispose to RA in SE positive individuals

New protective coatings against lampenflora growing in the Pommery Champagne cellar

Phototrophic microorganisms such as cyanobacteria and microalgae can proliferate readily in underground heritage sites where the introduction of artificial illumination equipment has significantly altered previously stable environmental conditions. The extended lampenflora biofilm growth on the bas-reliefs carved in the underground Pommery Champagne cellar in Reims (France) represents a recurring biocolonisation problem which requires periodic cleaning. The aim of this work was to limit the growth of lampenflora on chalk substrates using preventative biocidal treatments based on polyoxometalate ionic liquids (POM-ILs). Biocidal assays carried out in laboratory showed how two different colourless POM-IL coatings were more effective than commercial Preventol RI80 against two algal strains isolated from the Pommery bas reliefs, Pseudostichococcus monallantoides and Chromochloris zofingiensis. However, only one POM-IL variant was capable of sustained prevention of biofilm growth when applied to wet chalk, which replicates the more drastic natural environmental conditions of the cellar and can limit the performance of the biocidal coatings. Crucially, coating concentration studies demonstrate how POM-IL-coated slabs from previous experiments retain their biocidal activity and can prevent subsequent recolonisation following the re-inoculation of coated slabs with algae and cyanobacteria. Consequently, POM-ILs represent excellent candidates to eliminate lampenflora growth on the chalk bas-reliefs in the unique subterranean environment of the Pommery Champagne cellar. © 2022 The Author

Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression.

In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407). Additionally, we investigated differential allelic expression, a possible functional consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003). This allele was also expressed preferentially (p<10-6) with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1 = 0.004; p2 = 0.0177). Evidence for influence of rs6136 on transcription factor binding was also found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA

Testing for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in a European family-based study

INTRODUCTION: A candidate gene approach, in a large case-control association study in the Dutch population, has shown that a 480 kb block on chromosome 4q27 encompassing KIAA1109/Tenr/IL2/IL21 genes is associated with rheumatoid arthritis. Compared with case-control association studies, family-based studies have the added advantage of controlling potential differences in population structure. Therefore, our aim was to test this association in populations of European origin by using a family-based approach. METHODS: A total of 1,302 West European white individuals from 434 trio families were genotyped for the rs4505848, rs11732095, rs6822844, rs4492018 and rs1398553 polymorphisms using the TaqMan Allelic discrimination assay (Applied Biosystems). The genetic association analyses for each SNP and haplotype were performed using the Transmission Disequilibrium Test and the genotype relative risk. RESULTS: We observed evidence for association of the heterozygous rs4505848-AG genotype with rheumatoid arthritis (P = 0.04); however, no significance was found after Bonferroni correction. In concordance with previous findings in the Dutch population, we observed a trend of undertransmission for the rs6822844-T allele and rs6822844-GT genotype to rheumatoid arthritis patients. We further investigated the five SNP haplotypes of the KIAA1109/Tenr/IL2/IL21 gene region. We observed, as described in the Dutch population, a nonsignificant undertransmission of the AATGG haplotype to rheumatoid arthritis patients. CONCLUSIONS: Using a family-based study, we have provided a trend for the association of the KIAA1109/Tenr/IL2/IL21 gene region with rheumatoid arthritis in populations of European descent. Nevertheless, we failed to replicate a significant association of this region in our rheumatoid arthritis family sample. Further investigation of this region, including detection and testing of all variants, is required to confirm rheumatoid arthritis association

The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study

The integrin αvβ3, whose αv subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population

Biodistribution and Pharmacokinetics of O-Palmitoyl Tilisolol, a Lipophilic Prodrug of Tilisolol, after Intravenous Administration in Rats

The purpose of this study was to modify the biodistribution and pharmacokinetics of tilisolol, a β-blocker, using the palmitoyl prodrug approach. After intravenous administration of tilisolol and O-palmitoyl tilisolol in rats, drug concentrations were determined in blood, bile, urine, and several tissues. The concentration-time profiles of tilisolol and O-palmitoyl tilisolol were analyzed pharmacokinetically. The blood concentrations of O-palmitoyl tilisolol after intravenous administration of O-palmitoyl tilisolol were about 10-fold higher than those of tilisolol after intravenous administration of tilisolol. The biliary excretion rates of O-palmitoyl tilisolol and tilisolol after intravenous administration of O-palmitoyl tilisolol were about 10- to 100-fold larger than those of tilisolol after intravenous administration of tilisolol. In addition, the hepatic uptake clearance of O-palmitoyl tilisolol after intravenous administration of O-palmitoyl tilisolol was 3.6-fold higher than that of tilisolol after the intravenous administration of tilisolol. In the in vitro experiments, it was demonstrated that the distribution ratios between blood cells and plasma (blood/plasma) of O-palmitoyl tilisolol and tilisolol was 95.7 and 55.5%, respectively. These findings suggest that O-palmitoyl tilisolol exists as a binding form with biological components, especially blood cells, in systemic circulation. In conclusion, the palmitoyl prodrug approach is useful as a drug delivery system to deliver the parent drug to the liver