A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.

BackgroundRheumatoid arthritis (RA) can be divided into two major subsets based on the presence or absence of antibodies to citrullinated peptide antigens (ACPA). Until now, data from genome-wide association studies (GWAS) have only been published from ACPA-positive subsets of RA or from studies that have not separated the two subsets. The aim of the current study is to provide and compare GWAS data for both subsets.Methods and resultsGWAS using the Illumina 300K chip was performed for 774 ACPA-negative patients with RA, 1147 ACPA-positive patients with RA and 1079 controls from the Swedish population-based case-control study EIRA. Imputation was performed which allowed comparisons using 1,723,056 single nucleotide polymorphisms (SNPs). No SNP achieved genome-wide significance (2.9 × 10⁻⁸) in the comparison between ACPA-negative RA and controls. A case-case association study was then performed between ACPA-negative and ACPA-positive RA groups. The major difference in this analysis was in the HLA region where 768 HLA SNPs passed the threshold for genome-wide significance whereas additional contrasting SNPs did not reach genome-wide significance. However, one SNP close to the RPS12P4 locus in chromosome 2 reached a p value of 2 × 10⁶ and this locus can thus be considered as a tentative candidate locus for ACPA-negative RA.ConclusionsACPA-positive and ACPA-negative RA display significant risk allele frequency differences which are mainly confined to the HLA region. The data provide further support for distinct genetic aetiologies of RA subsets and emphasise the need to consider them separately in genetic as well as functional studies of this disease

Spectral variations of AeBe Herbig stars in the Mon R1 association

We present the change in the Halpha emission-line profile of the spectra of some AeBe Herbig stars. In the spectrum of VY Mon, Halpha may have one of three profile types: P Cyg, P Cyg III or single line in accordance with the brightness variations of the star. HD259431 now shows a double Halpha profile with the red component stronger than the blue component, while in the earlier observations the blue peak was higher than the red peak. Finally, the last Halpha profile of LkHalpha215 is very similar to that obtained by Finkenzeller et al.Comment: 4pages, 3figure

Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study.

Objectives Decreased thyroid volume has been related to increased prevalence of thyroid cancer.Subjects and methods One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63).Results Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%).Conclusions Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects

Environmental pressure from the 2014–15 eruption of Bárðarbunga volcano, Iceland

The effusive six months long 2014-2015 Bárðarbunga eruption (31 August-27 February) was the largest in Iceland for more than 200 years, producing 1.6 ± 0.3 km3 of lava. The total SO2 emission was 11 ± 5 Mt, more than the amount emitted from Europe in 2011. The ground level concentration of SO2 exceeded the 350 μg m−3 hourly average health limit over much of Iceland for days to weeks. Anomalously high SO2 concentrations were also measured at several locations in Europe in September. The lowest pH of fresh snowmelt at the eruption site was 3.3, and 3.2 in precipitation 105 km away from the source. Elevated dissolved H2SO4, HCl, HF, and metal concentrations were measured in snow and precipitation. Environmental pressures from the eruption and impacts on populated areas were reduced by its remoteness, timing, and the weather. The anticipated primary environmental pressure is on the surface waters, soils, and vegetation of Iceland

The Casimir force and the quantum theory of lossy optical cavities

We present a new derivation of the Casimir force between two parallel plane mirrors at zero temperature. The two mirrors and the cavity they enclose are treated as quantum optical networks. They are in general lossy and characterized by frequency dependent reflection amplitudes. The additional fluctuations accompanying losses are deduced from expressions of the optical theorem. A general proof is given for the theorem relating the spectral density inside the cavity to the reflection amplitudes seen by the inner fields. This density determines the vacuum radiation pressure and, therefore, the Casimir force. The force is obtained as an integral over the real frequencies, including the contribution of evanescent waves besides that of ordinary waves, and, then, as an integral over imaginary frequencies. The demonstration relies only on general properties obeyed by real mirrors which also enforce general constraints for the variation of the Casimir force.Comment: 18 pages, 6 figures, minor amendment

DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3′-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5′-terminated strand of the DNA break and to inhibit 3′ to 5′ degradation by Dna2, actions that generate and protect the 3′-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

Sublittoral soft bottom communities and diversity of Mejillones Bay in northern Chile (Humboldt Current upwelling system)

The macrozoobenthos of Mejillones Bay (23°S; Humboldt Current) was quantitatively investigated over a 7-year period from austral summer 1995/1996 to winter 2002. About 78 van Veen grab samples taken at six stations (5, 10, 20 m depth) provided the basis for the analysis of the distribution of 60 species and 28 families of benthic invertebrates, as well as of their abundance and biomass. Mean abundance (2,119 individuals m-2) was in the same order compared to a previous investigation; mean biomass (966 g formalin wet mass m-2), however, exceeded prior estimations mainly due to the dominance of the bivalve Aulacomya ater. About 43% of the taxa inhabited the complete depth range. Mean taxonomic Shannon diversity (H', Log e) was 1.54 ± 0.58 with a maximum at 20 m (1.95 ± 0.33); evenness increased with depth. The fauna was numerically dominated by carnivorous gastropods, polychaetes and crustaceans (48%). About 15% of the species were suspensivorous, 13% sedimentivorous, 11% detritivorous, 7% omnivorous and 6% herbivorous. Cluster analyses showed a significant difference between the shallow and the deeper stations. Gammarid amphipods and the polychaete family Nephtyidae characterized the 5-mzone, the molluscs Aulacomya ater, Mitrella unifasciata and gammarids the intermediate zone, while the gastropod Nassarius gayi and the polychaete family Nereidae were most prominent at the deeper stations. The communities of the three depth zones did not appear to be limited by hypoxia during non-El Niño conditions. Therefore, no typical change in community structure occurred during El Niño 1997–1998, in contrast to what was observed for deeper faunal assemblages and hypoxic bays elsewhere in the coastal Humboldt Current system

DNA resection in eukaryotes: deciding how to fix the break

DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation

Tri-meson-mixing of π\pi-η\eta-η′\eta' and ρ\rho-ω\omega-ϕ\phi in the light-cone quark model

The radiative transition form factors of the pseudoscalar mesons {$\pi$, $\eta$, $\eta'$} and the vector mesons {$\rho$, $\omega$, $\phi$} are restudied with $\pi$-$\eta$-$\eta'$ and $\rho$-$\omega$-$\phi$ in tri-meson-mixing pattern, which is described by tri-mixing matrices in the light-cone constituent quark model. The experimental transition decay widths are better reproduced with tri-meson-mixing than previous results in a two-mixing-angle scenario of only two-meson $\eta$-$\eta'$ mixing and $\omega$-$\phi$ mixing.Comment: 8 pages, 6 figures, final version to appear in EPJ