Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study.

OBJECTIVES: The genetic aetiology of osteoarthritis has not yet been elucidated. To enable a well-powered genome-wide association study (GWAS) for osteoarthritis, the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome-wide association scan. Here the authors report the findings of the stage 1 interim analysis. METHODS: The authors have performed a genome-wide association scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based controls from the UK. Replication of promising signals was carried out in silico in five further scans (44,449 individuals), and de novo in 14 534 independent samples, all of European descent. RESULTS: None of the association signals the authors identified reach genome-wide levels of statistical significance, therefore stressing the need for corroboration in sample sets of a larger size. Application of analytical approaches to examine the allelic architecture of disease to the stage 1 genome-wide association scan data suggests that osteoarthritis is a highly polygenic disease with multiple risk variants conferring small effects. CONCLUSIONS: Identifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.

Optical control of the antigen translocation by synthetic photo-conditional viral inhibitors.

The immune system makes use of major histocompatibility complex class I (MHC I) molecules to present peptides to other immune cells, which can evoke an immune response. Within this process of antigen presentation, the MHC I peptide loading complex, consisting of a transporter associated with antigen processing TAP, MHC I, and chaperones, is key to the initiation of immune response by shuttling peptides from the cytosol into the ER lumen. However, it is still enigmatic how the flux of antigens is precisely coordinated in time and space, limiting our understanding of antigen presentation pathways. Here, we report on the development of a synthetic viral TAP inhibitor that can be cleaved by light. This photo-conditional inhibitor shows temporal blockade of TAP-mediated antigen translocation, which is unleashed upon illumination. The recovery of TAP activity was monitored at single-cell resolution both in human immune cell lines and primary cells. The development of a photo-conditional TAP inhibitor thus expands the repertoire of chemical intervention tools for immunological processes.

Stringent tests of shell model calculations in fp shell nuclei (46, 48)Ti and (50,52)Cr from measurements of g factors and B(E2) values

Measurements of magnetic moments and lifetimes of 2(+)(1) and 4(+)(1) states of (46,48)Ti and (50,52)Cr were performed with high accuracy via projectile Coulomb excitation and the technique of transient magnetic fields. The high quality of the data allows for the first time to establish stringent constraints on large scale shell model calculations. Whereas the global behavior of the data is well explained by full fp shell model calculations, distinct deviations in the g factors and B(E2) values of (46,48)Ti from theoretical predictions can be attributed to excitations of the 40Ca core. This suggestion is supported by recent Monte Carlo calculations which provide evidence that 48Ca is a better inert core.

Performance evaluation of a blood gas system in a central and satellite laboratory.

In many hospitals blood gases are performed in several laboratories. It is important to establish that values obtained in all laboratories are identical and that the same quality control program is used. Evaluation of the performance of blood gas apparatus has been made in two of our laboratories. Result reproducibility was assessed by means of gas analyzer system control. Measurements were made in duplicate of patients' specimens in the same instrument and duplicate measurements of patient samples with both instruments. A13 day evaluation using this system was carried out in both laboratories during all shifts and showed excellent agreement with the manufacturer's reported values. The combined standard deviation for pH at all levels was 0.009,pCO2 -0.83 mmHg and pO2 - 3.9 mmHg. Patients' samples analyzed in the same instrument showed an absolute average difference between duplicates for pH of 0.003, pCO2 - 0.62 mmHg and pO2 -0.87 mmHg. The comparison of duplicate samples in the two instruments in the different laboratories showed an absolute average difference for pH of 0.009,pCO2-1.7mmHg and pO2 - 1.6 mmHg.

First nuclear moment measurement with radioactive beams by the recoil-in-vacuum technique: the g factor of the 2+1 state in 132Te.

Following Coulomb excitation of the radioactive ion beam (RIB) 132Te at HRIBF we report the first use of the recoil-in-vacuum (RIV) method to determine the g factor of the 2(+)(1) state: g(973.9 keV 2(+) 132Te) = (+)0.35(5). The advantages offered by the RIV method in the context of RIBs and modern detector arrays are discussed.

Subgingival temperature: relation to gingival crevicular fluid enzymes, cytokines, and subgingival plaque micro-organisms.

There have been no reports on the relationship of subgingival temperature to specific gingival crevicular fluid (GCF) components. Therefore, the purpose of this cross-sectional study was to determine whether there was any relationship between subgingival temperature and GCF levels of neutrophil elastase (NE), myeloperoxidase (MPO), beta-glucuronidase (BG), interleukin-1 alpha (IL-1), and interferon alpha (IFN). Furthermore, another objective was to confirm an association of subgingival temperature with clinical parameters and specific subgingival plaque micro-organisms as has been reported earlier. 27 human subjects each having healthy (n = 50), gingivitis (n = 59) and periodontitis (n = 53) sites were evaluated. The plaque index (PI), subgingival temperature, probing depth, attachment loss, bleeding index and gingival index were measured. GCF was sampled following the measurement of the PI and removal of the supragingival plaque. GCF samples were assayed for the enzymes NE, BG, MPO and the cytokines IFN-alpha and IL-1 alpha. A sterile Gracey curette was utilized at each sampled site to collect subgingival plaque. The plaque samples were evaluated using an immunoassay. Subgingival temperature was found to directly correlate with all clinical parameters (p < 0.001). Significant, albeit not large, correlations were found between subgingival temperature and NE (r = 0.35, p < 0.001), MPO (r = 0.26, p < 0.001) and BG (r = 0.23, p < 0.01). Temperature was found to correlate positively with E. corrodens (r = 0.33, p < 0.02) and F. nucleatum (r = 0.25, p < 0.05) but not with P. intermedia (r = 0.02, p = 0.9), P. gingivalis (r = 0.20, p = 0.1) and A. actinomycetemcomitans (r = 0.01, p > 0.9). In conclusion, subgingival temperature is correlated with the GCF enzymes, NE, MPO and BG as well as the clinical parameters and specific plaque micro-organisms associated with periodontal disease.