Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Frozen Storage and Thawing Methods Affect Biochemical and Sensory Attributes of Rainbow Trout

Rainbow trout were subjected to four thawing treatments after being stored at -18°C and -40°C for 0, 3, 7, 13 and 18 mo. Membrane integrity was estimated as the volume of centrifuged tissue fluid (CTF) and by lysosomal (3-N-acetylglucosaminidase (NAG) activity in CTF. Slow thawing, in air at 5°C, resulted in higher NAG activity in CTF and a larger volume of CTF than fast thawing, at 25°C in water, independent of storage time. After 3 or more months storage, a higher NAG activity in CTF and a larger volume of CTF were found in all - 18°C stored samples compared to that at -40°C. Sensory evaluation confirmed differences between trout stored at - 18°C and at - 40°C for 18 mo.</p

The effectiveness of the Arctic Council

Created in 1996, the Arctic Council has now been in operation long enough to justify a systematic effort to assess its effectiveness. To explore this topic, we created a questionnaire and circulated it to a large number of individuals who have participated in the work of the council in one capacity or another or who have followed the work of the council closely. This article analyses the quantitative and the qualitative input of those who responded to the questionnaire. The main conclusions are that: (1) the council has achieved considerable success in identifying emerging issues, framing them for consideration in policy venues and raising their visibility on the policy agenda and (2) changes now occurring in the Arctic will require significant adjustments to maintain the effectiveness of the council during the foreseeable future

Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria to epithelial surfaces. GBS adhesins have been identified to bind extracellular matrix components and cellular receptors. However, several putative adhesins have no host binding partner characterised. We report here that surface-expressed β protein of GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that an IgSF domain in β represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessment revealed that this newly identified IgI3 fold is not exclusively present in GBS but is predicted to be present in adhesins from other clinically important human pathogens. In agreement with this prediction, we found that CEACAM1 binds to an IgI3 domain found in an adhesin from a different streptococcal species. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs