The multiple shark Ig H chain genes rearrange and hypermutate autonomously.

Sharks and skates are representatives of the earliest vertebrates with an immune system based on V(D)J rearrangement. They possess a unique Ig gene organization consisting of 15 to >50 individual IgM loci, each with one VH, two DH, one JH, and one set of constant region exons. The present study attempts to understand how multiple Ig genes are regulated with respect to rearrangement initiation and to targeting during somatic hypermutation. The linkage of three single-copy IgH genes was determined, and single-cell genomic PCR studies in a neonatal animal were used to examine any relationship between relative gene position and likelihood of rearrangement. Our results show that one to three IgH genes are activated independently of linkage or allelic position and the data best fit with a probability model based on the hypothesis that V(D)J rearrangement occurs as a sequence of trials within the B cell. In the neonatal cell set, two closely related IgH, G2A, and G2B, rearranged at similar frequencies, and their membrane forms were expressed at similar levels, like in other young animals. However, older animals displayed a bias in favor of the G2A isotype, which suggests that although rearrangement at G2A and G2B was randomly initiated during primary repertoire generation, the two very similar IgM sequences appear to be differentially expressed with age and exposure to Ag. We performed genomic single-cell PCR on B cells from an immunized individual to study activation-induced cytidine deaminase targeting and found that hypermutation, like V(D)J rearrangement, occurred independently among the many shark IgH.

Correlation between pericardial, mediastinal, and intrathoracic fat volumes with the presence and severity of coronary artery disease, metabolic syndrome, and cardiac risk factors.

AIMS: To investigate the association of pericardial, mediastinal, and intrathoracic fat volumes with the presence and severity of coronary artery disease (CAD), metabolic syndrome (MS), and cardiac risk factors (CRFs). METHODS AND RESULTS: Two hundred and sixteen consecutive patients who underwent cardiac magnetic resonance (CMR) imaging and had a coronary angiogram within 12 months of the CMR were studied. Fat volume was measured by drawing region of interest curves, from short-axis cine views from base to apex and from a four-chamber cine view. Pericardial fat, mediastinal fat, intrathoracic fat (addition of pericardial and mediastinal fat volumes), and fat ratio (pericardial fat/mediastinal fat) were analysed for their association with the presence and severity of CAD (determined based on the Duke CAD Jeopardy Score), MS, CRFs, and death or myocardial infarction on follow-up. Pericardial fat volume was significantly greater in patients with CAD when compared with those without CAD [38.3 ± 25.1 vs. 31.9 ± 21.4 cm(3) (P = 0.04)]. A correlation between the severity of CAD and fat volume was found for pericardial fat (ß = 1, P < 0.01), mediastinal fat (ß = 1, P = 0.03), intrathoracic fat (ß = 2, P = 0.01), and fat ratio (ß = 0.005, P = 0.01). These correlations persisted for all four thoracic fat measurements even after performing a stepwise linear regression analysis for relevant risk factors. Patients with MS had significantly greater mediastinal and intrathoracic fat volumes when compared with those without MS [126 ± 33.5 vs. 106 ± 30.1 cm(3) (P < 0.01) and 165 ± 54.9 vs. 140 ± 52 cm(3) (P < 0.01), respectively]. However, there was no significant difference in pericardial fat, mediastinal fat, intrathoracic fat, or fat ratio between patients with or without myocardial infarction during the follow-up [33.6 ± 22.1 vs. 35.7 ± 23.8 cm(3) (P = 0.67); 115 ± 26.2 vs. 114 ± 33.8 cm(3) (P = 0.84); 149 ± 44.7 vs. 150 ± 55.7 cm(3) (P = 0.95); and 0.27 ± 0.15 vs. 0.28 ± 0.14 (P = 0.70), respectively]. There was no significant difference in pericardial fat, mediastinal fat, intrathoracic fat, or fat ratio between patients who were alive compared with those who died during follow-up [36.6 ± 26.6 vs. 35.3 ± 23.2 cm(3) (P = 0.76); 114 ± 40.2 vs. 114 ± 31.4 cm(3) (P = 0.95); 150 ± 64.7 vs. 149 ± 52.5 cm(3) (P = 0.92); and 0.29 ± 0.15 vs. 0.28 ± 0.14 (P = 0.85), respectively]. CONCLUSION: Our study confirms an association between pericardial fat volume with the presence and severity of CAD. Furthermore, an association between mediastinal and intrathoracic fat volumes with MS was found.