The 3D structure of the immunoglobulin heavy-chain locus: implications for long-range genomic interactions.

The immunoglobulin heavy-chain (Igh) locus is organized into distinct regions that contain multiple variable (V(H)), diversity (D(H)), joining (J(H)) and constant (C(H)) coding elements. How the Igh locus is structured in 3D space is unknown. To probe the topography of the Igh locus, spatial distance distributions were determined between 12 genomic markers that span the entire Igh locus. Comparison of the distance distributions to computer simulations of alternative chromatin arrangements predicted that the Igh locus is organized into compartments containing clusters of loops separated by linkers. Trilateration and triple-point angle measurements indicated the mean relative 3D positions of the V(H), D(H), J(H), and C(H) elements, showed compartmentalization and striking conformational changes involving V(H) and D(H)-J(H) elements during early B cell development. In pro-B cells, the entire repertoire of V(H) regions (2 Mbp) appeared to have merged and juxtaposed to the D(H) elements, mechanistically permitting long-range genomic interactions to occur with relatively high frequency.

Repetitive Head Impacts in Youth Football: Description and Relationship to White Matter Structure.

BACKGROUND: Few studies have examined white matter with diffusion tensor imaging in 8- to 12-year-old collision sport (CS) athletes. HYPOTHESIS: Youth CS athletes will demonstrate change in brain fractional anisotropy (FA) after a season of CS compared with an age-matched noncollision sport (NCS) cohort, and the number, magnitude, and location of hits will correlate with changes in the brain determined via FA for CS athletes. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: Thirty-five 8- to 12-year-old males in a youth tackle football league (CS) and 12 males from local swim teams (NCS) were recruited. Participants underwent brain magnetic resonance imaging with FA before and after the football season. Number, magnitude, and direction of head impacts were recorded for CS participants throughout the season. RESULTS: A total of 1905 hits were recorded in the CS group for the season, 341 (17.9%) collected during 7 games and 1564 (82.1%) observed during 31 practices. No significant interaction between group (CS and NCS) and time (pre- and postseason) was observed for FA (P > 0.05). Correlation analysis revealed a significantly positive and moderate relationship between increase of left cingulate cortex (CgC) FA from pre- to postseason and the total magnitude of lateral head impacts (r = 0.40; P = 0.03). CONCLUSION: There was no significant change in FA measurement of white matter integrity in a cohort of 8- to 12-year-old males after a season of youth football, nor was any difference detected in FA between youth football players and an age-matched cohort of swimmers. There was a significant correlation between total magnitude of hits sustained by youth football players and an increase in FA in the left CgC; whether this is adaptive or pathologic remains unknown. CLINICAL RELEVANCE: These data can be used within the body of knowledge to counsel patients regarding the known risks of youth tackle football regarding brain health.