Focus (geometry)

Abstract: In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, fibroblast foci are considered small, distinct lesions, although they have been proposed to form a highly interconnected reticulum as the leading edge of a "wave" of fibrosis. Here, we characterized fibroblast focus morphology and interrelationships in 3D using an integrated micro-CT and histological methodology. In 3D, fibroblast foci were morphologically complex structures, with large variations in shape and volume (range, 1.3 × 104 to 9.9 × 107 μm3). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm3 of lung tissue to a maximum of 11.1 per mm3 of lung tissue. Each focus was an independent structure, and no interconnections were observed. Together, our data indicate that in 3D fibroblast foci form a constellation of heterogeneous structures with large variations in shape and volume, suggesting previously unrecognized plasticity. No evidence of interconnectivity was identified, consistent with the concept that foci represent discrete sites of lung injury and repair.

Abstract: Quantitative stereologic relationships are applied in this report to the evaluation of F344 rat liver foci where the tissue sections exhibit congruent enzyme-altered areas of the several different phenotypes as well as enzyme-altered areas within a larger area of another enzyme alteration, that is, a "focus within a focus.' Quantitation of both the numbers and volume occupied by each of the phenotypes of the enzyme-altered foci was accomplished by the unique logic described in this report. The application of this logic to four representative experimental protocols with the use of three phenotypic markers demonstrated all possible congruent phenotypes as well as a small number of "foci within foci.' The variance of the quantitation of the experimental data was shown to depend on the number of focal transections identified in the sections, the number of sections examined, and the distribution of phenotypic alterations among foci.

Abstract: The breast cancer associated gene 1 (BRCA1)-A protein complex assembles at DNA damage-induced nuclear foci to facilitate repair of double-stranded breaks Here, we describe the first systematic comparison of the dynamics, copy number and organization of its core components at foci We show that the protein pools at individual foci generally comprise a small immobile fraction (∼20%) and larger mobile fraction (∼80%), which together occupy the same focal space but exist at different densities In the mobile fraction, Abraxas (CCDC98) and the heterodimer BARD1–BRCA1 share similar rates of dynamic exchange (complete turnover in ∼500 seconds) In contrast, RAP80, which is required for initial foci assembly, was more dynamic with 25-fold faster turnover at mature foci In addition, Abraxas, BARD1, BRCA1 and Merit40 (NBA1) were stably retained in the immobile fraction of foci under conditions causing loss of BRCC36 and RAP80, suggesting a shift to RAP80-independent localization after foci formation These results, combined with our finding that RAP80 (∼1200 copies per focus) is twofold more abundant than Abraxas/BARD1/BRCA1 at foci, suggest new models defining the dynamic organization of BRCA1-A complex at mature foci, wherein the unusually fast turnover of RAP80 may contribute to its regulation of BRCA1-dependent DNA repair