The three-dimensional organization of telomeres in the nucleus of mammalian cells

BACKGROUND: The observation of multiple genetic markers in situ by optical microscopy and their relevance to the study of three-dimensional (3D) chromosomal organization in the nucleus have been greatly developed in the last decade. These methods are important in cancer research because cancer is characterized by multiple alterations that affect the modulation of gene expression and the stability of the genome. It is, therefore, essential to analyze the 3D genome organization of the interphase nucleus in both normal and cancer cells. RESULTS: We describe a novel approach to study the distribution of all telomeres inside the nucleus of mammalian cells throughout the cell cycle. It is based on 3D telomere fluorescence in situ hybridization followed by quantitative analysis that determines the telomeres' distribution in the nucleus throughout the cell cycle. This method enables us to determine, for the first time, that telomere organization is cell-cycle dependent, with assembly of telomeres into a telomeric disk in the G2 phase. In tumor cells, the 3D telomere organization is distorted and aggregates are formed. CONCLUSIONS: The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability. Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases. Such new avenues of monitoring genomic instability could potentially impact on cancer biology, genetics, diagnostic innovations and surveillance of treatment response in medicine

Le forme della regalità nella Roma latino-sabina

The analysis of historical sources, onomastics data, and the festive calendar, shows that the most archaic Roman kingship was structured in the form of a diarchy between a lifelong king-priest and a temporary warrior-king: the latter ruled in the season of war, while in peacetime the city government was led in turn by the patres (interregnum). This diarchy could be the result of the influence, on Roman institutions, of the constitutional structures of the Greeks and of the Italic peoples, since among other Indo-European cultures, like Vedic India and the Celts, the pattern seems rather to be a triad — composed of a priest, a supreme king and a warrior king — surviving in Rome only at a theological level in the Pre-Capitoline triad Iuppiter Mars Quirinus. Given these premises, the subsequent Etruscan monarchy appears to be the result of the rising of the army commander to a tyrannical and lifelong power, and of the marginalization of the rex sacrorum, while the Republic seems a partial restoration of the oldest constitution

Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

International audienceDogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG(+) counterparts do not. Antigen boost modifies the gene expression profile of IgM(+) plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge