Detection of Single-Cell Apoptosis
Leonard A. Levin, Adriana Di Polo in Ocular Neuroprotection, 2003
Our initial definitions of the apoptotic process were based on a set of morphological changes that occurred in the cell nucleus and cytoplasm. As first described by Kerr using electron microscopy [1] the earliest visible change in the apoptotic cell was the aggregation of chromatin into compact masses along the nuclear membrane. Eventually, more and more compact granular masses appeared and filled the nucleus, combined with a gradual reduction in nuclear volume. At the same time the cytoplasm displayed progressive condensation, but with preservation of organelles. “Apoptotic bodies” consisting of discrete spherical or ovoid fragments containing highly condensed chromatin were then phagocytosed and lysed by nearby cells. Initially these changes were thought to encompass the entire apoptotic process, but now it is clear that apoptotic bodies are part of the final degradative phase of apoptosis (Fig. 1).
Chromatin Structure and Radiation Sensitivity
Shirley Lehnert in Biomolecular Action of Ionizing Radiation, 2007
The early conception of the cell nucleus was that it was a passive compartment, the main role of which was to keep genetic information separate from the surrounding cytoplasm. The DNA, organized in chromatin fibers, was envisioned as floating like spaghetti in a bowl of fluid nucleoplasm in which the only other structures were ribonucleoprotein particles and the nucleolus. The presence of a more complex substructure was revealed by micro- scopy and confirmed by the subsequent isolation of the nuclear matrix (NM) [1,2]. The NM is defined as the residual framework structure of the nucleus that maintains many of the overall architectural features of the cell nucleus including the nuclear lamina with complex pore structures, residual nucleoli, and an extensive fibrogranular structure in the nuclear interior. It is operationally defined as a subnuclear structure, which is insoluble following several different extraction procedures (Figure 9.1). It has been identified in a wide range of eukaryotes from yeast to man.
Historic Background
Lubomir S. Hnilica in The Structure and Biological Function of Histones, 1972
Johan Friedrich Miescher studied medicine in Basel and Gottingen. After completing his medical studies, Miescher became interested in the chemistry of natural products, especially in the cell nucleus. Although Miescher discovered DNA and protamines, premature death prevented him from further scientific exploits in this field. It was another student of Hoppe-Seyler, Albrecht Kossel, who laid a solid scientific base for the biochemical research on the cell nucleus, especially its proteins. During his life, among other honors Kossel received honorary degrees from the Universities in Cambridge, Dublin, Genf, Greifswald, St. Andrews, and Edinburgh, and was a member of numerous Academies of Science in several countries. During his very productive scientific life, Kossel published numerous papers describing his discoveries of histones, adenine, theophylline, histidine, etc. It is difficult to find a major university or research institute without one or more investigators studying the chemistry or biology of nuclear proteins.
ANA Detected by ELISA using Nucleus of Egg Cell as Antigen
Published in Journal of Immunoassay and Immunochemistry, 2008
Antinuclear antibodies, ANA, were usually detected with antigen of somatic cell nucleus. It has not been reported to detect ANA with egg cell nucleus as antigen. Enzyme linked immuosorbent assay, ELISA, coated with yolk was developed to detect ANA in our laboratory. A quality control test, cross absorption test, and cross antibody‐induced test with yolk were performed. Results showed a good agreement between our method and IFA through measurement of the same samples from patients suspected of having rheumatic connective tissue diseases (Kappa=0.668, P=0.000). The results were not influenced by the RF and different sources of egg. CVs of inter‐assay, were less than 10%. The cross absorption test was negative, as well; the ANA to somatic cell nucleus could be induced with egg cell nucleus. It is implied that there were both cross as well as overlapped Egg‐ANA and Somatic‐ANA. As egg nucleus, its volume was large, its purification was simple, so the better method might be established.
Specific energy from Auger and conversion electrons of
Published in Radiation Effects and Defects in Solids, 2011
E. Torres-García, T. Carrillo-Cazares
The typical radionuclides used to label anti-CD20 in the treatment of non-Hodgkin's lymphoma are 90Y, 131I, and 188Re, with the emission of beta particles, Auger electrons, and conversion electrons for the latter two. The aim of the present work was to calculate the contribution of high linear energy transfer radiation as Auger electrons (AE) and conversion electrons (CE) of 131I and 188Re-anti-CD20 to mean specific energy into the cell nucleus by Monte Carlo simulation (MCS), so as to infer therapeutic effectiveness on a dosimetric basis. MCS was used to quantify the frequency–mean specific energy into the cell nucleus, where the cell was modeled by two concentric spheres, considering two cell models. The results showed that 10% and 33% of the mean-specific energies (z¯) per disintegration imparted to the cell nucleus for both geometries are due to AE and CE; on the other hand, if the hit of AE and CE occurs, the contribution to (z¯) is about 64% and 86% for 131I and 188Re, respectively. According to the amount of specific energy from AE and CE into the cell nucleus by positive event, they can cause catastrophic effects in the nuclear DNA in the treatment of non-Hodgkin's lymphoma with 131I, 188Re-anti-CD20.
The International Nucleome Consortium
Published in Nucleus, 2015
Satoshi Tashiro, Christian Lanctôt
The eukaryotic genome adopts in the cell nucleus a 3-dimensional configuration that varies with cell types, developmental stages and environmental condition as well as between normal and pathological states. Understanding genome function will therefore require the elucidation of the structure-function relationship of the cell nucleus as a complex, dynamic biological system, referred to as the nucleome. This exciting and timely task calls for a multi-faceted, interdisciplinary and multi-national effort. We propose the establishment of an International Nucleome Consortium to coordinate this effort worldwide.