0000000000395367
AUTHOR
Michael Hausmann
When Three Isn't a Crowd: A Digyny Concept for Treatment-Resistant, Near-Triploid Human Cancers.
Near-triploid human tumors are frequently resistant to radio/chemotherapy through mechanisms that are unclear. We recently reported a tight association of male tumor triploidy with XXY karyotypes based on a meta-analysis of 15 tumor cohorts extracted from the Mitelman database. Here we provide a conceptual framework of the digyny-like origin of this karyotype based on the germline features of malignant tumors and adaptive capacity of digyny, which supports survival in adverse conditions. Studying how the recombinatorial reproduction via diploidy can be executed in primary cancer samples and HeLa cells after DNA damage, we report the first evidence that diploid and triploid cell sub-populati…
Superresolution imaging of biological nanostructures by spectral precision distance microscopy
For the improved understanding of biological systems on the nanoscale, it is necessary to enhance the resolution of light microscopy in the visible wavelength range beyond the limits of conventional epifluorescence microscopy (optical resolution of about 200 nm laterally, 600 nm axially). Recently, various far-field methods have been developed allowing a substantial increase of resolution ("superresolution microscopy", or "lightoptical nanoscopy"). This opens an avenue to 'nano-image' intact and even living cells, as well as other biostructures like viruses, down to the molecular detail. Thus, it is possible to combine light optical spatial nanoscale information with ultrastructure analyses…
Heterochromatin Networks: Topology, Dynamics, and Function (a Working Hypothesis)
Open systems can only exist by self-organization as pulsing structures exchanging matter and energy with the outer world. This review is an attempt to reveal the organizational principles of the heterochromatin supra-intra-chromosomal network in terms of nonlinear thermodynamics. The accessibility of the linear information of the genetic code is regulated by constitutive heterochromatin (CHR) creating the positional information in a system of coordinates. These features include scale-free splitting-fusing of CHR with the boundary constraints of the nucleolus and nuclear envelope. The analysis of both the literature and our own data suggests a radial-concentric network as the main structural…
Entering the Nano-Cosmos of the Cell by Means of Spatial Position Determination Microscopy (SPDM): Implications for Medical Diagnostics and Radiation Research
During the last 20 years fluorescence light microscopy has made an enormous progress towards fluorescence nanoscopy in order to elucidate the nanostructural organization of cellular machineries beyond classical limits of resolution in light microscopy. One of these novel techniques is Spatial Position Determination Microscopy (SPDM), an approach of molecular localization microscopy based on the application of specific fluorescence labelling of cellular structures by means of dyes that undergo reversible photobleaching resulting in blinking effects during image acquisition. This blinking allows spectral separation of individual molecules and thus precise localization and distances measuremen…
Differentiating cancer cells reveal early large-scale genome regulation by pericentric domains.
Abstract Finding out how cells prepare for fate change during differentiation commitment was our task. To address whether the constitutive pericentromere-associated domains (PADs) may be involved, we used a model system with known transcriptome data, MCF-7 breast cancer cells treated with the ErbB3 ligand heregulin (HRG), which induces differentiation and is used in the therapy of cancer. PAD-repressive heterochromatin (H3K9me3), centromere-associated-protein-specific, and active euchromatin (H3K4me3) antibodies, real-time PCR, acridine orange DNA structural test (AOT), and microscopic image analysis were applied. We found a two-step DNA unfolding after 15–20 and 60 min of HRG treatment, re…