TY - JOUR A1 - Krufczik, Matthias A1 - Sievers, Aaron A1 - Hausmann, Annkathrin A1 - Lee, Jin-Ho A1 - Hildenbrand, Georg A1 - Schaufler, Wladimir A1 - Hausmann, Michael T1 - Combining Low Temperature Fluorescence DNA-Hybridization, Immunostaining, and Super-Resolution Localization Microscopy for Nano-Structure Analysis of ALU Elements and Their Influence on Chromatin Structure JF - International Journal of Molecular Sciences N2 - Immunostaining and fluorescence in situ hybridization (FISH) are well established methods for specific labelling of chromatin in the cell nucleus. COMBO-FISH (combinatorial oligonucleotide fluorescence in situ hybridization) is a FISH method using computer designed oligonucleotide probes specifically co-localizing at given target sites. In combination with super resolution microscopy which achieves spatial resolution far beyond the Abbe Limit, it allows new insights into the nano-scaled structure and organization of the chromatin of the nucleus. To avoid nano-structural changes of the chromatin, the COMBO-FISH labelling protocol was optimized omitting heat treatment for denaturation of the target. As an example, this protocol was applied to ALU elements—dispersed short stretches of DNA which appear in different kinds in large numbers in primate genomes. These ALU elements seem to be involved in gene regulation, genomic diversity, disease induction, DNA repair, etc. By computer search, we developed a unique COMBO-FISH probe which specifically binds to ALU consensus elements and combined this DNA–DNA labelling procedure with heterochromatin immunostainings in formaldehyde-fixed cell specimens. By localization microscopy, the chromatin network-like arrangements of ALU oligonucleotide repeats and heterochromatin antibody labelling sites were simultaneously visualized and quantified. This novel approach which simultaneously combines COMBO-FISH and immunostaining was applied to chromatin analysis on the nanoscale after low-linear-energy-transfer (LET) radiation exposure at different doses. Dose-correlated curves were obtained from the amount of ALU representing signals, and the chromatin re-arrangements during DNA repair after irradiation were quantitatively studied on the nano-scale. Beyond applications in radiation research, the labelling strategy of immunostaining and COMBO-FISH with localization microscopy will also offer new potentials for analyses of subcellular elements in combination with other specific chromatin targets. KW - Genom Y1 - 2017 U6 - https://doi.org/https://doi.org/10.3390/ijms18051005 SN - 1422-0067 VL - 18 IS - 5 PB - MDPI AG ER - TY - JOUR A1 - Hausmann, Michael A1 - Ilić, Nataša A1 - Pilarczyk, Götz A1 - Lee, Jin-Ho A1 - Logeswaran, Abiramy A1 - Borroni, Aurora A1 - Krufczik, Matthias A1 - Theda, Franziska A1 - Waltrich, Nadine A1 - Bestvater, Felix A1 - Hildenbrand, Georg A1 - Cremer, Christoph A1 - Blank, Michael T1 - Challenges for Super-Resolution Localization Microscopy and Biomolecular Fluorescent Nano-Probing in Cancer Research JF - International Journal of Molecular Sciences N2 - Understanding molecular interactions and regulatory mechanisms in tumor initiation, progression, and treatment response are key requirements towards advanced cancer diagnosis and novel treatment procedures in personalized medicine. Beyond decoding the gene expression, malfunctioning and cancer-related epigenetic pathways, investigations of the spatial receptor arrangements in membranes and genome organization in cell nuclei, on the nano-scale, contribute to elucidating complex molecular mechanisms in cells and tissues. By these means, the correlation between cell function and spatial organization of molecules or molecular complexes can be studied, with respect to carcinogenesis, tumor sensitivity or tumor resistance to anticancer therapies, like radiation or antibody treatment. Here, we present several new applications for bio-molecular nano-probes and super-resolution, laser fluorescence localization microscopy and their potential in life sciences, especially in biomedical and cancer research. By means of a tool-box of fluorescent antibodies, green fluorescent protein (GFP) tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors in membranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2) in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by radiation or antibody treatment. The main purpose of this article is to demonstrate how nano-scaled distance measurements between bio-molecules, tagged by appropriate nano-probes, can be applied to elucidate structures and conformations of molecular complexes which are characteristic of tumorigenesis and treatment responses. These applications open new avenues towards a better interpretation of the spatial organization and treatment responses of functionally relevant molecules, at the single cell level, in normal and cancer cells, offering new potentials for individualized medicine. KW - Krebs, Medizin KW - Strahlentherapie Y1 - 2017 U6 - https://doi.org/https://doi.org/10.3390/ijms18102066 SN - 1422-0067 VL - 18 IS - 10 PB - MDPI AG ER - TY - JOUR A1 - Stuhlmüller, Michael A1 - Schwarz-Finsterle, Jutta A1 - Fey, Evelyn A1 - Lux, Johannes A1 - Bach, Margund A1 - Cremer, Christoph A1 - Hinderhofer, Katrin A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - In situ optical sequencing and structure analysis of a trinucleotide repeat genome region by localization microscopy after specific COMBO-FISH nano-probing JF - Nanoscale KW - Genom Y1 - 2015 U6 - https://doi.org/https://doi.org/10.1039/C5NR04141D SN - 2040-3364 VL - 7 IS - 42 SP - 17938 EP - 17946 PB - Royal Society of Chemistry (RSC) ER - TY - CHAP A1 - Falk, Martin A1 - Wolinsky, Michael A1 - Veldwijk, Marlon R. A1 - Hildenbrand, Georg A1 - Hausmann, Michael T1 - Gold nanoparticle enhanced radiosensitivity of cells: considerations and contradictions from model systems and basic investigations of cell damaging for radiation therapy T2 - Nanoparticle Enhanced Radiation Therapy KW - Krebs, Medizin KW - Strahlentherapie Y1 - 2020 SN - 9780750323963 U6 - https://doi.org/https://doi.org/10.1088/978-0-7503-2396-3ch10 SP - 10 EP - 1 PB - IOP Publishing ER - TY - JOUR A1 - Sievers, Aaron A1 - Wenz, Frederik A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Conservation of k-mer Composition and Correlation Contribution between Introns and Intergenic Regions of Animalia Genomes JF - Genes N2 - In this study, we pairwise-compared multiple genome regions, including genes, exons, coding DNA sequences (CDS), introns, and intergenic regions of 39 Animalia genomes, including Deuterostomia (27 species) and Protostomia (12 species), by applying established k-mer-based (alignment-free) comparison methods. We found strong correlations between the sequence structure of introns and intergenic regions, individual organisms, and within wider phylogenetical ranges, indicating the conservation of certain structures over the full range of analyzed organisms. We analyzed these sequence structures by quantifying the contribution of different sets of DNA words to the average correlation value by decomposing the correlation coefficients with respect to these word sets. We found that the conserved structures within introns, intergenic regions, and between the two were mainly a result of conserved tandem repeats with repeat units ≤ 2 bp (e.g., (AT)n), while other conserved sequence structures, such as those found between exons and CDS, were dominated by tandem repeats with repeat unit sizes of 3 bp in length and more complex DNA word patterns. We conclude that the conservation between intron and intergenic regions indicates a shared function of these sequence structures. Also, the similar differences in conserved structures with known origin, especially to the conservation between exons and CDS resulting from DNA codons, indicate that k-mer composition-based functional properties of introns and intergenic regions may differ from those of exons and CDS. KW - Genom Y1 - 2018 U6 - https://doi.org/https://doi.org/10.3390/genes9100482 SN - 2073-4425 VL - 9 IS - 10 PB - MDPI AG ER - TY - JOUR A1 - Eryilmaz, Marion A1 - Schmitt, Eberhard A1 - Krufczik, Matthias A1 - Theda, Franziska A1 - Lee, Jin-Ho A1 - Cremer, Christoph A1 - Bestvater, Felix A1 - Schaufler, Wladimir A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Localization Microscopy Analyses of MRE11 Clusters in 3D-Conserved Cell Nuclei of Different Cell Lines JF - Cancers N2 - In radiation biophysics, it is a subject of nowadays research to investigate DNA strand break repair in detail after damage induction by ionizing radiation. It is a subject of debate as to what makes up the cell’s decision to use a certain repair pathway and how the repair machinery recruited in repair foci is spatially and temporarily organized. Single-molecule localization microscopy (SMLM) allows super-resolution analysis by precise localization of single fluorescent molecule tags, resulting in nuclear structure analysis with a spatial resolution in the 10 nm regime. Here, we used SMLM to study MRE11 foci. MRE11 is one of three proteins involved in the MRN-complex (MRE11-RAD50-NBS1 complex), a prominent DNA strand resection and broken end bridging component involved in homologous recombination repair (HRR) and alternative non-homologous end joining (a-NHEJ). We analyzed the spatial arrangements of antibody-labelled MRE11 proteins in the nuclei of a breast cancer and a skin fibroblast cell line along a time-course of repair (up to 48 h) after irradiation with a dose of 2 Gy. Different kinetics for cluster formation and relaxation were determined. Changes in the internal nano-scaled structure of the clusters were quantified and compared between the two cell types. The results indicate a cell type-dependent DNA damage response concerning MRE11 recruitment and cluster formation. The MRE11 data were compared to H2AX phosphorylation detected by γH2AX molecule distribution. These data suggested modulations of MRE11 signal frequencies that were not directly correlated to DNA damage induction. The application of SMLM in radiation biophysics offers new possibilities to investigate spatial foci organization after DNA damaging and during subsequent repair. KW - Krebs, Medizin KW - Strahlentherapie KW - Brustkrebs Y1 - 2018 U6 - https://doi.org/https://doi.org/10.3390/cancers10010025 SN - 2072-6694 VL - 10 IS - 1 PB - MDPI AG ER - TY - JOUR A1 - Sievers, Aaron A1 - Sauer, Liane A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Eukaryotic Genomes Show Strong Evolutionary Conservation of k-mer Composition and Correlation Contributions between Introns and Intergenic Regions JF - Genes N2 - Several strongly conserved DNA sequence patterns in and between introns and intergenic regions (IIRs) consisting of short tandem repeats (STRs) with repeat lengths <3 bp have already been described in the kingdom of Animalia. In this work, we expanded the search and analysis of conserved DNA sequence patterns to a wider range of eukaryotic genomes. Our aims were to confirm the conservation of these patterns, to support the hypothesis on their functional constraints and/or the identification of unknown patterns. We pairwise compared genomic DNA sequences of genes, exons, CDS, introns and intergenic regions of 34 Embryophyta (land plants), 30 Protista and 29 Fungi using established k-mer-based (alignment-free) comparison methods. Additionally, the results were compared with values derived for Animalia in former studies. We confirmed strong correlations between the sequence structures of IIRs spanning over the entire domain of Eukaryotes. We found that the high correlations within introns, intergenic regions and between the two are a result of conserved abundancies of STRs with repeat units ≤2 bp (e.g., (AT)n). For some sequence patterns and their inverse complementary sequences, we found a violation of equal distribution on complementary DNA strands in a subset of genomes. Looking at mismatches within the identified STR patterns, we found specific preferences for certain nucleotides stable over all four phylogenetic kingdoms. We conclude that all of these conserved patterns between IIRs indicate a shared function of these sequence structures related to STRs. KW - Genom KW - Eukaryoten Y1 - 2021 U6 - https://doi.org/https://doi.org/10.3390/genes12101571 SN - 2073-4425 VL - 12 IS - 10 PB - MDPI AG ER - TY - JOUR A1 - Paschek, Klaus A1 - Roßmann, Arthur A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Analysis of Tidal Accelerations in the Solar System and in Extrasolar Planetary Systems JF - Applied Sciences N2 - Volcanism powered by tidal forces inside celestial bodies can provide enough energy to keep important solvents for living systems in the liquid phase. A prerequisite to calculate such tidal interactions and consequences is depending on simulations for tidal accelerations in a multi-body system. Unfortunately, from measurements in many extrasolar planetary systems, only few physical and orbital parameters are well-known enough for investigated celestial bodies. For calculating tidal acceleration vectors under missing most orbital parameter exactly, a simulation method is developed that is only based on a few basic parameters, easily measurable even in extrasolar planetary systems. Such a method as the one presented here allows finding a relation between the tidal acceleration vectors and potential heating inside celestial objects. Using the values and results of our model approach to our solar system as a “gold standard” for feasibility allowed us to classify this heating in relation to different forms of volcanism. This “gold standard” approach gave us a classification measure for the relevance of tidal heating in other extrasolar systems with a reduced availability of exact physical parameters. We help to estimate conditions for the identification of potential candidates for further sophisticated investigations by more complex established methods such as viscoelastic multi-body theories. As a first example, we applied the procedures developed here to the extrasolar planetary system TRAPPIST-1 as an example to check our working hypothesis. KW - Sonnensystem KW - Vulkanismus Y1 - 2021 U6 - https://doi.org/https://doi.org/10.3390/app11188624 SN - 2076-3417 VL - 11 IS - 18 PB - MDPI AG ER - TY - INPR A1 - Paschek, Klaus A1 - Roßmann, Arthur A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Analysis of Tidal Accelerations in the Solar System and in Extrasolar Planetary Systems N2 - Volcanism powered by tidal forces inside celestial bodies can provide enough energy to keep important solvents for living systems in the liquid phase. Moreover, tidal forces and their environmental consequences may strongly influence habitability of planets and other celestial bodies and may result in special forms of live and living conditions. A prerequisite to calculate such tidal interactions and consequences is depending on simulations for tidal accelerations in a multi-body system. Unfortunately, from measurements in many extrasolar planetary systems only few physical and orbital parameters are well enough known for investigated celestial bodies. For calculating tidal acceleration vectors under missing most orbital parameter exactly, a simulation method is developed that is only based on a few basic parameters, easily measurable even in extrasolar planetary systems. Such a method as being presented here, allows finding a relation between the tidal acceleration vectors and potential heating inside celestial objects. Using values and results of our model approach to our solar system as a “gold standard” for feasibility allowed us to classify this heating in relation to different forms of volcanism. This “gold standard” approach gave us a classification measure for the relevance of tidal heating in other extrasolar systems with a reduced availability of exact physical parameters. We would help to estimate conditions for the identification of potential candidates for further sophisticated investigations by more complex established methods like viscoelastic multi-body theories. As a first example, we applied the procedures developed here to the extrasolar planetary system TRAPPIST-1 as an example to check our working hypothesis. KW - Sonnensystem KW - Vulkanismus Y1 - 2021 U6 - https://doi.org/https://doi.org/10.20944/preprints202107.0408.v1 PB - MDPI AG ER - TY - CHAP A1 - Hausmann, Michael A1 - Neitzel, Charlotte A1 - Hahn, Hannes A1 - Winter, Ruth A1 - Falkova, Iva A1 - Heermann, Dieter W. A1 - Pilarczyk, Götz A1 - Hildenbrand, Georg A1 - Scherthan, Harry A1 - Falk, Martin T1 - Space and Time in the Universe of the Cell Nucleus after Ionizing Radiation Attacks: A Comparison of Cancer and Non-Cancer Cell Response T2 - The 1st International Electronic Conference on Cancers: Exploiting Cancer Vulnerability by Targeting the DNA Damage Response KW - Krebszelle KW - Strahlentherapie KW - Zellkern Y1 - 2021 U6 - https://doi.org/https://doi.org/10.3390/IECC2021-09219 PB - MDPI CY - Basel Switzerland ER - TY - JOUR A1 - Schäfer, Myriam A1 - Hildenbrand, Georg A1 - Hausmann, Michael T1 - Impact of Gold Nanoparticles and Ionizing Radiation on Whole Chromatin Organization as Detected by Single-Molecule Localization Microscopy JF - International Journal of Molecular Sciences N2 - In radiation tumor therapy, irradiation, on one hand, should cause cell death to the tumor. On the other hand, the surrounding non-tumor tissue should be maintained unaffected. Therefore, methods of local dose enhancements are highly interesting. Gold nanoparticles, which are preferentially uptaken by very-fast-proliferating tumor cells, may enhance damaging. However, the results in the literature obtained from cell culture and animal tissue experiments are very contradictory, i.e., only some experiments reveal increased cell killing but others do not. Thus, a better understanding of cellular mechanisms is required. Using the breast cancer cell model SkBr3, the effects of gold nanoparticles in combination with ionizing radiation on chromatin network organization were investigated by Single-Molecule Localization Microscopy (SMLM) and applications of mathematical topology calculations (e.g., Persistent Homology, Principal Component Analysis, etc.). The data reveal a dose and nanoparticle dependent re-organization of chromatin, although colony forming assays do not show a significant reduction of cell survival after the application of gold nanoparticles to the cells. In addition, the spatial organization of γH2AX clusters was elucidated, and characteristic changes were obtained depending on dose and gold nanoparticle application. The results indicate a complex response of ALU-related chromatin and heterochromatin organization correlating to ionizing radiation and gold nanoparticle incorporation. Such complex whole chromatin re-organization is usually associated with changes in genome function and supports the hypothesis that, with the application of gold nanoparticles, not only is DNA damage increasing but also the efficiency of DNA repair may be increased. The understanding of complex chromatin responses might help to improve the gold nanoparticle efficiency in radiation treatment. KW - Krebs, Medizin KW - Strahlentherapie Y1 - 2024 U6 - https://doi.org/https://doi.org/10.3390/ijms252312843 SN - 1422-0067 VL - 25 IS - 23 PB - MDPI AG ER - TY - JOUR A1 - Sievers, Aaron A1 - Bosiek, Katharina A1 - Bisch, Marc A1 - Dreessen, Chris A1 - Riedel, Jascha A1 - Froß, Patrick A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - K-mer Content, Correlation, and Position Analysis of Genome DNA Sequences for the Identification of Function and Evolutionary Features JF - Genes N2 - In genome analysis, k-mer-based comparison methods have become standard tools. However, even though they are able to deliver reliable results, other algorithms seem to work better in some cases. To improve k-mer-based DNA sequence analysis and comparison, we successfully checked whether adding positional resolution is beneficial for finding and/or comparing interesting organizational structures. A simple but efficient algorithm for extracting and saving local k-mer spectra (frequency distribution of k-mers) was developed and used. The results were analyzed by including positional information based on visualizations as genomic maps and by applying basic vector correlation methods. This analysis was concentrated on small word lengths (1 ≤ k ≤ 4) on relatively small viral genomes of Papillomaviridae and Herpesviridae, while also checking its usability for larger sequences, namely human chromosome 2 and the homologous chromosomes (2A, 2B) of a chimpanzee. Using this alignment-free analysis, several regions with specific characteristics in Papillomaviridae and Herpesviridae formerly identified by independent, mostly alignment-based methods, were confirmed. Correlations between the k-mer content and several genes in these genomes have been found, showing similarities between classified and unclassified viruses, which may be potentially useful for further taxonomic research. Furthermore, unknown k-mer correlations in the genomes of Human Herpesviruses (HHVs), which are probably of major biological function, are found and described. Using the chromosomes of a chimpanzee and human that are currently known, identities between the species on every analyzed chromosome were reproduced. This demonstrates the feasibility of our approach for large data sets of complex genomes. Based on these results, we suggest k-mer analysis with positional resolution as a method for closing a gap between the effectiveness of alignment-based methods (like NCBI BLAST) and the high pace of standard k-mer analysis. KW - Genom Y1 - 2017 U6 - https://doi.org/https://doi.org/10.3390/genes8040122 SN - 2073-4425 VL - 8 IS - 4 PB - MDPI AG ER - TY - JOUR A1 - Hikmat, Wisam Mohammed A1 - Sievers, Aaron A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Peculiar k-mer Spectra Are Correlated with 3D Contact Frequencies and Breakpoint Regions in the Human Genome JF - Genes KW - 3D genomics KW - Hi-C KW - k-mer KW - sequence analysis KW - Zellkern KW - Chromatin KW - Genom Y1 - U6 - https://doi.org/10.3390/genes15101247 VL - 15 IS - 10 ER - TY - JOUR A1 - Solov’yov, Andrey V. A1 - Verkhovtsev, Alexey V. A1 - Mason, Nigel J. A1 - Amos, Richard A. A1 - Bald, Ilko A1 - Baldacchino, Gérard A1 - Dromey, Brendan A1 - Falk, Martin A1 - Fedor, Juraj A1 - Gerhards, Luca A1 - Hausmann, Michael A1 - Hildenbrand, Georg A1 - Hrabovský, Miloš A1 - Kadlec, Stanislav A1 - Kočišek, Jaroslav A1 - Lépine, Franck A1 - Ming, Siyi A1 - Nisbet, Andrew A1 - Ricketts, Kate A1 - Sala, Leo A1 - Schlathölter, Thomas A1 - Wheatley, Andrew E. H. A1 - Solov’yov, Ilia A. T1 - Condensed Matter Systems Exposed to Radiation: Multiscale Theory, Simulations, and Experiment JF - Chemical Reviews N2 - This roadmap reviews the new, highly interdisciplinary research field studying the behavior of condensed matter systems exposed to radiation. The Review highlights several recent advances in the field and provides a roadmap for the development of the field over the next decade. Condensed matter systems exposed to radiation can be inorganic, organic, or biological, finite or infinite, composed of different molecular species or materials, exist in different phases, and operate under different thermodynamic conditions. Many of the key phenomena related to the behavior of irradiated systems are very similar and can be understood based on the same fundamental theoretical principles and computational approaches. The multiscale nature of such phenomena requires the quantitative description of the radiation-induced effects occurring at different spatial and temporal scales, ranging from the atomic to the macroscopic, and the interlinks between such descriptions. The multiscale nature of the effects and the similarity of their manifestation in systems of different origins necessarily bring together different disciplines, such as physics, chemistry, biology, materials science, nanoscience, and biomedical research, demonstrating the numerous interlinks and commonalities between them. This research field is highly relevant to many novel and emerging technologies and medical applications. KW - Kondensierte Materie KW - Strahlung Y1 - 2024 U6 - https://doi.org/https://doi.org/10.1021/acs.chemrev.3c00902 SN - 0009-2665 VL - 124 IS - 13 SP - 8014 EP - 8129 PB - American Chemical Society (ACS) ER - TY - JOUR A1 - Henn, Lukas A1 - Sievers, Aaron A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Specific Patterns in Correlations of Super-Short Tandem Repeats (SSTRs) with G+C Content, Genic and Intergenic Regions, and Retrotransposons on All Human Chromosomes JF - Genes N2 - The specific characteristics of k-mer words (2 ≤ k ≤ 11) regarding genomic distribution and evolutionary conservation were recently found. Among them are, in high abundance, words with a tandem repeat structure (repeat unit length of 1 bp to 3 bp). Furthermore, there seems to be a class of extremely short tandem repeats (≤12 bp), so far overlooked, that are non-random-distributed and, therefore, may play a crucial role in the functioning of the genome. In the following article, the positional distributions of these motifs we call super-short tandem repeats (SSTRs) were compared to other functional elements, like genes and retrotransposons. We found length- and sequence-dependent correlations between the local SSTR density and G+C content, and also between the density of SSTRs and genes, as well as correlations with retrotransposon density. In addition to many general interesting relations, we found that SINE Alu has a strong influence on the local SSTR density. Moreover, the observed connection of SSTR patterns to pseudogenes and -exons might imply a special role of SSTRs in gene expression. In summary, our findings support the idea of a special role and the functional relevance of SSTRs in the genome. KW - Genom KW - Genexpression Y1 - 2023 U6 - https://doi.org/https://doi.org/10.3390/genes15010033 SN - 2073-4425 VL - 15 IS - 1 PB - MDPI AG ER - TY - JOUR A1 - Sievers, Aaron A1 - Sauer, Liane A1 - Bisch, Marc A1 - Sprengel, Jan A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Moderation of Structural DNA Properties by Coupled Dinucleotide Contents in Eukaryotes JF - Genes N2 - Dinucleotides are known as determinants for various structural and physiochemical properties of DNA and for binding affinities of proteins to DNA. These properties (e.g., stiffness) and bound proteins (e.g., transcription factors) are known to influence important biological functions, such as transcription regulation and 3D chromatin organization. Accordingly, the question arises of how the considerable variations in dinucleotide contents of eukaryotic chromosomes could still provide consistent DNA properties resulting in similar functions and 3D conformations. In this work, we investigate the hypothesis that coupled dinucleotide contents influence DNA properties in opposite directions to moderate each other’s influences. Analyzing all 2478 chromosomes of 155 eukaryotic species, considering bias from coding sequences and enhancers, we found sets of correlated and anti-correlated dinucleotide contents. Using computational models, we estimated changes of DNA properties resulting from this coupling. We found that especially pure A/T dinucleotides (AA, TT, AT, TA), known to influence histone positioning and AC/GT contents, are relevant moderators and that, e.g., the Roll property, which is known to influence histone affinity of DNA, is preferably moderated. We conclude that dinucleotide contents might indirectly influence transcription and chromatin 3D conformation, via regulation of histone occupancy and/or other mechanisms. KW - Genom Y1 - 2023 U6 - https://doi.org/https://doi.org/10.3390/genes14030755 SN - 2073-4425 VL - 14 IS - 3 PB - MDPI AG ER - TY - JOUR A1 - Erenpreisa, Jekaterina A1 - Giuliani, Alessandro A1 - Yoshikawa, Kenichi A1 - Falk, Martin A1 - Hildenbrand, Georg A1 - Salmina, Kristine A1 - Freivalds, Talivaldis A1 - Vainshelbaum, Ninel A1 - Weidner, Jonas A1 - Sievers, Aaron A1 - Pilarczyk, Götz A1 - Hausmann, Michael T1 - Spatial-Temporal Genome Regulation in Stress-Response and Cell-Fate Change JF - International Journal of Molecular Sciences N2 - Complex functioning of the genome in the cell nucleus is controlled at different levels: (a) the DNA base sequence containing all relevant inherited information; (b) epigenetic pathways consisting of protein interactions and feedback loops; (c) the genome architecture and organization activating or suppressing genetic interactions between different parts of the genome. Most research so far has shed light on the puzzle pieces at these levels. This article, however, attempts an integrative approach to genome expression regulation incorporating these different layers. Under environmental stress or during cell development, differentiation towards specialized cell types, or to dysfunctional tumor, the cell nucleus seems to react as a whole through coordinated changes at all levels of control. This implies the need for a framework in which biological, chemical, and physical manifestations can serve as a basis for a coherent theory of gene self-organization. An international symposium held at the Biomedical Research and Study Center in Riga, Latvia, on 25 July 2022 addressed novel aspects of the abovementioned topic. The present article reviews the most recent results and conclusions of the state-of-the-art research in this multidisciplinary field of science, which were delivered and discussed by scholars at the Riga symposium. KW - Zellkern KW - Genom Y1 - 2023 U6 - https://doi.org/https://doi.org/10.3390/ijms24032658 SN - 1422-0067 VL - 24 IS - 3 PB - MDPI AG ER - TY - CHAP A1 - Hausmann, Michael A1 - Hildenbrand, Georg A1 - Pilarczyk, Götz T1 - Networks and Islands of Genome Nano-architecture and Their Potential Relevance for Radiation Biology BT - (A Hypothesis and Experimental Verification Hints) T2 - Results and Problems in Cell Differentiation N2 - The cell nucleus is a complex biological system in which simultaneous reactions and functions take place to keep the cell as an individualized, specialized system running well. The cell nucleus contains chromatin packed in various degrees of density and separated in volumes of chromosome territories and subchromosomal domains. Between the chromatin, however, there is enough “free” space for floating RNA, proteins, enzymes, ATPs, ions, water molecules, etc. which are trafficking by super- and supra-diffusion to the interaction points where they are required. It seems that this trafficking works somehow automatically and drives the system perfectly. After exposure to ionizing radiation causing DNA damage from single base damage up to chromatin double-strand breaks, the whole system “cell nucleus” responds, and repair processes are starting to recover the fully functional and intact system. In molecular biology, many individual epigenetic pathways of DNA damage response or repair of single and double-strand breaks are described. How these responses are embedded into the response of the system as a whole is often out of the focus of consideration. In this article, we want to follow the hypothesis of chromatin architecture’s impact on epigenetic pathways and vice versa. Based on the assumption that chromatin acts like an “aperiodic solid state within a limited volume,” functionally determined networks and local topologies (“islands”) can be defined that drive the appropriate repair process at a given damage site. Experimental results of investigations of the chromatin nano-architecture and DNA repair clusters obtained by means of single-molecule localization microscopy offer hints and perspectives that may contribute to verifying the hypothesis. KW - Zellkern KW - Genom Y1 - 2022 SN - 9783031065729 U6 - https://doi.org/https://doi.org/10.1007/978-3-031-06573-6_1 SN - 0080-1844 SP - 3 EP - 34 PB - Springer International Publishing CY - Cham ER - TY - JOUR A1 - Rodener, Daniel A1 - Schäfer, Myriam A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Assessing the Potential for Liquid Solvents from X-ray Sources: Considerations on Bodies Orbiting Active Galactic Nuclei JF - Galaxies N2 - We aim to establish a rough first prospect on the potential of certain biorelevant solvents (water, ammonia, and methane) being present in liquid form inside the uppermost few meters of several modeled rocky and icy surfaces of hypothetical bodies orbiting active galactic nuclei (AGNs) and investigate under which constraints this might occur. For this, we adjust and average X-ray spectra from a sample of 20 Type-1 Seyfert galaxies to calculate the mean snowline of the sample used. We then vary the hypothetical body’s orbit between 10% and 100% of the snowline radius and calculate a sub-surface attenuation within four different model surface compositions for each. We then use this as a continuous source term for a thermal model. Example bodies are systematically investigated with sizes between 1/30 and 20 earth radii, with further variations also considered (such as possible bound rotation), to end up with a perspective of solvent phases under a wide slew of different conditions. We find that liquid solvents are possible under a multitude of parameters, with temperature being the main constraint to liquid water whereas body size and pressure are the main constraint to liquid methane and ammonia. KW - Lösungsmittel KW - Röntgenspektrum Y1 - 2022 U6 - https://doi.org/https://doi.org/10.3390/galaxies10050101 SN - 2075-4434 VL - 10 IS - 5 PB - MDPI AG ER - TY - JOUR A1 - Pagáčová, Eva A1 - Štefančíková, Lenka A1 - Schmidt-Kaler, Franz A1 - Hildenbrand, Georg A1 - Vičar, Tomáš A1 - Depeš, Daniel A1 - Lee, Jin-Ho A1 - Bestvater, Felix A1 - Lacombe, Sandrine A1 - Porcel, Erika A1 - Roux, Stéphane A1 - Wenz, Frederik A1 - Kopecna, Olga A1 - Falková, Iva A1 - Hausmann, Michael A1 - Falk, Martin T1 - Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy JF - International Journal of Molecular Sciences N2 - From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the “physics” behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death. In the present study, we analyzed the influence of different nanoparticle materials (platinum (Pt), and gold (Au)), cancer cell types (HeLa, U87, and SKBr3), and doses (up to 4 Gy) of low-Linear Energy Transfer (LET) ionizing radiation (γ- and X-rays) on the extent, complexity and reparability of radiation-induced γH2AX + 53BP1 foci, the markers of double stand breaks (DSBs). Firstly, we sensitively compared the focus presence in nuclei during a long period of time post-irradiation (24 h) in spatially (three-dimensionally, 3D) fixed cells incubated and non-incubated with Pt nanoparticles by means of high-resolution immunofluorescence confocal microscopy. The data were compared with our preliminary results obtained for Au nanoparticles and recently published results for gadolinium (Gd) nanoparticles of approximately the same size (2–3 nm). Next, we introduced a novel super-resolution approach—single molecule localization microscopy (SMLM)—to study the internal structure of the repair foci. In these experiments, 10 nm Au nanoparticles were used that could be also visualized by SMLM. Altogether, the data show that different nanoparticles may or may not enhance radiation damage to DNA, so multi-parameter effects have to be considered to better interpret the radiosensitization. Based on these findings, we discussed on conclusions and contradictions related to the effectiveness and presumptive mechanisms of the cell radiosensitization by nanoparticles. We also demonstrate that SMLM offers new perspectives to study internal structures of repair foci with the goal to better evaluate potential differences in DNA damage patterns. KW - Krebs, Medizin KW - Strahlentherapie Y1 - 2019 U6 - https://doi.org/https://doi.org/10.3390/ijms20030588 SN - 1422-0067 VL - 20 IS - 3 PB - MDPI AG ER - TY - JOUR A1 - Falk, Martin A1 - Hausmann, Michael A1 - Lukasova, Emilie A1 - Biswas, Abin A1 - Hildenbrand, Georg A1 - Davidkova, Marie A1 - Krasavin, Evgeny A1 - Kleibl, Zdenek A1 - Falkova, Iva A1 - Jezkova, Lucie A1 - Stefancikova, Lenka A1 - Sevcik, Jan A1 - Hofer, Michal A1 - Bacikova, Alena A1 - Matula, Pavel A1 - Boreyko, Alla A1 - Vachelova, Jana A1 - Michaelidesova, Anna A1 - Kozubek, Stanislav T1 - Determining Omics Spatiotemporal Dimensions Using Exciting New Nanoscopy Techniques to Assess Complex Cell Responses to DNA Damage: Part - Structuromics JF - Critical Reviews in Eukaryotic Gene Expression KW - Radiologie Y1 - 2014 U6 - https://doi.org/https://doi.org/10.1615/CritRevEukaryotGeneExpr.v24.i3.40 SN - 1045-4403 VL - 24 IS - 3 SP - 225 EP - 247 PB - Begell House ER - TY - CHAP A1 - Hildenbrand, Georg A1 - Paschek, Klaus A1 - Schäfer, Myriam A1 - Hausmann, Michael T1 - Cryovolcanism in the Solar System and beyond: Considerations on Energy Sources, Geological Aspects, and Astrobiological Perspectives T2 - Astronomy and Planetary Science - From Cryovolcanism to Black Holes and Galactic Evolution N2 - Volcanism based on melting rocks (silicate volcanism) is long known on Earth and has also been found on Jupiter’s moon Io. Remnants of this type of volcanism have been identified also on other bodies in the solar system. Energy sources powered by accretion and the decay of radioactive isotopes seem to be dominant mainly inside larger bodies, which have enough volume to accumulate and retain this energy in significant amounts. On the other hand, the impact of tidal forces allows even tiny bodies to melt up and pass into the stage of cryovolcanism. The dependence of tidal heating on the size of the object is minor, but the masses of and the distances to accompanying bodies as well as the inner compositions of the heated body are central factors. Even though Io as an example of a body supporting silicate volcanism is striking, the physics of tidal forces might suggest a relatively high probability for cryovolcanism. This chapter aims at considering the parameters known and objects found so far in our solar system to give insights into where in our system and other planetary systems cryovolcanism might be expected. KW - Sonnensystem KW - Vulkanismus Y1 - 2022 SN - 9781803561196 U6 - https://doi.org/https://doi.org/10.5772/intechopen.105067 PB - IntechOpen ER - TY - JOUR A1 - Hausmann, Michael A1 - Neitzel, Charlotte A1 - Bobkova, Elizaveta A1 - Nagel, David A1 - Hofmann, Andreas A1 - Chramko, Tatyana A1 - Smirnova, Elena A1 - Kopecna, Olga A1 - Pagáčová, Eva A1 - Boreyko, Alla A1 - Krasavin, Evgeny A1 - Falkova, Iva A1 - Heermann, Dieter W. A1 - Pilarczyk, Götz A1 - Hildenbrand, Georg A1 - Bestvater, Felix A1 - Falk, Martin T1 - Single Molecule Localization Microscopy Analyses of DNA-Repair Foci and Clusters Detected Along Particle Damage Tracks JF - Frontiers in Physics KW - Krebszelle KW - Strahlentherapie KW - Genom KW - Zellkern Y1 - 2020 U6 - https://doi.org/https://doi.org/10.3389/fphy.2020.578662 SN - 2296-424X VL - 8 PB - Frontiers Media SA ER - TY - JOUR A1 - Bartosova, Maria A1 - Ridinger, David A1 - Marinovic, Iva A1 - Heigwer, Jana A1 - Zhang, Conghui A1 - Levai, Eszter A1 - Westhoff, Jens H. A1 - Schaefer, Franz A1 - Terjung, Stefan A1 - Hildenbrand, Georg A1 - Krunic, Damir A1 - Bestvater, Felix A1 - Hausmann, Michael A1 - Schmitt, Claus Peter A1 - Zarogiannis, Sotirios G. T1 - An Experimental Workflow for Studying Barrier Integrity, Permeability, and Tight Junction Composition and Localization in a Single Endothelial Cell Monolayer: Proof of Concept JF - International Journal of Molecular Sciences N2 - Endothelial and epithelial barrier function is crucial for the maintenance of physiological processes. The barrier paracellular permeability depends on the composition and spatial distribution of the cell-to-cell tight junctions (TJ). Here, we provide an experimental workflow that yields several layers of physiological data in the setting of a single endothelial cell monolayer. Human umbilical vein endothelial cells were grown on Transwell filters. Transendothelial electrical resistance (TER) and 10 kDa FITC dextran flux were measured using Alanyl-Glutamine (AlaGln) as a paracellular barrier modulator. Single monolayers were immunolabelled for Zonula Occludens-1 (ZO-1) and Claudin-5 (CLDN5) and used for automated immunofluorescence imaging. Finally, the same monolayers were used for single molecule localization microscopy (SMLM) of ZO-1 and CLDN5 at the nanoscale for spatial clustering analysis. The TER increased and the paracellular dextran flux decreased after the application of AlaGln and these functional changes of the monolayer were mediated by an increase in the ZO-1 and CLDN5 abundance in the cell–cell interface. At the nanoscale level, the functional and protein abundance data were accompanied by non-random increased clustering of CLDN5. Our experimental workflow provides multiple data from a single monolayer and has wide applicability in the setting of paracellular studies in endothelia and epithelia. KW - Endothelzelle KW - Nabelvene Y1 - 2021 U6 - https://doi.org/https://doi.org/10.3390/ijms22158178 SN - 1422-0067 VL - 22 IS - 15 PB - MDPI AG ER - TY - CHAP A1 - Hausmann, Michael A1 - Lee, Jin-Ho A1 - Sievers, Aaron A1 - Krufczik, Matthias A1 - Hildenbrand, Georg T1 - COMBinatorial Oligonucleotide FISH (COMBO-FISH) with Uniquely Binding Repetitive DNA Probes T2 - The Nucleus KW - Genom Y1 - 2020 SN - 9781071607626 U6 - https://doi.org/https://doi.org/10.1007/978-1-0716-0763-3_6 SN - 1064-3745 SP - 65 EP - 77 PB - Springer US CY - New York, NY ER - TY - JOUR A1 - Dobešová, Lucie A1 - Gier, Theresa A1 - Kopecna, Olga A1 - Pagáčová, Eva A1 - Vičar, Tomáš A1 - Bestvater, Felix A1 - Toufar, Jiří A1 - Bačíková, Alena A1 - Kopel, Pavel A1 - Fedr, Radek A1 - Hildenbrand, Georg A1 - Falková, Iva A1 - Falk, Martin A1 - Hausmann, Michael T1 - Incorporation of Low Concentrations of Gold Nanoparticles: Complex Effects on Radiation Response and Fate of Cancer Cells JF - Pharmaceutics N2 - (1) Background: In oncology research, a long-standing discussion exists about pros and cons of metal nanoparticle-enhanced radiotherapy and real mechanisms behind the tumor cell response to irradiation (IR) in presence of gold nanoparticles (GNPs). A better understanding of this response is, however, necessary to develop more efficient and safety nanoparticle (NP) types designed to disturb specific processes in tumor cells. (2) Aims and Methods: We combined 3D confocal microscopy and super-resolution single molecule localization microscopy (SMLM) to analyze, at the multiscale, the early and late effects of 10 nm-GNPs on DNA double strand break (DSB) induction and repair in tumor cells exposed to different doses of photonic low-LET (linear energy transfer) radiation. The results were correlated to different aspects of short and long-term cell viability. SkBr3 breast cancer cells (selected for the highest incidence of this cancer type among all cancers in women, and because most breast tumors are treated with IR) were incubated with low concentrations of GNPs and irradiated with 60Co γ-rays or 6 MV X-rays. In numerous post-irradiation (PI) times, ranging from 0.5 to 24 h PI, the cells were spatially (3D) fixed and labeled with specific antibodies against γH2AX, 53BP1 and H3K9me3. The extent of DSB induction, multi-parametric micro- and nano-morphology of γH2AX and 53BP1 repair foci, DSB repair kinetics, persistence of unrepaired DSBs, nanoscale clustering of γH2AX and nanoscale (hetero)chromatin re-organization were measured by means of the mentioned microscopy techniques in dependence of radiation dose and GNP concentration. (3) Results: The number of γH2AX/53BP1 signals increased after IR and an additional increase was observed in GNP-treated (GNP(+)) cells compared to untreated controls. However, this phenomenon reflected slight expansion of the G2-phase cell subpopulation in irradiated GNP(+) specimens instead of enhanced DNA damage induction by GNPs. This statement is further supported by some micro- and nano-morphological parameters of γH2AX/53BP1 foci, which slightly differed for cells irradiated in absence or presence of GNPs. At the nanoscale, Ripley’s distance frequency analysis of SMLM signal coordinate matrices also revealed relaxation of heterochromatin (H3K9me3) clusters upon IR. These changes were more prominent in presence of GNPs. The slight expansion of radiosensitive G2 cells correlated with mostly insignificant but systematic decrease in post-irradiation survival of GNP(+) cells. Interestingly, low GNP concentrations accelerated DSB repair kinetics; however, the numbers of persistent γH2AX/53BP1 repair foci were slightly increased in GNP(+) cells. (4) Conclusions: Low concentrations of 10-nm GNPs enhanced the G2/M cell cycle arrest and the proportion of radiosensitive G2 cells, but not the extent of DNA damage induction. GNPs also accelerated DSB repair kinetics and slightly increased presence of unrepaired γH2AX/53BP1 foci at 24 h PI. GNP-mediated cell effects correlated with slight radiosensitization of GNP(+) specimens, significant only for the highest radiation dose tested (4 Gy). KW - Strahlentherapie KW - Krebs, Medizin KW - Tumorzelle KW - Gold KW - Nanopartikel Y1 - 2022 U6 - https://doi.org/https://doi.org/10.3390/pharmaceutics14010166 SN - 1999-4923 VL - 14 IS - 1 PB - MDPI AG ER - TY - JOUR A1 - Hausmann, Michael A1 - Falk, Martin A1 - Neitzel, Charlotte A1 - Hofmann, Andreas A1 - Biswas, Abin A1 - Gier, Theresa A1 - Falkova, Iva A1 - Heermann, Dieter W. A1 - Hildenbrand, Georg T1 - Elucidation of the Clustered Nano-Architecture of Radiation-Induced DNA Damage Sites and Surrounding Chromatin in Cancer Cells: A Single Molecule Localization Microscopy Approach JF - International Journal of Molecular Sciences N2 - In cancer therapy, the application of (fractionated) harsh radiation treatment is state of the art for many types of tumors. However, ionizing radiation is a “double-edged sword”—it can kill the tumor but can also promote the selection of radioresistant tumor cell clones or even initiate carcinogenesis in the normal irradiated tissue. Individualized radiotherapy would reduce these risks and boost the treatment, but its development requires a deep understanding of DNA damage and repair processes and the corresponding control mechanisms. DNA double strand breaks (DSBs) and their repair play a critical role in the cellular response to radiation. In previous years, it has become apparent that, beyond genetic and epigenetic determinants, the structural aspects of damaged chromatin (i.e., not only of DSBs themselves but also of the whole damage-surrounding chromatin domains) form another layer of complex DSB regulation. In the present article, we summarize the application of super-resolution single molecule localization microscopy (SMLM) for investigations of these structural aspects with emphasis on the relationship between the nano-architecture of radiation-induced repair foci (IRIFs), represented here by γH2AX foci, and their chromatin environment. Using irradiated HeLa cell cultures as an example, we show repair-dependent rearrangements of damaged chromatin and analyze the architecture of γH2AX repair clusters according to topological similarities. Although HeLa cells are known to have highly aberrant genomes, the topological similarity of γH2AX was high, indicating a functional, presumptively genome type-independent relevance of structural aspects in DSB repair. Remarkably, nano-scaled chromatin rearrangements during repair depended both on the chromatin domain type and the treatment. Based on these results, we demonstrate how the nano-architecture and topology of IRIFs and chromatin can be determined, point to the methodological relevance of SMLM, and discuss the consequences of the observed phenomena for the DSB repair network regulation or, for instance, radiation treatment outcomes. KW - Krebszelle KW - Strahlentherapie Y1 - 2021 U6 - https://doi.org/https://doi.org/10.3390/ijms22073636 SN - 1422-0067 VL - 22 IS - 7 PB - MDPI AG ER - TY - JOUR A1 - Bobkova, Elizaveta A1 - Depes, Daniel A1 - Lee, Jin-Ho A1 - Jezkova, Lucie A1 - Falkova, Iva A1 - Pagacova, Eva A1 - Kopecna, Olga A1 - Zadneprianetc, Mariia A1 - Bacikova, Alena A1 - Kulikova, Elena A1 - Smirnova, Elena A1 - Bulanova, Tatiana A1 - Boreyko, Alla A1 - Krasavin, Evgeny A1 - Wenz, Frederik A1 - Bestvater, Felix A1 - Hildenbrand, Georg A1 - Hausmann, Michael A1 - Falk, Martin T1 - Recruitment of 53BP1 Proteins for DNA Repair and Persistence of Repair Clusters Differ for Cell Types as Detected by Single Molecule Localization Microscopy JF - International Journal of Molecular Sciences N2 - DNA double stranded breaks (DSBs) are the most serious type of lesions introduced into chromatin by ionizing radiation. During DSB repair, cells recruit different proteins to the damaged sites in a manner dependent on local chromatin structure, DSB location in the nucleus, and the repair pathway entered. 53BP1 is one of the important players participating in repair pathway decision of the cell. Although many molecular biology details have been investigated, the architecture of 53BP1 repair foci and its development during the post-irradiation time, especially the period of protein recruitment, remains to be elucidated. Super-resolution light microscopy is a powerful new tool to approach such studies in 3D-conserved cell nuclei. Recently, we demonstrated the applicability of single molecule localization microscopy (SMLM) as one of these highly resolving methods for analyses of dynamic repair protein distribution and repair focus internal nano-architecture in intact cell nuclei. In the present study, we focused our investigation on 53BP1 foci in differently radio-resistant cell types, moderately radio-resistant neonatal human dermal fibroblasts (NHDF) and highly radio-resistant U87 glioblastoma cells, exposed to high-LET 15N-ion radiation. At given time points up to 24 h post irradiation with doses of 1.3 Gy and 4.0 Gy, the coordinates and spatial distribution of fluorescently tagged 53BP1 molecules was quantitatively evaluated at the resolution of 10–20 nm. Clusters of these tags were determined as sub-units of repair foci according to SMLM parameters. The formation and relaxation of such clusters was studied. The higher dose generated sufficient numbers of DNA breaks to compare the post-irradiation dynamics of 53BP1 during DSB processing for the cell types studied. A perpendicular (90°) irradiation scheme was used with the 4.0 Gy dose to achieve better separation of a relatively high number of particle tracks typically crossing each nucleus. For analyses along ion-tracks, the dose was reduced to 1.3 Gy and applied in combination with a sharp angle irradiation (10° relative to the cell plane). The results reveal a higher ratio of 53BP1 proteins recruited into SMLM defined clusters in fibroblasts as compared to U87 cells. Moreover, the speed of foci and thus cluster formation and relaxation also differed for the cell types. In both NHDF and U87 cells, a certain number of the detected and functionally relevant clusters remained persistent even 24 h post irradiation; however, the number of these clusters again varied for the cell types. Altogether, our findings indicate that repair cluster formation as determined by SMLM and the relaxation (i.e., the remaining 53BP1 tags no longer fulfill the cluster definition) is cell type dependent and may be functionally explained and correlated to cell specific radio-sensitivity. The present study demonstrates that SMLM is a highly appropriate method for investigations of spatiotemporal protein organization in cell nuclei and how it influences the cell decision for a particular repair pathway at a given DSB site. KW - Genom KW - Krebs, Medizin KW - Strahlentherapie Y1 - 2018 U6 - https://doi.org/https://doi.org/10.3390/ijms19123713 SN - 1422-0067 VL - 19 IS - 12 PB - MDPI AG ER - TY - JOUR A1 - Hildenbrand, Georg A1 - Metzler, Philipp A1 - Pilarczyk, Götz A1 - Bobu, Vladimir A1 - Kriz, Wilhelm A1 - Hosser, Hiltraud A1 - Fleckenstein, Jens A1 - Krufczik, Matthias A1 - Bestvater, Felix A1 - Wenz, Frederik A1 - Hausmann, Michael ED - Baptista, Pedro V. T1 - Dose enhancement effects of gold nanoparticles specifically targeting RNA in breast cancer cells JF - PLOS ONE KW - Krebs, Medizin KW - Brustkrebs KW - Strahlentherapie Y1 - 2018 U6 - https://doi.org/https://doi.org/10.1371/journal.pone.0190183 SN - 1932-6203 VL - 13 IS - 1 PB - Public Library of Science (PLoS) ER - TY - JOUR A1 - Moser, Felipe A1 - Hildenbrand, Georg A1 - Müller, Patrick A1 - Al Saroori, Alexander A1 - Biswas, Abin A1 - Bach, Margund A1 - Wenz, Frederik A1 - Cremer, Christoph A1 - Burger, Nina A1 - Veldwijk, Marlon R. A1 - Hausmann, Michael T1 - Cellular Uptake of Gold Nanoparticles and Their Behavior as Labels for Localization Microscopy JF - Biophysical Journal KW - Krebs, Medizin KW - Strahlentherapie Y1 - 2016 U6 - https://doi.org/https://doi.org/10.1016/j.bpj.2016.01.004 SN - 0006-3495 VL - 110 IS - 4 SP - 947 EP - 953 PB - Elsevier BV ER - TY - JOUR A1 - Bosiek, Katharina A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Perspectives on Comets, Comet-like Asteroids, and Their Predisposition to Provide an Environment That Is Friendly to Life JF - Astrobiology KW - Komet KW - Planetoid Y1 - 2016 U6 - https://doi.org/https://doi.org/10.1089/ast.2015.1354 SN - 1531-1074 VL - 16 IS - 4 SP - 311 EP - 323 PB - Mary Ann Liebert Inc ER - TY - JOUR A1 - Hausmann, Michael A1 - Winkler, Ralph A1 - Hildenbrand, Georg A1 - Finsterle, Jutta A1 - Weisel, Andrea A1 - Rapp, Alexander A1 - Schmitt, Eberhard A1 - Janz, Siegfried A1 - Cremer, Christoph T1 - COMBO-FISH: specific labeling of nondenatured chromatin targets by computer-selected DNA oligonucleotide probe combinations JF - BioTechniques KW - Genom Y1 - 2003 U6 - https://doi.org/https://doi.org/10.2144/03353rr03 SN - 0736-6205 VL - 35 IS - 3 SP - 564 EP - 577 PB - Informa UK Limited ER - TY - GEN A1 - Lee, Jin-Ho A1 - Bobkova, Elizaveta A1 - Gier, Theresa A1 - Gote, Martin A1 - Schmidt-kaler, Fanz A1 - Brieger, Emily A1 - Maus, Emanuel A1 - Krufczik, Matthias A1 - Chojowski, Robert A1 - Korn, Friederike A1 - Sarah, Schumann A1 - Scherthan, Harry A1 - Falkova, Iva A1 - Falk, Martin A1 - Hausmann, Michael A1 - Hildenbrand, Georg T1 - Mechanisms and Challenges for Understanding Radiation Induced Changes in Chromatin Nanoarchitecture T2 - DRO 2018 N2 - The three-dimensional architecture of genomes acts as an additional level of mode for fundamental biological processes such as DNA damage response. In this context, nanoprobing and super-resolution microscopy are powerful methods for structural analyses of genomic targets in native chromatin of single cells at resolutions of single antibodies, proteins, histones, short DNA stretches, etc. We used multi-color chromatin nanoprobing and single molecule localization microscopy of established DNA damage and chromatin markers in 3D-conserved nuclei of different cell types exposed to various types and doses of ionizing radiation. Similarly, effect of gold nanoparticles on extent and direction of cellular radiation response was assessed. Our studies revealed the nanoarchitecture of damage foci with respect to γH2AX, Mre11 or 53BP1 and their molecular rearrangements during repair processes. Nanoscopy of genomic Alu resulted in linear-quadratic dose-effects for low to higher dose ranges and in changes of H3K9me3 distribution around Alu clusters upon radiation exposure. Preliminary results show post-irradiation time dependent changes in Alu chromatin. Moreover, gold nanoparticles incorporated into cells seem to act by an interplay of radiation enhancement and chromatin remodeling leading to altered radiosensitivity. Our results contribute to the understanding of cellular radiation responses, thereby laying the basis for improved biological dosimetry and radiotherapies in future. N2 - Poster KW - Genom Y1 - 2019 U6 - https://doi.org/https://doi.org/10.13140/RG.2.2.31391.20647 ER - TY - JOUR A1 - Ngwa, Wilfred A1 - Boateng, Francis A1 - Kumar, Rajiv A1 - Irvine, Darrell J. A1 - Formenti, Silvia A1 - Ngoma, Twalib A1 - Herskind, Carsten A1 - Veldwijk, Marlon R. A1 - Hildenbrand, Georg A1 - Hausmann, Michael A1 - Wenz, Frederik A1 - Hesser, Jürgen T1 - Smart Radiation Therapy Biomaterials JF - International Journal of Radiation Oncology*Biology*Physics KW - Krebs, Medizin KW - Strahlentherapie Y1 - 2017 U6 - https://doi.org/https://doi.org/10.1016/j.ijrobp.2016.10.034 SN - 0360-3016 VL - 97 IS - 3 SP - 624 EP - 637 PB - Elsevier BV ER - TY - JOUR A1 - Wiech, Thorsten A1 - Stein, Stefan A1 - Lachenmaier, Victoria A1 - Schmitt, Eberhard A1 - Schwarz-Finsterle, Jutta A1 - Wiech, Elisabeth A1 - Hildenbrand, Georg A1 - Werner, Martin A1 - Hausmann, Michael T1 - Spatial allelic imbalance of BCL2 genes and chromosome 18 territories in nonneoplastic and neoplastic cervical squamous epithelium JF - European Biophysics Journal KW - Genom KW - Krebs, Medizin Y1 - 2009 U6 - https://doi.org/https://doi.org/10.1007/s00249-009-0474-5 SN - 0175-7571 VL - 38 IS - 6 SP - 793 EP - 806 PB - Springer Science and Business Media LLC ER - TY - JOUR A1 - Müller, Patrick A1 - Lemmermann, Niels A. A1 - Kaufmann, Rainer A1 - Gunkel, Manuel A1 - Paech, Daniel A1 - Hildenbrand, Georg A1 - Holtappels, Rafaela A1 - Cremer, Christoph A1 - Hausmann, Michael T1 - Spatial distribution and structural arrangement of a murine cytomegalovirus glycoprotein detected by SPDM localization microscopy JF - Histochemistry and Cell Biology KW - Fluoreszenzmikroskopie Y1 - 2014 U6 - https://doi.org/https://doi.org/10.1007/s00418-014-1185-2 SN - 0948-6143 VL - 142 IS - 1 SP - 61 EP - 67 PB - Springer Science and Business Media LLC ER - TY - JOUR A1 - Hildenbrand, Georg A1 - Rapp, Alexander A1 - Spöri, Udo A1 - Wagner, Christian A1 - Cremer, Christoph A1 - Hausmann, Michael T1 - Nano-Sizing of Specific Gene Domains in Intact Human Cell Nuclei by Spatially Modulated Illumination Light Microscopy JF - Biophysical Journal KW - Genom KW - Zellkern KW - Fluoreszenzmikroskopie Y1 - 2005 U6 - https://doi.org/https://doi.org/10.1529/biophysj.104.056796 SN - 0006-3495 VL - 88 IS - 6 SP - 4312 EP - 4318 PB - Elsevier BV ER - TY - JOUR A1 - Kaufmann, Rainer A1 - Müller, P A1 - Hildenbrand, Georg A1 - Hausmann, Michael A1 - Cremer, Christoph T1 - Analysis of Her2/neu membrane protein clusters in different types of breast cancer cells using localization microscopy BT - ANALYSIS OF HER2/neu MEMBRANE PROTEIN CLUSTERS JF - Journal of Microscopy KW - Krebs, Medizin KW - Brustkrebs Y1 - 2010 U6 - https://doi.org/https://doi.org/10.1111/j.1365-2818.2010.03436.x SN - 0022-2720 VL - 242 IS - 1 SP - 46 EP - 54 PB - Wiley ER - TY - JOUR A1 - Burger, Nina A1 - Biswas, Abin A1 - Barzan, Daniel A1 - Kirchner, Anne A1 - Hosser, Hiltraud A1 - Hausmann, Michael A1 - Hildenbrand, Georg A1 - Herskind, Carsten A1 - Wenz, Frederik A1 - Veldwijk, Marlon R. T1 - A method for the efficient cellular uptake and retention of small modified gold nanoparticles for the radiosensitization of cells JF - Nanomedicine: Nanotechnology, Biology and Medicine KW - Gold KW - Nanopartikel Y1 - 2014 U6 - https://doi.org/https://doi.org/10.1016/j.nano.2014.03.011 SN - 1549-9634 VL - 10 IS - 6 SP - 1365 EP - 1373 PB - Elsevier BV ER - TY - JOUR A1 - Falk, Martin A1 - Hausmann, Michael A1 - Lukasova, Emilie A1 - Biswas, Abin A1 - Hildenbrand, Georg A1 - Davidkova, Marie A1 - Krasavin, Evgeny A1 - Kleibl, Zdenek A1 - Falkova, Iva A1 - Jezkova, Lucie A1 - Stefancikova, Lenka A1 - Sevcik, Jan A1 - Hofer, Michal A1 - Bacikova, Alena A1 - Matula, Pavel A1 - Boreyko, Alla A1 - Vachelova, Jana A1 - Michaelidesova, Anna A1 - Kozubek, Stanislav T1 - Determining Omics Spatiotemporal Dimensions Using Exciting New Nanoscopy Techniques to Assess Complex Cell Responses to DNA Damage: PART A-Radiomics JF - Critical Reviews in Eukaryotic Gene Expression KW - Radiologie Y1 - 2014 U6 - https://doi.org/https://doi.org/10.1615/CritRevEukaryotGeneExpr.2014010313 SN - 1045-4403 VL - 24 IS - 3 SP - 205 EP - 223 PB - Begell House ER - TY - CHAP A1 - Hausmann, Michael A1 - Pilarczyk, Götz A1 - Maus, Emanuel A1 - Hesser, Jürgen A1 - Hildenbrand, Georg T1 - Super-resolution microscopy of nanogold-labelling T2 - Nanoparticle Enhanced Radiation Therapy KW - Krebs, Medizin KW - Strahlentherapie Y1 - 2020 SN - 9780750323963 U6 - https://doi.org/https://doi.org/10.1088/978-0-7503-2396-3ch11 SP - 11 EP - 1 PB - IOP Publishing ER - TY - CHAP A1 - Hausmann, Michael A1 - Lee, Jin-Ho A1 - Hildenbrand, Georg T1 - 3D DNA FISH for analyses of chromatin-nuclear architecture T2 - Epigenetics Methods KW - Genom Y1 - 2020 SN - 9780128194140 U6 - https://doi.org/https://doi.org/10.1016/B978-0-12-819414-0.00020-3 SP - 399 EP - 418 PB - Elsevier ER -