@inproceedings{DoehringStanikPregleretal.2024, author = {D{\"o}hring, Thorsten and Stanik, Eva and Pregler, Jan and Stollenwerk, Manfred and Hildenbrand, Georg}, title = {Forschung zu Strahlensch{\"a}den mit dem Stratosph{\"a}renballon-Experiment ASTRABAX}, series = {DGaO-Proceedings}, volume = {2024}, booktitle = {DGaO-Proceedings}, number = {125}, pages = {1 -- 2}, year = {2024}, abstract = {Das Stratosph{\"a}renballon-Experiment ASTRABAX ist als multimodale Plattform der Material- und Biowissenschaften f{\"u}r Untersuchungen bei extremen Strahlenbelastungen konzipiert, mit Fokus auf dem UV-C-Spektralbereich und der kosmischen H{\"o}henstrahlung. Auswirkungen von Kombinationen aus hoch- und niederenergetischer Strahlung sind relevant, jedoch nicht ausreichend erforscht.}, subject = {Stratosph{\"a}ren-Ballon}, language = {de} } @article{SieversBosiekBischetal.2017, author = {Sievers, Aaron and Bosiek, Katharina and Bisch, Marc and Dreessen, Chris and Riedel, Jascha and Froß, Patrick and Hausmann, Michael and Hildenbrand, Georg}, title = {K-mer Content, Correlation, and Position Analysis of Genome DNA Sequences for the Identification of Function and Evolutionary Features}, series = {Genes}, volume = {8}, journal = {Genes}, number = {4}, publisher = {MDPI AG}, issn = {2073-4425}, doi = {https://doi.org/10.3390/genes8040122}, year = {2017}, abstract = {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.}, subject = {Genom}, language = {en} } @article{HikmatSieversHausmannetal., author = {Hikmat, Wisam Mohammed and Sievers, Aaron and Hausmann, Michael and Hildenbrand, Georg}, title = {Peculiar k-mer Spectra Are Correlated with 3D Contact Frequencies and Breakpoint Regions in the Human Genome}, series = {Genes}, volume = {15}, journal = {Genes}, number = {10}, doi = {10.3390/genes15101247}, subject = {Zellkern}, language = {de} } @article{Solov’yovVerkhovtsevMasonetal.2024, author = {Solov'yov, Andrey V. and Verkhovtsev, Alexey V. and Mason, Nigel J. and Amos, Richard A. and Bald, Ilko and Baldacchino, G{\´e}rard and Dromey, Brendan and Falk, Martin and Fedor, Juraj and Gerhards, Luca and Hausmann, Michael and Hildenbrand, Georg and Hrabovsk{\´y}, Miloš and Kadlec, Stanislav and Kočišek, Jaroslav and L{\´e}pine, Franck and Ming, Siyi and Nisbet, Andrew and Ricketts, Kate and Sala, Leo and Schlath{\"o}lter, Thomas and Wheatley, Andrew E. H. and Solov'yov, Ilia A.}, title = {Condensed Matter Systems Exposed to Radiation: Multiscale Theory, Simulations, and Experiment}, series = {Chemical Reviews}, volume = {124}, journal = {Chemical Reviews}, number = {13}, publisher = {American Chemical Society (ACS)}, issn = {0009-2665}, doi = {https://doi.org/10.1021/acs.chemrev.3c00902}, pages = {8014 -- 8129}, year = {2024}, abstract = {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.}, subject = {Kondensierte Materie}, language = {en} } @article{HennSieversHausmannetal.2023, author = {Henn, Lukas and Sievers, Aaron and Hausmann, Michael and Hildenbrand, Georg}, title = {Specific Patterns in Correlations of Super-Short Tandem Repeats (SSTRs) with G+C Content, Genic and Intergenic Regions, and Retrotransposons on All Human Chromosomes}, series = {Genes}, volume = {15}, journal = {Genes}, number = {1}, publisher = {MDPI AG}, issn = {2073-4425}, doi = {https://doi.org/10.3390/genes15010033}, year = {2023}, abstract = {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.}, subject = {Genom}, language = {en} } @article{SieversSauerBischetal.2023, author = {Sievers, Aaron and Sauer, Liane and Bisch, Marc and Sprengel, Jan and Hausmann, Michael and Hildenbrand, Georg}, title = {Moderation of Structural DNA Properties by Coupled Dinucleotide Contents in Eukaryotes}, series = {Genes}, volume = {14}, journal = {Genes}, number = {3}, publisher = {MDPI AG}, issn = {2073-4425}, doi = {https://doi.org/10.3390/genes14030755}, year = {2023}, abstract = {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.}, subject = {Genom}, language = {en} } @article{ErenpreisaGiulianiYoshikawaetal.2023, author = {Erenpreisa, Jekaterina and Giuliani, Alessandro and Yoshikawa, Kenichi and Falk, Martin and Hildenbrand, Georg and Salmina, Kristine and Freivalds, Talivaldis and Vainshelbaum, Ninel and Weidner, Jonas and Sievers, Aaron and Pilarczyk, G{\"o}tz and Hausmann, Michael}, title = {Spatial-Temporal Genome Regulation in Stress-Response and Cell-Fate Change}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {3}, publisher = {MDPI AG}, issn = {1422-0067}, doi = {https://doi.org/10.3390/ijms24032658}, year = {2023}, abstract = {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.}, subject = {Zellkern}, language = {en} } @incollection{HausmannHildenbrandPilarczyk2022, author = {Hausmann, Michael and Hildenbrand, Georg and Pilarczyk, G{\"o}tz}, title = {Networks and Islands of Genome Nano-architecture and Their Potential Relevance for Radiation Biology}, series = {Results and Problems in Cell Differentiation}, booktitle = {Results and Problems in Cell Differentiation}, publisher = {Springer International Publishing}, address = {Cham}, isbn = {9783031065729}, issn = {0080-1844}, doi = {https://doi.org/10.1007/978-3-031-06573-6_1}, pages = {3 -- 34}, year = {2022}, abstract = {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.}, subject = {Zellkern}, language = {en} } @article{RodenerSchaeferHausmannetal.2022, author = {Rodener, Daniel and Sch{\"a}fer, Myriam and Hausmann, Michael and Hildenbrand, Georg}, title = {Assessing the Potential for Liquid Solvents from X-ray Sources: Considerations on Bodies Orbiting Active Galactic Nuclei}, series = {Galaxies}, volume = {10}, journal = {Galaxies}, number = {5}, publisher = {MDPI AG}, issn = {2075-4434}, doi = {https://doi.org/10.3390/galaxies10050101}, year = {2022}, abstract = {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.}, subject = {L{\"o}sungsmittel}, language = {en} } @article{PagačovaŠtefančikovaSchmidtKaleretal.2019, author = {Pag{\´a}čov{\´a}, Eva and Štefanč{\´i}kov{\´a}, Lenka and Schmidt-Kaler, Franz and Hildenbrand, Georg and Vičar, Tom{\´a}š and Depeš, Daniel and Lee, Jin-Ho and Bestvater, Felix and Lacombe, Sandrine and Porcel, Erika and Roux, St{\´e}phane and Wenz, Frederik and Kopecna, Olga and Falkov{\´a}, Iva and Hausmann, Michael and Falk, Martin}, title = {Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy}, series = {International Journal of Molecular Sciences}, volume = {20}, journal = {International Journal of Molecular Sciences}, number = {3}, publisher = {MDPI AG}, issn = {1422-0067}, doi = {https://doi.org/10.3390/ijms20030588}, year = {2019}, abstract = {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.}, subject = {Krebs, Medizin}, language = {en} }