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Book ; Thesis: Analysis of causes and consequences of chromosomal instability in cancer

Endesfelder, David

2012

Author's details	vorgelegt von David Endesfelder
Language	English
Size	106 Bl. : graph. Darst.
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Duisburg, Essen, Univ., Diss., 2013
HBZ-ID	HT018160849
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Unraveling the kinetochore nanostructure in Schizosaccharomyces pombe using multi-color SMLM imaging.

Virant, David / Vojnovic, Ilijana / Winkelmeier, Jannik / Endesfelder, Marc / Turkowyd, Bartosz / Lando, David / Endesfelder, Ulrike

The Journal of cell biology

2023 Volume 222, Issue 4

Abstract: The key to ensuring proper chromosome segregation during mitosis is the kinetochore (KT), a tightly regulated multiprotein complex that links the centromeric chromatin to the spindle microtubules and as such leads the segregation process. Understanding ... ...

Abstract	The key to ensuring proper chromosome segregation during mitosis is the kinetochore (KT), a tightly regulated multiprotein complex that links the centromeric chromatin to the spindle microtubules and as such leads the segregation process. Understanding its architecture, function, and regulation is therefore essential. However, due to its complexity and dynamics, only its individual subcomplexes could be studied in structural detail so far. In this study, we construct a nanometer-precise in situ map of the human-like regional KT of Schizosaccharomyces pombe using multi-color single-molecule localization microscopy. We measure each protein of interest (POI) in conjunction with two references, cnp1CENP-A at the centromere and sad1 at the spindle pole. This allows us to determine cell cycle and mitotic plane, and to visualize individual centromere regions separately. We determine protein distances within the complex using Bayesian inference, establish the stoichiometry of each POI and, consequently, build an in situ KT model with unprecedented precision, providing new insights into the architecture.
MeSH term(s)	Bayes Theorem ; Centromere/metabolism ; Chromosome Segregation ; Kinetochores/ultrastructure ; Mitosis ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism ; Spindle Apparatus/metabolism
Chemical Substances	SAD1 protein, S pombe ; Schizosaccharomyces pombe Proteins
Language	English
Publishing date	2023-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202209096
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Article ; Online: The Potential of Omics in Biological Dosimetry

Daniela Hladik / Martin Bucher / David Endesfelder / Ursula Oestreicher

Radiation, Vol 2, Iss 6, Pp 78-

2022 Volume 90

Abstract: Biological dosimetry is an internationally recognized method for quantifying and estimating radiation dose following suspected or verified excessive exposure to ionising radiation. In severe radiation accidents where a large number of people are ... ...

Abstract	Biological dosimetry is an internationally recognized method for quantifying and estimating radiation dose following suspected or verified excessive exposure to ionising radiation. In severe radiation accidents where a large number of people are potentially affected, it is possible to distinguish irradiated from non-irradiated people in order to initiate appropriate medical care if necessary. In addition to severe incidents caused by technical failure, environmental disasters, military actions, or criminal abuse, there are also radiation accidents in which only one or a few individuals are affected in the frame of occupational or medical exposure. The requirements for biological dosimetry are fundamentally different for these two scenarios. In particular, for large-scale radiation accidents, pre-screening methods are necessary to increase the throughput of samples for a rough first-dose categorization. The rapid development and increasing use of omics methods in research as well as in individual applications provides new opportunities for biological dosimetry. In addition to the discovery and search for new biomarkers, dosimetry assays based on omics technologies are becoming increasingly interesting and hold great potential, especially for large-scale dosimetry. In the following review, the different areas of biological dosimetry, the problems in finding suitable biomarkers, the current status of biomarker research based on omics, the potential applications of assays using omics technologies, and also the limitations for the different areas of biological dosimetry are discussed.
Keywords	biological dosimetry ; omics ; transcriptomics ; proteomics ; metabolomics ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
Subject code	500
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The effect of data aggregation on dispersion estimates in count data models.

Errington, Adam / Einbeck, Jochen / Cumming, Jonathan / Rössler, Ute / Endesfelder, David

The international journal of biostatistics

2021 Volume 18, Issue 1, Page(s) 183–202

Abstract: For the modelling of count data, aggregation of the raw data over certain subgroups or predictor configurations is common practice. This is, for instance, the case for count data biomarkers of radiation exposure. Under the Poisson law, count data can be ... ...

Abstract	For the modelling of count data, aggregation of the raw data over certain subgroups or predictor configurations is common practice. This is, for instance, the case for count data biomarkers of radiation exposure. Under the Poisson law, count data can be aggregated without loss of information on the Poisson parameter, which remains true if the Poisson assumption is relaxed towards quasi-Poisson. However, in biodosimetry in particular, but also beyond, the question of how the dispersion estimates for quasi-Poisson models behave under data aggregation have received little attention. Indeed, for real data sets featuring unexplained heterogeneities, dispersion estimates can increase strongly after aggregation, an effect which we will demonstrate and quantify explicitly for some scenarios. The increase in dispersion estimates implies an inflation of the parameter standard errors, which, however, by comparison with random effect models, can be shown to serve a corrective purpose. The phenomena are illustrated by
MeSH term(s)	Data Aggregation ; Poisson Distribution
Language	English
Publishing date	2021-05-07
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-4679
ISSN (online)	1557-4679
DOI	10.1515/ijb-2020-0079
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Article ; Online: Improving the accuracy of dose estimates from automatically scored dicentric chromosomes by accounting for chromosome number.

Endesfelder, David / Kulka, Ulrike / Einbeck, Jochen / Oestreicher, Ursula

International journal of radiation biology

2020 Volume 96, Issue 12, Page(s) 1571–1584

Abstract: Purpose: The traditional workflow for biological dosimetry based on manual scoring of dicentric chromosomes is very time consuming. Especially for large-scale scenarios or for low-dose exposures, high cell numbers have to be analyzed, requiring ... ...

Abstract	Purpose: The traditional workflow for biological dosimetry based on manual scoring of dicentric chromosomes is very time consuming. Especially for large-scale scenarios or for low-dose exposures, high cell numbers have to be analyzed, requiring alternative scoring strategies. Semi-automatic scoring of dicentric chromosomes provides an opportunity to speed up the standard workflow of biological dosimetry. Due to automatic metaphase and chromosome detection, the number of counted chromosomes per metaphase is variable. This can potentially introduce overdispersion and statistical methods for conventional, manual scoring might not be applicable to data obtained by automatic scoring of dicentric chromosomes, potentially resulting in biased dose estimates and underestimated uncertainties. The identification of sources for overdispersion enables the development of methods appropriately accounting for increased dispersion levels. Materials and methods: Calibration curves based on in vitro irradiated (137-Cs; 0.44 Gy/min) blood from three healthy donors were analyzed for systematic overdispersion, especially at higher doses (>2 Gy) of low LET radiation. For each donor, 12 doses in the range of 0-6 Gy were scored semi-automatically. The effect of chromosome number as a potential cause for the observed overdispersion was assessed. Statistical methods based on interaction models accounting for the number of detected chromosomes were developed for the estimation of calibration curves, dose and corresponding uncertainties. The dose estimation was performed based on a Bayesian Markov-Chain-Monte-Carlo method, providing high flexibility regarding the implementation of priors, likelihood and the functional form of the association between predictors and dicentric counts. The proposed methods were validated by simulations based on cross-validation. Results: Increasing dose dependent overdispersion was observed for all three donors as well as considerable differences in dicentric counts between donors. Variations in the number of detected chromosomes between metaphases were identified as a major source for the observed overdispersion and the differences between donors. Persisting overdispersion beyond the contribution of chromosome number was modeled by a Negative Binomial distribution. Results from cross-validation suggested that the proposed statistical methods for dose estimation reduced bias in dose estimates, variability between dose estimates and improved the coverage of the estimated confidence intervals. However, the 95% confidence intervals were still slightly too permissive, suggesting additional unknown sources of apparent overdispersion. Conclusions: A major source for the observed overdispersion could be identified, and statistical methods accounting for overdispersion introduced by variations in the number of detected chromosomes were developed, enabling more robust dose estimation and quantification of uncertainties for semi-automatic counting of dicentric chromosomes.
MeSH term(s)	Adult ; Automation ; Calibration ; Chromosome Aberrations/radiation effects ; Chromosomes, Human/genetics ; Chromosomes, Human/radiation effects ; Female ; Humans ; Male ; Middle Aged ; Radiometry ; Uncertainty
Language	English
Publishing date	2020-10-16
Publishing country	England
Document type	Journal Article
ZDB-ID	3065-x
ISSN	1362-3095 ; 0020-7616 ; 0955-3002
ISSN (online)	1362-3095
ISSN	0020-7616 ; 0955-3002
DOI	10.1080/09553002.2020.1829152
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Article ; Online: Comparison of inexperienced operators and experts in γH2A.X and 53BP1 foci assay for high-throughput biodosimetry approaches in a mass casualty incident.

Bucher, Martin / Duchrow, Lukas / Endesfelder, David / Roessler, Ute / Gomolka, Maria

International journal of radiation biology

2020 Volume 96, Issue 10, Page(s) 1263–1273

Abstract: Purpose: In case of population exposure by ionizing radiation, a fast and reliable dose assessment of exposed and non-exposed individuals is crucial important. In initial triage, physicians have to take fast decisions whom to treat with adequate medical ...

Abstract	Purpose: In case of population exposure by ionizing radiation, a fast and reliable dose assessment of exposed and non-exposed individuals is crucial important. In initial triage, physicians have to take fast decisions whom to treat with adequate medical care. In addition, worries about significant exposure can be taken away from hundreds to thousands non- or low exposed individuals. Studies have shown that the γH2A.X radiation-induced foci assay is a promising test for fast triage decisions. However, in a large-scale scenario most biodosimetry laboratories will quickly reach their capacity limit. The aim of this study was to evaluate the benefit of inexperienced experimenters to speed up the foci assay and manual foci scoring. Materials and methods: The participants of two training courses performed the radiation-induced foci assay (γH2A.X) under the guidance of experts and scored foci (γH2A.X and 53BP1) on sham-irradiated and irradiated blood samples (0.05-1.5 Gy). The outcome of laboratory experiments and manual foci scoring by 26 operators with basic experience in laboratory work was statistically analyzed in comparison to the results from experts. Results: Inexperienced operators prepared slides with significant dose-effects (0, 0.1 and 1.0 Gy) for semi-automatic microscopic analyses. Manual foci scoring by inexperienced scorer resulted in a dose-effect curve for γH2A.X, 53BP1 and co-localized foci. In addition, inexperienced scorers were able to distinguish low irradiation doses from unirradiated cells. While 53BP1 foci scoring was in accordance to the expert counting, differences between beginners and expert increased for γH2A.X or co-localized foci. Conclusions: In case of a large-scale radiation event, inexperienced staff is useful to support laboratories in slide preparation for semi-automatic foci counting as well as γH2A.X and 53BP1 manual foci scoring for triage-mode biodosimetry. Slides can be clearly classified in the non-, low- or high-exposed category.
MeSH term(s)	Adult ; Artifacts ; Biological Assay ; Histones/metabolism ; Humans ; Mass Casualty Incidents ; Professional Competence ; Radiometry ; Tumor Suppressor p53-Binding Protein 1/metabolism
Chemical Substances	H2AX protein, human ; Histones ; Tumor Suppressor p53-Binding Protein 1
Language	English
Publishing date	2020-07-24
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3065-x
ISSN	1362-3095 ; 0020-7616 ; 0955-3002
ISSN (online)	1362-3095
ISSN	0020-7616 ; 0955-3002
DOI	10.1080/09553002.2020.1793024
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Article ; Online: Dose Variations Using an X-Ray Cabinet to Establish

Bucher, Martin / Weiss, Tina / Endesfelder, David / Trompier, Francois / Ristic, Yoann / Kunert, Patrizia / Schlattl, Helmut / Giussani, Augusto / Oestreicher, Ursula

Frontiers in public health

2022 Volume 10, Page(s) 903509

Abstract: In biological dosimetry, dose-response curves are essential for reliable retrospective dose estimation of individual exposure in case of a radiation accident. Therefore, blood samples are ... ...

Abstract	In biological dosimetry, dose-response curves are essential for reliable retrospective dose estimation of individual exposure in case of a radiation accident. Therefore, blood samples are irradiated
MeSH term(s)	Radiometry/methods ; Reproducibility of Results ; Retrospective Studies ; X-Rays
Language	English
Publishing date	2022-05-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2022.903509
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Book ; Online ; Thesis: Studying Large Multi-Protein Complexes Using Single Molecule Localization Microscopy

Virant, David [Verfasser] / Endesfelder, Ulrike [Akademischer Betreuer]

2020

Author's details	David Virant ; Betreuer: Ulrike Endesfelder
Keywords	Biowissenschaften, Biologie ; Life Science, Biology
Subject code	sg570
Language	English
Publisher	Philipps-Universität Marburg
Publishing place	Marburg
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article: Double-strand breaks in lymphocyte DNA of humans exposed to [

Brix, Gunnar / Günther, Elisabeth / Rössler, Ute / Endesfelder, David / Kamp, Alexandra / Beer, Ambros / Eiber, Matthias

EJNMMI research

2020 Volume 10, Issue 1, Page(s) 43

Abstract: Background: Given the increasing clinical use of PET/MRI, potential risks to patients from simultaneous exposure to ionising radiation and (electro)magnetic fields should be thoroughly investigated as a precaution. With this aim, the genotoxic potential ...

Abstract	Background: Given the increasing clinical use of PET/MRI, potential risks to patients from simultaneous exposure to ionising radiation and (electro)magnetic fields should be thoroughly investigated as a precaution. With this aim, the genotoxic potential of 2-deoxy-2-[ Methods: Thirty-two healthy young volunteers allocated to three study arms were exposed to [ Results: Absorbed doses to lymphocytes exposed over 60 to 120 min to [ Conclusion: There is no evidence of a synergism between [
Language	English
Publishing date	2020-04-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2619892-7
ISSN	2191-219X
ISSN	2191-219X
DOI	10.1186/s13550-020-00625-1
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Article ; Online: Biodose Tools: an R shiny application for biological dosimetry.

Hernández, Alfredo / Endesfelder, David / Einbeck, Jochen / Puig, Pedro / Benadjaoud, Mohamed Amine / Higueras, Manuel / Ainsbury, Elizabeth / Gruel, Gaëtan / Oestreicher, Ursula / Barrios, Leonardo / Barquinero, Joan Francesc

International journal of radiation biology

2023 Volume 99, Issue 9, Page(s) 1378–1390

Abstract: Introduction: In the event of a radiological accident or incident, the aim of biological dosimetry is to convert the yield of a specific biomarker of exposure to ionizing radiation into an absorbed dose. Since the 1980s, various tools have been used to ... ...

Abstract	Introduction: In the event of a radiological accident or incident, the aim of biological dosimetry is to convert the yield of a specific biomarker of exposure to ionizing radiation into an absorbed dose. Since the 1980s, various tools have been used to deal with the statistical procedures needed for biological dosimetry, and in general those who made several calculations for different biomarkers were based on closed source software. Here we present a new open source program, Biodose Tools, that has been developed under the umbrella of RENEB (Running the European Network of Biological and retrospective Physical dosimetry). Materials and methods: The application has been developed using the R programming language and the shiny package as a framework to create a user-friendly online solution. Since no unique method exists for the different mathematical processes, several meetings and periodic correspondence were held in order to reach a consensus on the solutions to be implemented. Results: The current version 3.6.1 supports dose-effect fitting for dicentric and translocation assay. For dose estimation Biodose Tools implements those methods indicated in international guidelines and a specific method to assess heterogeneous exposures. The app can include information on the irradiation conditions to generate the calibration curve. Also, in the dose estimate, information about the accident can be included as well as the explanation of the results obtained. Because the app allows generating a report in various formats, it allows traceability of each biological dosimetry study carried out. The app has been used globally in different exercises and training, which has made it possible to find errors and improve the app itself. There are some features that still need consensus, such as curve fitting and dose estimation using micronucleus analysis. It is also planned to include a package dedicated to interlaboratory comparisons and the incorporation of Bayesian methods for dose estimation. Conclusion: Biodose Tools provides an open-source solution for biological dosimetry laboratories. The consensus reached helps to harmonize the way in which uncertainties are calculated. In addition, because each laboratory can download and customize the app's source code, it offers a platform to integrate new features.
MeSH term(s)	Radiation Monitoring/methods ; Bayes Theorem ; Retrospective Studies ; Radiometry ; Software
Language	English
Publishing date	2023-02-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3065-x
ISSN	1362-3095 ; 0020-7616 ; 0955-3002
ISSN (online)	1362-3095
ISSN	0020-7616 ; 0955-3002
DOI	10.1080/09553002.2023.2176564
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