Transcriptional responses to radiation exposure facilitate the discovery of biomarkers functioning as radiation biodosimeters

The development of new methods for a retrospective quantification of the radiation dose of exposed individuals is of widespread interest. To this end, I developed a computational framework for biomarker discovery and radiation dose prediction and successfully identified gene signatures with which low and medium to high radiation doses can be accurately quantified. To enhance our understanding of the radiation-induced transcriptional response, I additionally analyzed microarray data of human PBLs after ex vivo gamma-irradiation and characterized affected functional processes and pathways

Klimaabgabe für Kohlekraftwerke: Ein richtiger Schritt zur Erreichung des Klimaziels?

Lange Zeit favorisierte das Bundesministerium für Wirtschaft und Energie eine zusätzliche Klimaabgabe für alte Kohlekraftwerke zur Erreichung der deutschen Klimaziele. Mit dem Kompromiss vom 1. Juli scheint dieser Vorschlag jetzt vom Tisch zu sein. Sind die Alternativvorschläge zur Erreichung der mittel- bis langfristigen klimapolitischen Ziele effektiver? Für Erik Gawel und Sebastian Strunz, Helmholtz-Zentrum für Umweltforschung – UFZ, Leipzig, ist die vom Koalitionsausschuss favorisierte Variante »die schlechteste« – ohne Stilllegung von CO2-Zertifikaten würden Altkraftwerke in einer überdies kurz- und mittelfristig gar nicht benötigten Kapazitätsreserve gehalten, die strukturellen Anreize für den Stromsektor dürften stark begrenzt sein. Der ursprüngliche Vorschlag des Bundeswirtschaftsministeriums hätte dagegen emissionsintensive Kraftwerke belastet, samt Stilllegung von Zertifikaten. So wäre der jüngsten Renaissance der Braunkohleverstromung strukturell entgegengesteuert worden. Auch nach Ansicht von Sonja Peterson, Institut für Weltwirtschaft an der Universität Kiel, gehen die Vorschläge, die jetzt alternativ zur Klimaabgabe diskutiert werden, in die falsche Richtung: »Sie kosten die deutschen Steuerzahler viel Geld, vergrößern die Ineffizienzen in Deutschland und der EU und sparen am Ende EU-weit keinerlei Emissionen ein.« Die diskutierte Klimaabgabe gehe immerhin in die richtige Richtung. Für Hartmut Möllring, Minister für Wissenschaft und Wirtschaft in Sachsen-Anhalt, ist dagegen die Ablehnung des Klimabeitrags »eine gute Nachricht«. Der angedachte Klimabeitrag sei ordnungspolitisch und verfassungsrechtlich bedenklich, ohne dass damit tatsächlich ein Beitrag zum Klimaschutz geleistet worden wäre. Carl-Friedrich Elmer, Martin Faulstich und Christian Hey, Sachverständigenrat für Umweltfragen (SRU), sehen in den an Stelle des Klimabeitrags beschlossenen Alternativen weniger effiziente und effektive Einzelmaßnahmen. Dessen ungeachtet könnte aber der Klimabeitra

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans : joint RENEB and EURADOS inter-laboratory comparisons

Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios

Inferring causal molecular networks: empirical assessment through a community-based effort

Inferring molecular networks is a central challenge in computational biology. However, it has remained unclear whether causal, rather than merely correlational, relationships can be effectively inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge that focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results constitute the most comprehensive assessment of causal network inference in a mammalian setting carried out to date and suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess the causal validity of inferred molecular networks

Inferring causal molecular networks: empirical assessment through a community-based effort

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense

Comparable dose estimates of blinded whole blood samples are obtained independently of culture conditions and analytical approaches. Second RENEB gene expression study

PURPOSE:This collaboration of five established European gene expression labs investigated the potential impact of culture conditions on the transcriptional response of peripheral blood to radiation exposure.MATERIALS AND METHODS:Blood from one healthy donor was exposed ex vivo to a Cobalt 60 source to produce a calibration curve in addition to four unknown doses. After exposure, the blood samples were either diluted with RPMI medium or left untouched. After 24-h incubation at 37 °C the diluted blood samples were lysed, while the undiluted samples were mixed with the preservative RNALater and all samples were shipped frozen to the participating labs. Samples were processed by each lab using microarray (one lab) and QRT-PCR (four labs).RESULTS:We show that although culture conditions affect the total amount of RNA recovered (p 0.5 Gy) measurements (p = .6).CONCLUSION:This study confirms the robustness of gene expression as a method for biological dosimetry

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans – joint RENEB and EURADOS inter-laboratory comparisons

PURPOSE:RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation.MATERIALS AND METHODS:The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation-induced thermoluminescent signals in glass screens taken from mobile phones.RESULTS:In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques.CONCLUSIONS:Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios

Epidemiological insights from a large-scale investigation of intestinal helminths in Medieval Europe

Helminth infections are among the World Health Organization’s top neglected diseases with significant impact in many Less Economically Developed Countries. Despite no longer being endemic in Europe, the widespread presence of helminth eggs in archaeological deposits indicates that helminths represented a considerable burden in past European populations. Prevalence of infection is a key epidemiological feature that would influence the elimination of endemic intestinal helminths, for example, low prevalence rates may have made it easier to eliminate these infections in Europe without the use of modern anthelminthic drugs. To determine historical prevalence rates we analysed 589 grave samples from 7 European sites dated between 680 and 1700 CE, identifying two soil transmitted nematodes (Ascaris spp. and Trichuris trichiura) at all locations, and two food derived cestodes (Diphyllobothrium latum and Taenia spp.) at 4 sites. The rates of nematode infection in the medieval populations (1.5 to 25.6% for T. trichiura; 9.3–42.9% for Ascaris spp.) were comparable to those reported within modern endemically infected populations. There was some evidence of higher levels of nematode infection in younger individuals but not at all sites. The genetic diversity of T. trichiura ITS-1 in single graves was variable but much lower than with communal medieval latrine deposits. The prevalence of food derived cestodes was much lower (1.0–9.9%) than the prevalence of nematodes. Interestingly, sites that contained Taenia spp. eggs also contained D. latum which may reflect local culinary practices. These data demonstrate the importance of helminth infections in Medieval Europe and provide a baseline for studies on the epidemiology of infection in historical and modern contexts. Since the prevalence of medieval STH infections mirror those in modern endemic countries the factors affecting STH decline in Europe may also inform modern intervention campaigns