The German Uranium Miners’ Biobank—A Biobank for OMICs Radiation Research

Systematic bio- and databanks are key prerequisites for modern radiation research to investigate radiation response mechanisms in the context of genetic, environmental and lifestyle-associated factors. This report presents the current status of the German Uranium Miners’ Biobank. In 2008, the bio- and databank was established at the Federal Office for Radiation Protection, and the sampling of biological materials from former uranium miners with and without lung cancer was initiated. For this purpose, various biological specimens, such as DNA and RNA, were isolated from blood samples as well as from formalin-fixed paraffin-embedded lung tissue. High-quality biomaterials suitable for OMICs research and the associated data on occupational radiation and dust exposure, and medical and lifestyle data from over 1000 individuals have been stored so far. Various experimental data, e.g., genome-wide SNPs, whole genome transcriptomic and miRNA data, as well as individual chromosomal aberration data from subgroups of biobank samples, are already available upon request for in-depth research on radiation-induced long-term effects, individual radiation susceptibility to lung cancer and radon-induced fingerprints in lung cancer. This biobank is the first systematic uranium miners´ biobank worldwide that is suitable for OMICs research on radiation-exposed workers. It offers the opportunity to link radiation-induced perturbations of biological pathways or processes and putative adverse outcome(s) by OMICs profiling at different biological organization levels.

Ingovernável da deficiência, sua radicalidade ontológica e seus devires clandestinos na educação e na filosofia

Este artigo analisa a dimensão ingovernável da deficiência, sua radicalidade ontológica e seus devires clandestinos na configuração neoliberal da biopolítica. Partimos para tanto do ensaio Os instintos e as instituições de Gilles Deleuze e do curso Os anormais de Michel Foucault, com vistas a discutir a proveniência da ingovernabilidade da deficiência e suas formas de governo pelas instituições educacionais. Retratamos o modo como o retardo de Charles Jouy revela um hiato entre a sua organização biológica, a mecânica instintual e a economia do prazer, encontrando aí sua ingovernabilidade não somente a ser governada, como também a servir de indagação às práticas inclusivas atuais, seus devires clandestinos e sua biopotência para resistir à governamentalidade neoliberal. Palavras-chave: Ingovernável. Deficiência. Corpo. Filosofias da diferença.The ungovernable of disability, its ontological radicality and its clandestine becomings in education and philosophyABSTRACT This article analyzes the ungovernable dimension of disability, its ontological radicality and its clandestine becomings in the neoliberal configuration of biopolitics. For this, we start from the essay The instincts and institutions by Gilles Deleuze and from the course The abnormals by Michel Foucault, with a view to discussing the origin of the ungovernability of disability and its forms of government by educational institutions. We portray how Charles Jouy's retardation reveals a gap between his biological organization, instinctual mechanics and the economy of pleasure, finding his ungovernability not only to be governed, but also to serve as an inquiry into current inclusive practices, their becomings clandestines and their biopotency to resist neoliberal governmentality.Keywords: Ungovernable. Deficiency. Body. Philosophies Of Difference.

Putting the Cell in Order

Organization is one of the most conspicuous features of cells. Not only are cells highly ordered (in the sense of regularity and predictability), but also they are organized: their order has purpose, or function. How does biological organization arise, and how is it transmitted from one generation to the next? A key element is genetic information encoded in DNA. Many scientists hold that DNA is the master molecule of life that prescribes all that cells are and do, and the general public has swallowed that doctrine whole. There is truth in this view of biological organization, inasmuch as genes do specify the chemical structure (and thereby the function) of proteins, nucleic acids, and (indirectly) many other biomolecules. But that is only part of an increasingly complex story. The higher levels of cell organization are not spelled out in the genes; they arise by self-organization, and are commonly transmitted to the next generation because the mother cell is architecturally continuous with its daughter. DNA provides an indispensable database, but does not direct the show. Organisms are better understood as complex interactive systems composed of genetically specified elements.

The Tangled Bank

Why are there so many kinds of organisms, and why do they cluster into discrete groups associated with particular locales? These and other ecological questions find answers in the expansive version of evolution that is presently emerging. Heredity, variation, natural selection, and adaptation are rooted in the level of genes, but incorporate features that grow out of the many tiers of biological organization. The communitarian view of life complements the one focused on the individual organism, and requires us to reexamine the meaning of both organism and individual. It embraces broad-gauge phenomena such as nutrient cycles, and gave birth to Gaia: the vision of Earth as a self-regulating system that has kept our planet hospitable to life for nearly 4 billion years.

Capturing a Comprehensive Picture of Biological Events From Adverse Outcome Pathways in the Drug Exposome

Background: The chemical part of the exposome, including drugs, may explain the increase of health effects with outcomes such as infertility, allergies, metabolic disorders, which cannot be only explained by the genetic changes. To better understand how drug exposure can impact human health, the concepts of adverse outcome pathways (AOPs) and AOP networks (AONs), which are representations of causally linked events at different biological levels leading to adverse health, could be used for drug safety assessment.Methods: To explore the action of drugs across multiple scales of the biological organization, we investigated the use of a network-based approach in the known AOP space. Considering the drugs and their associations to biological events, such as molecular initiating event and key event, a bipartite network was developed. This bipartite network was projected into a monopartite network capturing the event–event linkages. Nevertheless, such transformation of a bipartite network to a monopartite network had a huge risk of information loss. A way to solve this problem is to quantify the network reduction. We calculated two scoring systems, one measuring the uncertainty and a second one describing the loss of coverage on the developed event–event network to better investigate events from AOPs linked to drugs.Results: This AON analysis allowed us to identify biological events that are highly connected to drugs, such as events involving nuclear receptors (ER, AR, and PXR/SXR). Furthermore, we observed that the number of events involved in a linkage pattern with drugs is a key factor that influences information loss during monopartite network projection. Such scores have the potential to quantify the uncertainty of an event involved in an AON, and could be valuable for the weight of evidence assessment of AOPs. A case study related to infertility, more specifically to “decrease, male agenital distance” is presented.Conclusion: This study highlights that computational approaches based on network science may help to understand the complexity of drug health effects, with the aim to support drug safety assessment.

Biomarker Studies in Stress Biology: From the Gene to Population, from the Organism to the Application

Endpoints assessed at the population or community level are most often the result of the sum of effects on individuals, arising from the effects at the cellular and molecular levels. Within this framework, these lower biological level endpoints are more responsive at an early stage of exposure, making them potential toolboxes to be used as early-warning markers to address stress. Given this, by linking responses and understanding organisms’ metabolism and physiology, the possibilities for the use of biomarkers in stress biology are vast. Here, biomarker comprehensive examples are given to enlighten the need to link levels of biological organization, and their usefulness for a myriad of fields and applications is presented and discussed.

Marine research and management topics addressed by process-based ecosystem models

The earth’s oceans and ecosystems face climatic changes and multiple anthropogenic stressors. In the face of this, managers of the marine environment are increasingly adopting the ecosystem approach to underpin their decision making. Process-based ecosystem models (frequently referred to as dynamic models) synthesize existing observational and experimental knowledge into a numerical framework, but an obstacle to the incorporation of these models in management is the lack of credibility due to limited control of uncertainty in the results. The 13 papers in this Theme Section highlight how ecosystem models are, or can be, applied as management tools, and the various ways in which they quantify uncertainty and evaluate the skill. The papers span all levels of biological organization from individuals to populations and ecosystems, and cover a wide selection of anthropogenic pressures. Bearing in mind that the interpretation of observations is in fact also a model with representativeness error, we advocate a closer combination of observations and models to bring both methods forward. With the current challenges to the marine ecosystem and our uses of it, the more tools marine managers have in their ‘toolbox’, the better; dynamic modelling is one such very important tool, and its inclusion in ecosystem management should be continuously assessed.

Physiological Performance Curves: When Are They Useful?

This review serves as an introduction to a special issue of Frontiers in Physiology, focused on the importance of physiological performance curves across phylogenetic and functional boundaries. Biologists have used performance curves to describe the effects of changing environmental conditions on animal physiology since the late 1800s (at least). Animal physiologists have studied performance curves extensively over the past decades, and there is a good foundation to understanding how the environment affects physiological functions of individuals. Our goal here was to build upon this research and address outstanding questions regarding the mutability and applicability of performance curves across taxonomic groups and levels of biological organization. Performance curves are not fixed at a taxonomic, population, or individual level – rather they are dynamic and can shift in response to evolutionary pressures (e.g., selection) and epigenetic programming (e.g., plasticity). The mechanisms underlying these shifts are being increasingly used to predict the efficacy with which plasticity and heritability of performance curves can render individuals and populations less vulnerable to climate change. Individual differences in physiological performance curves (and plasticity of performance curves) can also have cascading effects at higher levels of biological organization. For instance, individual physiology likely influences group behaviors in non-additive ways. There is a need therefore to extend the concept of performance curves to social interactions and sociality. Collectively, this special issue emphasizes the power of how within- and between-individual shifts in performance curves might scale up to the population-, species-, and community-level dynamics that inform conservation management strategies.