From Goya to Afghanistan. An essay on the ratio and ethics of medical war pictures

For centuries pictures of the dead and wounded have been part and parcel of war communications. Often the intentions were clear, ranging from medical instructions to anti-war protests. The public's response could coincide with or diverge from the publisher's intention. Following the invention of photography in the nineteenth century, and the subsequent claim of realism, the veracity of medical war images became more complex. Analysing and understanding such photographs have become an ethical obligation with democratic implications. We performed a multidisciplinary analysis of War Surgery (2008), a book containing harsh, full-colour photographs of mutilated soldiers from the Iraq and Afghanistan wars. Our analysis shows that, within the medical context, this book is a major step forward in medical war communication and documentation. In the military context the book can be conceived as an attempt to put matters right given the enormous sacrifice some individuals have suffered. For the public, the relationship between the 'reality' and 'truth' of such photographs is ambiguous, because only looking at the photographs without reading the medical context is limiting. If the observer is not familiar with medical practice, it is difficult for him to fully assess, signify and acknowledge the value and relevance of this book. We therefore assert the importance of the role of professionals and those in the humanities in particular in educating the public and initiating debate. © 2010 Taylor & Francis

Dynamic metabolic control: towards precision engineering of metabolism

Advances in metabolic engineering have led to the synthesis of a wide variety of valuable chemicals in microorganisms. The key to commercializing these processes is the improvement of titer, productivity, yield, and robustness. Traditional approaches to enhancing production use the “push–pull-block” strategy that modulates enzyme expression under static control. However, strains are often optimized for specific laboratory set-up and are sensitive to environmental fluctuations. Exposure to sub-optimal growth conditions during large-scale fermentation often reduces their production capacity. Moreover, static control of engineered pathways may imbalance cofactors or cause the accumulation of toxic intermediates, which imposes burden on the host and results in decreased production. To overcome these problems, the last decade has witnessed the emergence of a new technology that uses synthetic regulation to control heterologous pathways dynamically, in ways akin to regulatory networks found in nature. Here, we review natural metabolic control strategies and recent developments in how they inspire the engineering of dynamically regulated pathways. We further discuss the challenges of designing and engineering dynamic control and highlight how model-based design can provide a powerful formalism to engineer dynamic control circuits, which together with the tools of synthetic biology, can work to enhance microbial production

Slow-growing cells within isogenic populations have increased RNA polymerase error rates and DNA damage

Isogenic cells show a large degree of variability in growth rate, even when cultured in the same environment. Such cell-to-cell variability in growth can alter sensitivity to antibiotics, chemotherapy and environmental stress. To characterize transcriptional differences associated with this variability, we have developed a method--FitFlow--that enables the sorting of subpopulations by growth rate. The slow-growing subpopulation shows a transcriptional stress response, but, more surprisingly, these cells have reduced RNA polymerase fidelity and exhibit a DNA damage response. As DNA damage is often caused by oxidative stress, we test the addition of an antioxidant, and find that it reduces the size of the slow-growing population. More generally, we find a significantly altered transcriptome in the slow-growing subpopulation that only partially resembles that of cells growing slowly due to environmental and culture conditions. Slow-growing cells upregulate transposons and express more chromosomal, viral and plasmid-borne transcripts, and thus explore a larger genotypic--and so phenotypic--space.This work was supported by grants to B.L. from the European Research Council Consolidator Grant (IR-DC 616434), Spanish Ministry of Economy and Competitiveness (BFU2011-26206), the AXA Research Fund, Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), and the EMBL-CRG Systems Biology Program. This work was supported by grants to L.B.C. from the department and the AGAUR program (2014 SGR 0974). R.D. acknowledges support from Swiss National Science Foundation through Early Postdoc Mobility Fellowship. D.v.D. was supported by an NWO Rubicon fellowship (825.14.016)