Ultraviolet stress delays chromosome replication in light/dark synchronized cells of the marine cyanobacterium Prochlorococcus marinus PCC9511.

International audienceBACKGROUND: The marine cyanobacterium Prochlorococcus is very abundant in warm, nutrient-poor oceanic areas. The upper mixed layer of oceans is populated by high light-adapted Prochlorococcus ecotypes, which despite their tiny genome (approximately 1.7 Mb) seem to have developed efficient strategies to cope with stressful levels of photosynthetically active and ultraviolet (UV) radiation. At a molecular level, little is known yet about how such minimalist microorganisms manage to sustain high growth rates and avoid potentially detrimental, UV-induced mutations to their DNA. To address this question, we studied the cell cycle dynamics of P. marinus PCC9511 cells grown under high fluxes of visible light in the presence or absence of UV radiation. Near natural light-dark cycles of both light sources were obtained using a custom-designed illumination system (cyclostat). Expression patterns of key DNA synthesis and repair, cell division, and clock genes were analyzed in order to decipher molecular mechanisms of adaptation to UV radiation. RESULTS: The cell cycle of P. marinus PCC9511 was strongly synchronized by the day-night cycle. The most conspicuous response of cells to UV radiation was a delay in chromosome replication, with a peak of DNA synthesis shifted about 2 h into the dark period. This delay was seemingly linked to a strong downregulation of genes governing DNA replication (dnaA) and cell division (ftsZ, sepF), whereas most genes involved in DNA repair (such as recA, phrA, uvrA, ruvC, umuC) were already activated under high visible light and their expression levels were only slightly affected by additional UV exposure. CONCLUSIONS: Prochlorococcus cells modified the timing of the S phase in response to UV exposure, therefore reducing the risk that mutations would occur during this particularly sensitive stage of the cell cycle. We identified several possible explanations for the observed timeshift. Among these, the sharp decrease in transcript levels of the dnaA gene, encoding the DNA replication initiator protein, is sufficient by itself to explain this response, since DNA synthesis starts only when the cellular concentration of DnaA reaches a critical threshold. However, the observed response likely results from a more complex combination of UV-altered biological processes

Does Plasminogen Activator Inhibitor-1 Drive Lymphangiogenesis?

The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and by regulating endothelial cell survival and migration. Protease system's role in lymphangiogenesis is unknown yet. Thus, based on its important pro-angiogenic effect, we hypothesized that PAI-1 may regulate lymphangiogenesis associated at least with metastatic dissemination of cancer cells. To address this issue, we studied the impact of PAI-1 deficiency in various murine models of tumoral lymphangiogenesis. Wild-type PAI-1 proficient mice were used as controls. We provide for the first time evidence that PAI-1 is dispensable for tumoral lymphangiogenesis associated with breast cancers either induced by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by using two inflammatory models. PAI-1 deficiency did neither affect the development of lymphangioma nor burn-induced corneal lymphangiogenesis. These novel data suggest that vascular remodelling associated with lymphangiogenesis and angiogenesis involve different molecular determinants. PAI-1 does not appear as a potential therapeutic target to counteract pathological lymphangiogenesis

European hydrogen train the trainer framework for responders: Outcomes of the HyResponder project

HyResponder is a European Hydrogen Train the Trainer programme for responders. This paper describes the key outputs of the project and the steps taken to develop and implement a long-term sustainable train the trainer programme in hydrogen safety for responders across Europe and beyond. This FCH2 JU (now Clean Hydrogen Joint Undertaking) funded project has built on the successful outcomes of the previous HyResponse project. HyResponder has developed further and updated educational, operational, and virtual reality training for trainers of responders to reflect the state-of-the-art in hydrogen safety, including liquid hydrogen, and expand the programme across Europe and specifically within the 10 countries represented directly within the project consortium: Austria, Belgium, the Czech Republic, France, Germany, Italy, Norway, Spain, Switzerland, and the United Kingdom. For the first time, four levels of educational materials from fire fighter through to specialist have been developed. The digital training resources are available on the e-Platform (https://hyresponder.eu/e-platform/). The revised European Emergency Response Guide is now available to all stakeholders. The resources are intended to be used to support national training programs. They are available in 8 languages: Czech, Dutch, English, French, German, Italian, Norwegian and Spanish. Through the HyResponder activities, trainers from across Europe have undertaken joint actions which are in turn being used to inform the delivery of regional and national training both within and beyond the project. The established pan-European network of trainers is shaping the future in the important for inherently safer deployment of hydrogen systems and infrastructure across Europe and enhancing the reach and impact of the programme

An algorithm to identify patients with treated type 2 diabetes using medico-administrative data

<p>Abstract</p> <p>Background</p> <p>National authorities have to follow the evolution of diabetes to implement public health policies. An algorithm was developed to identify patients with treated type 2 diabetes and estimate its annual prevalence in Luxembourg using health insurance claims when no diagnosis code is available.</p> <p>Methods</p> <p>The DIABECOLUX algorithm was based on patients' age as well as type and number of hypoglycemic agents reimbursed between 1995 and 2006. Algorithm validation was performed using the results of a national study based on medical data. Sensitivity, specificity and predictive values were estimated.</p> <p>Results</p> <p>The sensitivity of the DIABECOLUX algorithm was found superior to 98.2%. Between 2000 and 2006, 22,178 patients were treated for diabetes in Luxembourg, among whom 21,068 for type 2 diabetes (95%). The prevalence was estimated at 3.79% in 2006 and followed an increasing linear trend during the period. In 2005, the prevalence was low for young age classes and increased rapidly from 40 to 70 for male and 80 for female, reaching a peak of, respectively 17.0% and 14.3% before decreasing.</p> <p>Conclusions</p> <p>The DIABECOLUX algorithm is relevant to identify treated type 2 diabetes patients. It is reproducible and should be transferable to every country using medico-administrative databases not including diagnosis codes. Although undiagnosed patients and others with lifestyle recommendations only were not considered in this study, this algorithm is a cheap and easy-to-use tool to inform health authorities. Further studies will use this tool with the aim of improving the quality of health care dedicated to diabetic patients in Luxembourg.</p

Highly efficient separation of actinides from lanthanides by a phenanthroline-derived bis-triazine ligand

The synthesis, lanthanide complexation, and solvent ex- traction of actinide(III) and lanthanide(III) radiotracers from nitric acid solutions by a phenanthroline-derived quadridentate bis-triazine ligand are described. The ligand separates Am(III) and Cm(III) from the lanthanides with remarkably high efficiency, high selectivity, and fast extraction kinetics compared to its 2,2'-bipyridine counterpart. Structures of the 1:2 bis-complexes of the ligand with Eu(III) and Yb(III) were elucidated by X-ray crystallography and force field calculations, respec-tively. The Eu(III) bis-complex is the first 1:2 bis-complex of a quadridentate bis-triazine ligand to be characterized by crystallography. The faster rates of extraction were verified by kinetics measurements using the rotating membrane cell technique in several diluents. The improved kinetics of metal ion extraction are related to the higher surface activity of the ligand at the phase interface. The improvement in the ligand's properties on replacing the bipyridine unit with a phenanthroline unit far exceeds what was anticipated based on ligand design alone