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Scerbo P.,French Natural History Museum | Scerbo P.,Aix - Marseille University | Girardot F.,French Natural History Museum | Vivien C.,French Natural History Museum | And 9 more authors.
PLoS ONE | Year: 2012

Vertebrate development requires progressive commitment of embryonic cells into specific lineages through a continuum of signals that play off differentiation versus multipotency. In mammals, Nanog is a key transcription factor that maintains cellular pluripotency by controlling competence to respond to differentiation cues. Nanog orthologs are known in most vertebrates examined to date, but absent from the Anuran amphibian Xenopus. Interestingly, in silico analyses and literature scanning reveal that basal vertebrate ventral homeobox (ventxs) and mammalian Nanog factors share extensive structural, evolutionary and functional properties. Here, we reassess the role of ventx activity in Xenopus laevis embryos and demonstrate that they play an unanticipated role as guardians of high developmental potential during early development. Joint over-expression of Xenopus ventx1.2 and ventx2.1-b (ventx1/2) counteracts lineage commitment towards both dorsal and ventral fates and prevents msx1-induced ventralization. Furthermore, ventx1/2 inactivation leads to down-regulation of the multipotency marker oct91 and to premature differentiation of blastula cells. Finally, supporting the key role of ventx1/2 in the control of developmental potential during development, mouse Nanog (mNanog) expression specifically rescues embryonic axis formation in ventx1/2 deficient embryos. We conclude that during Xenopus development ventx1/2 activity, reminiscent of that of Nanog in mammalian embryos, controls the switch of early embryonic cells from uncommitted to committed states. © 2012 Scerbo et al.


EDA-EMERGE aims to train a new generation of young scientists in the interdisciplinary techniques required to meet the major challenges in the monitoring, assessment and management of toxic pollution in European river basins considering the enormous complexity of contamination, effects and cause-effect relationships. By integrating innovative mode-of-action based biodiagnostic tools including in vitro tests, transgenic organisms and omics techniques with powerful fractionation and cutting edge analytical and computational structure elucidation tools, a new generation of effect directed analysis (EDA) approaches will be developed for the identification of toxicants in European surface and drinking waters. Innovative method development by young researchers at major universities, research centres and private companies will be closely interlinked with a joint European demonstration program and higher tier EDA and extensive training courses. EDA-EMERGE ESRs will learn to organise and run international and interdisciplinary sampling and monitoring campaigns and benefit from the expertise of one of the most experienced private companies in this field. Strong networking between academia, the private sector and leading regulators in the field of river basin management and pollution management ensures the relevance of the research for practice and excellent employment opportunities for EDA-EMERGE ESRs. The combination of cutting edge science with training in multiple complementary (soft) skills offered with a strong emphasis on commercial exploitation and media competence will further enhance employability of well-trained ESRs not only in research and academia but far beyond. An internationally composed advisory board will introduce new perspectives of monitoring, assessment and management of emerging pollutants within and outside of Europe.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 4.02M | Year: 2013

The ability to manipulate cellular pluripotency and differentiation holds the as yet unrealized promise of regenerative medicine to produce replacement cells and tissues. To this end a deep understanding of the regulation of differentiation potential in the context of normal embryonic development is crucial. The recent revolution in sequencing technology has enabled high throughput and genome-wide analysis of cellular behaviour. The challenge with the new opportunities in genome-scale quantitative data gathering is to reach a more fundamental, systems level understanding of complex biological phenomena such as development and differentiation. The mission of the DevCom network is to train a new generation of promising scientists to bridge the gap between developmental and computational biology, and to prepare this generation for the emerging field of New Biology in which systems-level, quantitative and computational approaches are fully integrated in the analysis of profound scientific problems related to pluripotency and differentiation. The DevCom research plan revolves around early embryonic regulatory networks and disease networks in vertebrate embryos of the Xenopus and zebrafish model systems. The training plan involves interdisciplinary training with exposure to both academic and business settings. The trainees will acquire technical expertise in embryonic anatomy and development, genomic profiling, sequence conservation and evolutionary relationships of regulatory elements, genetic and chemical screens, mass spectrometry, informatics, statistics and computational modelling, and will be trained in a range of soft and complementary skills. Therefore the DevCom Training and Research Programmes are designed to foster readiness for leading roles in academia and industry and will have a lasting impact on the training programmes of participating institutions.


PubMed | Eawag - Swiss Federal Institute of Aquatic Science and Technology, European Commission - Joint Research Center Ispra, Procter and Gamble, Consultancy for Environmental & Human Toxicology & Risk Assessment Lyon Agency and 8 more.
Type: Review | Journal: Environmental toxicology and chemistry | Year: 2016

The need for alternative approaches to the use of vertebrate animals for hazard assessment of chemicals and pollutants has become of increasing importance. It is now the first consideration when initiating a vertebrate ecotoxicity test, to ensure that unnecessary use of vertebrate organisms is minimized wherever possible. For some regulatory purposes, the use of vertebrate organisms for environmental risk assessments has been banned; in other situations, the number of organisms tested has been dramatically reduced or the severity of the procedure refined. However, there is still a long way to go to achieve a complete replacement of vertebrate organisms to generate environmental hazard data. The development of animal alternatives is based not just on ethical considerations but also on reducing the cost of performing vertebrate ecotoxicity tests and in some cases on providing better information aimed at improving environmental risk assessments. The present Focus article provides an overview of the considerable advances that have been made toward alternative approaches for ecotoxicity assessments over the last few decades. Environ Toxicol Chem 2016;35:2637-2646. 2016 SETAC.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENV.2013.6.2-2 | Award Amount: 16.30M | Year: 2013

SOLUTIONS will deliver a conceptual framework for the evidence-based development of environmental and water policies. This will integrate innovative chemical and effect-based monitoring tools with a full set of exposure, effect and risk models and assessment options. Uniquely, SOLUTIONS taps (i) expertise of leading European scientists of major FP6/FP7 projects on chemicals in the water cycle, (ii) access to the infrastructure necessary to investigate the large basins of Danube and Rhine as well as relevant Mediterranean basins as case studies, and (iii) innovative approaches for stakeholder dialogue and support. In particular, International River Commissions, EC working groups and water works associations will be directly supported with consistent guidance for the early detection, identification, prioritization, and abatement of chemicals in the water cycle. A user-friendly tool providing access to a set of predictive models will support stakeholders to improve management decisions, benefiting from the wealth of data generated from monitoring and chemical registration. SOLUTIONS will give a specific focus on concepts and tools for the impact and risk assessment of complex mixtures of emerging pollutants, their metabolites and transformation products. Analytical and effect-based screening tools will be applied together with ecological assessment tools for the identification of toxicants and their impacts. Beyond state-of-the-art monitoring and management tools will be elaborated allowing risk identification for aquatic ecosystems and human health. The SOLUTIONS approach will provide transparent and evidence-based lists of River Basin Specific Pollutants for the case study basins and support the review of the list of WFD priority pollutants.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 3.03M | Year: 2009

Current demographic trends indicate that by the year 2020 almost 1 in 5 of the European population will be aged over 65. However, although life expectancy is increasing in the developed world, the period of good health enjoyed by its people is not keeping pace. The ageing population is thus a major health and economic issue for Europe. Although ageing is a complex process, we know much about its actions at the cellular and tissue level. In contrast, our understanding of how the various age-related changes interact to result in frailty and disease is incomplete. There is therefore a pressing need to carry out multidisciplinary research to identify factors contributing to age-related frailty and to develop interventions to promote healthy ageing. While Europe has many excellent research teams working on age-related diseases, such as neurodegeneration, there is little attempt to pool resources and identify underlying common age-related processes that predispose to pathology and represent rational targets for intervention. In addition, there is a lack of scientists trained in multidisciplinary ageing research and the challenge of an ageing population will not be met unless we increase research capacity in this area. NINA is a multi-site ITN that will make a significant impact upon research capacity by training 12 early stage researchers and 2 experienced researchers, integrating research and training at 10 world class European institutes. Fellows will benefit from the expertise of academic partners and training will be enhanced by the intersectoral experience provided by two industrial partners and a non-governmental organisation. NINA will tackle crucial health research challenges by directing the multidisciplinary programme at the identification of key factors driving the ageing process. NINA will focus on the age-related changes influencing the interactions of the brain, immune and endocrine systems to understand how these changes impact upon health.


News Article | November 13, 2016
Site: www.theguardian.com

Looking out over the Danube river as it passes through central Budapest, Gabor Farkass, director of Hungarian Plastics Association, bemoans his local authority’s careless attitude to recycling . “There are some sad pictures coming out in the media, because [scientists] check the riverbed, they check inside fish and birds, and they find a load of plastic,” he says. After barely surviving decades of heavy pollution by industries in the communist era, the ecological status of the Danube river has dramatically improved. But threats from new sources of pollution are looming on the world’s most international river, which tracks almost 1,800 miles through 10 countries and four capitals. The river is seeing a rise in plastic waste, pesticide run off and pharmaceutical waste. But perhaps the biggest difficulty is working out exactly what and where these problems are. The last Joint Danube Survey report by International Commission for the Protection of the Danube River (ICPDR) lists the top 20 hazardous substances to the entire river and found that just seven of them are officially reported on. “We have a massive lack of information about what kind of pollutants industries are releasing into the Danube,” says Adam Kovacs, technical expert for pollution control at the ICPDR. He says that EU legislation is behind industrial development. One of the newer pollution threats is microplastics, which can affect fish and fish larvae that confuse the particles with food sources. A study in Austria last year discovered that 40 tonnes of microplastics, pieces of plastic 5mm or smaller in diameter, are being transported each year through the country’s stretch of the river alone. It found that littering, wind carry and ineffective waste management are key contributors as larger plastic particles in the environment breakdown into smaller microplastics. If the synopsis sounds bleak, that’s because it is; despite the apparent urgency there is not yet a standardised scientific methodology for measuring microplastics in environmental samples. Scientists admit they know little about the long-term impacts to the Danube, human health, or the wider natural environment. A vast number of industries use plastics in items ranging from automotive parts, cleaning agents and cosmetics to packaging, agricultural and pharmaceutical items. “Our ministry is working with plastics manufacturers, trying to reduce their plastic output into the Danube down to zero.” says Franz Wagner, from Austria’s federal ministry of agriculture, forestry, environment and water management, which funded research into the phenomena after nets in a study on Danube fish larvae also landed lots of plastic particles. Rudiger Baunemann, director general at PlasticsEurope, a continent-wide association for manufacturers, defends the industry, which he says is doing its best to help keep plastics out of the natural environment altogether. He says it’s unfair to put the sole blame on companies for the problem. Tackling it “needs to be a joint effort between industries, authorities, NGOs, and other stakeholders,” he says. Farkass insists that recycling is a crucial element in tackling the scourge of plastics pollution to the Danube. Waste management facilities, especially highly effective ones, which are hugely expensive to develop, are key in tackling pollution issues, he says. Kovacs believes that future treatment plants will have an additional processing phase specifically for micro-pollutants. Pollution from microplastics, however, is only a part of emerging threats to the river. Recent foreign investments in agriculture in downstream Danube countries, such as a $500m (£400m) investment in Hungary and Romania from seed giant Monsanto, are expected to increase pollution pressure over the next few years. When fertilisers reach the river, they can lead to eutrophication (a depletion of oxygen), causing algae to grow explosively, which eventually asphyxiates organisms living underneath. Using mostly EU funds, Hungary has invested heavily in Budapest’s modern central wastewater treatment plant, which sits adjacent to the Danube shores near Ràkóczi Bridge. The capital’s waste enters the pungent-smelling plant as brown hazardous sludge, to eventually gush out into the river as treated clear water. But stark political and economical disparities between the richer upper and poorer lower Danube countries, often means that such infrastructure becomes less effective the further downstream you go. The 2008 economic crisis hampered an EU roadmap to improve waste facilities throughout all Danube countries. However, there are signs of hope. Romania, one of the poorest countries along the Danube is leading a pan-European project, DANUBIUS-RI, to tackle some of the problems affecting the river. “The goal is to understand the formation, distribution and impacts of emerging pollutants from microplastics, agriculture and pharmaceuticals,” says project leader Adrian Stanica. The region has been hamstrung by its communist past, says Ciprian Nanu, another member of the project and secretariat at European Innovation Partnership on Water, and this has traditionally made it hard to engage with business. But he is trying to pull together business, NGOs and other organisations to overcome this. “We have to start now to build business relations in order to introduce innovation in regional markets.” The project is looking to engage innovative water tech businesses, similar to WatchFrog, which is developing technologies to measure and monitor a range of micro-pollutants in waterways.


Pasquier D.,CNRS Developmental Biology Laboratory | Pasquier D.,University Pierre and Marie Curie | Pasquier D.,WatchFrog | Dupre A.,CNRS Developmental Biology Laboratory | And 3 more authors.
PLoS ONE | Year: 2011

Ovulated eggs possess maternal apoptotic execution machinery that is inhibited for a limited time. The fertilized eggs switch off this time bomb whereas aged unfertilized eggs and parthenogenetically activated eggs fail to stop the timer and die. To investigate the nature of the molecular clock that triggers the egg decision of committing suicide, we introduce here Xenopus eggs as an in vivo system for studying the death of unfertilized eggs. We report that after ovulation, a number of eggs remains in the female body where they die by apoptosis. Similarly, ovulated unfertilized eggs recovered in the external medium die within 72 h. We showed that the death process depends on both cytochrome c release and caspase activation. The apoptotic machinery is turned on during meiotic maturation, before fertilization. The death pathway is independent of ERK but relies on activating Bad phosphorylation through the control of both kinases Cdk1 and JNK. In conclusion, the default fate of an unfertilized Xenopus egg is to die by a mitochondrial dependent apoptosis activated during meiotic maturation. © 2011 Du Pasquier et al.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-IAPP | Phase: PEOPLE-2007-3-1-IAPP | Award Amount: 1.66M | Year: 2008

SME RECEPTOR is a transfer of knowledge programme which will bring top scientists from industry and academia together to address key questions in nuclear receptor research. The programme of research, which is implemented through the two way exchange of researchers between three leading research organisations and three specialist innovative SMEs, will develop methodology to tackle one of the most pressing medical challenges in Europe characterization of the nuclear receptor role and the development of drugs targeting the complex symptoms characterized by the metabolic syndrome. SME RECEPTOR will exploit new opportunities for drug design provided by advances in bioinformatics and transgenic technology. This will enhance the understanding of basis mechanisms underlying nuclear receptor actions and their translation into the physiological regulation of diseases. Since cardiovascular toxicity is a major factor involved in both early and late drug failure, SME RECEPTOR will primarily focus on the development of early screening methods for cardiovascular toxicity, as well as to expand the knowledge of the governing molecular mechanisms. A key factor is the ability to translate the knowledge generated within this exchange programme into more advanced and efficient development of novel pharmaceuticals within the industry. The project will generate a group of scientists with unique knowledge and international expertise in nuclear receptor biology as well as nuclear receptor targeting pharmaceuticals. The mutually beneficial two way transfer of knowledge between industry and academia will provide a career boost to the researchers who will acquire leading new knowledge, complementary training and a detailed understanding of the research culture in their opposite sector. The project will further promote industry-academic networking, creating a strategic long-lasting industry-academia partnership.

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