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Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-04-2016 | Award Amount: 7.35M | Year: 2017

Over 130,000 children born in Europe every year will have a congenital anomaly (CA; birth defect). These CAs, which are often rare diseases, are a major cause of infant mortality, childhood morbidity and long-term disability. EUROCAT is an established European network of population-based registries for the epidemiologic surveillance of CAs. EUROlinkCAT will use the EUROCAT infrastructure to support 21 EUROCAT registries in 13 European countries to link their CA data to mortality, hospital discharge, prescription and educational databases. Each registry will send standard aggregate tables and analysis results to a Central Results Repository (CRR) thus respecting data security issues surrounding sensitive data. The CRR will contain standardised summary data and analyses on an estimated 200,000 children with a CA born from 1995 to 2014 up to age 10, enabling hypotheses on their health and education to be investigated at an EU level. This enhanced information will allow optimisation of personalised care and treatment decisions for children with rare CAs. Registries will be supported in using social media platforms to connect with families who live with CAs in their regions. A novel sustainable e-forum, ConnectEpeople, will link these families with local, national and international registries and information resources. ConnectEpeople will involve these families in setting research priorities and ensuring a meaningful dissemination of results. Findings will provide evidence to inform national treatment guidelines, such as concerning screening programs, to optimise diagnosis, prevention and treatment for these children and reduce health inequalities in Europe. An economic evaluation of the hospitalisation costs associated with CA will be provided. The CRR and associated documentation, including linkage and standardisation procedures and ConnectEpeople forum will be available post-EUROlinkCAT thus facilitating future local and EU level analyses.

Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: INFRA-2010-1.2.3 | Award Amount: 6.26M | Year: 2010

Biodiversity science brings information science and technologies to bear on the data and information generated by the study of organisms, their genes, and their interactions. ViBRANT will help focus the collective output of biodiversity science, making it more transparent, accountable, and accessible. Mobilising these data will address global environmental challenges, contribute to sustainable development, and promote the conservation of biological diversity. Through a platform of web based informatics tools and services we have built a successful data-publishing framework (Scratchpads) that allows distributed groups of scientists to create their own virtual research communities supporting biodiversity science. The infrastructure is highly user-oriented, focusing on the needs of research networks through a flexible and scalable system architecture, offering adaptable user interfaces for the development of various services. In just 28 months the Scratchpads have been adopted by over 120 communities in more than 60 countries, embracing over 1,500 users. ViBRANT will distribute the management, hardware infrastructure and software development of this system and connect with the broader landscape of biodiversity initiatives including PESI, Biodiversity Heritage Library (Europe), GBIF and EoL. The system will also inform the design of the LifeWatch Service Centre and is aligned with the ELIXIR and EMBRC objectives, all part of the ESFRI roadmap. ViBRANT will extend the userbase, reaching out to new multidisciplinary communities including citizen scientists by offering an enhanced suite of services and functionality.

News Article | February 15, 2017

A one-off injection could one day lower your cholesterol levels for the rest of your life. People born with natural mutations that disable a specific gene have a lower risk of heart disease, with no apparent side effects. Now a single injection has successfully disabled this same gene in animal tests for the first time. This potential treatment would involve permanently altering the DNA inside some of the cells of a person’s body, so doctors will have to be sure it is safe before trying it in people. But the benefits could be enormous. In theory, it could help millions live longer and healthier lives. The results of the animal study were described by Lorenz Mayr, of pharmaceutical firm AstraZeneca, at a genomics meeting in London on 1 February. Mayr, who leads the company’s research into a DNA editing technique called CRISPR, wouldn’t say whether AstraZeneca plans to pursue this approach, but he was clearly excited as he presented the findings. “The idea would be to do it as a one-off,” he later told New Scientist. “It should be permanent.” Heart attacks and strokes kill a quarter of people living in rich nations, and high levels of “bad” LDL cholesterol in the blood greatly increases the risk. For this reason, millions of people now take statins to lower their LDL cholesterol levels. While statins undoubtedly extend the lives of many people, some experience side effects such as muscle pain, leading drug companies to look for alternative treatments. In 2005, it was discovered that a few people naturally have very low cholesterol levels, thanks to mutations that prevent their livers from making a protein called PCSK9. “They have a lower incidence of cardiovascular disease and no apparent side effects whatsoever,” says Gilles Lambert at the University of Reunion Island, who studies PCSK9. The PCSK9 protein normally circulates in the blood, where it degrades a protein found on the surface of blood vessels. This second protein removes LDL cholesterol from the blood: the faster it is degraded by PCSK9, the higher a person’s cholesterol levels. But people who lack PCSK9 due to genetic mutations have more of this LDL-removal protein, and therefore less cholesterol in their blood. To mimic this effect, two companies have developed approved antibodies that remove the PCSK9 protein from the blood. These are very effective at lowering cholesterol and no serious side effects have been reported so far, Lambert says. It is yet to be shown if they reduce the risk of cardiovascular disease, but the first trial results are due to be announced in March. However, the antibody drugs are extremely expensive and need to be injected every two to four weeks, so even if the antibodies work as well as hoped, they cannot be dished out to millions like statins. All attempts to develop conventional drugs to block PCSK9 have failed. But gene editing provides a radical alternative. Using the CRISPR technique, the team at AstraZeneca have disabled human versions of the PCSK9 gene in mice. They did this by injecting the CRISPR Cas 9 protein and a guiding RNA sequence into the animals. The RNA guide helps the Cas9 protein bind to a specific site in the gene. It then cuts the gene at that point, and when the break is repaired, errors that disable the gene are likely to be introduced. There was an even bigger fall in cholesterol levels in the mice given the CRISPR treatment than in those injected with the antibody drugs. This gene editing approach would be a closer mimic of what happens in people born with PCSK9-disabling mutations than injecting antibodies, says pharmacologist Patricia McGettigan of Queen Mary University of London, who has looked at the safety of PCSK9 therapies. “That might actually be really productive,” she says. The big worry about using gene editing to alter DNA inside the body is that it could also cause unintended “off-target” mutations. In the worst case, these could turn cells cancerous. Mayr says the team has tested for off-target effects in 26 different tissues in the mice, and that the results will be published soon. “It’s very promising in terms of safety,” he told New Scientist. What’s more, the CRISPR method is constantly being improved. Other teams have developed modified versions of the CRISPR protein that are so precise off-target effects occur no more often than natural mutations in cells. Even so, Lambert thinks human trials are at least a decade away. “For now it’s very far-fetched,” he says. An alternative approach that should have fewer off-target effects would be to use modified forms of the CRISPR protein to switch off the PCSK9 gene without altering its DNA. Instead of changing the genome, this kind of editing targets the epigenome instead – the chemical “tags” added to DNA that influence how active particular genes are. Many think epigenome editing will prove more useful than conventional genome editing for treating diseases. “I think the future is CRISPR 3.0 and 4.0,” Mayr says, referring to epigenome editing.

Chaudhari N.,Vellore Institute of Technology | Talwar P.,Vellore Institute of Technology | Parimisetty A.,University of Reunion Island | d'Hellencourt C.L.,University of Reunion Island | Ravanan P.,Vellore Institute of Technology
Frontiers in Cellular Neuroscience | Year: 2014

Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded-protein response (UPR) through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS).Toxic accumulation of ROS within ER and mitochondria disturbs fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways have been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease, and others. In this review, we have discussed the UPR signaling pathways, and networking between ER stress-induced inflammatory pathways, oxidative stress, and mitochondrial signaling events, which further induce or exacerbate ER stress. © 2014 Chaudhari, Talwar, Parimisetty, Lefebvre d'Hellencourt and Ravanan.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRADEV-1-2014 | Award Amount: 3.24M | Year: 2015

It has been robustly demonstrated that variations in the circulation of the middle atmosphere influence weather and climate throughout the troposphere all the way to the Earths surface. A key part of the coupling between the troposphere and stratosphere occurs through the propagation and breaking of planetary-scale Rossby waves and gravity waves. Limited observation of the middle atmosphere and these waves in particular limits the ability to faithfully reproduce the dynamics of the middle atmosphere in numerical weather prediction and climate models. ARISE2 capitalizes upon the work of the EU-funded first ARISE project combining for the first time international networks with complementary technologies such as infrasound, lidar and airglow. This joint network provided advanced data products that started to be used as benchmarks for weather forecast models. The ARISE network also allows enhanced and detailed monitoring of other extreme events in the Earth system such as erupting volcanoes, magnetic storms, tornadoes and tropical thunderstorms. In order to improve the ability of the network to monitor atmospheric dynamics, ARISE2 proposes to extend i) the existing network coverage in Africa and the high latitudes, ii) the altitude range in the stratosphere and mesosphere, iii) the observation duration using routine observation modes, and to use complementary existing infrastructures and innovative instrumentations. Data will be collected over the long term to improve weather forecasting to monthly or seasonal timescales, to monitor atmospheric extreme events and climate change. Compared to the first ARISE project, ARISE2 focuses on the link between models and observations for future assimilation of data by operational weather forecasting models. Among the applications, ARISE2 proposes infrasound remote volcano monitoring to provide notifications to civil aviation. The data portal will provide high-quality data and advanced data products to a wide scientific community.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: BG-03-2014 | Award Amount: 6.76M | Year: 2015

TASCMAR project aspires to develop new tools and strategies in order to overcome existing bottlenecks in the biodiscovery and industrial exploitation of novel marine derived biomolecules (secondary metabolites and enzymes) with applications in the pharmaceuticals, nutraceuticals, cosmeceuticals and fine chemicals industries. Exploitation of neglected and underutilized marine invertebrates and symbionts from mesophotic zone will be combined with innovative approaches for the cultivation and extraction of marine organisms from lab to pilot-scale, using the unique prototypes Platotex and Zippertex, both reaching the Technology Readiness Level 7. Thus, marine dedicated cultivation and extraction equipment will be built and validated. These unique improvements will ensure sustainable supply of biomass and promote the production of high added value bioactive marine compounds. An integrated, holistic technological metabolomic approach will be applied, in conjunction with bioactivity profiling, as filtering and bio-prioritisation tools. Moreover, state-of-the-art analytical instrumentation and in-house databases will be employed for the dereplication and characterization of valuable compounds. A panel of libraries (marine organisms, extracts, pure metabolites and biocatalysts) will be constructed and exploited throughout the project. A focused panel of in-vitro, cell-based, in-ovo and in-vivo bioassays for discovering metabolites with anti-ageing and/or angiogenesis modulating activity will frame the entire work-flow and will reveal the lead compounds. In addition, the catalytic potential of mesophotic symbionts and deriving enzymes candidates will be evaluated in fine chemicals and bioremediation industries. The project activities will be constantly assessed via effective management for their societal, economical and environmental impact in order to find the best compromise between industrial development and sustainable growth.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.3.3-3 | Award Amount: 5.06M | Year: 2010

Since 2005 Chikungunya fever has affected millions of people producing a high fever and a debilitating arthralgia which can persist for months and progress to chronic arthritis. Chikungunya virus has been associated with periodic outbreaks of human disease and is spread by mosquitoes. The current epidemic rose to prominence in 2005/6 following infection of >250,000 people on La Runion. The virus rapidly spread to other islands in the Indian Ocean, India and SE Asia. Chikungunya cases in returning travellers have been reported. In summer 2007 a traveller from India to Italy initiated a locally transmitted outbreak which included one death from encephalitis. The mosquitoes transmitting this infection are spreading and increasing in Europe and could spread as far north as the British Isles. There are diagnostics tests, these require standardisation. The pathogenic mechanisms leading to myalgia, arthralgia, rare encephalitis and chronic arthritis are unknown precluding rational therapeutic intervention. There are no antivirals. There is no licensed vaccine. This project will integrate the expertise of EU laboratories with a long and strong track record of research on alphaviruses with EU laboratories that started work on CHIKV following the outbreak in La Runion and laboratories from SE Asia working on this virus. The project will generate new molecular and cellular tools for research and applied studies, including high-throughput screening and vaccines; standardise, quality assure and distribute key diagnostic tests and develop new ones; determine virus genetic changes across time, geographical regions and species; discover interactions between virus and human cells to inform rational design of therapeutics; study immune responses in the chronic disease in humans, including whether virus persists in joints, the cell types involved and the relationship to immune responses; characterise rodent and non-human primate models of acute and chronic infection to further study the pathogenesis and provide models for antiviral and vaccine screens; screen libraries of characterized pharmaceutical and bioactive compounds for antiviral activity and develop a vaccine which at the end of this project is ready to enter clinical trials.

Ballas R.,University of Reunion Island | Beguin L.,Mutualiste Clinic
Journal of Shoulder and Elbow Surgery | Year: 2013

Hypothesis: A stemless reverse shoulder prosthesis with humeral cup was developed to allow stemless press-fit fixation, to preserve bone stock. Our hypothesis was that a stemless reverse shoulder arthroplasty could produce the same functional results without compromising humeral fixation. Methods: This is a continuous, prospective, single-surgeon series including prostheses implanted from 2004 to 2009. Patients received pre- and postoperative clinical evaluation with measurement of joint mobility, the Oxford Shoulder score, and the Constant-Murley score by independent evaluators. Standard radiographs and computed tomographic arthrography were performed. Results: Fifty-six implants were reviewed at a mean of 58 months (38-95). The Constant-Murley score improved from 29 to 62 points and the Oxford Shoulder score from 46 to 17 points. Active elevation in forward flexion improved from 79° to 140°. One intraoperative complication was recorded: a metaphyseal-diaphyseal humeral bone crack without consequence. One revision surgery due to early instability was performed using a conventional implant. No humeral loosening was observed. Five cases of scapular notching were reported. Conclusion: This is the first study reporting results with mid-term follow-up for a stemless reverse shoulder arthroplasty. The clinical results are comparable to conventional prostheses with stem. The absence of a humeral stem preserves bone stock for possible later revisions. © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees.

Rondeau P.,University of Reunion Island | Bourdon E.,University of Reunion Island
Biochimie | Year: 2011

Oxidative stress and protein modifications are frequently observed in numerous disease states. Glucose constitutes a vital nutrient necessary to cellular oxygen metabolism. However, hyperglycemia-associated damage is an important factor in diabetes disorders. Albumin, the major circulating protein in blood, can undergo increased glycation in diabetes. From recent studies, it has become evident that protein glycation has important implications for protein activity, unfolding, and degradation, as well as for cell functioning. After giving a brief overview of the key role of albumin in overall antioxidant defense, this review examines its role as a target of glycation reactions. A synthesis of state of the art methods for measuring and characterizing albumin glycation is detailed. In light of recent data, we then report the impact of glycation on the structure of albumin and its various activities, especially its antioxidant and binding capacities. The biological impact of glycated albumin on cell physiology is also discussed, specifically the role of the protein as a biological marker of diabetes. © 2010 Elsevier Masson SAS. All rights reserved.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: REGPOT | Award Amount: 2.02M | Year: 2011

La Runion Island is an outermost European region located in the South Western Indian Ocean. It was severely hit in 2005 and 2006 by a Chikungunya epidemic that affected a third of the population and led to dramatic socio-economical consequences. As a result, the CRVOI (Centre de Recherche et de Veille sur les maladies mergentes dans lOcean Indien), was launched in 2007 to be dedicated to the investigation of human and animal infectious diseases emerging in tropical regions. This Center complements, in a holistic approach of EIDs research, the existing laboratories of the Universit de La Runion working on plant emerging pathogens, phytochemistry, ecology, immunology and social sciences. RUN-Emerge aims at tackling the weaknesses resulting from the remoteness of this island, i.e. essentially scientific isolation and insufficient human resources. The main objectives are (i) to foster an inter disciplinary approach towards EIDs investigation, (ii) to tighten links of the Universit de La Runion with research partners from South Western Indian Ocean ICPCs working in this field and (iii) to open up the partnership to European leading groups, thereby extending the European Research Area and laying the ground for future participation to FP7 calls.

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