The proposed project “Readiness of ICOS for Necessities of integrated Global Observations” (RINGO) aims to further development of ICOS RI and ICOS ERIC and foster its sustainability. The challenges are to further develop the readiness of ICOS RI along five principal objectives: 1. Scientific readiness. To support the further consolidation of the observational networks and enhance their quality. This objective is mainly science-guided and will increase the readiness of ICOS RI to be the European pillar in a global observation system on greenhouse gases. 2. Geographical readiness. To enhance ICOS membership and sustainability by supporting interested countries to build a national consortium, to promote ICOS towards the national stakeholders, to receive consultancy e.g. on possibilities to use EU structural fund to build the infrastructure for ICOS observations and also to receive training to improve the readiness of the scientists to work inside ICOS. 3. Technological readiness. To further develop and standardize technologies for greenhouse gas observations necessary to foster new knowledge demands and to account for and contribute to technological advances. 4. Data readiness. To improve data streams towards different user groups, adapting to the developing and dynamic (web) standards. 5. Political and administrative readiness. To deepen the global cooperation of observational infrastructures and with that the common societal impact. Impact is expected on the further development and sustainability of ICOS via scientific, technical and managerial progress and by deepening the integration into global observation and data integration systems.

Antisense Oligonucleotides (ASO) and gene therapy approaches hold great promise for the treatment of genetic diseases and Duchenne muscular dystrophy (DMD) in particular. Some of these therapeutic strategies have even reached market approval, however none of the currently approved therapies addresses the brain comorbidities associated with DMD, which are found in more than 50% of affected individuals. These include intellectual disability, neurodevelopmental problems such as autism, Attention Deficit and Obsessive-Compulsive Disorder. In contrast to the muscle and cardiac phenotypes, little is known about the reversibility of these central deficits and only few therapeutic studies have focused on the brain aspect of DMD. We have previously characterized and identified specific and pertinent neurobehavioral outcomes in mouse models of DMD as well as engineered and optimized all the genetic tools required for an efficient restoration of the brain dystrophin isoforms responsible for brain defects. Preliminary results indicate that some neurobehavioral deficits can be improved by partial rescue of Dp427 in the postnatal brain. These results set the ground for our proposed BRAIN-DYS project aiming to restore different dystrophin isoforms in order to improve cognitive / behavioral features in various DMD mouse models, representative of the most common mutation profiles observed in patients. In particular, we aim to rescue the main isoforms expressed in the brain using antisense and gene therapy approaches to assess the full reversibility of these deficits. Our multidisciplinary consortium combines the complementary expertise in antisense/gene therapy and neurobiology of DMD to achieve the major milestones of this project. The BRAIN-DYS project has the potential to bring gene-correction strategies closer to a full compensation of symptoms and comorbidities in DMD patients.

ENVRI-FAIR is the connection of the ESFRI Cluster of Environmental Research Infrastructures (ENVRI) to the European Open Science Cloud (EOSC). Participating research infrastructures (RI) of the environmental domain cover the subdomains Atmosphere, Marine, Solid Earth and Biodiversity / Ecosystems and thus the Earth system in its full complexity. The overarching goal is that at the end of the proposed project, all participating RIs have built a set of FAIR data services which enhances the efficiency and productivity of researchers, supports innovation, enables data- and knowledge-based decisions and connects the ENVRI Cluster to the EOSC. This goal is reached by: (1) well defined community policies and standards on all steps of the data life cycle, aligned with the wider European policies, as well as with international developments; (2) each participating RI will have sustainable, transparent and auditable data services, for each step of data life cycle, compliant to the FAIR principles. (3) the focus of the proposed work is put on the implementation of prototypes for testing pre-production services at each RI; the catalogue of prepared services is defined for each RI independently, depending on the maturity of the involved RIs; (4) the complete set of thematic data services and tools provided by the ENVRI cluster is exposed under the EOSC catalogue of services.

Asthma is a common chronic respiratory disease, which can cause lifelong respiratory morbidity. It is widely accepted that asthma has origins early in life. Microbial and chemical exposures are two important risk factors for asthma in young children, but current knowledge remains insufficient to develop efficient prevention strategies. The recent development of high-throughput sequencing approaches to characterize both the environmental and the human microbiome has strengthened evidence for the role of microbial communities in asthma pathogenesis. This emerging field is seen as a major opportunity to provide new insight into the pathways linking early-life environment to disease development. However, major questions remain regarding (1) the exact role of specific airway microbiota profiles, and their evolution, in asthma development; (2) the impact of modifiable risk factors in the early-life environment on airway microbiota; and (3) whether airway microbiota mediates and/or modulates the environment-asthma association. The need for large, prospective studies with repeated assessment of airway microbiota in early life has been emphasized. Our proposal is centered on young children attending daycares, an environment where many of them spend a high amount of time, and which is thought to impact asthma risk. The central goal of the CRESMINA project is to study the relationships between daycare environment, nasal microbiota, and respiratory health in young children attending daycare centers, with 3 specific aims: (1) to determine the association of environmental exposures in daycare with baseline and longitudinal nasal microbiota profiles, for the following daycare-related exposures: number and characteristics of occupants, environmental microbiota (settled dust), indoor air chemical exposures and cleaning/disinfection practices; (2) to determine the association of baseline and longitudinal nasal microbiota profiles with respiratory health (primary outcome: longitudinal wheezing phenotypes from infancy to age 4 years); (3) to examine the mediating and/or modulating role of nasal microbiota in the association between environmental exposures in daycare and respiratory health. These questions will be examined in the CRESPI study (Respiratory health of Children in daycare), a cohort of 2000 children attending daycare in Paris region, which will be initiated in January 2019 in the context of an ANSES-funded project (CRESPINET), and will include detailed characterization of chemical exposures in daycare centers. The CRESMINA proposal builds on the subset of infants (age <1 year at baseline, n~800) enrolled in the CRESPI cohort. We plan to: characterize the children’s nasal microbiota based on two nasal swab collections, in infancy and at age 24 months; improve characterization of daycare environment by measuring environmental microbiota in settled dust; and improve characterization of respiratory health outcomes by extending follow-up until age 4 years. Composition of both nasal and environment microbiota will be characterized by 16S rRNA gene sequencing, using methods recommended by the NIH Human Microbiome Projects. Statistical analyses of Aims 1 to 3 will include characterization of baseline/longitudinal microbiota profiles and longitudinal wheezing profiles through clustering approaches, multinomial logistic regression models with adjustment for a large set of potential confounders, and use of recent methods (marginal structural models) for mediation analysis based on causal inference approaches. In summary, the CRESMINA project will identify specific nasal microbiota profiles differentially associated with early-life determinants of asthma and with poor respiratory outcomes; and disentangle their potential mediating / modulating roles. This knowledge could be key to the development of targeted strategies to modulate risk of developing asthma in children.

While zeolites or Metal-Organic Frameworks (MOFs) are suitable in numerous fields involving adsorption-desorption processes, their poor electronic conductivity, associated to the nature of the constitutive bonds involving the very electronegative oxygen, is a noticeable drawback in every application involving electron transfer. This project thus aims at bridging the gap between such insulating, porous materials and dense inorganic conductors, by focusing on the preparation and in-depth characterization of new crystalline hybrid organic-inorganic chalcogenides, with the final aim at combining in the designed solids porosity, electronic conductivity and multi-redox (cationic/inorganic and anionic/organic) activity. Our strategy relies on the use of sulfur-based, 1,2-dithiolene type ligands. With their fully delocalized frontier orbitals, three accessible redox states and ability to form stable complexes with both 3d and 4d metal ions, they can be considered as ideal non innocent ligands (meaning that at least one frontier orbital of the derived complex involves both the cation and the p system of the ligand). This leads to unique electronic properties and complex electrochemical behaviors in solution, but such properties have been scarcely exploited in extended solids yet. Synthesis, structure resolution and physico-chemical studies of new coordination networks will then be the core of the project. It relies on the combination of (i) innovative synthetic strategies, (ii) the thorough determination of the crystal structures by a combination of advanced diffraction methods and spectroscopies, (ii) the in-depth investigation of the electronic properties by a combination of experimental and computational tools. Finally, the performance of these solids as electrode materials for ion-batteries and hydrogen evolution reaction (HER) will be evaluated, anticipating that their characteristics allow overcoming some limitations of O-based MOFs and inorganic sulfides for such applications.