Dogs and cats play important social roles in our societies. As a result, expenses for their food and health are increasing every year. As humans, pets suffer from inherited disorders. The USA have spent a huge amount of money to develop molecular tools used to develop diagnostic tools. There is no doubt that breeders worldwide will soon economically depend upon these tests to eliminate these diseases from the gene pool of their animals.The aim of BIOMARKS is to develop diagnostic or prognostic markers for veterinary diagnostic of cardiac and neurological diseases. In a second time, these markers would be evaluated and used for diagnostic of the homologous diseases in human. These markers are genetic markers allowing development of DNA tests or biological markers (circulating proteins) allowing the development of ELISA tests. BIOMARKS project is organised in a pipeline where several diseases could be treated sequentially by expert partners. A first set of analysed diseases includes hypertrophic cardiomyopathy, dilated cardiomyopathy, centronuclear myopathy, cerebellar ataxia, epilepsy and deafness. These animal models are spontaneous inherited diseases and fit ethical requirements. By gathering complementary skills of the partners, the project aims at setting up a pipeline to• develop biological markers for diagnostic and/or prognosticobtain genetic markers by identifying the disease-associated locus in genome and causative mutation in involved genes for diagnostic DNA test ,reinforce the knowledge base of homologous human inherited disease useful for developing, in the future, animal models that could be used for therapeutic strategiesMost of partners from the proposed consortium are already involved in common scientific projects. They will be immediately efficient in a complementary approach. Results from initial research will be rapidly used by the two highly-specialized SMEs to develop diagnostic tools and markersSubprojects

The main goal of the « ACTISURF » project is to propose a new generation of joint prosthesis (hip, knee, ankle) made of bioactive titanium alloy TAl6V, capable of limiting and preventing joint infections. Even though conditions of prevention are drastic, about 1.5% of joint prostheses will be infected. The aging of the population associated with the increase of annual joint prosthesis implantations, make this new generation of biomaterial very attractive because it allows significant redcution of joint infection rates and the direct and indirect costs associated to these pathologies - reeducation, compensation of after-effects, temporary lost of salary, professional reclassifying. Among the 220 000 implanted joint prostheses, 4000 will be infected representing a minimal cost of about 400 millions euros. Titanium alloy is bioactive by chemical grafting of a polyanionic polymer exhibiting inhibition properties of bacterial adhesion. In addition, the grafted polymer is compatbile to osseous tissues and allows to control the inflammatory response. The partners of ACTISURF project present the complentary expertises in chemistry, biology and medicine necessary to this pluridisciplinary study : industrial partner commercialsing joint protheses, surface chemists, biologists of the in vitro cell response, microbiologists specialiezd in infection and inflmmatory response in vitro and in vivo, clinicians veterinary, orthopedists in charge of a reference center for the treatment of joint infections.

The sanitary problem posed by cyanobacterial bloom in surface water ecosystems has been recognized by the WHO since 1999 (Guideline for Drinking Water). To understand better the risks associated with this phenomenon advanced, pluridisciplinary investigations are necessary to: 1) define the distribution of toxic cyanobacteria and their toxins in regions that are marked by important human frequentation such as urban and peri-urban areas (objective1); 2) determine the ecological factors that contribute to the cyanobacterial bloom (objective 2); 3) evaluate the acute toxicity associated with the cyanobacterial metabolites and cyanotoxins using medaka fish embryos, a well known model organism in toxicology studies; 4) study the induced cellular mechanisms that lead to cellular dysfunction (death, proliferation, chronic toxicity); 5) estimate the health risk for the human population as a function of utilization of the water body (to integrate the results obtained from the precedent objectives). The research groups involved in this proposal have worked on the different aspect of the problem for many years and this project will permit to pool their scientific and project management talents to progress efficiently on this health and environmental problem that requires urgent responses. The proposed study on the cyanobacterial distribution concerns Ile-de-France, a peri-urban region densely populated and encompasses 980 water bodies. Such a large area contributes to the originality of this study, considering the fact that the region is under constant socio-economic pressure and evolution. Special attention will be paid to the sampling strategy and statistical sampling design will be implemented. Identification and biomass measurements of cyanobacteria will be performed by well-established methods (microscopy, cellular counts). A submersible spectroflurometer will also be used for rapid in situ monitoring of cyanobacterial biomasses. Water bodies will be characterized by different limnological (physico-chemical and biological) and environmental (watershed hydrology, land occupation, recreational uses) variables. Numerical methods will be used for data treatment to characterize the spatial distribution of cyanobacteria and their relationships with the different descriptors of surface water bodies. For the sites with significant blooms, chemical analysis (HPLC, MS) will permit the identification of the major metabolites and toxicity will be evaluated using simple and established tests (enzyme inhibition or cytotoxicology tests). For these water bodies, the toxicity of cyanobacteria and water will be assayed on the medaka fish embryos with yolk-sac (acute toxicity). This approach will lead us to identify the risk prone sites and to research known molecules and as well as new compounds responsible for the toxicity. Another toxicological problem refers to the mode of action of dangerous cyanotoxins. Neurotoxins are relatively easier to detect and identify at least for the known ones by in-vitro tests and by chemical methods when reference standards exists (e.g. anatoxin-a). However, for cyantoxins that are carcinogen, evaluating the risk is difficult since the mechanism leading to the carcinogenesis is not known. The most frequently encountered molecules are the microcystins (71 variants) of which the most toxic is the microcystin-LR; although, its effect is widely investigated, the results obtained are highly dispersed. Taking into account this fact, we want to investigate the carcinogenesis mechanism using the adult medaka fish, which is recommended in Japan and USA for this purpose (National Toxicology Program Pathology). The investigation is organized into two distinct parts: first, anatomopathology study linked with immunocytochemistry to localize the MC-LR and second, proteomic analysis of the liver considering the fact that MC-LR is a known hepatotoxin. Analysis of the evolution of the protein expression and its phosphorylation will aid in discerning the metabolic pathways and help to evaluate the consequences such as cellular apoptosis or orientation towards carcinogenesis. Finally, the obtained results will be used to contribute to the evaluation of the risk of exposition to cyanobacteria in water body used for recreational activities. The objectives described in this project is in accordance with the expectations of the project proposition that are called under the thematic 2.1.1 “Les déterminants environnementaux: les contaminants, les milieux, les expositions ” and specifically, it is oriented towards the “toxins” produced by cyanobacteria by focusing on the capacity of these microorganisms to produce toxins related to the environmental constraints and on their potential effect on the human health via the availability of the toxins, transfer to the organism and toxicological effects. The objectives 1 and 2 described in the project also fall under the thematic 2.1.2 “Le rôle des modifications de l'environnement dans la dynamique des agents infectieux et les interactions avec l'hôte”. Similarly, the objectives 3 and 4 are in tandem with the orientation defined in 2.1.3 “Les impacts des conditions environnementales sur la santé humaine”.