Ischemic stroke in sepsis shock is associated with increased mortality and long-term cognitive impairment. Due to its critical position, the brain vessel recanalization is an emergency. However, in sepsis context, the therapeutic strategies available are limited. Thus, innovative approaches targeting the fibrinolysis impairment are absolutely warranted. Granulocyte-derived Extracellular Vesicles (Gran-EVs) are circulating fibrinolytic carriers whose binding molecules allow them to reach the fibrin clot. The fibrinolytic Gran-EVs were associated with less coagulopathy and a better prognosis in sepsis shock patients. Consistently, in a murine model of sepsis, it was recently observed that the repeated injection of fibrinolytic Gran-EVs significantly 1/increased the mouse fibrinolytic circulating activity 2/reduced the number of thrombi in vital organs and 3/improved mouse survival. In addition, it was shown that Gran-EVs from septic patients lyse a thrombus according to their fibrinolytic potential. Therefore, our hypothesis is that injection of granulocyte-derived EVs with a highly fibrinolytic activity may improve the septic shock prognosis by participating to the organ thrombi resolution in vivo. Two research groups, respectively renowned in EV biology and their impact in the cardiovascular system (C2VN) and neurovascular diseases (PhIND) will join their force to carry out this project whose aims are 1/to produce and characterize gran-EVs with a highly fibrinolytic activity; 2/to evaluate their effect on thrombus resolution in vivo in mouse models of sepsis, and 3/to evaluate their therapeutic potential on sepsis-associated thromboembolic stroke compared to currently available thrombolytic therapies. The ultimate goal of this project is to pave the ground of an innovative therapeutic EV-based strategy in septic shock-associated cerebral stroke relevant for future clinical translation.

The CHLOR2NOU project aims to develop new monitoring tools for CLD and its TPs, to provide new knowledge on the fate and risk of CLD TPs, and to explore realistic alternative approaches for pollution remediation. The postulate of the non-degradability of CLDs commonly admitted for several decades has had a strong negative impact on pollution management by ruling out the possibility of CLD degradation. The representation of CLD in the FWI society and in the scientific community is therefore of paramount importance. The CHLOR2NOU project is divided into 7 Work Packages that bring together scientists from various background: the WP1 with the synthesis of CLD TPs, CLD baits and fluorescent macromolecular cages; the WP2 that deals with innovative analytical methods: (i) routine laboratory method for the detection of CLD TPs in environmental and food matrices, (ii) immunoassay using a CLD-selective antibody, (iii) a semi-high-throughput detection protocol based on the recognition of CLD by a fluorescent macromolecular cage; the WP3 dedicated to toxicological and ecotoxicological studies in order to define the toxicity profile of CLD TPs; the WP4 with several analytical campaigns to obtain a first estimate of the possible exposure to CLD TPs; the WP5 that aims at studying the fate of CLD TPs, in particular in FWI soils, while defining degradation indicators; the WP6 that is focused on the study of realistic agronomic and environmental conditions capable to favor CLD degradation; the last WP centered on the representation of CLD in the FWI society at large. A co-construction method will be used to help the population and stakeholders to better assimilate the scientific results.

The L-function of a mathematical object - a number field, an algebraic variety, or an automorphic representation - is a bridge between that analytic and arithmetical study of this object. The central motive organizing this project is a concrete, specific incarnation of this classical theme which has been made possible after recent results obtained by its members: special values of L-functions have two components, a transcendental component (the regulator) and a number-theoretic component; each exhaustive and precise result on the arithmetic of the second component therefore has its counterpart in the first, and vice-versa. Let us open this circle of ideas by noting that the recent proofs of the main conjecture of Iwasawa theory for modular forms and its potential generalization to other automorphic forms, which are p-adic results, allow for the effective computation of p-adic regulators, p-adic periods and p-adic L-functions of these forms, an effective variant of integral p-adic Hodge theory. Effective computation of the p-adic regulator has a counterpart for motives in positive characteristic, where it is known to be intimately linked to the open problem of the existence of a functional equation for the L-function and to the determination of the special values of said L-function. Likewise, effective computation of regulators has an analytic counterpart, under the guise of effective Brauer-Siegel theorems for number fields as well as abelian varieties; results that yield majoration and minoration of special values of L-functions. This circle of idea is completed when it is noted that the asymptotic results given by the Brauer-Siegel themselves have applications in the Iwasawa theory of tower of number fields and algebraic varieties. That mutual interplay between analytic, effective and p-adic properties of special values of L-functions is what we propose to investigate.