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Disrupted-in-schizophrenia-1 (DISC1) is a scaffold protein that plays a pivotal role in orchestrating signaling pathways involved in neurodevelopment, neural migration, and synaptogenesis. Among those, it has recently been reported that the role DISC1 in the Akt/mTOR pathway can shift from a global translational repressor to a translational activator in response to oxidative stress induced by arsenic. In this study we are providing evidence that DISC1 can directly bind arsenic via a C-terminal cysteine motif (C-X-C-X-C). A series of fluorescence-based binding assays were conducted with a truncated C-terminal domain construct of DISC1 and a of series of single, double, and triple cysteine mutants. We found that arsenous acid, a trivalent arsenic derivative, specifically binds to the C-terminal cysteine motif of DISC1 with low micromolar affinity. All three cysteines of the motif are required for high-affinity binding. Electron microscopy experiments combined with in silico structural predictions revealed that that the C-terminal of DISC1 forms an elongated tetrameric complex. The cysteine motif is consistently predicted to be located within a loop, fully exposed to solvent, providing a simple molecular framework to explain the high-affinity of DISC1 toward arsenous acid. This study sheds light on a novel functional facet of DISC1 as an arsenic binding protein and highlights its potential role as both a sensor and translational modulator within the Akt/mTOR pathway.

LIBER new strategy 2023-2027. With this strategy plan LIBER has chosen to work on an actionable strategy for the coming five-year period, as this will be a crucial period in transforming the digital environment for research and scholarly communications in an Open Science setting. The actions proposed by this strategy plan will ensure that research libraries have a crucial role in this transformation

France is engaged since a few years in a national planning of its actions in favour of Open Science, which reaches a certain maturity in 2022. The first plan was announced in 2018 at the annual LIBER conference. In 2021, a second plan was published. Libraries have taken up the issue from the beginning and their role in Open Science has been decisive. At a local level, institutions regularly integrate library services into their strategies and often entrust them with the preparation and management of strategic issues. At a national level, the Ministry of Higher Education and Research is working closely with libraries on the development of open science and on the determination of (open) public research funding criteria. Supporters of Open Science, first-rate partners and leaders in their field of expertise, libraries have participated in 2018 and 2021 in setting up a national policy that responds to critical issues of openness and sharing of publicly funded research results, then in federating and animating active academic and research communities around these issues. This paper aims to show why research libraries in France are participating in the development of this policy, and how they are contributing to the implementation of actions that ensure its growing success. The French government has based its Open Science strategy on complementary approaches that guarantee a coherent vision : publications, data, codes, open educational resources, evaluation of research, sovereignty issues, taking into account the European and international dimension of Open Science. Libraries have found their place in this ecosystem. Committed to the most concrete actions in the short term, characterized by a reflexive hindsight, endowed with a long term vision, libraries are key players regarding issues related to the dissemination, transmission and preservation of knowledge : they have built their role as strategic advisors to public authorities and ensured their recognition and representativeness within the decision-making bodies. As vectors of innovation and keepers of a structured scientific memory, libraries have shown their capacity to federate and manage academic communities around the challenges of opening up research results, data and publications, showcasing their role as key partners for researchers. This paper shall present national achievements made possible by, with and through libraries: texts, documents, practical guides, examples of researchers, engineers and librarians communities; it shall also give some examples of implementation of these policies within higher education institutions. It will explain through practical cases why and how libraries have played an essential role in the launch of French national policies and are now playing a decisive role in its evolution. It will present the main French policy and strategic directions on Open Science and detail the specific aspects related to the action of research libraries. Il will as a result illustrate how libraries, through their expertise but also thanks to their European and cross-professional vision, have been and are working successfully towards the implementation of Open Science strategies in higher education and research institutions, where the national policy finds support and relays

Les tests immunochromatographiques font partie des tests POC les plus utilisés pour le diagnostic rapide des maladies infectieuses. Ces tests sont utilisés depuis de très nombreuses années mais ils ont pris aujourd’hui une place importante dans le diagnostic et l’auto diagnostic à l’officine comme à l’hôpital. Leur place parmi les DMDIV et les nouvelles contraintes réglementaires liées à leur mise sur le marché fait partie des challenges à relever pour les années à venir. Les technologies innovantes ont permis aux tests immunochromatographiques de se développer à grande échelle et de plus en plus de laboratoires s’intéressent à ces tests afin d’obtenir de nouveaux marchés. Durant la pandémie de Covid-19, les tests immunochromatographiques ont été massivement utilisés sous différentes formes : antigéniques, sérologiques et autotests. Ces tests présentent de nombreux atouts mais aussi certains inconvénients notamment leur fiabilité. Ce travail a pour but d’exposer les différents aspects des tests immunochromatographiques et les perspectives de développement pour le futur.

The functional properties of RNA-binding proteins (RBPs) require allosteric regulation through inter-domain communication. Despite the foundational importance of allostery to biological regulation, almost no studies have been conducted to describe the biophysical nature by which inter-domain communication manifests in RBPs. Here, we show through high-pressure studies with hnRNP A1 that inter-domain communication is vital for the unique stability of its N- terminal domain containing a tandem of RNA Recognition Motifs (RRMs). Despite high sequence similarity and nearly identical tertiary structures, the two RRMs exhibit drastically different stability under pressure. RRM2 unfolds completely under high-pressure as an individual domain, but when appended to RRM1, it remains stable. Variants in which inter-domain communication is disrupted between the tandem RRMs show a large decrease in stability under pressure. Carrying these mutations over to the full-length protein for in vivo experiments revealed that the mutations affected the ability of the disordered C-terminus to engage in protein-protein interactions and more importantly, they also influenced the RNA binding capacity. Collectively, this work reveals that thermodynamic coupling between the tandem RRMs of hnRNP A1 accounts for its allosteric regulatory functions.

Disrupted-in-schizophrenia-1 (DISC1) is a scaffold protein that plays a pivotal role in orchestrating signaling pathways involved in neurodevelopment, neural migration, and synaptogenesis. Among those, it has recently been reported that the role DISC1 in the Akt/mTOR pathway can shift from a global translational repressor to a translational activator in response to oxidative stress induced by arsenic. In this study we are providing evidence that DISC1 can directly bind arsenic via a C-terminal cysteine motif (C-X-C-X-C). A series of fluorescence-based binding assays were conducted with a truncated C-terminal domain construct of DISC1 and a of series of single, double, and triple cysteine mutants. We found that arsenous acid, a trivalent arsenic derivative, specifically binds to the C-terminal cysteine motif of DISC1 with low micromolar affinity. All three cysteines of the motif are required for high-affinity binding. Electron microscopy experiments combined with in silico structural predictions revealed that that the C-terminal of DISC1 forms an elongated tetrameric complex. The cysteine motif is consistently predicted to be located within a loop, fully exposed to solvent, providing a simple molecular framework to explain the high-affinity of DISC1 toward arsenous acid. This study sheds light on a novel functional facet of DISC1 as an arsenic binding protein and highlights its potential role as both a sensor and translational modulator within the Akt/mTOR pathway., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest with the contents of this article.