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International audience; Bats are asymptomatic hosts for numerous viruses, including highly pathogenic zoonotic henipaviruses, Nipah (NiV) and Hendra. Understanding of how bats control viral infection requires better characterization of bat-derived viruses and development of relevant permissive cellular models. We analysed NiV isolate obtained from a Pteropus lylei bat in Cambodia in 2003 (CSUR381), where human outbreaks of NiV infection have not been detected so far. Full-genome sequencing and phylogenetic analyses confirmed that CSUR381 is part of the NiV-Malaysia genotype. Cell permissiveness was similar in both bat and human cell lines and replication of CSUR381 was alike to other two NiV isolates. In the hamster animal model CSUR381 induced lethal infection. These data suggest that the Cambodia batderived NiV isolate has high pathogenic potential, providing an insight for better risk assessment for future NiV outbreaks in Southeast Asia. Most of the available bat cells are immortalized lines, significantly impacting the overall cell response that may alter the virus-cell interactions. Therefore, by applying a somatic reprogramming protocol to Pteropus bat primary cells, using a novel combination of ESRRB, CDX2 and c-MYC transcription factors, we generated bat reprogrammed cells exhibiting neural stem cell-like characteristics. These cells present a unique interferon-stimulated transcriptomic signature but still produce and respond to IFN type I. In contrast to primary bat cells, these reprogrammed cells are highly susceptible to infection by Henipavirus, even more than Vero cells, commonly used for virus isolation. Future direct reprogramming of bat primary cells into various differentiated cell types should facilitate the isolation of new bat viruses and further studies of virus-bat interaction, towards better understating of the efficient bat anti-viral response.

BCR pathway inhibitors idelalisib and ibrutinib were the first small molecule targeted agents for B-cell malignancies. In spite of encouraging response rates in various forms of B cell diseases, patients will eventually develop relapse due to the emergence of resistant cells. To better identify the possible mechanisms of resistance we developed and characterized idelalisib- and ibrutinib-resistant variants of the human non Hodgkin’s lymphoma cell lines DoHH2 and Daudi. These resistant variants displayed a cross-resistance profile limited to PI3K inhibitors, BTK inhibitors and a SYK inhibitor but not to unrelated agents. A number of alterations were observed in the resistant lines, including a strong reduction of BLINK and the AKT3. A new SNP in PLCgamma2 (Leu848Phe) closely related to a previously reported SNP associated to ibrutinib resistance (Leu845Phe) was observed in both DAUDI-based resistant cell lines but was absent in wild type cells. Resistant lines tended to express larger amounts of CD38 and were found to display enhanced sensitivity to anti-CD38 antibodies. These results identify potential novel mechanisms of resistance to idelalisib and ibrutinib and raise the possibility that cells resistant to BCR pathway inhibitors might possess enhanced sensitivity to anti-CD38 antibodies.

This chapter aims to help the new investment arbitration practitioner identify and find the main legal sources for dealing with international investment law issues. Three different topics need to be addressed in order to cover, as extensively as possible, the legal issues generally raised during an arbitration based on an international investment agreement. First, even though the stare decisis rule does not exist in international arbitration, including investment arbitration, previous rulings are often used and analyzed by arbitrators. Second, when dealing with investment arbitration, it is likely that the claim will be treaty based. Finally, and most importantly, in international investment disputes, arbitral tribunals rely on all the sources of public international law identified in Article 38(1) of the Statute of the International Court of Justice, which provides for the Court to apply.

Caicedo Demoulin José Joaquín, Fouret Julien, Prost Mario. Jurisprudence de la Cour internationale de justice. In: Revue Québécoise de droit international, volume 22-2, 2009. pp. 137-229.

Fouret Julien, Prost Mario. Sommaire de la Chronique de règlement pacifique des différends internationaux. In: Revue Québécoise de droit international, volume 16-1, 2003. pp. 125-126.

Fouret Julien, Khayat Dany. Le Centre international pour le règlement des différends relatifs aux investissements. In: Revue Québécoise de droit international, volume 17-1, 2004. pp. 159-212.