Hydrography and Jack mackerel stock in the South Pacific - Final report

This study aims (i) to identify the most likely population structure hypotheses of Jack mackerel, (ii) to identify management objectives for Jack mackerel, and (iii) to evaluate sustainable management strategies to achieve these objectives. These three elements were considered through literature review, statistical and population dynamics modelling. Two different conclusions were drawn: a conclusion towards most likely population structure and a conclusion towards most likely stock structure

Modelling South Pacific jack mackerel spatial population dynamics and fisheries

Since the 1970s, South Pacific jack mackerel (Trachurus murphyi) is one of theworld’s most important commercial exploited fish stock. The peak in the catch was achieved in the 1990s, after which the catch for all fleets steadily decreased due to strong fishing mortality and potentially unfavourable environmental conditions. An application of the ecosystem and fish population model SEAPODYM was developed for this species in the South Pacific Ocean to determine the extent of environmental and fisheries drivers on the stock dynamics. We combined publicly available fishing data, acoustic biomass estimates and expert knowledge to optimise fish population dynamics parameters (habitats, movements, natural and fishing mortality). Despite a large proportion of missing catch over the simulation period, the model provides realistic distributions of biomass, a good fit-to-data and is in agreementwith the literature. The feeding habitat is predicted to be delineated by water temperature between 15°C for the first cohorts and 8.5°C for the oldest and dissolved oxygen concentration above 1.8 ml/L. Optimal spawning temperature is estimated to 15.57°C (S.E.: 0.75°C). The core habitat is predicted off Central Chile which is also the main fishing ground. There are other areas of higher fish concentration east of New Zealand, in the eastern part of the southern convergence and off Peru and northern Chile. However, there is a clear continuity between these different large sub-populations. Fishing is predicted to have by far the highest impact, a result that should be reinforced if all fishing mortality could be included

PD-1 blockade aggravates Epstein–Barr Virus⁺ post-transplant lymphoproliferative disorder in humanized mice resulting in central nervous system involvement and CD4⁺ T cell dysregulations.

Post-transplant lymphoproliferative disorder (PTLD) is one of the most common malignancies after solid organ or allogeneic stem cell transplantation. Most PTLD cases are B cell neoplasias carrying Epstein-Barr virus (EBV). A therapeutic approach is reduction of immunosuppression to allow T cells to develop and combat EBV. If this is not effective, approaches include immunotherapies such as monoclonal antibodies targeting CD20 and adoptive T cells. Immune checkpoint inhibition (ICI) to treat EBV+ PTLD was not established clinically due to the risks of organ rejection and graft-versus-host disease. Previously, blockade of the programmed death receptor (PD)-1 by a monoclonal antibody (mAb) during ex vivo infection of mononuclear cells with the EBV/M81+ strain showed lower xenografted lymphoma development in mice. Subsequently, fully humanized mice infected with the EBV/B95-8 strain and treated in vivo with a PD-1 blocking mAb showed aggravation of PTLD and lymphoma development. Here, we evaluated vis-a-vis in fully humanized mice after EBV/B95-8 or EBV/M81 infections the effects of a clinically used PD-1 blocker. Fifteen to 17 weeks after human CD34+ stem cell transplantation, Nod.Rag.Gamma mice were infected with two types of EBV laboratory strains expressing firefly luciferase. Dynamic optical imaging analyses showed systemic EBV infections and this triggered vigorous human CD8+ T cell expansion. Pembrolizumab administered from 2 to 5 weeks post-infections significantly aggravated EBV systemic spread and, for the M81 model, significantly increased the mortality of mice. ICI promoted Ki67+CD30+CD20+EBER+PD-L1+ PTLD with central nervous system (CNS) involvement, mirroring EBV+ CNS PTLD in humans. PD-1 blockade was associated with lower frequencies of circulating T cells in blood and with a profound collapse of CD4+ T cells in lymphatic tissues. Mice treated with pembrolizumab showed an escalation of exhausted T cells expressing TIM-3, and LAG-3 in tissues, higher levels of several human cytokines in plasma and high densities of FoxP3+ regulatory CD4+ and CD8+ T cells in the tumor microenvironment. We conclude that PD-1 blockade during acute EBV infections driving strong CD8+ T cell priming decompensates T cell development towards immunosuppression. Given the variety of preclinical models available, our models conferred a cautionary note indicating that PD-1 blockade aggravated the progression of EBV+ PTLD