Mercury concentrations in tuna blood and muscle mirror seawater methylmercury in the Western and Central Pacific Ocean

International audienceUnderstanding the relationship between mercury in seafood and the distribution of oceanic methylmercury is key to understand human mercury exposure. Here, we determined mercury concentrations in muscle and blood of bigeye and yellowfin tunas from the Western and Central Pacific. Results showed similar latitudinal patterns in tuna blood and muscle, indicating that both tissues are good candidates for mercury monitoring. Complementary tuna species analyses indicated species- and tissue- specific mercury patterns, highlighting differences in physiologic processes of mercury uptake and accumulation associated with tuna vertical habitat. Tuna mercury content was correlated to ambient seawater methylmercury concentrations, with blood being enriched at a higher rate than muscle with increasing habitat depth. The consideration of a significant uptake of dissolved methylmercury from seawater in tuna, in addition to assimilation from food, might be interesting to test in models to represent the spatiotemporal evolutions of mercury in tuna under different mercury emission scenarios

Murlentamab, a Low Fucosylated Anti-Müllerian Hormone Type II Receptor (AMHRII) Antibody, Exhibits Anti-Tumor Activity through Tumor-Associated Macrophage Reprogrammation and T Cell Activation

International audienceAMHRII, the anti-Müllerian hormone receptor, is selectively expressed in normal sexual organs but is also re-expressed in gynecologic cancers. Hence, we developed murlentamab, a humanized glyco-engineered anti-AMHRII monoclonal antibody currently in clinical trial. Low-fucosylated antibodies are known to increase the antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) potency of effector cells, but some preliminary results suggest a more global murlentamab-dependent activation of the immune system. In this context, we demonstrate here that the murlentamab opsonization of AMHRII-expressing ovarian tumor cells, in the presence of unstimulated- or tumor-associated macrophage (TAM)-like macrophages, significantly promotes macrophage-mediated ADCC and shifts the whole microenvironment towards a pro-inflammatory and anti-tumoral status, thus triggering anti-tumor activity. We also report that murlentamab orients both unstimulated- and TAM-like macrophages to an M1-like phenotype characterized by a strong expression of co-stimulation markers, pro-inflammatory cytokines and chemokines, favoring T cell recruitment and activation. Moreover, we show that murlentamab treatment shifts CD4+ Th1/Th2 balance towards a Th1 response and activates CD8+ T cells. Altogether, these results suggest that murlentamab, through naïve macrophage orientation and TAM reprogrammation, stimulates the anti-tumor adaptive immune response. Those mechanisms might contribute to the sustained clinical benefit observed in advanced cancer patients treated with murlentamab. Finally, the enhanced murlentamab activity in combination with pembrolizumab opens new therapeutic perspectives

Trophic position increases with thermocline depth in yellowfin and bigeye tuna across the Western and Central Pacific Ocean

International audienceEstimates of trophic position are used to validate ecosystem models and understand food web structure. A consumer's trophic position can be estimated by the stable nitrogen isotope values (delta N-15) of its tissue, once the baseline isotopic variability has been accounted for. Our study established the first data-driven baseline delta N-15 isoscape for the Western and Central Pacific Ocean using particulate organic matter. Bulk delta N-15 analysis on 1039 muscle tissue of bigeye and yellowfin tuna were conducted together with amino acid compound-specific delta N-15 analysis (AA-CSIA) on a subset of 21 samples. Both particulate organic matter and tuna bulk delta N-15 values varied by more than 10 parts per thousand across the study area. Fine-scaled trophic position maps were constructed and revealed higher tuna trophic position (by similar to 1) in the southern latitudes compared to the equator. AA-CSIA confirmed these spatial patterns for bigeye and, to a lesser extent, yellowfin tuna. Using generalized additive models, spatial variations of tuna trophic positions were mainly related to the depth of the 20 degrees C isotherm, a proxy for the thermocline behavior, with higher tuna trophic position estimates at greater thermocline depths. We hypothesized that a deeper thermocline would increase tuna vertical habitat and access to mesopelagic prey of higher trophic position. Archival tagging data further suggested that the vertical habitat of bigeye tuna was deeper in the southern latitudes than at the equator. These results suggest the importance of thermocline depth in influencing tropical tuna diet, which affects their vulnerability to fisheries, and may be altered by climate change

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed