Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein

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Activation of invariant NKT cells by the helminth parasite schistosoma mansoni

Mouse CD1d-restricted NKT cells, including invariant (i)NKT cells, are innate cells activated by glycolipid Ags and play important roles in the initiation and regulation of immune responses. Through their ability to promptly produce large amounts of Th1 and/or Th2 cytokines upon TCR engagement, iNKT cells exert crucial functions in the immune/inflammatory system during bacterial, protozoan, fungal, and viral infections. However, their roles during metazoan parasite infection, which are generally associated with strong Th2 responses, still remain elusive. In this study, we show that during the course of murine schistosomiasis, iNKT cells exhibit an activated phenotype and that following schistosome egg encounter in the liver, hepatic iNKT cells produce both IFN-gamma and IL-4 in vivo. We also report that schistosome egg-sensitized dendritic cells (DCs) activate, in a CD1d-dependent manner, iNKT cells to secrete IFN-gamma and IL-4 in vitro. Interestingly, transfer of egg-sensitized DCs promotes a strong Th2 response in recipient wild-type mice, but not in mice that lack iNKT cells. Engagement of TLRs in DCs is not necessary for iNKT cell stimulation in response to egg-sensitized DCs, suggesting an alternative pathway of activation. Finally, we propose that self, rather than parasite-derived, CD1d-restricted ligands are implicated in iNKT cell stimulation. Taken together, our data show for the first time that helminths can activate iNKT cells to produce immunoregulatory cytokines in vivo, enabling them to influence the adaptive immune response.     

Nutrient fluxes and water quality in the drainage network of the Scheldt basin over the last 50 years

and use and urban activity in the catchment of the Scheldt river system have deeply changed during the last 50 years, modifying in turn the water quality of the drainage network and the fluxes of nutrient transferred to the estuary and to the sea. Based on the RIVERSTRAHLER model, developed for establishing the link between the biogeochemical functioning of large river systems and the constraints set by the meteorology, the morphology of the drainage network and the human activity in the watershed, we reassembled the data available to document these constraints in the Scheldt basin since the last half of the XXth century and we used them to reconstruct the variations of nutrient and oxygen concentrations at the outlet of the Scheldt drainage network. We compared the results with the water quality data at the entrance of the estuarine zone available since the 1960s. Both model results and observational data show a very severe deterioration of water quality (with deep oxygen depletion) in the beginning of the 1960s, while a clear trend to improvement is apparent since the late 1980s. The budget of nutrient loadings from the watershed, retention within the drainage network and delivery to the estuarine zone is established on an annual basis for the 50 last years. The yearly fluxes of nutrient delivered by the river to the estuary and the sea show a severe depletion of silica with respect to nitrogen compared with the requirements of diatoms, and a clear shift from the early 1990s from nitrogen to phosphorus potential limitation. Seasonal variations of nutrient delivery are however much more pronounced for nitrogen, with much less inputs during the dry seasons, while phosphorus inputs, mainly from point sources are more constant, so that nitrogen limitation can still occur during summer. Compared with similar budget estimations carried out for the Seine river system, the Scheldt basin, in spite of its much higher population density, does not deliver higher specific fluxes of nutrient (presently about 2000 kgN/km²/yr, 80 kgP/km²/yr and 1000 kgSi/km²/yr), owing to very efficient processes of nutrient retention.     

Analyses of the functional regions of DEAD-box RNA "helicases" with deletion and chimera constructs tested in vivo and in vitro

The DEAD-box family of putative RNA helicases is composed of ubiquitous proteins that are found in nearly all organisms and that are involved in virtually all processes involving RNA. They are characterized by two tandemly linked, RecA-like domains that contain 11 conserved motifs and highly variable amino- and carboxy-terminal flanking sequences. For this reason, they are often considered to be modular multi-domain proteins. We tested this by making extensive BLASTs and sequence alignments to elucidate the minimal functional unit in nature. We then used this information to construct chimeras and deletions of six essential yeast proteins that were assayed in vivo. We purified many of the different constructs and characterized their biochemical properties in vitro. We found that sequence elements can only be switched between closely related proteins and that the carboxy-terminal sequences are important for high ATPase and strand displacement activities and for high RNA binding affinity. The amino-terminal elements were often toxic when overexpressed in vivo, and they may play regulatory roles. Both the amino and the carboxyl regions have a high frequency of sequences that are predicted to be intrinsically disordered, indicating that the flanking regions do not form distinct modular domains but probably assume an ordered structure with ligand binding. Finally, the minimal functional unit of the DEAD-box core starts two amino acids before the isolated phenylalanine of the Q motif and extends to about 35 residues beyond motif VI. These experiments provide evidence for how a highly conserved structural domain can be adapted to different cellular needs.     

Budget of methane emissions from soils, livestock and the river network at the regional scale of the Seine basin (France)

We used various approaches to establish a comprehensive budget of methane (CH₄) emissions from the Seine basin, including direct emissions from livestock and soils as well as emissions from the drainage network. For the direct emissions from livestock, we used official livestock census numbers and emission factors (CH₄ emitted by each animal species per head per year) available in the literature. For the emissions from soils, we based our estimates on experimental measurements in closed chambers installed on different agricultural plots, forest, and grasslands in 2008 and 2009. The results were extrapolated to the whole Seine basin, including grassland, cropland, and forest soil distributions in the Seine basin. The CH₄ emissions from the Seine drainage network were also based on measurements of sampled waters in various rivers and streams (from headwaters to estuary) during different seasons in 2007, 2008, and 2010. After chemical analysis of CH₄ concentrations in the water samples using a gas chromatographic technique and calculation of the CH₄ supersaturation by stream order in rivers of the Seine basin (from 1 to 8) and by season we could estimate the CH₄ emissions for the whole water surface area of the Seine drainage network. The livestock of the Seine basin produce CH₄ emissions amounting to 166 × 10⁶ kg C year^?1, among which cattle are responsible for 85 %. The total CH₄ emission from the Seine drainage network was estimated at 0.3 × 10⁶ kg C year^?1, large rivers being responsible for the largest proportion. Ebullition could account for an additional 0.2 × 10⁶ kg C year^?1. Soils of the Seine basin are a net sink for CH₄ (9.4 × 10⁶ kg C year^?1). The water and soils fluxes are low with regard to emissions by livestock, but domestic waste, through landfills, could contribute an additional 40 × 10⁶ kg C year^?1.