Efficient therapeutic options are needed to control the spread of SARS-CoV-2 that has caused more than 922,000 fatalities as of September 13th, 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block ACE2 attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Cocktails including S2M11, S2E12 or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.
Lymphoid tissue plasmacytoid and conventional dendritic cells (DCs) are continuously regenerated from hematopoietic stem cells. The cytokine dependence and biology of plasmacytoid and conventional DCs suggest that regeneration might proceed through common DC-restricted developmental intermediates. By selecting for cytokine receptor expression relevant to DC development, we identify here highly cycling Lin(-)c-Kit(int)Flt3(+)M-CSFR(+) cells with a distinct gene-expression profile in mouse bone marrow that, on a clonal level in vitro and as a population both in vitro and in vivo, efficiently generated plasmacytoid and conventional DCs but no other lineages, which increased in number after in vivo injection of the cytokine Flt3 ligand. These clonogenic common DC progenitors thus define a cytokine-regulated DC developmental pathway that ensures the supply of various DC populations.
The rhizodeposition of plants dramatically influence the surrounding soil and its microflora. Root exudates have pronounced selective and promoting effects on specific microbial populations which are able to respond with chemotaxis and fast growth responses, such that only a rather small subset of the whole soil microbial diversity is finally colonizing roots successfully. The exudates carbon compounds provide readily available nutrient and energy sources for heterotrophic organisms but also contribute e.g. complexing agents, such as carboxylates, phenols or siderophores for the mobilization and acquisition of rather insoluble minerals. Root exudation can also quite dramatically alter the pH-and redox-milieu in the rhizosphere. In addition, not only specific stimulatory compounds, but also antimicrobials have considerable discriminatory effect on the rhizosphere microflora. In the "biased rhizosphere" concept, specific root associated microbial populations are favored based on modification of the root exudation profile. Rhizosphere microbes may exert specific plant growth promoting or biocontrol effects, which could be of great advantage for the plant host. Since most of the plant roots have symbiotic fungi, either arbuscular or ectomycorrhizal fungi, the impact of plants towards the rhizosphere extends also to the mycorrhizosphere. The selective effect of the roots towards the selection of microbes also extends towards the root associated and symbiotic fungi. While microbes are known to colonize plant roots endophytically, also mycorrhiza are now known to harbor closely associated bacterial populations even within their hyphae.The general part of the manuscript is followed by the more detailed presentation of specific examples for the selection and interaction of roots and microbes, such as in the rhizosphere of strawberry, potato and oilseed rape, where the soil-borne plant pathogen Verticillium dahliae can cause high yield losses; the potential of biocontrol by specific constituents of the rhizosphere microbial community is demonstrated. Furthermore, plant cultivar specificity of microbial communities is described in different Plant Soil (2009) 321:235-257 potato lines including the case of transgenic lines. Finally, also the specific selective effect of different Medicago species on the selection of several arbuscular mycorrhizal taxa is presented.
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