The current coronavirus disease 2019 (COVID-19) pandemic was the result of the rapid transmission of a highly pathogenic coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is no efficacious vaccine or therapeutic. Toward the development of a vaccine, here we expressed and evaluated as potential candidates four versions of the spike (S) protein using an insect cell expression system: receptor binding domain (RBD), S1 subunit, the wild-type S ectodomain (S-WT), and the prefusion trimer-stabilized form (S-2P). We showed that RBD appears as a monomer in solution, whereas S1, S-WT, and S-2P associate as homotrimers with substantial glycosylation. Cryo-electron microscopy analyses suggested that S-2P assumes an identical trimer conformation as the similarly engineered S protein expressed in 293 mammalian cells but with reduced glycosylation. Overall, the four proteins confer excellent antigenicity with convalescent COVID-19 patient sera in enzyme-linked immunosorbent assay (ELISA), yet show distinct reactivities in immunoblotting. RBD, S-WT and S-2P, but not S1, induce high neutralization titres (>3-log) in mice after a three-round immunization regimen. The high immunogenicity of S-2P could be maintained at the lowest dose (1 μg) with the inclusion of an aluminium adjuvant. Higher doses (20 μg) of S-2P can elicit high neutralization titres in non-human primates that exceed 40-times the mean titres measured in convalescent COVID-19 subjects. Our results suggest that the prefusion trimer-stabilized SARS-CoV-2 S-protein from insect cells may offer a potential candidate strategy for the development of a recombinant COVID-19 vaccine.
Nitrogen is a requisite and highly demanded element for living organisms on Earth. However, increasing human activities have greatly altered the global nitrogen cycle, especially in rivers and streams, resulting in eutrophication, formation of hypoxic zones, and increased production of N2O, a powerful greenhouse gas. This review focuses on three aspects of the nitrogen cycle in streams and rivers. We firstly introduce the distributions and concentrations of nitrogen compounds in streams and rivers as well as the techniques for tracing the sources of nitrogen pollution. Secondly, the overall picture of nitrogen transformations in rivers and streams conducted by organisms is described, especially focusing on the roles of suspended particle-water surfaces in overlying water, sediment-water interfaces, and riparian zones in the nitrogen cycle of streams and rivers. The coupling of nitrogen and other element (C, S, and Fe) cycles in streams and rivers is also briefly covered. Finally, we analyze the nitrogen budget of river systems as well as nitrogen loss as N2O and N2 through the fluvial network and give a summary of the effects and consequences of human activities and climate change on the riverine nitrogen cycle. In addition, future directions for the research on the nitrogen cycle in river systems are outlined.
Present-day estimations of global nitrogen loss (N-loss) are underestimated. Commonly, N-loss from rivers is thought to be caused by denitrification only in bed-sediments. However, coupled nitrification-denitrification occurring in overlying water with suspended sediments (SPS) where oxic and anoxic/low oxygen zones may coexist is ignored for N-loss in rivers. Here the Yellow and Yangtze Rivers were taken as examples to investigate the effect of SPS, which exists in many rivers of the world, on N loss through coupled nitrification-denitrification with nitrogen stable (N) isotopic tracer simulation experiments and in-situ investigation. The results showed even when SPS was surrounded by oxic waters, there were redox conditions that transitioned from an oxic surface layer to anoxic layer near the particle center, enabling coupled nitrification-denitrification to occur around SPS. The production rate of N from NH-N (R) increased with increasing SPS concentration ([SPS]) as a power function (R=a·[SPS]) for both the SPS-water and bed sediment-SPS-water systems. The power-functional increase of nitrifying and denitrifying bacteria population with [SPS] accounted for the enhanced coupled nitrification-denitrification rate in overlying water. SPS also accelerated denitrification in bed-sediment due to increased NO concentration caused by SPS-mediated nitrification. For these two rivers, 1gL SPS will lead to N-loss enhancement by approximately 25-120%, and the enhancement increased with organic carbon content of SPS. Thus, we conclude that SPS in overlying water is a hot spot for nitrogen loss in river systems and current estimates of in-stream N-loss are underestimated without consideration of SPS; this may partially compensate for the current imbalance of global nitrogen inputs and sinks.
The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.
Abstract. This work aims to estimate soil moisture and vegetation height from Global Navigation Satellite System (GNSS) Signal to Noise Ratio (SNR) data using direct and reflected signals by the land surface surrounding a ground-based antenna. Observations are collected from a rainfed wheat field in southwestern France. Surface soil moisture is retrieved based on SNR phases estimated by the Least Square Estimation method, assuming the relative antenna height is constant. It is found that vegetation growth breaks up the constant relative antenna height assumption. A vegetation-height retrieval algorithm is proposed using the SNR-dominant period (the peak period in the average power spectrum derived from a wavelet analysis of SNR). Soil moisture and vegetation height are retrieved at different time periods (before and after vegetation's significant growth in March). The retrievals are compared with two independent reference data sets: in situ observations of soil moisture and vegetation height, and numerical simulations of soil moisture, vegetation height and above-ground dry biomass from the ISBA (interactions between soil, biosphere and atmosphere) land surface model. Results show that changes in soil moisture mainly affect the multipath phase of the SNR data (assuming the relative antenna height is constant) with little change in the dominant period of the SNR data, whereas changes in vegetation height are more likely to modulate the SNR-dominant period. Surface volumetric soil moisture can be estimated (R2 = 0.74, RMSE = 0.009 m3 m−3) when the wheat is smaller than one wavelength (∼ 19 cm). The quality of the estimates markedly decreases when the vegetation height increases. This is because the reflected GNSS signal is less affected by the soil. When vegetation replaces soil as the dominant reflecting surface, a wavelet analysis provides an accurate estimation of the wheat crop height (R2 = 0.98, RMSE = 6.2 cm). The latter correlates with modeled above-ground dry biomass of the wheat from stem elongation to ripening. It is found that the vegetation height retrievals are sensitive to changes in plant height of at least one wavelength. A simple smoothing of the retrieved plant height allows an excellent matching to in situ observations, and to modeled above-ground dry biomass.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.