The Arctic is warming far faster than the global average, threatening the release of large amounts of carbon presently stored in frozen permafrost soils. Increasing Earth's albedo by the injection of ...sulfate aerosols into the stratosphere has been proposed as a way of offsetting some of the adverse effects of climate change. We examine this hypothesis in respect of permafrost carbon-climate feedbacks using the PInc-PanTher process model driven by seven earth system models running the Geoengineering Model Intercomparison Project (GeoMIP) G4 stratospheric aerosol injection scheme to reduce radiative forcing under the Representative Concentration Pathway (RCP) 4.5 scenario. Permafrost carbon released as CO
is halved and as CH
by 40% under G4 compared with RCP4.5. Economic losses avoided solely by the roughly 14 Pg carbon kept in permafrost soils amount to about US$ 8.4 trillion by 2070 compared with RCP4.5, and indigenous habits and lifestyles would be better conserved.
The HIV-1 envelope glycoprotein (Env) trimer contains the receptor binding sites and membrane fusion machinery that introduce the viral genome into the host cell. As the only target for broadly ...neutralizing antibodies (bnAbs), Env is a focus for rational vaccine design. We present a cryo-electron microscopy reconstruction and structural model of a cleaved, soluble Env trimer (termed BG505 SOSIP. 664 gp140) in complex with a CD4 binding site (CD4bs) bnAb, PGV04, at 5.8 angstrom resolution. The structure reveals the spatial arrangement of Env components, including the V1/V2, V3, HR1, and HR2 domains, as well as shielding glycans. The structure also provides insights into trimer assembly, gp120-gp41 interactions, and the CD4bs epitope cluster for bnAbs, which covers a more extensive area and defines a more complex site of vulnerability than previously described.
Iceberg calving from all Antarctic ice shelves has never been directly measured, despite playing a crucial role in ice sheet mass balance. Rapid changes to iceberg calving naturally arise from the ...sporadic detachment of large tabular bergs but can also be triggered by climate forcing. Here we provide a direct empirical estimate of mass loss due to iceberg calving and melting from Antarctic ice shelves. We find that between 2005 and 2011, the total mass loss due to iceberg calving of 755 ± 24 gigatonnes per year (Gt/y) is only half the total loss due to basal melt of 1516 ± 106 Gt/y. However, we observe widespread retreat of ice shelves that are currently thinning. Net mass loss due to iceberg calving for these ice shelves (302 ± 27 Gt/y) is comparable in magnitude to net mass loss due to basal melt (312 ± 14 Gt/y). Moreover, we find that iceberg calving from these decaying ice shelves is dominated by frequent calving events, which are distinct from the less frequent detachment of isolated tabular icebergs associated with ice shelves in neutral or positive mass balance regimes. Our results suggest that thinning associated with ocean-driven increased basal melt can trigger increased iceberg calving, implying that iceberg calving may play an overlooked role in the demise of shrinking ice shelves, and is more sensitive to ocean forcing than expected from steady state calving estimates.
Significance The floating parts of the Antarctic ice sheet (“ice shelves”) help to hold back the flow of the grounded parts, determining the contribution to global sea level rise. Using satellite images, we measured, for the first time, all icebergs larger than 1 km ² calving from the entire Antarctic coastline, and the state of health of all the ice shelves. Some large ice shelves are growing while many smaller ice shelves are shrinking. We find high rates of iceberg calving from Antarctic ice shelves that are undergoing basal melt-induced thinning, which suggests the fate of ice shelves may be more sensitive to ocean forcing than previously thought.
We have investigated the immunogenicity in rabbits of native-like, soluble, recombinant SOSIP.664 trimers based on the env genes of four isolates of human immunodeficiency virus type 1 (HIV-1); ...specifically BG505 (clade A), B41 (clade B), CZA97 (clade C) and DU422 (clade C). The various trimers were delivered either simultaneously (as a mixture of clade A + B trimers) or sequentially over a 73-week period. Autologous, Tier-2 neutralizing antibody (NAb) responses were generated to the clade A and clade B trimers in the bivalent mixture. When delivered as boosting immunogens to rabbits immunized with the clade A and/or clade B trimers, the clade C trimers also generated autologous Tier-2 NAb responses, the CZA97 trimers doing so more strongly and consistently than the DU422 trimers. The clade C trimers also cross-boosted the pre-existing NAb responses to clade A and B trimers. We observed heterologous Tier-2 NAb responses albeit inconsistently, and with limited overall breath. However, cross-neutralization of the clade A BG505.T332N virus was consistently observed in rabbits immunized only with clade B trimers and then boosted with clade C trimers. The autologous NAbs induced by the BG505, B41 and CZA97 trimers predominantly recognized specific holes in the glycan shields of the cognate virus. The shared location of some of these holes may account for the observed cross-boosting effects and the heterologous neutralization of the BG505.T332N virus. These findings will guide the design of further experiments to determine whether and how multiple Env trimers can together induce more broadly neutralizing antibody responses.
Respiratory syncytial virus (RSV) is capable of transient viremia and extrapulmonary dissemination. Recently, this virus has been identified in fetal cord blood, suggesting the possibility of in ...utero acquisition in humans. Here, we assess permissivity and kinetics of RSV replication in primary human placental cells, examine their potential to transfer this infection to neighboring cells, and measure the inflammatory response evoked by the virus.
Human placental villus tissue was collected immediately upon delivery and processed for isolation of placental cytotrophoblast, fibroblast, and macrophage (Hofbauer) cells. Isolated cells were infected with a recombinant RSV-A2 strain (rrRSV) expressing red fluorescent protein (RFP) and analyzed by fluorescence microscopy, Western blot, and quantitative PCR (qPCR). Based on RFP expression, rrRSV exhibited differential tropism for the three major placental cell types. Placental fibroblasts and Hofbauer cells were permissive and supported productive rrRSV replication. While infected cytotrophoblast cells expressed viral glycoprotein (G protein), only limited RSV replication was detected. Importantly, qPCR and fluorescence-focused unit assay revealed that the viral progeny remains trapped within infected Hofbauer cells for up to 30 days, with no release into surrounding media. Yet, Hofbauer cells passed the infection onto overlaid naïve 16HBE cells, suggesting contact-dependent trans-infection. Lastly, a significant increase in proinflammatory cytokines, particularly IL-6, TNF-alpha, and IFN-gamma was measured in the supernatant of infected Hofbauer cells by multiplex cytokine assay and conventional ELISA.
This study demonstrates that RSV can replicate in human placenta, exhibits differential tropism for distinct placental cell types, can be stored and transferred to neighboring cells by Hofbauer cells, and elicits an inflammatory response. It also supports the hypothesis that this respiratory virus can be vertically transferred to the fetus and potentially affect its development and the outcome of pregnancies.
The HIV-1 envelope glycoprotein trimer is covered by an array of N-linked glycans that shield it from immune surveillance. The high density of glycans on the trimer surface imposes steric constraints ...limiting the actions of glycan-processing enzymes, so that multiple under-processed structures remain on specific areas. These oligomannose glycans are recognized by broadly neutralizing antibodies (bNAbs) that are not thwarted by the glycan shield but, paradoxically, target it. Our site-specific glycosylation analysis of a soluble, recombinant trimer (BG505 SOSIP.664) maps the extremes of simplicity and diversity of glycan processing at individual sites and reveals a mosaic of dense clusters of oligomannose glycans on the outer domain. Although individual sites usually minimally affect the global integrity of the glycan shield, we identify examples of how deleting some glycans can subtly influence neutralization by bNAbs that bind at distant sites. The network of bNAb-targeted glycans should be preserved on vaccine antigens.
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•Quantitative, site-specific N-glycan analysis of a soluble HIV-1 Env trimer•A map of the extremes of simplicity and diversity at individual glycan sites•The fine structure of the mannose patch area of the Env trimer•How individual glycan sites influence HIV-1 Env-pseudovirus neutralization
Behrens et al. present detailed, quantitative, site-specific analyses of N-glycosylation sites of a soluble recombinant HIV-1 envelope glycoprotein trimer. The results highlight structural and antigenic details of the glycan shield that will be valuable for designing next-generation HIV-1 Env vaccines and understanding virus neutralization by broadly active antibodies.
The HIV envelope glycoprotein (Env) is densely covered with self-glycans that should help shield it from recognition by the human immune system. Here, we examine how a particularly potent family of ...broadly neutralizing antibodies (Abs) has evolved common and distinct structural features to counter the glycan shield and interact with both glycan and protein components of HIV Env. The inferred germline antibody already harbors potential binding pockets for a glycan and a short protein segment. Affinity maturation then leads to divergent evolutionary branches that either focus on a single glycan and protein segment (e.g., Ab PGT124) or engage multiple glycans (e.g., Abs PGT121–123). Furthermore, other surrounding glycans are avoided by selecting an appropriate initial antibody shape that prevents steric hindrance. Such molecular recognition lessons are important for engineering proteins that can recognize or accommodate glycans.
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•Potent broadly neutralizing HIV antibody PGT124 contacts both glycan and protein•PGT124 contrasts with other family members by contacting only a single glycan•Inferred germline antibody incorporates features important for protein and glycan recognition•Antibody maturation diversifies modes of glycan recognition
Structural data reveal how a family of human antibodies has evolved diverse solutions to interact with and penetrate the HIV envelope glycan defensive shield so as to potently neutralize HIV.
Untangling the influence of human activities on food-web stability and persistence is complex given the large numbers of species and overwhelming number of interactions within ecosystems. Although ...biodiversity has been associated with stability, the actual structures and processes that confer stability to diverse food webs remain largely unknown. Here we show that real food webs are structured such that top predators act as couplers of distinct energy channels that differ in both productivity and turnover rate. Our theoretical analysis shows that coupled fast and slow channels convey both local and non-local stability to food webs. Alarmingly, the same human actions that have been implicated in the loss of biodiversity also directly erode the very structures and processes that we show to confer stability on food webs.
Progress on priming HIV-1 immunity Sanders, Rogier W; Moore, John P
Science (American Association for the Advancement of Science),
2024-May-17, 2024-05-17, 20240517, Letnik:
384, Številka:
6697
Journal Article
Recenzirano
Four new studies inform on the multistep path to generate broadly active HIV-1 antibodies.
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