The spatial variability in isotopic composition of surface snow and snowpits on the East Antarctic Ice Sheet

The water isotope composition of snow precipitations, archived in the Antarctic ice sheet every year, is an important proxy of climatic conditions. This signal depends on several parameters such as local temperature, altitude, moisture source areas and air mass pathways. However, especially in areas where snow accumulation is very low (as on the East Antarctic Plateau), the isotopic composition is affected by additional spatial variability induced by the interactions between the atmosphere and snow surface, and the pristine signal may be modified through isotopic exchanges, sublimation processes and mechanical mixing originated from wind action. Here, we present the isotopic composition (D and 18O) and the second-order parameter d-excess of surface snow and snowpit samples collected during the Italian-French campaign in Antarctica (2019-2020). The sampling sites cover the area from Dumont D'Urville to Concordia Station and from Concordia Station towards the South Pole (EAIIST – East Antarctic International Ice Sheet Traverse). These data, compared with a previous dataset of Antarctic surface snow isotopic composition (Masson-Delmotte et al. 2008), are analyzed to determine the variability of the spatial relationship between precipitation isotopic composition and local temperature in relation to geographical parameters (latitude, distance from the coast and elevation). The interpretation of these factors determining the isotope signature is the base to better define the amount of the effects caused by subsequent interaction between atmosphere and surface snow, and by the wind action. Understanding the spatial variability of this proxy, which strongly decreases the signal-to-noise ratio, could permit to improve the use of the “isotopic thermometer” to quantify past changes in temperature based on the stable isotopic record of deep ice cores

Profiling Human Antibody Responses by Integrated Single-Cell Analysis

Comprehensive characterization of the antigen-specific B cells induced during infections or following vaccination would facilitate the discovery of novel antibodies and inform how interventions shape protective humoral responses. The analysis of human B cells and their antibodies has been performed using flow cytometry to evaluate memory B cells and expanded plasmablasts, while microtechnologies have also provided a useful tool to examine plasmablasts/plasma cells after vaccination. Here we present an integrated analytical platform, using arrays of subnanoliter wells (nanowells), for constructing detailed profiles for human B cells comprising the immunophenotypes of these cells, the distribution of isotypes of the secreted antibodies, the specificity and relative affinity for defined antigens, and for a subset of cells, the genes encoding the heavy and light chains. The approach combines on-chip image cytometry, microengraving, and single-cell RT-PCR. Using clinical samples from HIV-infected subjects, we demonstrate that the method can identify antigen-specific neutralizing antibodies, is compatible with both plasmablasts/plasma cells and activated memory B cells, and is well-suited for characterizing the limited numbers of B cells isolated from tissue biopsies (e.g., colon biopsies). The technology should facilitate detailed analyses of human humoral responses for evaluating vaccines and their ability to raise protective antibody responses across multiple anatomical compartments

Sub-millennial climate variability from high-resolution water isotopes in the EPICA Dome C ice core

The EPICA Dome C (EDC) ice core provides the longest continuous climatic record, covering the last 800 000 years (800 kyr). A unique opportunity to investigate decadal to millennial variability during past glacial and interglacial periods is provided by the high-resolution water isotopic record (δ18O and δD) available for the EDC ice core. We present here a continuous compilation of the EDC water isotopic record at a sample resolution of 11 cm, which consists of 27 000 δ18O measurements and 7920 δD measurements (covering, respectively, 94 % and 27 % of the whole EDC record), including published and new measurements (2900 for both δ18O and δD) for the last 800 kyr. Here, we demonstrate that repeated water isotope measurements of the same EDC samples from different depth intervals obtained using different analytical methods are comparable within analytical uncertainty. We thus combine all available EDC water isotope measurements to generate a high-resolution (11 cm) dataset for the past 800 kyr. A frequency decomposition of the most complete δ18O record and a simple assessment of the possible influence of diffusion on the measured profile shows that the variability at the multi-decadal to multi-centennial timescale is higher during glacial than during interglacial periods and higher during early interglacial isotopic maxima than during the Holocene. This analysis shows as well that during interglacial periods characterized by a temperature optimum at the beginning, the multi-centennial variability is strongest over this temperature optimum.publishedVersio

Broadly neutralizing antibody responses in a large longitudinal sub-Saharan HIV primary infection cohort

Author Summary Understanding how HIV-1-broadly neutralizing antibodies (bnAbs) develop during natural infection is essential to the design of an efficient HIV vaccine. We studied kinetics and correlates of neutralization breadth in a large sub-Saharan African longitudinal cohort of 439 participants with primary HIV-1 infection. Broadly nAb responses developed in 15% of individuals, on average three years after infection. Broad neutralization was associated with high viral load, low CD4+ T cell counts, virus subtype C infection and HLA*A3(-) genotype. A correlation with high overall plasma IgG levels and anti-Env binding titers was also found. Specificity mapping of the bnAb responses showed that glycan-dependent epitopes, in particular the N332 region, were most commonly targeted, in contrast to other bnAb epitopes, suggesting that the HIV Env N332-glycan epitope region may be a favorable target for vaccine design

Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans

The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development.This project has received funding from the European Union’s Horizon 2020 Research and Innovation program under grant agreement 681137 (to K.J.D. and I.H.), the Medical Research Council (MRC) (to K.J.D. [MR/K024426/1]), The Rosetrees Trust (to K.J.D. [M686]) and Fondation Dormeur, Vaduz (to K.J.D). This research was funded or supported by the National Institute for Health Research Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the National Institute for Health Research (NIHR), or the Department of Health. N.R. acknowledges funding from Ministry of Science and Education grants CTQ2017-90039-R, RTC-2017-6126-1, and CTQ2011-27874 (fellowship to K.B.) and the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (grant MDM-2017-0720). F.A. was funded by the Wellcome Trust (104958/Z/14/Z). J.A. was supported by the Spanish Ministry of Science, Innovation and Universities through the grant PID2019-109395GB-I00. J.A. and S.M. acknowledge support of BBSRC (grant BB/P010660/1). T.H. and S.W. were funded by Biotechnology and Biological Sciences Research Council (BBSRC) Norwich Research Park Doctoral Training Grant BB/M011216/1. IAVI’s work is made possible by generous support from many donors, including the Bill & Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan in partnership with The World Bank, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation, the United Kingdom Department for International Development (DFID), and the United States Agency for International Development. The full list of IAVI donors is available at www.iavi.org. Brendan McAtarsney and Jonathan Hare from the IAVI Human Immunology Lab (HIL) for coordinating the samples transfers and shipments. Monica Agromayor and the KCL Nikon Centre for assistance and advice on confocal microscopy. NMRI strain Schistosoma mansoni-infected Biomphalaria glabrata snails were provided by the NIAID Schistosomiasis Resource Center, Rockville, USA.Peer reviewe

An MPER antibody neutralizes HIV-1 using germline features shared among donors.

The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC50). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens

Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans

The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development

The extraordinary March 2022 East Antarctica "heat" wave. Part I: observations and meteorological drivers

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The extraordinary March 2022 East Antarctica "heat" wave. Part II: impacts on the Antarctic ice sheet

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