scholarly journals Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aleksandar Antanasijevic ◽  
Leigh M. Sewall ◽  
Christopher A. Cottrell ◽  
Diane G. Carnathan ◽  
Luis E. Jimenez ◽  
...  
Keyword(s):  
High Resolution ◽  
Polyclonal Antibody ◽  
Vaccine Development ◽  
Mutational Analysis ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
Glycosylation Sites ◽  
High Resolution Analysis ◽  
Resolution Analysis ◽  
Resolution Mapping

AbstractEngineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic.

scholarly journals Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM

2021 ◽  
Author(s):  
Aleksandar Antanasijevic ◽  
Leigh M. Sewall ◽  
Christopher A. Cottrell ◽  
Diane G. Carnathan ◽  
Luis E. Jimenez ◽  
...  
Keyword(s):  
High Resolution ◽  
Polyclonal Antibody ◽  
Vaccine Development ◽  
Mutational Analysis ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
Binding Modes ◽  
High Resolution Mapping ◽  
High Resolution Analysis ◽  
Resolution Mapping

In BriefHerein, we evaluated the immunogenicity of several BG505 SOSIP-based HIV Env immunogens in the rhesus macaque animal model using a combination of serology and biophysical approaches. We applied electron cryo-microscopy for high-resolution mapping of elicited polyclonal antibody responses, which provided detailed insights into the binding modes of the most common classes of antibodies elicited by BG505 SOSIP immunogens as well as the critical differences in immunogenicity that can occur as a consequence of engineered stabilizing mutations and partial glycan occupancy at different sites.SummaryEngineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic.Graphical abstract

scholarly journals Genome-Wide High-Resolution Mapping by Recurrent Intermating Using Arabidopsis thaliana as a Model

Genetics ◽  
1996 ◽  
Vol 142 (1) ◽  
pp. 247-258
Author(s):  
Sin-Chieh Liu ◽  
Stanley P Kowalski ◽  
Tien-Hung Lan ◽  
Kenneth A Feldmann ◽  
Andrew H Paterson
Keyword(s):  
High Resolution ◽  
Recombinant Inbred ◽  
Additional Information ◽  
High Resolution Mapping ◽  
Genome Wide ◽  
A Genome ◽  
High Resolution Analysis ◽  
Resolution Analysis ◽  
Resolution Mapping ◽  
Map Resolution

We demonstrate a method for developing populations suitable for genome-wide high-resolution genetic linkage mapping, by recurrent intermating among F2 individuals derived from crosses between homozygous parents. Comparison of intermated progenies to F2 and “recombinant inbred” (RI) populations from the same pedigree corroborate theoretical expectations that progenies intermated for four generations harbor about threefold more information for estimating recombination fraction between closely linked markers than either RI-selfed or F2 individuals (which are, in fact, equivalent in this regard). Although intermated populations are heterozygous, homozygous “intermated recombinant inbred” (IRI) populations can readily be generated, combining additional information afforded by intermating with the permanence of RI populations. Intermated populations permit fine-mapping of genetic markers throughout a genome, helping to bridge the gap between genetic map resolution and the DNA-carrying capacity of modern cloning vectors, thus facilitating merger of genetic and physical maps. Intermating can also facilitate high-resolution mapping of genes and QTLs, accelerating map-based cloning. Finally, intermated populations will facilitate investigation of other fundamental genetic questions requiring a genome-wide high-resolution analysis, such as comparative mapping of distantly related species, and the genetic basis of heterosis.

Very High Resolution Analysis of the Dynamics of a Coronal Plasmoid

1994 ◽  
Vol 144 ◽  
pp. 593-596
Author(s):  
O. Bouchard ◽  
S. Koutchmy ◽  
L. November ◽  
J.-C. Vial ◽  
J. B. Zirker
Keyword(s):  
High Resolution ◽  
Solar Eclipse ◽  
Total Solar Eclipse ◽  
Field Of View ◽  
Small Field ◽  
High Resolution Analysis ◽  
Ccd Observations ◽  
Resolution Analysis ◽  
Very High ◽  
Small Field Of View

AbstractWe present the results of the analysis of a movie taken over a small field of view in the intermediate corona at a spatial resolution of 0.5“, a temporal resolution of 1 s and a spectral passband of 7 nm. These CCD observations were made at the prime focus of the 3.6 m aperture CFHT telescope during the 1991 total solar eclipse.

scholarly journals How to Effectively Control Energy Consumption Growth in China’s 29 Provinces: A Paradigm of Multi-Regional Analysis Based on EAALMDI Method

2021 ◽  
Vol 13 (3) ◽  
pp. 1093
Author(s):  
Yunlong Zhao ◽  
Geng Kong ◽  
Chin Hao Chong ◽  
Linwei Ma ◽  
Zheng Li ◽  
...  
Keyword(s):  
Energy Consumption ◽  
High Resolution ◽  
Energy Policy ◽  
Policy Making ◽  
Regional Analysis ◽  
Policy Implications ◽  
Consumption Growth ◽  
High Resolution Analysis ◽  
Resolution Analysis ◽  
Consumption Control

Controlling energy consumption to reduce greenhouse gas emissions has become a global consensus in response to the challenge of climate change. Most studies have focused on energy consumption control in a single region; however, high-resolution analysis of energy consumption and personalized energy policy-making, for multiple regions with differentiated development, have become a complicated challenge. Using the logarithmic mean Divisia index I (LMDI) decomposition method based on energy allocation analysis (EAA), this paper aims to establish a standard paradigm for a high-resolution analysis of multi-regional energy consumption and provide suggestions for energy policy-making, taking 29 provinces of China as the sample. The process involved three steps: (1) determination of regional priorities of energy consumption control by EAA, (2) revealing regional disparity among the driving forces of energy consumption growth by LMDI, and (3) deriving policy implications by comparing the obtained results with existing policies. The results indicated that 29 provinces can be divided into four groups, with different priorities of energy consumption control according to the patterns of coal flows. Most provinces have increasing levels of energy consumption, driven by increasing per capita GDP and improving living standards, while its growth is restrained by decreasing end-use energy intensity, improving energy supply efficiency, and optimization of industrial structures. However, some provinces are not following these trends to the same degree. This indicates that policy-makers must pay more attention to the different driving mechanisms of energy consumption growth among provinces.

scholarly journals A Back Migration from Asia to Sub-Saharan Africa Is Supported by High-Resolution Analysis of Human Y-Chromosome Haplotypes

2002 ◽  
Vol 70 (5) ◽  
pp. 1197-1214 ◽  
Author(s):  
Fulvio Cruciani ◽  
Piero Santolamazza ◽  
Peidong Shen ◽  
Vincent Macaulay ◽  
Pedro Moral ◽  
...  
Keyword(s):  
High Resolution ◽  
Y Chromosome ◽  
Sub Saharan Africa ◽  
High Resolution Analysis ◽  
Resolution Analysis ◽  
Sub Saharan ◽  
Human Y Chromosome
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