1,720,997 research outputs found
A single amino acid distorts the Fc γ receptor IIIb/CD16b structure upon binding immunoglobulin G1 and reduces affinity relative to CD16a
Get PDFTherapeutic mAbs engage Fc γ receptor III (CD16) to elicit a protective cell-mediated response and destroy the target tissue. Newer drugs designed to bind CD16a with increased affinity surprisingly also elicit protective CD16b-mediated responses. However, it is unclear why IgG binds CD16a with more than 10-fold higher affinity than CD16b even though these receptors share more than 97% identity. Here we identified one residue, Gly-129, that contributes to the greater IgG binding affinity of CD16a. The CD16b variant D129G bound IgG1 Fc with 2-fold higher affinity than CD16a and with 90-fold higher affinity than the WT. Conversely, the binding affinity of CD16a-G129D was decreased 128-fold relative to WT CD16a and comparably to that of WT CD16b. The interaction of IgG1 Fc with CD16a, but not with CD16b, is known to be sensitive to the composition of the asparagine-linked carbohydrates (N-glycans) attached to the receptor. CD16a and CD16b-D129G displaying minimally processed oligomannose N-glycans bound to IgG1 Fc with about 5.2-fold increased affinity compared with variants with highly processed complex-type N-glycans. CD16b and the CD16a-G129D variant exhibited a smaller 1.9-fold affinity increase with oligomannose N-glycans. A model of glycosylated CD16b bound to IgG1 Fc determined to 2.2 Å resolution combined with a 250-ns all-atom molecular dynamics simulation showed that the larger Asp-129 residue deformed the Fc-binding surface. These results reveal how Asp-129 in CD16b affects its binding affinity for IgG1 Fc and suggest that antibodies engineered to engage CD16b with high affinity must accommodate the Asp-129 side chain.This research was originally published in the Journal of Biological Chemistry. Roberts, Jacob T., and Adam W. Barb. "A single amino acid distorts the Fc γ receptor IIIb/CD16b structure upon binding immunoglobulin G1 and reduces affinity relative to CD16a." Journal of Biological Chemistry 293, no. 51 (2018): 19899-19908. © the Author(s). doi: 10.1074/jbc.RA118.005273.</p
Primary Human Natural Killer Cells Retain Proinflammatory IgG1 at the Cell Surface and Express CD16a Glycoforms with Donor-dependent Variability
Get PDFPost-translational modification confers diverse functional properties to immune system proteins. The composition of serum proteins such as immunoglobulin G (IgG) strongly associates with disease including forms lacking a fucose modification of the crystallizable fragment (Fc) asparagine(N)-linked glycan that show increased effector function, however, virtually nothing is known about the composition of cell surface receptors or their bound ligands in situ due to low abundance in the circulating blood. We isolated primary NK cells from apheresis filters following plasma or platelet donation to characterize the compositional variability of Fc g receptor IIIa / CD16a and its bound ligand, IgG1. CD16a N162-glycans showed the largest differences between donors; one donor displayed only oligomannose-type N-glycans at N162 that correlate with high affinity IgG1 Fc binding while the other donors displayed a high degree of compositional variability at this site. Hybrid-type N-glycans with intermediate processing dominated at N45 and highly modified, complex-type N-glycans decorated N38 and N74 from all donors. Analysis of the IgG1 ligand bound to NK cell CD16a revealed a sharp decrease in antibody fucosylation (43.2 ±11.0%) versus serum from the same donors (89.7 ±3.9%). Thus, NK cells express CD16a with unique modification patterns and preferentially bind IgG1 without the Fc fucose modification at the cell surface.This research was originally published in Molecular and Cellular Proteomics. Patel, Kashyap R., Joel D. Nott, and Adam W. Barb. "Primary human natural killer cells retain proinflammatory IgG1 at the cell surface and express CD16a glycoforms with donor-dependent variability." Molecular & Cellular Proteomics 2019; 18:2178-2190. © Patel et al. doi: 10.1074/mcp.RA119.001607.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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