3,941 research outputs found
T Cell responses to whole SARS Coronavirus in humans
No full textEffective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-γ ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8+ T cell responses were more frequent and of a greater magnitude than CD4+ T cell responses (p < 0.001).
Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27+/CD45RO+) with a significantly higher frequency of polyfunctional CD4+ T cells producing IFN-γ, TNF-α, and IL-2, and CD8+ T cells producing IFN-γ, TNF-α, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation
A single amino acid distorts the Fc γ receptor IIIb/CD16b structure upon binding immunoglobulin G1 and reduces affinity relative to CD16a
No full textTherapeutic 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
Reaches of Lake Creek, Deadwood Creek, and Nelson Creek near Deadwood, Lane County, Oregon
No full textby Jed T. Roberts and Matt C. Williams.This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Includes bibliographical references (page 9).Mode of access: Internet from the Oregon Government Publications Collection.Text in English
Lower reach of Gate Creek near Vida, Lane County, Oregon
No full textby Jed T. Roberts and Matt C. Williams.This archived document is maintained by the State Library of Oregon as part of the Oregon Documents Depository Program. It is for informational purposes and may not be suitable for legal purposes.Includes bibliographical references (page 8).Mode of access: Internet from the Oregon Government Publications Collection.Text in English
David Roberts Oral History Collection
No full textThe David Roberts oral history collection was created by Roberts, an Atlanta University student, in the summer of 1973. The interviews were for a history seminar taught by Dr.Clarence Bacote (HIS 406: Introductory Graduate Course in United States History). Roberts interviewed members of Atlantas African American community who were born in the late 19th century. Most of the subjects were Georgia natives and a few were graduates of Atlanta University Center schools. He asked them to discuss their memories of various prominent African Americans and events, as well as living conditions for African Americans in the first half of the 20th century. He generally asked them the same questions and let them elaborate at will. He was especially interested in segregation and race relations, and asked about the way African Americans were treated in the justice system, hospitals, and in the workplace. He also asked about their memories of Atlanta specifically, including the riot of 1906, Ku Klux Klan visits, and Booker T. Washington High School, the first high school for African Americans in Atlanta.
At the AUC Robert W. Woodruff Library we are always striving to improve our digital collections. We welcome additional information about people, places, or events depicted in any of the works in this collection. To submit information, please contact us at [email protected].
Author response to: Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis
No full textLetter to the EditorThis commentary is an author response to Yu and colleagues regarding the manuscript entitled ‘Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: Systematic review and meta-analysis’. We address their concern regarding minor errors in our manuscript, our search strategy and assessment of heterogeneity.Maleesa M. Pathirana, Zohra S. Lassi, Claire T. Roberts, and Prabha H. Andraweer
A new look at the pathogenesis of asthma
No full textAsthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.<br/
Exploiting knowledge of immune selection in HIV-1 to detect HIV-specific CD8 T-cell responses
No full textSince HLA-restricted cytotoxic T-cell responses select specific polymorphisms in HIV-1 sequences and HLA diversity is relatively static in human populations, we investigated the use of peptide epitopes based on sites of HLA-associated adaptation in HIV-1 sequences to stimulate and detect T-cell responses ex vivo. These "HLA-optimised" peptides captured more HIV-1 Nef-specific responses compared with overlapping peptides of a single consensus sequence, in interferon-γ enzyme linked immunospot assays. Sites of immune selection can reveal more immunogenic epitopes in HLA-diverse populations and offer insights into the nature of HLA-epitope targeting, which could be applied in vaccine design
Mixed Bruce-Roberts numbers
No full text[EN] We extend the notions of mu*- sequences and Tjurina numbers of functions to the framework of Bruce-Roberts numbers, that is, to pairs formed by the germ at 0 of a complex analytic variety X. Cn and a finitely R( X)-determined analytic function germ f : (Cn, 0). (C, 0). We analyze some fundamental properties of these numbers.Part of this work was developed during the stay of the first author at the Departamento de Matematica of ICMC, Sao Carlos, Universidade de Sao Paulo (Brazil), in February and July 2018. The first author wishes to thank this institution for their hospitality and working conditions and to FAPESP for financial support. The first author was partially supported by MICINN Grant PGC2018-094889-B-I00 and FAPESP Grant 2014/00304-2. The second author was partially supported by CNPq Grant 306306/2015-8 and FAPESP Grant 2014/00304-2.Bivià-Ausina, C.; Ruas, M. (2020). Mixed Bruce-Roberts numbers. Proceedings of the Edinburgh Mathematical Society. 63(2):456-474. https://doi.org/10.1017/S0013091519000543S456474632Damon, J. (1996). Higher multiplicities and almost free divisors and complete intersections. Memoirs of the American Mathematical Society, 123(589), 0-0. doi:10.1090/memo/0589Wahl, J. M. (1983). Derivations, automorphisms and deformations of quasihomogeneous singularities. Proceedings of Symposia in Pure Mathematics, 613-624. doi:10.1090/pspum/040.2/713285De Goes Grulha, N. (2008). THE EULER OBSTRUCTION AND BRUCE-ROBERTS’ MILNOR NUMBER. The Quarterly Journal of Mathematics, 60(3), 291-302. doi:10.1093/qmath/han011Greuel, G.-M. (1975). Der Gau�-Manin-Zusammenhang isolierter Singularit�ten von vollst�ndigen Durchschnitten. Mathematische Annalen, 214(3), 235-266. doi:10.1007/bf01352108Gaffney, T. (1996). Multiplicities and equisingularity of ICIS germs. Inventiones Mathematicae, 123(1), 209-220. doi:10.1007/bf01232372Damon, J. (2002). On the freeness of equisingular deformations of plane curve singularities. Topology and its Applications, 118(1-2), 31-43. doi:10.1016/s0166-8641(01)00040-2Bruce, J. W., & Roberts, R. M. (1988). Critical points of functions on analytic varieties. Topology, 27(1), 57-90. doi:10.1016/0040-9383(88)90007-9Decker, W. , Greuel, G.-M. , Pfister, G. and Schönemann, H. , Singular 4-0-2. A computer algebra system for polynomial computations. Available at http://www.singular.uni-kl.de (2015).Looijenga, E. J. N. (1984). Isolated Singular Points on Complete Intersections. doi:10.1017/cbo9780511662720AHMED, I., RUAS, M. A. S., & TOMAZELLA, J. N. (2013). Invariants of topological relative right equivalences. Mathematical Proceedings of the Cambridge Philosophical Society, 155(2), 307-315. doi:10.1017/s0305004113000297Aleksandrov, A. G. (1986). COHOMOLOGY OF A QUASIHOMOGENEOUS COMPLETE INTERSECTION. Mathematics of the USSR-Izvestiya, 26(3), 437-477. doi:10.1070/im1986v026n03abeh001155Briançon, J., & Maynadier-Gervais, H. (2002). Sur le nombre de Milnor d’une singularité semi-quasi-homogène. Comptes Rendus Mathematique, 334(4), 317-320. doi:10.1016/s1631-073x(02)02256-2Giusti, M., & Henry, J.-P.-G. (1980). Minorations de nombres de Milnor. Bulletin de la Société mathématique de France, 79, 17-45. doi:10.24033/bsmf.1907Hauser, H., & Müller, G. (1993). Affine varieties and lie algebras of vector fields. Manuscripta Mathematica, 80(1), 309-337. doi:10.1007/bf03026556Liu, Y. (2018). Milnor and Tjurina numbers for a hypersurface germ with isolated singularity. Comptes Rendus Mathematique, 356(9), 963-966. doi:10.1016/j.crma.2018.07.004Nuno-Ballesteros, J. J., Orefice, B., & Tomazella, J. N. (2011). THE BRUCE-ROBERTS NUMBER OF A FUNCTION ON A WEIGHTED HOMOGENEOUS HYPERSURFACE. The Quarterly Journal of Mathematics, 64(1), 269-280. doi:10.1093/qmath/har032Ohmoto, T., Suwa, T., & Yokura, S. (1997). A remark on the Chern classes of local complete intersections. Proceedings of the Japan Academy, Series A, Mathematical Sciences, 73(5), 93-95. doi:10.3792/pjaa.73.93Lê Tráng, D. (1974). Calculation of Milnor number of isolated singularity of complete intersection. Functional Analysis and Its Applications, 8(2), 127-131. doi:10.1007/bf0107859
Site-specific N-glycan Analysis of Antibody-binding Fc γ Receptors from Primary Human Monocytes
No full textFcγRIIIa (CD16a) and FcγRIIa (CD32a) on monocytes are essential for proper effector functions including antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Indeed, therapeutic monoclonal antibodies (mAbs) that bind FcγRs with greater affinity exhibit greater efficacy. Furthermore, post-translational modification impacts antibody binding affinity, most notably the composition of the asparagine(N)-linked glycan at N162 of CD16a. CD16a is widely recognized as the key receptor for the monocyte response, however the post-translational modifications of CD16a from endogenous monocytes are not described. Here we isolated monocytes from individual donors and characterized the composition of CD16a and CD32a N-glycans from all modified sites. The composition of CD16a N-glycans varied by glycosylation site and donor. CD16a displayed primarily complex-type biantennary N-glycans at N162, however some individuals expressed CD16a V158 with ∼20% hybrid and oligomannose types which increased affinity for IgG1 Fc according to surface plasmon resonance binding analyses. The CD16a N45-glycans contain markedly less processing than other sites with >75% hybrid and oligomannose forms. N38 and N74 of CD16a both contain highly processed complex-type N-glycans with N-acetyllactosamine repeats and complex-type biantennary N-glycans dominate at N169. The composition of CD16a N-glycans isolated from monocytes included a higher proportion of oligomannose-type N-glycans at N45 and less sialylation plus greater branch fucosylation than we observed in a recent analysis of NK cell CD16a. The additional analysis of CD32a from monocytes revealed different features than observed for CD16a including the presence of a predominantly biantennary complex-type N-glycans with two sialic acids at both sites (N64 and N145).This research was originally published in Molecular and Cellular Proteomics. Roberts, Jacob T., Kashyap R. Patel, and Adam W. Barb. "Site-specific N-glycan analysis of antibody-binding Fc γ receptors from primary human monocytes." Molecular & Cellular Proteomics 2020; 19:362-374. © Roberts et al. doi: 10.1074/mcp.RA119.001733.</p
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