278 research outputs found
Author Correction: A detailed map of Higgs boson interactions by the ATLAS experiment ten years after the discovery
No full textIn the version of this article initially published, the ATLAS Collaboration
author names, affiliations and acknowledgements were omitted and
have now been included in the HTML and PDF versions of the article
Modulation of antigen-specific T-cells as immune therapy for chronic infectious diseases and cancer
No full textCopyright: © 2014 Li, Symonds, Miao, Sanderson and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.This article has been made available through the Brunel Open Access Publishing Fund.T-cell responses are induced by antigen presenting cells (APC) and signals from the microenvironment. Antigen persistence and inflammatory microenvironments in chronic infections and cancer can induce a tolerant state in T-cells resulting in hyporesponsiveness, loss of effector function, and weak biochemical signaling patterns in response to antigen stimulation. Although the mechanisms of T-cell tolerance induced in chronic infection and cancer may differ from those involved in tolerance to self-antigen, the impaired proliferation and production of IL-2 in response to antigen stimulation are hallmarks of all tolerant T cells. In this review, we will summarize the evidence that the immune responses change from non-self to “self”-like in chronic infection and cancer, and will provide an overview of strategies for re-balancing the immune response of antigen-specific T cells in chronic infection and cancer without affecting the homeostasis of the immune system.Arthritis Research UK and Medical Research Council UK
Dufour et al. Source Data.xlsx
No full textDataset used to create every graph of the paper "Phenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes" in Nature Communications
Author list: Caroline Dufour1, Corentin Richard1, Marion Pardons1, Marta Massanella1, Antoine Ackaoui1, Ben Murrell2, Bertrand Routy1, Réjean Thomas3, Jean-Pierre Routy4, Rémi Fromentin1, Nicolas Chomont1
1Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, H2X 0A9, Quebec, Canada
2Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 171 77, Sweden
3Clinique médicale l’Actuel, Montreal, H2L 4P9, Quebec, Canada
4Division of Hematology & Chronic Viral Illness Service, McGill University Heath Centre, Montreal, H4A 3J1, Quebec, Canada</p
The ingenol-based protein kinase C agonist GSK445A is a potent inducer of HIV and SIV RNA transcription
No full textAuthor summaryAntiretroviral therapy (ART) is not a definitive cure HIV infection, in part, because the virus is able to integrate its genetic material in the host cell and remain in a dormant but fully replication-competent form during ART. These latently-infected cells can persist for long periods of time and remain hidden from the host's immune system. If ART is stopped, the virus can reactivate from this pool of infected cells and resume HIV replication and disease progression. As such, finding and eliminating cells with latent HIV infection is priority for HIV cure research. One approach is to use compounds referred to as latency-reversing agents, that can induce HIV reactivation during ART. The goal of this approach is to facilitate elimination of infected cells by the virus itself once it reactivates or by the host's immune system, once virus induction renders the cells detectable by the immune system, while also preventing the virus from infecting new cells due to the continued presence of ART. In this study we report on the activity of a novel latency-reversing agent called GSK445A, a potent activator of the enzyme protein kinase C (PKC). We show that GSK445A can induce HIV and simian immunodeficiency virus (SIV) latency reversal in vitro and has a tolerable saftey profile in nonhuman primates that should permit further testing of this PKC-agonist in strategies to cure HIV.
Activation of the NF-kappa B signaling pathway by Protein Kinase C (PKC) agonists is a potent mechanism for human immunodeficiency virus (HIV) latency disruption in vitro. However, significant toxicity risks and the lack of evidence supporting their activity in vivo have limited further evaluation of PKC agonists as HIV latency-reversing agents (LRA) in cure strategies. Here we evaluated whether GSK445A, a stabilized ingenol-B derivative, can induce HIV/simian immunodeficiency virus (SIV) transcription and virus production in vitro and demonstrate pharmacological activity in nonhuman primates (NHP). CD4(+) T cells from people living with HIV and from SIV+ rhesus macaques (RM) on antiretroviral therapy (ART) exposed in vitro to 25 nM of GSK445A produced cell-associated viral transcripts as well as viral particles at levels similar to those induced by PMA/Ionomycin, indicating that GSK445A can potently reverse HIV/SIV latency. Importantly, these concentrations of GSK445A did not impair the proliferation or survival of HIV-specific CD8(+) T cells, but instead, increased their numbers and enhanced IFN-gamma production in response to HIV peptides. In vivo, GSK445A tolerability was established in SIV-naive RM at 15 mu g/kg although tolerability was reduced in SIV-infected RM on ART. Increases in plasma viremia following GSK445A administration were suggestive of increased SIV transcription in vivo. Collectively, these results indicate that GSK445A is a potent HIV/SIV LRA in vitro and has a tolerable safety profile amenable for further evaluation in vivo in NHP models of HIV cure/remission
Development of a polychromatic flow cytometry panel for the evaluation of HIV-specific T cell responses
No full textIncludes abstract.Includes bibliographical references (leaves 99-115).Investigating T cell responses in HIV infection has revealed several correlates of viral control, but their importance is not fully understood. Further studies to understand the relationship between HIV and the immune system are warranted. The advent of polychromatic flow cytometry has allowed for in depth analysis of T cell functions and phenotypes in HIV infection, including the measurement of T cells that can produce multiple immune molecules simultaneously. The aim of this study was to develop a polychromatic flow cytometry panel to measure multiple functional markers, and optimise a stimulation and staining protocol for use in the laboratory
The production and characterisation of inorganic combinatorial libraries
No full textWith the increasing demand for research into new materials, techniques which are able to produce and characterise a large number of samples rapidly are becoming indispensable. Thin film technology has the potential to improve the amount of information contained on deposited samples by creating compositionally graded libraries. Conventionally, raster scan methods are used to interrogate such libraries. The production of combinatorial samples by methods not previously employed in this role has been carried out. Both solution based electrochemical deposition and electrostatic spray vaporisation production methods have been successfully modified to produce thin film continuous compositional spread (CCS) samples. Additional samples have been produced by off-axis direct current magnetron sputtering, a method already established in the combinatorial field. Presented here is a different approach to provide high-throughput data collection and analysis of combinatorial libraries using an X-ray diffraction (XRD) probe. An extended X-ray beam was used to illuminate the polycrystalline libraries and a large area detector used to collect the data. A new partitioning algorithm has been employed to analyze the collected data and extract the crystallographic information from the illuminated area. The results of the technique have been compared with the raster scans showing that the algorithm provides reliable data equivalent to multiple point data collections with significantly increased data acquisition speed. With the new chemical libraries and other simplified samples the partitioning method has been shown to be appropriate for the analysis of both distinct composition high density chemical libraries and also CCS samples. To achieve the validation of the new method the new libraries have been illumination with the extended beam X-ray source. The resultant superimposed diffraction patterns are partitioned with the novel software and compared with conventional XRD. The resolution of the partitioning method has been shown to be in the 1 mm range when applied to CCS libraries and 1.5 mm for high density chemical libraries. For randomly orientated polycrystalline samples the d-spacing change between the partitioned data and the corresponding raster scanned data is not statistically significant. This corresponds to d-spacing determination with a precession of < 0.01 Å when used with the Bruker D8 diffractometer and our geometry
Charged-particle distributions at low transverse momentum in =13 TeV pp interactions measured with the ATLAS detector at the LHC
No full textSee paper for full list of authors - 15 pages plus author list + cover pages (32 pages total), 5 figures, 2 tables, submitted to EPJC, All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2015-17/International audienceMeasurements of distributions of charged particles produced in proton--proton collisions with a centre-of-mass energy of 13 TeV are presented. The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 170 b. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators
Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
No full textPlasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the “Interferon paradox” previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity. © The Author(s) 2024
Author Correction: A detailed map of Higgs boson interactions by the ATLAS experiment ten years after the discovery
No full textMeasurements of top-quark pair differential cross-sections in the channel in collisions at TeV using the ATLAS detector
No full textSee paper for full list of authors - 43 pages in total, author list starting page 26, 5 figures, 5 tables, submitted to EPJC, all figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/TOPQ-2016-04/International audienceThis article presents measurements of differential cross-sections in a fiducial phase-space region, using an integrated luminosity of 3.2 fb of proton--proton data at a centre-of-mass energy of TeV recorded by the ATLAS experiment at the LHC in 2015. Differential cross-sections are measured as a function of the transverse momentum and absolute rapidity of the top quark, and of the transverse momentum, absolute rapidity and invariant mass of the system. The events are selected by requiring one electron and one muon of opposite electric charge, and at least two jets, one of which must be tagged as containing a -hadron. The measured differential cross-sections are compared to predictions of next-to-leading order generators matched to parton showers and the measurements are found to be consistent with all models within the experimental uncertainties with the exception of the POWHEG-Box + HERWIG++ predictions, which differ significantly from the data in both the transverse momentum of the top quark and the mass of the system
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