The authors report on a two-step immunization scheme that leads to the maturation of VRC01-like antibodies capable of accommodating the N276 glycan and displaying autologous tier 2 neutralizing activities. The study provides information that is critical for the upcoming Phase I clinical trial of one of the Stamatatos lab’s HIV vaccine immunogens. The trial will be conducted by the HIV Vaccine Trials Network at Fred Hutch.
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The long-term effects of CD19-targeted chimeric antigen receptor–modified T-cell immunotherapy (CD19-CARTx) for B-cell malignancies on humoral immunity are unclear. We examined antiviral humoral immunity in 39 adults with B-cell malignancies who achieved durable complete remission without additional therapy for >6 months after CD19-CARTx. Despite CD19+ B-cell aplasia in all patients, the incidence of viral infections occurring >90 days post–CD19-CARTx was low…
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We used duplex sequencing to detect low-frequency mutations in the BCL6 super-enhancer locus in normal human B cells. The landscape of preexisting mutations is remarkably conserved across different ethnicities and reveals clustered mutational hotspots that correlate with reported sites of clonal mutations and translocation breakpoints in human B cell lymphomas. This high-resolution genomic landscape revealed by duplex sequencing offers accurate and thorough…
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Robust inflammatory responses are essential to control microbial infections. At the same time, it is critical to resolve inflammation to minimize tissue damage as a consequence of an overactive immune response. The authors identified a host innate immune gene, zinc-finger antiviral protein (ZAP), that plays a dual role in clearing alphavirus infection and controlling interferon-induced inflammation. Through alternative polyadenylation and differential post-translational modification, this gene can be diversified to perform differential functions.
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The authors applied functional genomics and bioinformatics analyses to a model of acute HIV infection. By comparing animals that do get disease to those that do not get disease, they found that protection against disease is linked to programming of a wound-healing innate immune response. This response suppresses inflammation while directing wound healing processes that protect against HIV disease.
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When DUX4 is expressed in the early embryo, there is a significant epigenetic reprogramming that contributes to the establishment of a pluripotent state. The authors have shown that DUX4 induces the expression of the histone variants H3.X and H3.Y. These histones become incorporated into the chromatin of DUX4 induced genes and create a chromatin memory of their activation by DUX4, manifesting in greater perdurance of expression and greater sensitivity to re-activation.
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The pineal gland is one of the key output organs of your biological clock, and is activated during the dark phase of the 24-hour day to make and secrete the hormone of night, melatonin. The authors identified other melatonin-related hormones that the gland was making and their effects on circadian rhythm, as it is called. They also tested whether these molecules could act on the body’s receptors for night hormones.
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Many cytoskeletal proteins perform fundamental biological processes and are evolutionarily ancient. For example, the superfamily of actin-related proteins (Arps) specialized early in eukaryotic evolution for diverse cellular roles in the cytoplasm and the nucleus. Despite its strict conservation across eukaryotes, we find that the Arp superfamily has undergone dramatic lineage-specific diversification in Drosophila. Our phylogenomic analyses reveal four independent Arp gene…
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The sequence and assembly of human genomes using long‐read sequencing technologies has revolutionized our understanding of structural variation and genome organization. We compared the accuracy, continuity, and gene annotation of genome assemblies generated from either high‐fidelity (HiFi) or continuous long‐read (CLR) datasets from the same complete hydatidiform mole human genome. We find that the HiFi sequence data assemble an additional…
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Interleukin-10 (IL-10) is a multi-faceted anti-inflammatory cytokine which plays an essential role in immune tolerance. Indeed, deficiency of IL-10 or its receptor results in aberrant immune responses that lead to immunopathology. Graft-versus-host disease (GVHD) is the limiting complication of allogeneic stem cell transplantation (SCT) and results from an imbalance in pathological versus regulatory immune networks. A number of immune cells…
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