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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Short tandem repeats (STRs) and variable number tandem repeats (VNTRs) are among the most mutable regions of our genome but are frequently underascertained in studies of disease and evolution. Using long-read sequence data from apes and humans, we present a sequence-based evolutionary framework for ∼20,000 phased STRs and VNTRs. We identify 1,584 tandem repeats that are specifically expanded in human…
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Immune Predictors of Mortality Following RNA Virus Infection

The authors used a screen of genetically diverse mice infected with RNA viruses in combination with comprehensive pre-infection immunophenotyping to identify baseline immune correlates of protection from mortality to virus infection. They defined distinct T-cell correlates associated with survival following viral challenge. This study underscores the need for a protective immune response to be balanced in order to protect the host not only from uncontrolled virus replication but also from disease associated with robust immunity.
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