KRAB zinc finger protein diversification drives mammalian interindividual methylation variability [Genetics]

Most transposable elements (TEs) in the mouse genome are heavily modified by DNA methylation and repressive histone modifications. However, a subset of TEs exhibit variable methylation levels in genetically identical individuals, and this is associated with epigenetically conferred phenotypic differences, environmental adaptability, and transgenerational...

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Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion [Microbiology]

Cholesterol 25-hydroxylase (CH25H) is an interferon (IFN)-stimulated gene that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an IFN-stimulated gene screen against vesicular stomatitis virus (VSV)-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol...

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Tolerogenic nanoparticles suppress central nervous system inflammation [Immunology and Inflammation]

Therapeutic approaches for the induction of immune tolerance remain an unmet clinical need for the treatment of autoimmune diseases, including multiple sclerosis (MS). Based on its role in the control of the immune response, the ligand-activated transcription factor aryl hydrocarbon receptor (AhR) is a candidate target for novel immunotherapies. Here,...

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HLA polymorphism and tapasin independence influence outcomes of HIV and dengue virus infection [Commentaries]

Processing and presentation of self-antigens and foreign antigens and their loading into class I and class II molecules of the major histocompatibility complex (MHC) constitute a major feature of the cellular immune response and induce CD8 and CD4 T cell immune responses (1, 2), respectively. The MHC complex, in human,...

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A complete rule set for designing symmetry combination materials from protein molecules [Biophysics and Computational Biology]

Diverse efforts in protein engineering are beginning to produce novel kinds of symmetric self-assembling architectures, from protein cages to extended two-dimensional (2D) and three-dimensional (3D) crystalline arrays. Partial theoretical frameworks for creating symmetric protein materials have been introduced, but no complete system has been articulated....

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Autologous IgG antibodies block outgrowth of a substantial but variable fraction of viruses in the latent reservoir for HIV-1 [Microbiology]

In untreated HIV-1 infection, rapid viral evolution allows escape from immune responses. Viral replication can be blocked by antiretroviral therapy. However, HIV-1 persists in a latent reservoir in resting CD4+ T cells, and rebound viremia occurs following treatment interruption. The reservoir, which is maintained in part by clonal expansion, can...

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An engineered 4-1BBL fusion protein with “activity on demand” [Applied Biological Sciences]

Engineered cytokines are gaining importance in cancer therapy, but these products are often limited by toxicity, especially at early time points after intravenous administration. 4-1BB is a member of the tumor necrosis factor receptor superfamily, which has been considered as a target for therapeutic strategies with agonistic antibodies or using...

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Did volcano eruptions alter the trajectories of the Roman Republic and the Ptolemaic Kingdom? Moving beyond black-box determinism [Letters (Online Only)]

McConnell et al. (1) suggest that the eruption of Alaska’s Okmok volcano in 43 BCE strongly affected historical events in the late Roman Republic and the Ptolemaic Kingdom. This interpretation is problematic, first because classical sources can plausibly be interpreted in completely different ways. The handling of natural disasters and...

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Reply to Strunz and Braeckel: Agricultural failures logically link historical events to extreme climate following the 43 BCE Okmok eruption [Letters (Online Only)]

We report (1) ice core evidence that unambiguously identifies massive sulfur fallout over much of the Arctic, attributed using tephra geochemistry to eruption of Alaska’s Okmok volcano, with climate model simulations indicating 2 y of extreme temperatures and precipitation throughout the Northern Hemisphere starting in early 43 BCE. This climate...

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Neuroticism may reflect emotional variability when correcting for the confound with the mean [Letters (Online Only)]

Kalokerinos et al. (1) demonstrate that emotional variability, as assessed via the SD, is not significantly associated with neuroticism once the confound with mean negative emotion is controlled for, r = 0.05. To control for this confound, the authors use the relative SD (RSD), which mathematically corrects for the nonlinear...

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