Publications by authors named "Christopher Monit"

Background: The NF-κB family of transcription factors and associated signalling pathways are abundant and ubiquitous in human immune responses. Activation of NF-κB transcription factors by viral pathogen-associated molecular patterns, such as viral RNA and DNA, is fundamental to anti-viral innate immune defences and pro-inflammatory cytokine production that steers adaptive immune responses. Diverse non-viral stimuli, such as lipopolysaccharide and cytokines, also activate NF-κB and the same anti-pathogen gene networks.

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The control of re-occurring pandemic pathogens requires understanding the origins of new pandemic variants and the factors that drive their global spread. This is especially important for GII.4 norovirus, where vaccines under development offer promise to prevent hundreds of millions of annual gastroenteritis cases.

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The type one interferon induced restriction factor Myxovirus resistance B (MxB) restricts HIV-1 nuclear entry evidenced by inhibition of 2-LTR but not linear forms of viral DNA. The HIV-1 capsid is the key determinant of MxB sensitivity and cofactor binding defective HIV-1 capsid mutants P90A (defective for cyclophilin A and Nup358 recruitment) and N74D (defective for CPSF6 recruitment) have reduced dependency on nuclear transport associated cofactors, altered integration targeting preferences and are not restricted by MxB expression. This has suggested that nuclear import mechanism may determine MxB sensitivity.

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Background: Studying site-specific amino acid frequencies by eye can reveal biologically significant variability and lineage-specific adaptation. This so-called 'sequence gazing' often informs bioinformatics and experimental research. But it is important to also account for the underlying phylogeny, since similarities may be due to common descent rather than selection pressure, and because it is important to distinguish between founder effects and convergent evolution.

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The vertebrate protein SAMHD1 is highly unusual in having roles in cellular metabolic regulation, antiviral restriction, and regulation of innate immunity. Its deoxynucleoside triphosphohydrolase activity regulates cellular dNTP concentration, reducing levels below those required by lentiviruses and other viruses to replicate. To counter this threat, some primate lentiviruses encode accessory proteins that bind SAMHD1 and induce its degradation; in turn, positive diversifying selection has been observed in regions bound by these lentiviral proteins, suggesting that primate SAMHD1 has coevolved to evade these countermeasures.

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Article Synopsis
  • A decade after the Berlin patient was reported as the only known case of HIV-1 cure, a new case demonstrates potential for HIV-1 remission through less severe treatment methods.
  • An adult HIV-1 patient successfully underwent allogeneic stem-cell transplantation from a CCR5Δ32/Δ32 donor for Hodgkin's lymphoma and maintained HIV-1 remission for 18 months post-treatment.
  • Current findings indicate that with this less toxic approach, similar outcomes to the Berlin patient may be achievable, although definitive conclusions about a cure remain uncertain.
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Summary: Existing ancestral sequence reconstruction techniques are ill-suited to investigating substitutions on a single branch of interest. We present SubRecon, an implementation of a hybrid technique integrating joint and marginal reconstruction for protein sequence data. SubRecon calculates the joint probability of states at adjacent internal nodes in a phylogeny, i.

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