Publications by authors named "G Menzies"

Motivation: Benzo[]pyrene, a notorious DNA-damaging carcinogen, belongs to the family of polycyclic aromatic hydrocarbons commonly found in tobacco smoke. Surprisingly, nucleotide excision repair (NER) machinery exhibits inefficiency in recognizing specific bulky DNA adducts including Benzo[]pyrene Diol-Epoxide (BPDE), a Benzo[]pyrene metabolite. While sequence context is emerging as the leading factor linking the inadequate NER response to BPDE adducts, the precise structural attributes governing these disparities remain inadequately understood.

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The contraction of CAG/CTG repeats is an attractive approach to correct the mutation that causes at least 15 neuromuscular and neurodegenerative diseases, including Huntington's disease and Myotonic Dystrophy type 1. Contractions can be achieved in vivo using the Cas9 D10A nickase from Streptococcus pyogenes (SpCas9) using a single guide RNA (sgRNA) against the repeat tract. One hurdle on the path to the clinic is that SpCas9 is too large to be packaged together with its sgRNA into a single adeno-associated virus.

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Background: Genome-wide association studies demonstrate that Alzheimer's disease (AD) has a highly polygenic architecture, where thousands of independent genetic variants explain risk with high classification accuracy. This AD polygenic risk score (AD-PRS) has been previously linked to preclinical cognitive and neuroimaging features observed in asymptomatic individuals. However, shared variance between AD-PRS and neurocognitive features are small, suggesting limited preclinical utility.

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Low molecular weight alginate oligosaccharides have been shown to exhibit anti-microbial activity against a range of multi-drug resistant bacteria, including . Previous studies suggested that the disruption of calcium (Ca)-DNA binding within bacterial biofilms and dysregulation of quorum sensing (QS) were key factors in these observed effects. To further investigate the contribution of Ca binding, G-block (OligoG) and M-block alginate oligosaccharides (OligoM) with comparable average size DPn 19 but contrasting Ca binding properties were prepared.

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The RNA-dependent RNA polymerase of the severe acute respiratory syndrome coronavirus 2 virus is error prone, with errors being corrected by the exonuclease (NSP14) proofreading mechanism. However, the mutagenesis and subsequent evolutionary trajectory of the virus is mediated by the delicate interplay of replicase fidelity and environmental pressures. Here, we have shown that a single, distal mutation (F60S) in NSP14 can have a profound impact upon proofreading with an increased accumulation of mutations and elevated evolutionary rate being observed.

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