Biology subjects

Stevenson, C.

Publications and source records attributed to Stevenson, C..

3 recordsLinked to original sources

bioRxiv2018

Molecular Subtyping reveals Immune Alterations associated with Progression of Bronchial Premalignant Lesions

Bronchial premalignant lesions (PMLs) are precursors of lung squamous cell carcinoma, but have variable outcome, and we lack tools to identify and treat PMLs at highest risk for progression to invasive cancer. Profiling endobronchial biopsies of PMLs obtained from high-risk smokers by RNA-Seq identified four PML subtypes with differences in epithelial and immune processes. One molecular subtype (Proliferative) is enriched with dysplastic lesions and exhibits up-regulation of metabolic and cell cycle pathways and down-regulation of ciliary processes. RNA-Seq profiles from normal-appearing uninvolved large airway brushings could identify subjects with Proliferative lesions with high specificity. Expression of interferon signaling and antigen processing/presentation pathways are decreased in progressive/persistent Proliferative lesions and immunofluorescence indicates a depletion of innate and adaptive immune cells in these lesions. Molecular biomarkers measured in PMLs or the uninvolved airway can enhance histopathological grading and suggests that immunoprevention strategies may be effective in intercepting the progression of PMLs to lung cancer.

cancer biology↗

bioRxiv2018

Uncoupled activation and cyclisation in catmint reductive terpenoid biosynthesis

Terpene synthases typically form complex molecular scaffolds by concerted activation and cyclization of linear starting materials in a single enzyme active site. Here we show that iridoid synthase, an atypical reductive terpene synthase, catalyses the activation of its substrate 8-oxogeranial into a reactive enol intermediate but does not catalyse the subsequent cyclisation into nepetalactol. This discovery led us to identify a class of nepetalactol-related short-chain dehydrogenase enzymes (NEPS) from catmint (Nepeta mussinii) which catalyse the stereoselective cyclisation of the enol intermediate into nepetalactol isomers. Subsequent oxidation of nepetalactols by NEPS1 provides nepetalactones, metabolites that are well known for both insect-repellent activity and euphoric effect in cats. Structural characterisation of the NEPS3 cyclase reveals it binds to NAD+ yet does not utilise it chemically for a non-oxidoreductive formal [4+2] cyclisation. These discoveries will complement metabolic reconstructions of iridoid and monoterpene indole alkaloid biosynthesis.

biochemistry↗

bioRxiv2017

Learning And Recognition Of Tactile Temporal Sequences By Mice And Humans

The world around us is replete with stimuli that unfold over time. When we hear an auditory stream like music or speech or scan a texture with our fingertip, physical features in the stimulus are concatenated in a particular order, and this temporal patterning is critical to interpreting the stimulus. To explore the capacity of mice and humans to learn tactile sequences, we developed a task in which subjects had to recognise a continuous modulated noise sequence delivered to whiskers or fingertips, defined by its temporal patterning over hundreds of milliseconds. GO and NO-GO sequences differed only in that the order of their constituent noise modulation segments was temporally scrambled. Both mice and humans efficiently performed tactile sequence learning. Mouse performance relied mainly on detecting relative changes in noise amplitude over time, whereas humans appeared to have access to more cues, including the duration of noise modulation segments.

neuroscience↗