1. Diapause, seasonal physiological dormancy, is the primary life history strategy used by insect species inhabiting temperate climates for seasonal synchronisation. Biotic signals for diapause induction originating from host plants may provide dependable cues for insects expanding from subtropical regions.2. We investigated the effect of plant-mediated photoperiod cues on diapause initiation within the Colorado potato beetle, Leptinotarsa decemlineata Say. The effect of photoperiod changes on potato leaf composition and its subsequent correlation with diapause initiation was tested.3. Analyses revealed a significant effect of short-day (LD 8 : 16 h and LD 10 : 14 h) photoperiod growth regimens on both nitrogen content in potato leaves and diapause initiation within L. decemlineata.4. Potato plants grown under short day conditions displayed significantly higher levels of leaf nitrogen compared with long-day treated plants. Over 65% of beetles feeding upon short-day treated plants initiated diapause compared with < 20% of beetles placed upon long-day treated plants.5. The observation of seasonality-induced diapause signals by host plants signifies an important addition to the current array of plant-insect interactions. The present results suggest that seasonal synchrony may be the result of a more integrated system whereby host plant photoperiodism acts as an intermediate or supplementary physiological cue for diapause initiation.
Serine/Threonine Kinase 11 (STK11) encodes an important tumor suppressor that is frequently mutated in lung adenocarcinoma. Clinical studies have shown that mutations in STK11 resulting in loss of function correlate with resistance to anti-PD-1 monoclonal antibody therapy in KRAS-driven non-small cell lung cancer (NSCLC), but the molecular mechanisms responsible remain unclear. Despite this uncertainty, STK11 functional status is emerging as a reliable biomarker for predicting non-response to anti-PD-1 therapy in NSCLC patients. The clinical utility of this biomarker ultimately depends upon accurate classification of STK11 variants. For nonsense variants occurring early in the STK11 coding region, this assessment is straightforward. However, rigorously demonstrating the functional impact of missense variants remains an unmet challenge. Here we present data characterizing four STK11 splice-site variants by analyzing tumor mRNA, and 28 STK11 missense variants using an in vitro kinase assay combined with a cell-based p53-dependent luciferase reporter assay. The variants we report were identified in primary human NSCLC biopsies in collaboration with the University of Vermont Genomic Medicine group. Additionally, we compare our experimental results with data from 22 in silico predictive algorithms. Our work highlights the power, utility and necessity of functional variant assessment and will aid STK11 variant curation, provide a platform to assess novel STK11 variants and help guide anti-PD-1 therapy utilization in KRAS-driven NSCLCs.
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