Biology subjects

Wilkinson, J.

Publications and source records attributed to Wilkinson, J..

5 recordsLinked to original sources

bioRxiv2026

Winter warming shapes gut microbiome composition and directional dysbiosis in a temperate lizard

Environmental temperature shapes ectotherm gut microbiomes through direct effects on community structure and indirect effects mediated by host physiology. Due to climate change, winter temperatures are rising, in some regions faster than summer temperatures. However, warming effects on the microbiome during overwintering remain poorly understood compared to the active season, limiting predictions of host-microbiome responses across the annual cycle. We experimentally tested how winter warming influences gut microbiome diversity and composition in the common wall lizard (Podarcis muralis). Thirty-nine lizards were overwintered under cold (4{+/-}1{degrees}C), mild (8{+/-}1{degrees}C), or fluctuating (5 days cold, 2 days mild) temperatures, and 80 faecal samples were collected post-emergence for 16S rRNA gene sequencing. Winter warming did not alter alpha diversity but induced consistent shifts in community composition relative to the cold treatment, with distinct responses to constant versus fluctuating warming. Constant mild temperatures enriched fewer taxa, including putatively opportunistic or pathogenic genera, potentially signalling microbiome imbalance. In contrast, fluctuating warming and the baseline cold treatment preserved a broader suite of fermentative bacteria, likely supporting more stable gut homeostasis. Both warming treatments increased directional dysbiosis relative to the cold treatment, though without increasing interindividual variability, indicating structured reassembly rather than stochastic change. Our findings suggest that winter warming can subtly negatively affect gut microbiomes and host health, while fluctuating temperatures may buffer negative effects. We show that overwintering is an important, yet overlooked, period through which climate warming can shape host-microbiome dynamics.

ecology↗

bioRxiv2020

Site wind right: Identifying low-impact wind development areas in the Central United States

To help avoid the most catastrophic effects of climate change, society needs to achieve net-zero greenhouse gas emissions by mid-century. Wind energy provides a clean, renewable source of electricity; however, improperly sited wind facilities pose known threats to wildlife populations and contribute to degradation of natural habitats. To support a rapid transition to low-carbon energy while protecting imperiled species, we identified potential low-impact areas for wind development in a 17-state region of the central U.S. By combining maps of sensitive habitats and species with wind speed and land use information, we demonstrate that there is significant potential to develop wind energy in the Great Plains while avoiding significant negative impacts to wildlife. These low-impact areas have the potential to yield approximately 1,099-1,832 GW of wind capacity. This is equivalent to 10-18 times current U.S. installed wind capacity. Our analysis demonstrates that ambitious low-carbon energy goals are achievable on sites with minimal risk of wildlife conflict.

ecology↗

bioRxiv2019

JARID2 facilitates transcriptional reprogramming in glioblastoma in response to standard treatment

BackgroundGlioblastoma (GBM) is a fatal and incurable brain cancer with a dismal prognosis. In order to impact on this disease, we need to understand how infiltrating, non resectable tumour cells resist chemoradiation and facilitate disease recurrence. To this end, we generated or acquired bulk tumour RNA sequencing data from 45 paired primary and locally recurrent GBM tumours (split into original and validation cohorts) from patients that received standard treatment. We also generated DNA methylation profiles for 9 pairs and sequenced RNA from single cells isolated from a patient derived GBM spheroid model at different timepoints following in vitro chemoradiation.\n\nResultsWe have identified a set of genes with Jumonji and AT-Rich Interacting Domain 2 (JARID2) binding sites in their promoters that are universally dysregulated in post-standard treatment recurrent GBMs compared to the primary tumour. The direction of dysregulation is patient-dependent and not associated with differential promoter DNA methylation. Our in vitro experiments suggest that this dysregulation occurs dynamically following treatment as opposed to resulting from selection of cells with specific expression profiles.\n\nConclusionJARID2 is an accessory protein to a chromatin remodeling complex, responsible for histone modifications observed during cell state transitions in both normal brain and GBM. We propose that JARID2 facilitates GBM recurrence following treatment by indirect transcriptional reprogramming of surviving cells in whichever manner is needed to reproduce the phenotypic heterogeneity required for tumour regrowth in vivo. The mechanism of this reprogramming may present a therapeutic vulnerability for more effective treatment of GBM.

cancer biology↗

bioRxiv2019

Lead optimisation of dehydroemetine for repositioned use in malaria

Drug repositioning offers an effective alternative to de novo drug design to tackle the urgent need for novel anti-malarial treatments. The anti-amoebic compound, emetine dihydrochloride, has been identified as a potent in-vitro inhibitor of the multi-drug resistant strain K1 of Plasmodium falciparum (IC50: 47 nM + 2.1 nM). 2,3-dehydroemetine, a synthetic analogue of emetine dihydrochloride has been claimed to have less cardiotoxic effects than emetine. The structures of two diastereoisomers of 2,3-dehydroemetine were modelled on the reported emetine binding site on cryo-EM structure 3J7A and it was found that (-)-R,S-dehydroemetine mimicked the bound pose of emetine more closely than (-)-S,S-dehydroisoemetine. (-)-R,S-dehydroemetine was also found to be highly potent against the multi-drug resistant K1 strain of P. falciparum in comparison with (-)-S,S-dehydroisoemetine, which loses its potency due to the change of configuration at C-1. In addition to its effect on the asexual erythrocytic stages of P. falciparum, the compounds exhibited gametocidal properties with no cross-resistance against any of the multi-drug resistant strains tested. Drug interaction studies showed (-)-R,S-dehydroemetine to have synergistic antimalarial activity with atovaquone and proguanil. Emetine dihydrochloride, and (-)-R,S-dehydroemetine failed to show any inhibition of the hERG potassium channel and displayed atovoquone-like activity on the mitochondrial membrane potential.

microbiology↗

bioRxiv2017

Analysis of multistage in vitro fertilization data with mixed multilevel outcomes using joint modelling approaches

In vitro fertilization comprises a sequence of interventions concerned with the creation and culture of embryos which are then transferred to the patients uterus. While the clinically important endpoint is birth, the responses to each stage of treatment contain additional information about the reasons for success or failure. Joint analysis of the sequential responses is complicated by mixed outcome types defined at two levels (patient and embryo). We develop three methods for multistage analysis based on joining submodels for the different responses using latent variables and entering outcome variables as covariates for downstream responses. An application to routinely collected data is presented, and the strengths and limitations of each method are discussed.

epidemiology↗