Biology subjects

Bradley, H.

Publications and source records attributed to Bradley, H..

3 recordsLinked to original sources

bioRxiv2025

Caudata macrogenetics: Species range size predicts intraspecific genetic variation in global salamanders

AimGenetic diversity contains valuable information about ecological and evolutionary aspects of species. Intraspecific genetic variation is shaped by species natural history traits and by characteristics of geography and climate within their ranges. Amphibians are of ecological and conservation interest because of their global distribution, deep history, trait diversity, and roles within ecological communities. Here, we studied genetic variation within salamanders to investigate predictors of nucleotide diversity and spatial patterns of genetic differentiation. LocationGlobal. Time PeriodPresent. Major Taxa StudiedSalamanders. MethodsWe repurposed mitochondrial DNA sequences and ecological data from open-access databases for 220 salamander species. We calculated nucleotide diversity ({pi}) and tested for isolation by distance (IBD) and isolation by environment (IBE). We analyzed these three variables with random forest and phylogenetic comparative methods using 28 predictors expected to be associated with genetic variation. ResultsWe recovered 8,108 Cytb sequences with their associated geographic coordinates, of which 7,007 sequences were manually curated by us. Range size, lineage age, and sample size were important predictors of genetic variation. We found higher diversity in regions including the Neotropics and central-eastern Europe. The absence of phylogenetic signal in {pi}, IBD, and IBE suggests that genetic variation is shaped by local ecological and geographical factors rather than by shared ancestry. Main ConclusionsOur finding of range size as an important predictor aligns with theoretical expectations that species with larger ranges tend to harbor more genetic diversity. Furthermore, lineage age being an important predictor is in line with the clade-age hypothesis, in which species with longer divergence times have higher genetic diversity because they have had more time to accumulate genetic variation. Our results underscore the importance of integrating spatial data into macrogenetic studies, providing valuable information for future studies and conservation strategies targeting regions with high or low genetic diversity.

evolutionary biology↗

bioRxiv2024

Single cell variation and rapid emergence of phenotypic heterogeneity in cell lines- a cautionary tale for devotees of CRISPR-Cas9.

The use and publication of research utilising CRISPR/cas9 in gene editing and knock outs (KOs) within cell lines is now widespread and has proved extremely powerful in the interrogation of gene function. However, the potential of experimental artefacts resulting from the need to generate single cell clones post gene-manipulation has been somewhat overlooked. In this study, we show that the commonly used pulmonary cell line A549 displays significant heterogeneity in terms of their gene expression, and that individual cells from a population exhibit dramatically different susceptibility to viral infection from a range of viruses including respiratory syncytial virus (RSV), influenza A virus (IAV), Hazara virus (HAZV), lymphocytic choriomeningitis virus (LCMV) and Bunyamwera virus (BUNV). Moreover, we demonstrate the rapid re-emergence of phenotypic heterogeneity even after cloning. These results demonstrate the need for caution in interpreting results from CRISPR screens and CRISPR-KO validation studies, especially in the study of viral infection.

microbiology↗

bioRxiv2019

Lipid metabolism links nutrient-exercise timing to insulin sensitivity in men classified as overweight or obese.

ContextPre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. We hypothesised that in men with overweight/obesity, acute exercise before versus after nutrient ingestion would increase whole-body and intramuscular lipid utilization, translating into greater increases in oral glucose insulin sensitivity over 6-weeks of training.\n\nDesign and ParticipantsWe showed in men with overweight/obesity (mean{+/-}SD for BMI: 30.2{+/-}3.5 kgxm-2 for acute, crossover study, 30.9{+/-}4.5 kgxm-2 for randomized, controlled, training study) a single exercise bout before versus after nutrient provision increased lipid utilisation at the whole-body level, but also in both type I (p<0.01) and type II muscle fibres (p=0.02). We then used a 6-week training intervention to show sustained, 2-fold increases in lipid utilisation with exercise before versus after nutrient provision (p<0.01).\n\nMain Outcome MeasuresPostprandial glycemia was not differentially affected by exercise training before vs after nutrient provision (p>0.05), yet plasma was reduced with exercise training before, but not after nutrient provision (p=0.03), resulting in increased oral glucose insulin sensitivity when training was performed before versus after nutrient provision (25{+/-}38 vs -21{+/-}32 mLxmin-1xm-2; p=0.01) and this was associated with increased lipid utilisation during exercise (r=0.50, p=0.02). Regular exercise prior to nutrient provision augmented remodelling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (p<0.05).\n\nConclusionsExperiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (i.e., in the fasted state) may exert beneficial effects on lipid utilisation and reduce postprandial insulinemia.\n\nPrecisExercise in the fasted-versus fed-state increased intramuscular and whole-body lipid use, translating into increased muscle adaptation and insulin sensitivity when regularly performed over 6 weeks.

physiology↗