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Biology subjects

Page, J. L.

Publications and source records attributed to Page, J. L..

4 recordsLinked to original sources

Dispersal Behaviour and Movement Patterns of Pheasants from Woodland Release Pens.

The large-scale release of ring-necked pheasants, Phasianus colchicus, for recreational shooting in the UK raises concerns about ecological impacts, particularly on sensitive ecological sites. Current assumptions suggest dispersal is typically <500m from release pens, yet empirical evidence is limited. This study tracked 110 GPS-tagged pheasants from 11 woodland release pens across nine shooting estates, monitoring movements through pre-shooting, shooting and post-shooting phases. Most birds (73%) travelled a maximum distance beyond 500m during at least one of the three phases, with mean maximum distances of 863m, 1,493m and 1,307m per phase. During at least one phase, 26% of the 110 tagged birds spent most of their time (>50%) beyond 500m and 16% beyond 1,000m from their release pens. Early post-release movements were concentrated near pens, but ranging behaviour expanded during subsequent phases, with the percentages of birds spending >50% of their time beyond 500m and 1,000m, respectively: pre-shooting 6%, 2%; shooting 24%, 16%; post-shooting 13%, 9%. Accounting for mortality, the percentages of surviving birds spending >50% of their time beyond 500m and 1,000m increased: pre-shooting (n=110) 6%, 2%; shooting (n=71) 37%, 25%; post-shooting (n=27) 52%, 37%. Dispersal was greater with earlier release dates, higher pen and estate stocking densities and lower vegetative habitat quality in pens. Movements were directional rather than uniform, with most cohorts concentrating activity within a limited directional arc specific to the release site. Conservation site incursions occurred in 28 (25%) tagged birds, particularly where pens were closest to site boundaries; although 10 (36%) tagged birds encroached on conservation sites 872-2,319m from their release pen. These findings show that dispersal of released pheasants is further, more directed, and persistent than currently assumed.

ecology↗

DFFB suppresses interferon to enable cancer persister cell regrowth

Oncogene targeted cancer therapies can provide deep responses but frequently suffer from acquired resistance.1 Therapeutic approaches to treat tumours which have acquired drug resistance are complicated by continual tumour evolution and multiple co-occurring resistance mechanisms.2,3 Rather than treating resistance after it emerges, it may possible to prevent it by inhibiting the adaptive processes which initiate resistance but these are poorly understood.4 Here we report that residual cancer persister cells that survive oncogene targeted therapy are growth arrested by drug stress-induced intrinsic Type I interferon (IFN) signaling. To escape growth arrest, persister cells leverage apoptotic machinery to transcriptionally suppress interferon-stimulated genes (ISGs). Mechanistically, persister cells sublethally engage apoptotic caspases to activate DNA endonuclease DNA Fragmentation Factor B (DFFB, also known as Caspase-Activated DNase (CAD)) which induces DNA damage, mutagenesis, and stress response factor Activating Transcription Factor 3 (ATF3). ATF3 limits Activator Protein-1 (AP1)-mediated ISG expression sufficiently to allow persister cell regrowth. Persister cells deficient in DFFB or ATF3 exhibit high ISG expression and are consequently unable to regrow. Therefore, sublethal apoptotic stress paradoxically promotes regrowth of residual cancer cells that survive drug treatment.

cancer biology↗

Lineage Recording Reveals the Phylodynamics, Plasticity and Paths of Tumor Evolution

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth, expansion to neighboring and distal tissues, and therapeutic resistance. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma which enabled us to track tumor evolution from single transformed cells to metastatic tumors at unprecedented resolution. We found that loss of the initial, stable alveolar-type2-like state was accompanied by transient increase in plasticity. This was followed by adoption of distinct fitness-associated transcriptional programs which enable rapid expansion and ultimately clonal sweep of rare, stable subclones capable of metastasizing to distant sites. Finally, we showed that tumors develop through stereotypical evolutionary trajectories, and perturbing additional tumor suppressors accelerates tumor progression by creating novel evolutionary paths. Overall, our study elucidates the hierarchical nature of tumor evolution, and more broadly enables the in-depth study of tumor progression.

cancer biology↗

NMR chemical shift assignments of RNA oligonucleotides to expand the RNA chemical shift database

RNAs play myriad functional and regulatory roles in the cell. Despite their significance, three-dimensional structure elucidation of RNA molecules lags significantly behind that of proteins. NMR-based studies are often rate-limited by the assignment of chemical shifts. Automation of the chemical shift assignment process can greatly facilitate structural studies, however, accurate chemical shift predictions rely on a robust and complete chemical shift database for training. We searched the Biological Magnetic Resonance Data Bank (BMRB) to identify sequences that had no (or limited) chemical shift information. Here, we report the chemical shift assignments for 12 RNA hairpins designed specifically to help populate the BMRB.

biophysics↗