Biology subjects

Nicoll, M.

Publications and source records attributed to Nicoll, M..

2 recordsLinked to original sources

bioRxiv2026

Inbreeding depression and population viability in a recovering population of Mauritius kestrels

Inbreeding depression (the reduction in fitness associated with inbreeding) has been demonstrated in a wide range of animals, but despite its ubiquity, is not an inevitable consequence of inbreeding. As a result, there is uncertainty about the extent to which inbreeding depression poses an ongoing risk to endangered species currently experiencing significant demographic recovery. Quantifying inbreeding depression will be critical if we want to understand these risks. A comprehensive quantification of the fitness costs of inbreeding requires detailed individual-based longitudinal data so lifetime impacts can be assessed. Here, we use an extraordinarily detailed long-term dataset on Mauritius kestrels (Falco punctatus) to explore inbreeding depression in a population currently experiencing significant demographic recovery. To do so, we constructed a social pedigree of 1,758 individuals and combined this with 1,240 nest records and 1,411 individual resighting histories to explore lifetime fitness effects over a 30-year period. Inbreeding increased significantly over time as the population recovered before stabilising. Inbred eggs were less likely to survive to fledging. Inbred adult male and female birds had significantly lower annual reproductive success than outbred individuals because of a lower annual egg-to-fledgling survival probability. This resulted in significantly lower lifetime reproductive success in inbred females but not males, which showed a negative trend. Population growth was negative and extinction risk increased slightly at current levels of inbreeding. These impacts will become more severe should inbreeding levels increase in the future, which is highly likely given ongoing genomic erosion. Taken together, our results demonstrate significant fitness costs associated with inbreeding in Mauritius kestrels, which pose an ongoing risk to population viability. This suggests that monitoring and managing inbreeding risks in endangered species will likely be required even in populations that are showing significant demographic recovery in response to conservation interventions.

ecology↗

bioRxiv2022

Global Profiling of c-Jun and JunB transcription factor binding sites in an ALK+ ALCL cell line

Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is a T cell lymphoma which features translocations or inversion involving the ALK tyrosine kinase gene, and results in oncogenic fusion proteins (e.g. NPM-ALK). The elevated expression and/or activation of activator protein-1 (AP-1) transcription factors, c-Jun and JunB, is another molecular feature of ALK+ ALCL. c-Jun/JunB transcriptional targets are important in the pathobiology of this lymphoma, and several are also therapeutic targets. To better understand c-Jun/JunB function in ALK+ ALCL, we performed chromatin immunoprecipitation-sequencing experiments in the Karpas 299 ALK+ ALCL cell line to comprehensively identify sites bound by these transcription factors. We identified 13,083 c-Jun and 40,369 JunB binding sites, and [~]60% of sites bound by c-Jun were shared with JunB. Many sites were associated with genes known or predicted to be important in the pathogenesis of ALK+ ALCL. Pathway enrichment analysis of genes associated with both c-Jun and JunB binding sites revealed a significant over-representation for pathways associated with cancer and cell signalling. Furthermore, we identified several c-Jun and JunB binding sites associated with the NIBAN2/FAM129B gene. FAM129B is a PH domain-containing phosphoprotein that promotes proliferation in multiple cell types. However, while we found that FAM129B knock-down resulted in modest cell cycle alteration in most ALK+ ALCL cell lines, this did not appear to result in a significant proliferation defect. Finally, we found that inhibition of NPM-ALK and MEK/Erk signalling altered FAM129B electrophoretic mobility and decreased phosphorylation of FAM129B on serine residues known to be Erk phosphosites. In summary, this study is the first to globally profile sites bound by c-Jun/JunB in ALK+ ALCL. It reveals novel putative targets for these transcription factors in ALK+ ALCL, and identifies FAM129B as a novel phosphoprotein downstream of NPM-ALK signalling.

cancer biology↗