Biology subjects

Bell, D. A.

Publications and source records attributed to Bell, D. A..

3 recordsLinked to original sources

bioRxiv2026

RAPID DECLINE OF NESTING PEREGRINE FALCONS IN THE SAN FRANCISCO BAY REGION OF CALIFORNIA SYNCHRONOUS WITH AN H5N1 OUTBREAK

After rebounding from near extirpation during the organochlorine era, breeding Peregrine Falcons (Falco peregrinus) in California are again facing adversity, this time consistent with an outbreak of a highly pathogenic avian influenza. Following the first detection of the H5N1 variant clade 2.3.4.4b virus in California wild birds in July 2022, we assembled data from long-term monitoring (2000-2025) of peregrine breeding territory occupancy in the broad vicinity of San Francisco Bay to examine possible impacts on falcon populations. Prior to the outbreak, 47 focal breeding territories had shown nearly complete occupancy by pairs (98.5% of 390 site-years), with very few vacancies, single birds in attendance, or subadult pair members. Within 8 mo of the outbreak, occupancy had dropped to 65.1%, and 2 yrs later (2025), only 36.2% of sites remained occupied. An uptick in site-occupancy by single birds also occurred after the outbreak, but it is unclear whether these were survivors or floaters attempting to fill vacant territories where both pair members had perished. The high vacancy rates signaled an impact upon floaters (nonbreeding adults) that normally buffer breeding site-occupancy in healthy peregrine populations. From October 2022 through November 2025, 17 peregrine fatalities were diagnosed with H5N1 within the counties comprising our study area. Evidence that H5N1 caused these territory vacancies includes, (1) the striking temporal coincidence of occupancy loss with the outbreak, and (2) the lethality of the virus to peregrines and its confirmed presence in peregrine prey in our study area. Our study reaffirms the value of long-term territory occupancy monitoring in this sentinel species.

ecology↗

bioRxiv2019

Germline and somatic genetic variants in the p53 pathway interact to affect cancer risk, progression and drug response

Insights into oncogenesis derived from cancer susceptibility loci could facilitate better cancer management and treatment through precision oncology. However, therapeutic applications have thus far been limited by our current lack of understanding regarding both their interactions with somatic cancer driver mutations and their influence on tumorigenesis. Here, by integrating germline datasets relating to cancer susceptibility with tumour data capturing somatically-acquired genetic variation, we provide evidence that single nucleotide polymorphism (SNPs) and somatic mutations in the p53 tumor suppressor pathway can interact to influence cancer development, progression and treatment response. We go on to provide human genetic evidence of a tumor-promoting role for the pro-survival activities of p53, which supports the development of more effective therapy combinations through their inhibition in cancers retaining wild-type p53. SignificanceWe describe significant interactions between heritable and somatic genetic variants in the p53 pathway that affect cancer susceptibility, progression and treatment response. Our results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and identify novel therapeutic targets.

cancer biology↗

bioRxiv2019

Single-cell analyses identify tobacco smoke exposure-associated, dysfunctional CD16+ CD8 T cells with high cytolytic potential in peripheral blood

Tobacco smoke exposure has been found to impact immune response, leukocyte subtypes, DNA methylation, and gene expression in human whole blood. Analysis with single cell technologies will resolve smoking associated (sub)population compositions, gene expression differences, and identification of rare subtypes masked by bulk fraction data. To characterize smoking-related gene expression changes in primary immune cells, we performed single-cell RNA sequencing (scRNAseq) on >45,000 human peripheral blood mononuclear cells (PBMCs) from smokers (n=4) and nonsmokers (n=4). Major cell type population frequencies showed strong correlation between scRNAseq and mass cytometry. Transcriptomes revealed an altered subpopulation of Natural Killer (NK)-like T lymphocytes in smokers, which expressed elevated levels of FCGR3A (gene encoding CD16) compared to other CD8 T cell subpopulations. Relatively rare in nonsmokers (median: 1.8%), the transcriptionally unique subset of CD8 T cells comprised 7.3% of PBMCs in smokers. Mass cytometry confirmed a significant increase (p = 0.03) in the frequency of CD16+ CD8 T cells in smokers. The majority of CD16+ CD8 T cells were CD45RA positive, indicating an effector memory re-expressing CD45RA T cell (TEMRA) phenotype. We expect that cigarette smoke alters CD8 T cell composition by shifting CD8 T cells toward differentiated functional states. Pseudotemporal ordering of CD8 T cell clusters revealed that smokers cells were biased toward later pseudotimes, and characterization of established markers in CD8 T cell subsets indicates a higher frequency of terminally differentiated cells in smokers than in nonsmokers, which corresponded with a lower frequency in naive CD8 T cells. Consistent with an end-stage TEMRA phenotype, FCGR3A-expressing CD8 T cells were inferred as the most differentiated cluster by pseudotime analysis and expressed markers linked to senescence. Examination of differentially expressed genes in other PBMCs uncovered additional senescence-associated genes in CD4 T cells, NKT cells, NK cells, and monocytes. We also observed elevated Tregs, inducers of T cell senescence, in smokers. Taken together, our results suggest smoking-induced, senescence-associated immune cell dysregulation contributes to smoking-mediated pathologies.

immunology↗