Cancer-selective, single agent chemoradiosensitising gold nanoparticles

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics

Molecular characterization of a marine turtle tumor epizootic, profiling external, internal and postsurgical regrowth tumors

Sea turtle populations are under threat from an epizootic tumor disease (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at many longer-affected sites globally. However, we do not yet understand the precise environmental, mutational and viral events driving fibropapillomatosis tumor formation and progression. Here we perform transcriptomic and immunohistochemical profiling of five fibropapillomatosis tumor types: external new, established and postsurgical regrowth tumors, and internal lung and kidney tumors. We reveal that internal tumors are molecularly distinct from the more common external tumors. However, they have a small number of conserved potentially therapeutically targetable molecular vulnerabilities in common, such as the MAPK, Wnt, TGFβ and TNF oncogenic signaling pathways. These conserved oncogenic drivers recapitulate remarkably well the core pan-cancer drivers responsible for human cancers. Fibropapillomatosis has been considered benign, but metastatic-related transcriptional signatures are strongly activated in kidney and established external tumors. Tumors in turtles with poor outcomes (died/euthanized) have genes associated with apoptosis and immune function suppressed, with these genes providing putative predictive biomarkers. Together, these results offer an improved understanding of fibropapillomatosis tumorigenesis and provide insights into the origins, inter-tumor relationships, and therapeutic treatment for this wildlife epizootic

International overview of sea turtle fibropapillomatosis: a survey of expert opinions and trends

IntroductionMarine environments offer a wealth of opportunities to improve understanding and treatment options for cancers, through insights into a range of fields from drug discovery to mechanistic insights. By applying One Health principles the knowledge obtained can benefit both human and animal populations, including marine species suffering from cancer. One such species is green sea turtles (Chelonia mydas), which are under threat from fibropapillomatosis (FP), an epizootic tumor disease (animal epidemic) that continues to spread and increase in prevalence globally. In order to effectively address this epizootic, a more thorough understanding is required of the prevalence of the disease and the approaches to treating afflicted turtles.MethodsTo identify knowledge gaps and assess future needs, we conducted a survey of sea turtle FP experts. The survey consisted of 47 questions designed to assess general perceptions of FP, the areas where more information is needed, local FP trends, the disease status, and mitigation needs, and was voluntarily completed by 44 experts across a broad geographic range.ResultsOver 70% of respondents both recognized FP as a cancerous panzootic disease, and reported that FP is increasing in prevalence. They report several factors contributing to this increase. Nearly all of the respondents reported that FP research, patient treatment and rehabilitation required more funding in their area, and reported inadequate facilities and capacity for dealing with FP patients. Treatment approaches varied: just over 70% of the medical experts that responded surgically remove FP tumors, either using laser or scalpel. Just under half of respondents use anti-cancer drugs in their treatment of FP. Internal tumors were reported as justification for euthanasia by 61.5% of respondents, and 30.8% reported severe external tumors to be sufficient grounds for euthanasia. Most medical respondents (93.3%) routinely perform necropsy on deceased or euthanized FP-afflicted turtles. Over 80% of respondents considered large-scale multidisciplinary collaboration ‘extremely important’ for advancing the field of FP research.DiscussionThe survey responses provide a valuable insight into the current status of FP in sea turtles, FP treatment, rehabilitation and research, and help to identify critical FP-related areas most in need of attention

Threatened mammals, birds, amphibians and fish in Ireland

SIGLEGBUnited Kingdo

Inadvertent human genomic bycatch and intentional capture raise beneficial applications and ethical concerns with environmental DNA

The field of environmental DNA (eDNA) is advancing rapidly, yet human eDNA applications remain underutilized and underconsidered. Broader adoption of eDNA analysis will produce many well-recognized benefits for pathogen surveillance, biodiversity monitoring, endangered and invasive species detection, and population genetics. Here we show that deep-sequencing-based eDNA approaches capture genomic information from humans (Homo sapiens) just as readily as that from the intended target species. We term this phenomenon human genetic bycatch (HGB). Additionally, high-quality human eDNA could be intentionally recovered from environmental substrates (water, sand and air), holding promise for beneficial medical, forensic and environmental applications. However, this also raises ethical dilemmas, from consent, privacy and surveillance to data ownership, requiring further consideration and potentially novel regulation. We present evidence that human eDNA is readily detectable from 'wildlife' environmental samples as human genetic bycatch, demonstrate that identifiable human DNA can be intentionally recovered from human-focused environmental sampling and discuss the translational and ethical implications of such findings.Funding for the initial HGB eDNA study was generously provided by the National Save the Sea Turtle Foundation under project name Fibropapillomatosis Training and Research Initiative (D.J.D.), a Welsh Government Sêr Cymru II and the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 663830-BU115 (D.J.D.). This research was also supported by Gumbo Limbo Nature Center d/b/a Friends of Gumbo Limbo (a 501c3 non-profit organization) through a generous donation through their Graduate Research Grant programme (J.A.F.) and by an Irish Research Council Government of Ireland Postgraduate Scholarship, under project no. GOIPG/2020/1056 (L.W.). Intentional human eDNA research was funded by D.J.D.’s University of Florida start-up funds. M.R.S. was supported by an EMBO long-term fellowship (ALTF 544-2021). We thank M. Q. Martindale, N. Condron, K. Yetsko, S. Creer, A. Pacetti, E. Ryan, C. Eastman and all of our generous co-authors on the wildlife and pathogen research papers for which these HGB samples were originally generated8,17. We thank P. Murphy and R. Rolfe for facilitating eDNA extraction of Irish samples in their lab in the Zoology Department, Trinity College Dublin, and A. Krstic, W. Kolch, A. G. Munoz and the Conway Core Facilities staff for facilitating qPCR of the Irish samples at Systems Biology Ireland and the Conway Institute of Biomolecular and Biomedical Research at University College Dublin. We also thank F. Duffy and I. Duffy for assistance with sampling; M. ten Cate and A. Whilde for gifting supplies; K. Foote, A. Rich and the NPS staff of the Fort Matanzas National Monument for valuable assistance with permitting and facilitating access to Rattlesnake Island and site selection; and S. Loesgen (University of Florida) for the SH-SY5Y cells. Finally, we thank the anonymous study participants who permitted us to collect their footprints and room air for human eDNA analysis, with full ethical approval and informed consent

Shotgun sequencing of airborne eDNA achieves rapid assessment of whole biomes, population genetics and genomic variation

Biodiversity and its associated genetic diversity are being lost at an unprecedented rate. Simultaneously, the distributions of flora, fauna, fungi, microbes and pathogens are rapidly changing. Novel technology can help to capture and record genetic diversity before it is lost and to measure population shifts and pathogen distributions. Here we report the rapid application of shotgun long-read environmental DNA (eDNA) analysis for non-invasive biodiversity, genetic diversity and pathogen assessments from air. We also compared air eDNA with water and soil eDNA. Coupling long-read sequencing with established cloud-based biodiversity pipelines enabled a 2-day turnaround from airborne sample collection to completed analysis by a single investigator. To determine the full utility of airborne eDNA, we also conducted a local bioinformatic analysis and deep short-read shotgun sequencing. From outdoor air eDNA alone, comprehensive genetic analysis was performed, including population genetics (phylogenetic placement) of a charismatic mammal (bobcat, Lynx rufus) and a venomous spider (golden silk orb weaver, Trichonephila clavipes), and haplotyping humans (Homo sapiens) from natural complex community settings, such as subtropical forests and temperate locations. The rich datasets also enabled deeper analysis of specific species and genomic regions of interest, including viral variant calling, human variant analysis and antimicrobial resistance gene surveillance from airborne DNA. Our results highlight the speed, versatility and specificity of pan-biodiversity monitoring via non-invasive eDNA sampling using current benchtop/portable and cloud-based approaches. Furthermore, they reveal the future feasibility of scaling down (equipment and temporally) these approaches for near real-time analysis. Together these approaches can enable rapid simultaneous detection of all life and its genetic diversity from air, water and sediment samples for unbiased non-targeted information-rich genomics-empowered (1) biodiversity monitoring, (2) population genetics, (3) pathogen and disease-vector genomic surveillance, (4) allergen and narcotic surveillance, (5) antimicrobial resistance surveillance and (6) bioprospecting