Biology subjects

Quinn, M.

Publications and source records attributed to Quinn, M..

10 recordsLinked to original sources

bioRxiv2026

A Patient-Derived Ex Vivo Tissue Model of Cholangiocarcinoma Using Precision-Cut Tissue Slices

Background & Aims: Cholangiocarcinoma (CCA) is an aggressive malignancy with poor five-year survival. Improving outcomes requires preclinical models that faithfully recapitulate the native tumour microenvironment. Precision-Cut Tissue Slices (PCTS) retain in-vivo architecture and represent a promising candidate. We aimed to establish a patient-derived PCTS model of CCA, characterise its response to ex-vivo culture, and assess its use as a platform for therapeutic testing. Methods: PCTS were generated from 25 patients undergoing curative-intent resection for presumed CCA (2022-2024) and cultured for up to 15 days. Viability and histological architecture were assessed serially. Quantitative proteomics (SWATH-DIA) was performed at Days 0, 3, 7 and 15. A subset were treated with staurosporine or clinically relevant chemotherapy (5'-deoxy-5-fluorouridine, gemcitabine {+/-} cisplatin). Results: PCTS viability was maintained to Day 15, with no significant reduction from baseline. PCTS retain tumour architecture, cytokeratin-19-positivity and resident CD3+/CD68+ immune cells during culture. Proteomic profiling quantified 4,578 proteins and identified a staged response, with differentially abundant proteins increasing from 8 (Day 3) to 127 (Day 7) and 180 (Day 15), stabilising thereafter. This comprised of an early loss of inflammatory and stromal proteins, sustained cellular stress responses and metabolic reprogramming. CCA subtype-specific proteomic signatures were preserved throughout culture. Staurosporine produced dose-dependent cytotoxicity whilst chemotherapy responses were variable. Conclusions: Patient-derived CCA PCTS maintain viability, tumour architecture and subtype identity for 15 days while undergoing a defined proteomic response to culture, and retain pharmacological responsiveness,

cancer biology↗

bioRxiv2025

A high-resolution diel survey of surface ocean metagenomes, metatranscriptomes, and transfer RNA transcripts

The roles of marine microbes in ecosystem processes are inherently linked to their ability to sense, respond, and ultimately adapt to environmental change. Capturing the nuances of this perpetual dialogue and its long-term implications requires insight into the subtle drivers of microbial responses to environmental change that are most accessible at the shortest scales of time. Here, we present a multi-omics dataset comprising surface ocean metagenomes, metatranscriptomes, tRNA transcripts, and biogeochemical measurements, collected every 1.5 hours for 48 hours at two stations within coastal and adjacent offshore waters of the tropical Pacific Ocean. We expect that this integrated dataset of multiple sequence types and environmental parameters will facilitate novel insights into microbial ecology, microbial physiology, and ocean biogeochemistry and help investigate the different mechanisms of adaptation that drive microbial responses to environmental change.

microbiology↗

bioRxiv2025

Phaeochromocytomas and paragangliomas harbour tumour-initiating SOX2+ stem cells

Phaeochromocytomas (PCCs) and paragangliomas (PGLs), are rare neuroendocrine tumours that arise in the neural crest (NC)-derived adrenal medulla and the paraganglia, respectively. Approximately 10%-15% of patients with PCCs and 35%-40% with PGLs go on to develop metastatic disease, leading to a reported median overall survival of 7 years. The development of prognostic markers and subsequent personal therapeutic strategies are hindered by a lack of understanding of tumourigenesis. In other organs, cells with stem-like properties are at the root of tumour initiation and maintenance, due to their ability to self- renew and give rise to differentiated cells. We have recently shown that, in the human adrenal, a subset of sustentacular cells, endowed with a support role, are in fact SOX2+ postnatal adrenomedullary stem cells, that are specified along the neural crest migratory route. In this study, we intended to determine if SOX2+ cells in PCCs and PGLs can behave as tumour-initiating stem cells. Using expression and transcriptomic studies, we demonstrate the presence of SOX2/SOX2-expressing cells across a broad range of PCCs and PGLs, irrespective of tumour aggressiveness, location, and causative mutation. In silico analyses reveal the co-expression of SOX2 and chromaffin cell markers in the tumour, and the active proliferation of these double-positive cells. Isolation of these cells in vitro in stem cell-promoting media, and their xenotransplantation on chicken chorioallantoic membranes, demonstrates that they have the potential to expand and metastasise in ovo, supporting their potential as tumour-initiating cells.

cancer biology↗

bioRxiv2024

Fallow deer approaching humans are also more likely to be seropositive for Toxoplasma gondii.

Toxoplasma gondii (T. gondii) is a trophically-transmitted protozoan parasite that has been suggested to facilitate its transmission by altering intermediate hosts anti-predator behaviour, thus increasing the likelihood of completing the cycle inside its definitive host i.e. domestic and wild felines. T. gondii has been linked to reduced risk-aversion, slower reaction times, and more exploratory behaviours in intermediate hosts, including most famously weakened aversion to the scent of feline predators in mice. Studies examining this phenomenon, however, have almost exclusively been carried out in laboratory conditions with small mammals, whereas little is known about the role of T. gondii within more complex ecological contexts involving large mammals in the wild. Under such scenario, the goals of our study were three-fold. Firstly, to determine the prevalence of T. gondii infection in a population of free-living fallow deer (Dama dama) living in a park at the edge of a metropolis. Secondly, to find a link between deer seropositivity and space use in the park, namely proximity to buildings with domestic cats, where deer may have been more likely to contract the disease. Finally, to determine whether infection with T. gondii was linked to risk taking behaviour in these free ranging large mammals, namely likelihood to approach park visitors. To achieve our goals, we estimated seropositivity and combined it with spatial distribution and behavioural data of individually-recognizable deer ranging from those that avoid humans (risk-avoiders) to those who beg for food (risk-takers). We found T. gondii to be quite widespread in this population with a seropositive of 20% (24 out of 120 individuals). Contrary to our expectations, we found no correlation between T. gondii seropositivity and space use in the park, therefore not allowing us to engage with the dynamics of disease contraction. We did however find that fallow deer taking the risk of approaching humans were also more likely to be seropositive. Are risk taking individuals more likely to contract the disease? Or, alternatively, do they take more risk because they have contracted the disease? The causal mechanism behind our result has yet to be disentangled, opening new scenarios in research aimed at tackling host manipulation in this parasite. It is a fact, however, that those animals that were more likely to be in contact with the public were also those more likely to be seropositive, adding key empirical evidence to the study of zoonotic diseases. Our study is a significant contribution on the transmission and maintenance dynamics of T. gondii, offering new insights on the need to conduct longitudinal studies able to disentangle the causal mechanism and T. gondiis ability to manipulate its intermediate host.

animal behavior and cognition↗

bioRxiv2023

Fawn bedsite selection by a large ungulate living in a peri-urban area

Human-wildlife conflict in expanding peri-urban and urban areas is of increasing concern, as a result of growing human populations along with the associated anthropogenic footprint on wildlife habitats. Empirical data from wildlife research carried out within human dominated landscapes are key to understanding the effects of human pressures on wildlife ecology and behaviour, exploring wildlife behavioural flexibility (or phenotypic plasticity), and informing wildlife management decisions. Here, we explored how female fallow deer (Dama dama) responded to human and dog presence during the birthing period in the largest walled urban park in Europe. We collected data on 477 bedsites utilised by 283 neonate fawns across three consecutive fawning seasons, gathered fine-scale data on humans and dogs space use, and built Resource Selection Functions at multiple spatial scales. We found that, when choosing bedsites to give birth and leave fawns unattended, fallow deer mothers significantly avoided hotspots of park visitors on foot (and their dogs) along the hiking trail routes. Bedsites were also unlikely to be in close proximity of paved roads used by vehicle traffic. Additionally, fallow deer mothers were found to select for dense understory vegetation for bedsites, providing low visibility to conceal their offspring. Our results provide detailed insights into bedsite spatial and habitat selection by a large herbivore in response to human activities, and we provide clear indications to wildlife managers to preserve established fawning sites and alleviate human-wildlife conflict during a critical period of the deer annual biological cycle.

animal behavior and cognition↗

bioRxiv2023

Sex-specific relationship between maternal and neonate cortisol in a free-ranging large mammal

Maternal phenotypes can have long-term effects on offspring phenotypes. These maternal effects may begin during gestation, when maternal glucocorticoid (GC) levels may affect foetal GC levels, thereby having an organizational effect on the offspring phenotype. Recent studies have showed that maternal effects may be different between the sexes. However, how maternal GC levels relate to foetal levels is still not completely understood. Here we related, for the first time in a free-ranging large mammal, the fallow deer (Dama dama), maternal GC levels with foetal in utero GC levels. We did this in a non-invasive way by quantifying cortisol metabolites from faecal samples collected from pregnant does during late gestation, as proxy for maternal GC level. These were then related to GC levels from hair of their neonate offspring (n = 40). We have shown that maternal GC levels were positively associated with foetal GC levels, but only in female offspring. These findings highlight sex differences, which may have evolved to optimize male growth at the cost of survival.

ecology↗

bioRxiv2022

Securing algal endosymbiont communities for reef-building corals

Photosynthetic dinoflagellates that live in symbiosis with corals (family Symbiodiniaceae) are fundamental for the survival of coral reef ecosystems. During coral bleaching events, it is assumed that these symbionts remain available in the water column, in sediments, or are seeded from unbleached coral colonies. Yet, this hypothesis has not been verified and it remains unclear whether some diversity of Symbiodiniaceae may be lost in the process. Culture methods have been developed for some Symbiodiniaceae, but for the vast majority of these photosynthetic symbionts, known culture methods are not successful at maintaining them for extensive periods. For these unculturable symbionts, cryopreservation, which places cells and tissues in suspended animation for days to decades, offers the best hope for saving the biodiversity of these crucial coral partners. Some cryopreservation processes use slow freezing, but if the cells are sensitive to low temperatures, as is the case for Symbiodiniaceae, then rapid freezing, called vitrification, is needed. We here, tested two published vitrification protocols that had been designed for algal symbionts extracted from Hawaiian corals, but we were unable to recover living symbionts after vitrification and warming. Therefore, we report a successful optimisation of the former vitrification protocols, which we tested on algal symbionts freshly extracted from three Hawaiian coral species, the development of ultra-rapid laser-warming cryopreservation techniques for symbionts, and banking procedures for algal symbionts. We also present some successful uptake of cryopreserved algal symbionts by coral larvae, although at a low rate. It is unclear why the former vitrification protocols failed but we propose that it may have been related to thermal stress and bleaching events that occurred on several occasions throughout the Hawaiian Islands. Maintenance of biodiversity is essential for sustaining functional, productive ecosystems with the adaptability to effectively recover from disturbances. By successfully cryopreserving and banking coral symbionts, we provide a critically needed component for securing Symbiodiniaceae biodiversity into the future.

zoology↗

bioRxiv2019

Laboratory Analysis of an Outbreak of Candida auris in New York from 2016 to 2018-Impact and Lessons Learned

Candida auris is a multidrug-resistant yeast which has emerged in healthcare facilities worldwide, however little is known about identification methods, patient colonization, spread, environmental survival, and drug resistance. Colonization on both biotic and abiotic surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in NY from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/non-selective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of ribosomal genes for C. auris genotyping. Results included: a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates, as well as identification of 277 clinical cases and 350 colonized cases from 151 healthcare facilities including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, c) demonstration of relatively heavier colonization of C. auris in nares compared to the axilla/groin, and d) predominance of the South Asia Clade I with intrinsic resistance to fluconazole and elevated minimum inhibitory concentration (MIC) to voriconazole (81%), amphotericin B (61%), 5-FC (3%) and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak.

microbiology↗

bioRxiv2019

Affordable Remote Monitoring of Plant Growth and Facilities using Raspberry Pi Computers

O_LIPremise of the study: Environmentally controlled facilities, such as growth chambers, are essential tools for experimental research. Automated remote monitoring of such facilities with low-cost hardware can greatly improve both the reproducibility and the accurate maintenance of their conditions.\nC_LIO_LIMethods and Results: Using a Raspberry Pi computer, open-source software, environmental sensors, and a camera, we developed a cost-effective system for monitoring growth chamber conditions, which we have called GMpi. Coupled with our software, GMpi_Pack, our setup automates sensor readings, photography, alerts when conditions fall out of range, and data transfer to cloud storage services.\nC_LIO_LIConclusions: The GMpi offers low-cost access to environmental data logging, improving reproducibility of experiments, as well as reinforcing the stability of controlled environmental facilities. The device is also flexible and scalable, allowing customization and expansion to include other features such as machine vision.\nC_LI

bioinformatics↗

bioRxiv2017

Myomerger Induces Fusion Of Non-Fusogenic Cells And Is Required For Myoblast Fusion

Despite the importance of cell fusion for mammalian development and physiology, the factors critical for this process remain to be fully defined1. This lack of knowledge has severely limited our ability to reconstitute cell fusion, which is necessary to decipher the biochemical mechanisms driving plasma membrane merger. Myomaker (Tmem8c) is a muscle-specific protein required for myoblast fusion2,3. Expression of myomaker in fibroblasts drives their fusion with myoblasts, but not with other myomaker-fibroblasts, highlighting the requirement of additional myoblast-derived factors for fusion. Here, we demonstrate that Gm7325, named myomerger, induces the fusion of myomaker-expressing fibroblasts. Cell mixing experiments reveal that while myomaker renders cells fusion-competent, myomerger induces fusogenicity. Thus, myomaker and myomerger confer fusogenic activity to normally non-fusogenic cells. Myomerger is skeletal muscle-specific and only expressed during developmental and regenerative myogenesis. Disruption of myomerger in myoblast cell lines through Cas9-mutagenesis generated non-fusogenic myocytes. Genetic deletion of myomerger in mice results in a paucity of muscle fibers demonstrating a requirement for myomerger in normal muscle formation. Myomerger deficient myocytes exhibit an ability to differentiate and harbor organized sarcomeres, however remain mono-nucleated. These data identify myomerger as a fundamental myoblast fusion protein and establishes a system that begins to reconstitute mammalian cell fusion.

developmental biology↗