Biology subjects

O'Brien, D.

Publications and source records attributed to O'Brien, D..

13 recordsLinked to original sources

bioRxiv2026

First detected incursions of avian influenza H5N1 clade 2.3.4.4b into mainland Australia from the Southern Ocean

High pathogenicity avian influenza H5N1 clade 2.3.4.4b has caused a panzootic of devastating impact to poultry and wildlife globally. The Australian continent and broader Oceania until recently remained the last major region without confirmed detections. Here we report the first H5N1 clade 2.3.4.4b detections from two live seabirds - a brown skua and a southern giant petrel - found on the south coast of Western Australia in June 2026. Virus genome sequencing showed that both viruses were most closely related to H5N1 viruses detected recently on sub-Antarctic islands in the Southern Indian Ocean. In time-calibrated phylogeographic analyses, both viruses sampled in Western Australia clustered with viruses from Heard Island, a sub-Antarctic external territory of Australia. Ancestral location reconstruction also identified Heard Island as the most probable source location, although unsampled intermediate locations cannot be excluded. The two Western Australian detections were estimated to be independent incursions from Heard Island, rather than local transmission on mainland Australia. There was no evidence of reassortment with endemic avian influenza viruses in Australia, and both virus sequences retained key avian-like genetic markers and lacked known substitutions for reduced antiviral susceptibility. These detections revealed a Southern Ocean pathway of recurrent H5N1 incursions into Australia, highlighting the risk of potential establishment on the mainland and the need for heightened surveillance and rapid, nationally-coordinated, virus genomic characterisation.

microbiology↗

bioRxiv2026

Limited predictability of tree-level responses to drought across European forests

Climate change is increasing the frequency, duration and severity of extreme events such as heatwaves and droughts, pushing trees near or beyond their ecophysiological limits. Understanding what governs variability in how trees respond to drought - such as intrinsic factors related to their size, age, and species, or extrinsic factors shaped by their local competitive environment - is critical for predicting long-term forest resilience to climate change and developing climate-smart forest management strategies. Here, we use tree ring data from 2909 trees belonging to sixteen species distributed across Europes major forest types to comprehensively assess what factors contribute most to a trees ability to withstand and recover from extreme drought events. We found that trees with larger living crowns generally exhibited higher post-drought growth recovery and resilience, while trees exposed to lower drought intensities showed greater resistance. Conversely, neither the density nor the diversity of a trees local competitive neighbourhood had any clear influence on its response to drought. More generally, we found that our ability to predict whether a tree would exhibit resilience to drought was low (R2 = 13-21) and was largely driven by species-specific responses and topographic variation across forest types, rather than by tree- and stand-level attributes. These findings highlight that drought responses are inherently complex and strongly influenced by forest type and by heterogeneous responses among species. Integrating tree-ring, physiological, and remote-sensing data with mechanistic models represents a promising avenue for improving forecasts of future forest resilience to climate change.

ecology↗

bioRxiv2025

Nutrient requirements for cell differentiation progression in Batrachochytrium dendrobatidis

Batrachochytrium dendrobatidis (Bd) is the causative agent of the deadly amphibian disease chytridiomycosis, which has decimated amphibian populations across the globe. Bd reproduces via a multistage asexual pathway. The Bd life cycle begins with a motile zoospore. Upon contact with a surface, the zoospore anchors itself and forms a cyst. The cyst then develops into a germling that produces rhizoid structures. Finally, the germling matures into a zoosporangium which then releases multiple new zoospores. In this study, we investigated the effects of nutrients on the growth and differentiation of Bd. The presence of carbohydrates, vitamins, and trace minerals had a negligible effect on Bds ability to progress through its life cycle. In contrast, the amino acids L-leucine and L-isoleucine (and to a lesser extent L-arginine) were required for cysts to germinate into germlings. However, none of these amino acids were able to sustain further cellular development. Furthermore, the presence of nitrate or ammonium aided progression from germlings into immature zoosporangia that were not able to produce zoospores. The progression to mature zoosporangia was blocked by nitrite or the combined action of calcium ions and bicarbonate. The addition of soluble and insoluble protein sources alone also allowed Bd to develop into immature zoosporangia and affected the rate of development. Finally, protein sources in combination with L-amino acids allowed the completion of the Bd cycle by allowing development from zoospores to mature zoosporangia that were able to release new zoospores. ImportanceEven though the cell differentiation cycle of Bd has been microscopically described, not much is known about the requirements for Bd to progress throughout its life stages. The identification of the molecular cues that allow Bd cell cycle progression may be crucial to disease mitigation efforts. As a corollary, we have identified conditions that allow for the arrest of Bd at various stages of its life cycle. By changing the metabolite availability, we can efficiently obtain cultures enriched for zoospores, cysts, germlings, immature zoosporangia, or spore-releasing zoosporangia. The ability to temporarily freeze and then restart Bd at different points of its life cycle, can allow for determining the mechanisms behind individual transitions between cell types.

microbiology↗

bioRxiv2025

Stress-dependent activation of PQM-1 orchestrates a second-wave proteostasis response for organismal survival

Stress responses are controlled by specialized stress-responsive proteostasis transcription factors that rapidly upregulate protein quality components to re-establish protein homeostasis and safeguard survival. Here we show that the zinc finger transcription factor PQM-1 is crucial for stress survival in response to thermal and oxidative challenges. We provide mechanistic insight into the regulation of PQM-1 during stress that depends on ILS-DAF-16 signaling, as well as phosphorylation on threonine residue 268 that is located within a conserved AKT motif. Our data show that in reproductively mature adults and during well-fed conditions, PQM-1 induction requires DAF-16 and occurs during the recovery period post heat shock. Moreover, PQM-1 co-localizes with DAF-16 in the nucleus during the stress recovery phase. This regulatory dependency on DAF-16 is bypassed under dietary restriction, allowing PQM-1 to promote stress resilience independent of the ILS pathway. During both conditions, PQM-1 is crucial for the upregulation of cytosolic and endoplasmic reticulum stress response genes required for organismal recovery and stress resilience. Our transcriptional and bioinformatic analysis reveals that PQM-1 regulates a distinct set of target genes during the stress recovery phase, suggesting that PQM-1 may be involved in vital secondary wave stress response. Thus, our findings uncover a previously unrecognized mechanism of stress-dependent PQM-1 activation that integrates multiple environmental cues to ensure proteostasis and organismal survival.

genetics↗

bioRxiv2025

Halting predicted vertebrate declines requires tackling multiple drivers of biodiversity loss

Anthropogenic threats are reshaping Earths biodiversity at an unprecedented rate and scale1-3. Conservation policies often prioritise threats like habitat loss and exploitation based on their global prevalence. However, these assessments rarely quantify the impacts of individual or interacting threats, potential masking the true effects of the Anthropocene4-6. Here, we quantitatively analyse the trends of 3,129 vertebrate populations worldwide with documented exposure to specific and multiple threats. Populations impacted solely by habitat loss or exploitation, the most prevalent threats, do not show the fastest declines. Rather, populations exposed to disease, invasive species, pollution, and climate change decline more rapidly. However, habitat loss and exploitation - along with climate change - do act as additive interactive threats, amplifying population declines. Notably, these interactive threats contribute to population declines, more than temporal or spatial sources of variation. Finally, counterfactual scenarios show that to achieve global non-negative vertebrate population trends, we need to mitigate the effects of multiple threats. These findings underscore the urgency of addressing the compounding effects of multiple threats to halt biodiversity loss and suggest that the local-scale impacts of climate change may be more severe than previously recognized.

ecology↗

bioRxiv2024

Mycobacterium ulcerans challenge strain selection for a Buruli ulcer controlled human infection model

Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M. ulcerans JKD8049 as a suitable human challenge strain. This non-genetically modified Australian isolate is susceptible to clinically relevant antibiotics, can be cultured in animal-free and surfactant-free media, can be enumerated for precise dosing, and has stable viability following cryopreservation. Infectious challenge of humans with JKD8049 is anticipated to imitate natural infection, as M. ulcerans JKD8049 is genetically stable following in vitro passage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration of M. ulcerans JKD8049 for controlled human infection.

microbiology↗

bioRxiv2023

Integrative Multi-omic Profiling of Two Human Decedents Receiving Pig Heart Xenografts Reveals Strong Perturbations in Early Immune-Cell and Cellular Metabolism Responses.

BackgroundRecent advances in xenotransplantation in living and decedent humans using pig xenografts have laid promising groundwork towards future emergency use and first in human trials. Major obstacles remain though, including a lack of knowledge of the genetic incompatibilities between pig donors and human recipients which may led to harmful immune responses against the xenograft or dysregulation of normal physiology. In 2022 two pig heart xenografts were transplanted into two brain-dead human decedents with a minimized immunosuppression regime, primarily to evaluate onset of hyper-acute antibody mediated rejection and sustained xenograft function over 3 days. MethodsWe performed multi-omic profiling to assess the dynamic interactions between the pig and human genomes in the first two pig heart-xenografts transplants into human decedents. To assess global and specific biological changes that may correlate with immune-related outcomes and xenograft function, we generated transcriptomic, lipidomic, proteomic and metabolomics datasets, across blood and tissue samples collected every 6 hours over the 3-day procedures. ResultsSingle-cell datasets in the 3-day pig xenograft-decedent models show dynamic immune activation processes. We observe specific scRNA-seq, snRNA-seq and geospatial transcriptomic changes of early immune-activation leading to pronounced downstream T-cell activity and hallmarks of early antibody mediated rejection (AbMR) and/or ischemia reperfusion injury (IRI) in the first xenograft recipient. Using longitudinal multiomic integrative analyses from blood in addition to antigen presentation pathway enrichment, we also observe in the first xeno-heart recipient significant cellular metabolism and liver damage pathway changes that correlate with profound physiological dysfunction whereas, these signals are not present in the other xenograft recipient. ConclusionsSingle-cell and multiomics approaches reveal fundamental insights into early molecular immune responses indicative of IRI and/or early AbMR in the first human decedent, which was not evident in the conventional histological evaluations.

systems biology↗

bioRxiv2023

Urbanisation generates multiple trait syndromes for terrestrial taxa worldwide

Cities can host significant biological diversity. Yet, urbanisation leads to the loss of habitats and, potentially, to local extinctions. Understanding how multiple taxa respond to urbanisation globally is essential to promote and conserve biodiversity in cities and surrounding landscapes. Using a dataset with site-level occurrence and trait data of 5302 species from six terrestrial fauna taxonomic groups across 379 cities on 6 continents, we show that urbanisation produces taxon-specific changes in trait composition, with traits related to reproductive strategy consistently showing the strongest response. The effect of urbanisation on community trait composition is strongest at the largest spatial scale considered, and more closely linked to landscape composition (% urban) than arrangement (aggregation), although latitude and climatic variables remain a stronger influence. This study did not find evidence in support of a global urban taxa syndrome, but instead we suggest that there are four general urban trait syndromes, with resources associated with reproduction and diet likely to be driving patterns in traits associated with mobility and body size. Functional diversity measures showed a wide range of responses, leading to a shift in trait space that is most likely driven by the distribution and abundance of critical resources, and the urban trait syndrome displayed by individual species within a community. Further research is required to understand the interactions between the four general urban trait syndromes, resource distribution and abundance and changes in functional diversity of taxa at different spatial and temporal scales. Maximising opportunities to support species within taxa groups with different urban trait syndromes should be pivotal in conservation and management programmes within and among cities. This will reduce the likelihood of biotic homogenisation at the taxa level, and helps ensure that urban environments have the ecological capacity to respond to challenges such as climate change, further habitat fragmentation and loss, and other disruptions. These actions are critical if we are to reframe the role of cities in global biodiversity loss.

ecology↗

bioRxiv2023

A practical method to improve the efficiency of pollination in maize breeding and genetics research

Seed increase through manual pollination is a critical part of maize breeding and genetics research to advance generations in breeding programs, to create desired research crosses, and produce hybrid seed for trials. Pollination in the field and in controlled environments relies on the availability of high-quality pollen at the time that recipient silks are receptive. Generally, pollinations are made by capturing pollen from the tassel in a paper pollinating bag placed on the tassels one day prior to pollination and newly released pollen is then transferred to silks on the target plant. In the field, maize pollen is only viable for one to four hours following dehiscence and the rate of desiccation is influenced by environmental conditions. We have developed a method which increases the lifespan of pollen and allows pollen from a single tassel to be used to pollinate many ears by mixing fresh pollen with a dilutant that can be stored for multiple days. We identified characteristics of the size of suitable substrates and selected a PEEK based substrate for regular utilization. We evaluated pollen viability and empirically demonstrated the capability to store pollen up to nine days when pollen is mixed with a PEEK substrate and stored at 6{degrees}C. The pollen storage method was used to make successful pollinations across 24 maize inbred lines tested and was generally equivalent to the standard manual pollination process. This method has the potential to increase the efficiency of breeding operations and may be useful in an array of genetic studies. Core Ideas* Manual pollinations in breeding and genetics research requires pollen available when recipient silks are viable. * The method collects and stores maize pollen for at least five days and facilitates efficient pollination. * Pollen is mixed with polyetheretherketone and uses field-collected pollen and simple storage conditions. * The method can increase the number of pollinations per tassel and generates a reasonable number of viable seeds.

genetics↗

bioRxiv2021

Exogene: A performant workflow for detecting viral integrations from paired-end next-generation sequencing data

The integration of viruses into the human genome is known to be associated with tumorigenesis in many cancers, but the accurate detection of integration breakpoints from short read sequencing data is made difficult by human-viral homologies, viral genome heterogeneity, coverage limitations, and other factors. To address this, we present Exogene, a sensitive and efficient workflow for detecting viral integrations from paired-end next generation sequencing data. Exogenes read filtering and breakpoint detection strategies yield integration coordinates that are highly concordant with those found in long read validation sets. We demonstrate this concordance across 6 TCGA Hepatocellular carcinoma (HCC) tumor samples, identifying integrations of hepatitis B virus that are validated by long reads. Additionally, we applied Exogene to targeted capture data from 426 previously studied HCC samples, achieving 98.9% concordance with existing methods and identifying 238 high-confidence integrations that were not previously reported. Exogene is applicable to multiple types of paired-end sequence data, including genome, exome, RNA-Seq or targeted capture.

bioinformatics↗

bioRxiv2021

In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions

Conventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression to liver fibrosis, liver failure, and activation of tumorigenic pathways. Here we demonstrate for the first time a cure of HT1 by direct, in vivo administration of a therapeutic lentiviral vector targeting the expression of a human fumarylacetoacetate hydrolase (FAH) transgene in the porcine model of HT1. This therapy was well tolerated and provided stable long-term expression of FAH in pigs with HT1. Genomic integration displayed a benign profile, with subsequent fibrosis and tumorigenicity gene expression patterns similar to wild-type animals as compared to NTBC-treated or diseased untreated animals. Indeed, the phenotypic and genomic data following in vivo lentiviral vector administration demonstrate comparative superiority over other therapies including ex vivo cell therapy and therefore support clinical application of this approach.

cell biology↗

bioRxiv2020

Reporting to the Convention on Biology Diversity: How are countries assessing and protecting their genetic diversity?

Genetic diversity is critically important for all species-domesticated and wild- to adapt to environmental change, and for ecosystem resilience to extreme events. International agreements such as the Convention on Biological Diversity (CBD) have committed to conserve and sustainably and equitably use all levels of biodiversity-genes, species and ecosystems-globally. However, assessment and monitoring of genetic diversity are often overlooked, and there are large knowledge and policy gaps regarding genetic diversity conservation. In this study, we present the first quantitative analysis of genetic diversity assessments conducted by Parties to the CBD. We conducted a detailed, systematic analysis of 114 CBD 5th (submitted 2014) and 6th (submitted 2018) National Reports to quantitatively assess actions, progress on targets, values and indicators related to genetic diversity. First, we found that the importance of genetic diversity is recognised by most Parties to the CBD, and that recognition increased over time. However, genetic targets mainly addressed genetic diversity within cultivated plants, farm animals, and crop wild relatives, with little focus on other wild species. Also, actions for conserving genetic diversity primarily concerned ex-situ facilities and policy, rather than monitoring and intervention for maintaining genetic diversity in situ. The most commonly used indicators of genetic diversity status were the number of genetic resources in conservation facilities, number of threatened breeds, and Red List Index, which are not well correlated to genetic erosion in most species -- highlighting that genetic change is poorly monitored by current indicators. Lastly, analyses of genetic data observations, indigenous use and knowledge of genetic diversity, and strategies being developed and implemented to conserve genetic diversity are highly under-reported. We make several recommendations for the post-2020 CBD Biodiversity Framework to improve awareness, assessment, and monitoring, and facilitate consistent and complete reporting of progress of genetic diversity in future National Reports. Article Impact StatementAn analysis of genetic diversity in CBD National Reports neglects non-domesticated species and demonstrates need for sufficient indicators.

scientific communication and education↗

bioRxiv2019

Ectopic hepatocyte transplantation cures the pig model of tyrosinemia

The effectiveness of cell-based therapies to treat liver failure is limited by the diseased liver environment. Herein we provide preclinical proof-of-concept for the treatment of liver failure through hepatocyte transplantation into lymph nodes in a large-animal model of hereditary tyrosinemia type 1 (HT1), a metabolic liver disease caused by deficiency of fumarylacetoacetate hydrolase (FAH) enzyme. FAH-deficient pigs received autologous hepatocyte transplantation into mesenteric lymph nodes after ex vivo transduction with a lentiviral vector carrying the pig Fah gene. Hepatocytes showed early (6 hour) and durable (8 month) engraftment in lymph nodes, with reproduction of vascular and hepatic microarchitecture. Subsequently, hepatocytes migrated to and repopulated the native diseased liver. The corrected cells generated enough liver mass to clinically ameliorate disease as early as 97 days post-transplantation, with complete normalization of tyrosine levels and liver function tests. Integration site analysis defined the corrected hepatocytes in the liver as a subpopulation of hepatocytes in the lymph nodes, indicating that the lymph nodes served as a source for healthy hepatocytes to repopulate a diseased liver. Ectopic transplantation of hepatocytes cures the pig model of HT1 and presents a promising approach to the treatment of liver disease in patients with pre-existing liver damage and fibrosis.\n\nOne Sentence SummaryTransplantation of corrected hepatocytes in mesenteric lymph nodes can cure fatal metabolic liver disease by providing organized liver tissue and by repopulating the diseased liver in the pig tyrosinemia model.

molecular biology↗