Biology subjects

Allen, E.

Publications and source records attributed to Allen, E..

At least 19 recordsLinked to original sources

bioRxiv2026

Metastatic Osteosarcoma is Characterized by Loss of Osteoblastic Lineage Fidelity

Osteosarcoma (OS) is a rare and aggressive bone cancer with limited therapeutic progress in several decades. To characterize the transcriptional diversity of malignant cell states in OS, we analyzed single-nucleus RNA sequencing data from 24 tumors, including both primary and metastatic lesions. We identified a canonical osteoblastic cell state that predominated in primary tumor cells, but was dampened in metastases. Integrating tumor data with data from embryonic skeletal development and an experimental osteoblast differentiation model revealed that metastatic OS cells resemble poorly specified mesenchyme enriched for non-osseous programs. Clonal populations in metastatic samples acquired mesenchymal cell states distinct from paired primary tumors. Similar cell state shifts were evident in post-treatment primary tumors relative to paired pre-treatment samples. Our results suggest that localized post-treatment and metastatic OS malignant cells lose osteoblastic lineage fidelity, which may represent a unifying axis of disease evolution and reveal new therapeutic vulnerabilities.

Cancer Biology↗

bioRxiv2026

Laboratory adaptation and complete genome assembly of a Beposo, Ghana strain of the human hookworm Necator americanus

Laboratory models are invaluable tools for studying parasite biology and pathogenesis, especially for helminth infections. However, the complex life cycles and frequently narrow host specificity of helminths present challenges to maintaining access to critical parasite material in a laboratory setting. This is especially true of Necator americanus, the most common species of hookworm that infects humans globally. Here we report the successful laboratory adaptation of an African strain of N. americanus, originally isolated from infected individuals in Beposo, Ghana. The Beposo strain has been successfully passaged across 9 generations in Golden Syrian hamsters maintained on oral dexamethasone. Differential susceptibility to mebendazole and albendazole was evaluated using an egg hatch assay, and DNA sequencing of the beta-tubulin isotype 1 gene did not identify known resistance-associated mutations in the endemic strain. Sequencing of the mitochondrial COX1 gene revealed that specimens of N. americanus from Ghana, along with reported sequences from Togo, are distinct from those from South America and Asia. Complementary microsatellite-based population analysis revealed substantial genetic variation in the founding parasite population. To further characterize the novel Beposo strain, a draft hybrid genome assembly was generated from genomic DNA extracted from a single adult male worm via an optimized Oxford Nanopore Technologies MinION library preparation approach tailored to low-input sample types. This high-quality assembly, including a complete mitogenome, is 202.8Mb in 950 contigs with an N50 >449 kb. It contains >95% of conserved nematode orthologs in complete single copy and is estimated by homology-based gene prediction to contain 12,804 genes. This study represents the first comprehensive characterization of a strain of N. americanus originating in Africa that has been successfully adapted to a laboratory animal model.

microbiology↗

bioRxiv2026

Mucin modulates phage infection dynamics and biofilm formation in enteropathogenic Yersinia enterocolitica

Mucosal barriers serve as a multifunctional interface and nutrient-rich habitat for diverse microbes, including bacteria and bacteriophages. Some phages can bind to mucin glycoproteins via carbohydrate-interacting modules and provide an additional layer of mucosal immunity by shielding the underlying epithelium from invading bacteria. However, the role of mucins in shaping phage-bacterium interactions remains poorly understood. We investigated the dynamics between highly pathogenic Yersinia enterocolitica serotype O:8 and its mucus-adherent phage fMtkYen801 under in vitro mucosal environment. We assessed how mucin supplementation, varying phage doses, nutrient and temperature conditions influence phage-bacterium dynamics and biofilm formation. We found that pre-exposure to mucins led to enhanced phage replication in the bacterial host, with a 2-log increase in phage titers, and high abundance of surviving bacteria. Interestingly, mucin glycoproteins also provided Y. enterocolitica a nutrient source and a chemical cue to modulate its growth and biofilm biogenesis. Genomic analysis of phage-resistant bacterial variants revealed mutations in virulence, quorum sensing, and antibiotic resistance genes in both mucin enrichment and control groups, suggesting potential fitness tradeoffs during resistance evolution. Collectively, these findings highlight the importance of mucosal surfaces as an important ecological driver of phage-host interactions in Y. enterocolitica, a significant enteric pathogen, and emphasize the need for investigating these dynamics under complex, physiologically relevant systems to inform better phage therapy strategies against mucosal bacterial infections.

microbiology↗

bioRxiv2026

Natural variation of gibberellin levels in maize tissues across North America

Gibberellins (GA) are endogenous phytohormones that regulate growth and development throughout the plant lifecycle. While GA has been extensively studied under controlled conditions for their fundamental role in plant adaptation and agronomic trait development, field-based data on their natural variation across diverse agricultural genotypes and environments remains limited. To address this knowledge gap, we analyzed bioactive gibberellin A1 (GA1) and gibberellin A4 (GA4) across multiple maize hybrids grown in diverse field environments using high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study provides comprehensive quantitation of GA1 and GA4 levels in maize tissues across diverse commercial hybrids grown under standard agricultural practices, revealing hormonal variation due to genetic background and environmental conditions. Our findings demonstrate that GA1 and GA4 concentrations from conventional maize samples varied across tissue types and field sites. Analysis of variance components indicated that the site variation was statistically significant at the 5% significance level in five out of ten GA and tissue combinations, while the genetic component was significant only for GA4 in grain samples. Notably, significant interaction between hybrid and site was observed for both GA1 and GA4 in stalk tissue. Positive correlations between GA1 and GA4 were observed consistently across tissues except root. These results underscore the common metabolic pathways involved in regulating GA levels in maize and provide the first comprehensive dataset of GA1 and GA4 variation under real-world agricultural conditions. Our findings offer insights into the interplay between genetics, environment, and hormonal regulation in maize and suggest potential targets for breeding programs aimed at improving agronomic traits such as yield.

plant biology↗

bioRxiv2024

Measuring heritability in messy prebiotic chemical systems

A key question in origins-of-life research, is whether heritability, and thus evolution, could have preceded genes. Out-of-equilibrium chemical reaction networks with multiple autocatalytic motifs may provide chemical "memory" and serve as units of heritability, but experimental validation is lacking. We established conditions that may be conducive to the emergence of heritable variation and developed methods to search for heritability and autocatalysis. We prepared a food set (FS) of three organic species, three inorganic salts and pyrite. We conducted a serial dilution experiment where FS was incubated for 24 hours, after which a 20% fraction was transferred into freshly prepared FS that went through the same procedure, repeated for 10 generations. To serve as controls, we also incubated the fresh solutions in each generation. We compared the chemical composition of transfer vials and no-transfer controls using liquid chromatography-mass spectrometry (LCMS), with metrics adapted from ecology and evolutionary biology. While variability was high, focusing on a subset of chemicals with more consistent patterns revealed evidence of heritable variation among vials. Using rule-based chemical reaction network inference, constrained by the LCMS data, we identified a plausible FS-driven chemical reaction network that was found to contain numerous autocatalytic cycles.

evolutionary biology↗

bioRxiv2024

High affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells

Regulatory T cells (Tregs) are promising cellular therapies to induce immune tolerance in organ transplantation and autoimmune disease. The success of chimeric antigen receptor (CAR) T-cell therapy for cancer has sparked interest in using CARs to generate antigen-specific Tregs. Here, we compared CAR with endogenous T cell receptor (TCR)/CD28 activation in human Tregs. Strikingly, CAR Tregs displayed increased cytotoxicity and diminished suppression of antigen-presenting cells and effector T (Teff) cells compared with TCR/CD28 activated Tregs. RNA sequencing revealed that CAR Tregs activate Teff cell gene programs. Indeed, CAR Tregs secreted high levels of inflammatory cytokines, with a subset of FOXP3+ CAR Tregs uniquely acquiring CD40L surface expression and producing IFN{gamma}. Interestingly, decreasing CAR antigen affinity reduced Teff cell gene expression and inflammatory cytokine production by CAR Tregs. Our findings showcase the impact of engineered receptor activation on Treg biology and support tailoring CAR constructs to Tregs for maximal therapeutic efficacy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=54 SRC="FIGDIR/small/587467v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@11e5bd8org.highwire.dtl.DTLVardef@1fe86forg.highwire.dtl.DTLVardef@d4eb2borg.highwire.dtl.DTLVardef@9b89d1_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Identifying regulators of associative learning using a protein-labelling approach in C. elegans

The ability to learn and form memories is critical for animals to make choices that promote their survival. The biological processes underlying learning and memory are mediated by a variety of genes in the nervous system, acting at specific times during memory encoding, consolidation, and retrieval. Many studies have utilised candidate gene approaches or random mutagenesis screens in model animals to explore the key molecular drivers for learning and memory. We propose a complementary approach to identify this network of learning regulators: the proximity-labelling tool TurboID, which promiscuously biotinylates neighbouring proteins, to snapshot the proteomic profile of neurons during learning. To do this, we expressed the TurboID enzyme in the entire nervous system of C. elegans and exposed animals to biotin only during the training step of an appetitive gustatory learning paradigm. Our approach revealed hundreds of proteins specific to trained worms, including components of molecular pathways previously implicated in memory in multiple species such as insulin signalling, G protein-coupled receptor signalling, and MAP kinase signalling. Most (87-95%) of the proteins identified are neuronal, with relatively high representation for neuron classes involved in locomotion and learning. We validated several novel regulators of learning, including cholinergic receptors (ACC-1, ACC-3, LGC-46) and putative arginine kinase F46H5.3. These previously uncharacterised learning regulators all showed a clear impact on appetitive gustatory learning, with F46H5.3 showing an additional effect on aversive gustatory memory. Overall, we show that proximity labelling can be used in the brain of a small animal as a feasible and effective method to advance our knowledge on the biology of learning.

neuroscience↗

bioRxiv2023

ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface

Vaccines against SARS-CoV-2 have been proven to be an effective means of decreasing COVID-19 mortality, hospitalization rates, and transmission. One of the vaccines deployed worldwide is ChAdOx1 nCoV-19, which uses an adenovirus vector to drive the expression of the original SARS-CoV-2 spike on the surface of transduced cells. Using cryo-electron tomography and subtomogram averaging, we determined the native structures of the vaccine product expressed on cell surfaces in situ. We show that ChAdOx1-vectored vaccines expressing the Beta SARS-CoV-2 variant produce abundant native prefusion spikes predominantly in one-RBD-up conformation. Furthermore, the ChAdOx1 vectored HexaPro stabilized spike yields higher cell surface expression, enhanced RBD exposure, and reduced shedding of S1 compared to the wild-type. We demonstrate in situ structure determination as a powerful means for studying antigen design options in future vaccine development against emerging novel SARS-CoV-2 variants and broadly against other infectious viruses.

microbiology↗

bioRxiv2022

Dysregulation of neural activity and microglia function following exposure to the global environmental contaminant perfluorooctane sulfonate (PFOS)

BackgroundPer- and polyfluoroalkyl substances (PFAS) are biopersistent pollutants that have become global contaminants as a result of their diverse applications in commerce and industry. While some in vitro and epidemiological studies have explored the neurotoxic potential of perfluorooctane sulfonate (PFOS), a prevalent PFAS congener, it is unknown how developmental exposure to PFOS affects neuronal communication and other developmentally critical neural cell types, including microglia. ObjectivesWe sought to determine the extent to which PFOS exposure disrupts brain health, neuronal activity, and neuron-microglia communication during brain development. In addition, while PFOS impairs humoral immunity, its impact on innate immune cells, including resident microglia, is unclear. As such, we aimed to determine whether microglia are cellular targets of PFOS and, if so, whether disrupted microglial development and/or function could contribute to or is influenced by PFOS-induced neural dysfunction. MethodsZebrafish were chronically exposed to either control solution (0.1% DMSO), 7 {micro}M PFOS, 14 {micro}M PFOS, 28 {micro}M PFOS, or 64 {micro}M perfluorooctanoic acid (PFOA). We used in vivo imaging and gene expression analysis to assess microglial populations in the developing brain and to determine shifts in microglial state. We functionally challenged microglial using a larval brain injury model and, to assess the neuronal signaling environment, performed functional neuroimaging experiments utilizing the photoconvertible calcium indicator CaMPARI. These studies were paired with optogenetic manipulations of neurons and microglia, an untargeted metabolome wide association study (MWAS), and larval swim behavior assessments. ResultsDevelopmental PFOS exposure resulted in a shift away from the homeostatic microglia state, as determined by functional and morphological changes, as well as transcriptional upregulation of the microglia activation gene p2ry12. PFOS-induced effects on microglia state exacerbated microglia responses to brain injury in the absence of increased cell death or inflammation. PFOS exposure also heightened neural calcium activity, and optogenetic silencing of neurons or microglia independently was sufficient to normalize microglial responses to injury. An untargeted MWAS of larval brains revealed PFOS-exposed larvae had neurochemical signatures of excitatory-inhibitory imbalance. Behaviorally, PFOS-exposed larvae also exhibited anxiety-like thigmotaxis. To test whether the neuronal and microglial phenotypes were specific to PFOS, we exposed embryos to PFOA, a known immunotoxic PFAS. PFOA did not alter thigmotaxis, neuronal activity, or microglial responses, further supporting a role for neuronal activity as a critical modifier of microglial function following PFOS exposure. DiscussionTogether, this study provides the first detailed account of the effects of PFOS exposure on neural cell types in the developing brain in vivo and adds neuronal hyperactivity as an important endpoint to assess when studying the impact of toxicant exposures on microglia function.

neuroscience↗

bioRxiv2022

Partitioned Local Depth analysis of time course transcriptomic data reveals elaborate community structure

Transcriptome studies that provide temporal information are valuable for identifying groups of similarly-behaving transcripts, giving insight into overarching gene regulatory networks. Nevertheless, inferring transcriptional networks from time series data is challenging, in part because it is difficult to holistically consider both local relationships and global structure of these complex and overlapping transcriptional responses. To address this need, we employed the Partitioned Local Depth (PaLD) method to examine four time series transcriptomic datasets generated using the model plant Arabidopsis thaliana. Here, we provide a self-contained description of the method and demonstrate how it can be used to make predictions about gene regulatory networks based on time series data. The analysis provides a global network representation of the data from which graph partitioning methods and neighborhood analysis can reveal smaller, more well-defined groups of like-responding transcripts. These groups of transcripts that change in response to hormone treatment (e.g., auxin or ethylene) or high salinity were demonstrated to be enriched in common biological function and/or binding of transcription factors that were not identified with prior analyses of this data using other clustering and inference methodologies. These results reveal the ability of PaLD to generate predictions about gene regulatory networks using time series transcriptomic data, which can be of value to the systems biology community.

systems biology↗

bioRxiv2022

Phenotypic and transcriptional response of Daphnia pulicaria to the combined effects of temperature and predation

Daphnia, an ecologically important zooplankton species in lakes, shows both genetic adaptation and phenotypic plasticity in response to temperature and fish predation, but little is known about the molecular basis of these responses and their potential interactions. We performed a factorial experiment exposing laboratory-propagated Daphnia pulicaria clones from two lakes in the Sierra Nevada mountains of California to normal or high temperature (15{degrees}C or 25{degrees}C) in the presence or absence of fish kairomones, then measured changes in life history and gene expression. Exposure to kairomones increased upper thermal tolerance limits for physiological activity in both clones. Cloned individuals matured at a younger age in response to higher temperature and kairomones, while size at maturity, fecundity and population intrinsic growth were only affected by temperature. At the molecular level, both clones expressed more genes differently in response to temperature than predation, but specific genes involved in metabolic, cellular, and genetic processes responded differently between the two clones. Although gene expression differed more between clones from different lakes than experimental treatments, similar phenotypic responses to predation risk and warming arose from these clone-specific patterns. Our results suggest that phenotypic plasticity responses to temperature and kairomones interact synergistically, with exposure to fish predators increasing the tolerance of Daphnia pulicaria to stressful temperatures, and that similar phenotypic responses to temperature and predator cues can be produced by divergent patterns of gene regulation.

ecology↗

bioRxiv2021

Anticancer immunotherapies transition postcapillary venules into high-endothelial venules that generate TCF1+ T lymphocyte niches through a feed-forward loop

The lack of T-cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation of tumor-associated tertiary-lymphoid-like structures (TA-TLS), which are the local site of humoral and cellular immune responses against cancers, are associated with good prognosis and have recently been detected in Immune Checkpoint Blockade (ICB)-responding patients. However, how these lymphoid aggregates develop remains poorly understood. By employing scRNA sequencing, endothelial fate mapping, and functional multiplex immune profiling, we demonstrate that antiangiogenic immune-modulating therapies evoke the transition of postcapillary venules into inflamed high endothelial venules (HEVs), which generate permissive TA-TLS-like lymphocyte niches with PD1neg and PD1+TCF1+CD8 T cell progenitors that differentiate into GrzB+TCF1neg TIM3+ PD1+ CD8 T effector cells. Tumor-HEVs require continuous CD8 and NK cell-derived lymphotoxin signals revealing that tumor-HEV maintenance is actively sculpted by the adaptive immune system through a feed-forward loop. In BriefHua & Vella et al. reveal that effective antiangiogenic immunotherapy transitions postcapillary venules into inflamed high-endothelial venules (HEV), sustained by CD8 T and NK cell-derived signals through a feed-forward loop. Thereby, tumoral HEVs establish perivascular niches in which TCF1+ PD1+ lymphocytes expand and produce cytolytic PD1+ TIM3+ CD8 T cells that facilitate anti-tumoral immunity. HighlightsO_LIHigh endothelial venule induction by anticancer immunotherapies generates perivascular immune niches permissive for TCF1+ PD1+ CD8 progenitor T cell expansion and production of TCF1neg PD1+ TIM3+ CD8 effector T cells C_LIO_LITumoral high-endothelial venules exhibit characteristics of inflamed lymph node HEVs and postcapillary venules C_LIO_LIPostcapillary venules dynamically transdifferentiate into high-endothelial venules in tumors, which requires continuous signals from surrounding immune cells C_LIO_LICD8 and NK cells drive tumoral high-endothelial venule formation during antiangiogenic immunotherapies in a feed-forward loop via lymphotoxin beta receptor signaling C_LI

cancer biology↗

bioRxiv2021

Survival of hatchery grown native oysters is associated with specific gut-associated bacteria at various locations within the Puget Sound

The Olympia oyster (Ostrea lurida) of the Puget Sound suffered a dramatic population crash, but restoration efforts hope to revive this native species. One overlooked variable in the process of assessing ecosystem health is association of bacteria with marine organisms and the environments they occupy. Oyster microbiomes are known to differ significantly between species, tissue type, and the habitat in which they are found. The goals of this study were to determine the impact of field site and habitat on the oyster microbiome and to identify core oyster-associated bacteria in the Puget Sound. Olympia oysters from one parental family were deployed at four sites in the Puget Sound both inside and outside of eelgrass (Zostera marina) beds. Using 16S rRNA gene amplicon sequencing of the oyster gut, shell, surrounding seawater and sediment, we demonstrate that gut-associated bacteria are distinct from the surrounding environment and vary by field site. Furthermore, regional differences in the gut microbiota are associated with the survival rates of oysters at each site after two months of field exposure. However, habitat type had no influence on microbiome diversity. Further work is needed to identify the specific bacterial dynamics that are associated with oyster physiology and survival rates. ImportanceThe outcomes of this study demonstrate the need to monitor microbial ecology at potential oyster restoration sites, specifically for the native Olympia oyster in the Puget Sound. Some areas of Puget Sound may be less amenable to Olympia oyster restoration than others due to microbiome colonization trends. Furthermore, this study puts the oyster microbiome in the context of its surroundings, providing a holistic perspective on the factors that may influence oyster performance and microbial ecology.

microbiology↗

bioRxiv2020

A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice

A self-transcribing and replicating RNA (STARR) based vaccine (LUNAR(R)-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolong SARS-CoV-2 spike glycoprotein expression. A single prime vaccination in mice led to robust antibody responses, with neutralizing antibody titers increasing up to day 60. Activation of cell mediated immunity produced a strong viral antigen specific CD8+ T lymphocyte response. Assaying for intracellular cytokine staining for IFN-{gamma} and IL-4 positive CD4+ T helper lymphocytes as well as anti-spike glycoprotein IgG2a/IgG1 ratios supported a strong Th1 dominant immune response. Finally, single LUNAR-COV19 vaccination at both 2 g and 10 g doses completely protected human ACE2 transgenic mice from both mortality and even measurable infection following wild-type SARS-CoV-2 challenge. Our findings collectively suggest the potential of Lunar-COV19 as a single dose vaccine.

immunology↗

bioRxiv2020

Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.

immunology↗

bioRxiv2020

The Southern Bluefin Tuna mucosal microbiome is influenced by husbandry method, net pen location, and anti-parasite treatment

Aquaculture is the fastest growing primary industry worldwide. Marine finfish culture in open ocean net pens, or pontoons, is one of the largest growth areas and is currently the only way to rear high value fish such as bluefin tuna. Ranching involves catching wild juveniles, stocking in floating net pens and fattening for four to eight months. Tuna experience several parasite-induced disease challenges in culture that can be mitigated by application of praziquantel (PZQ) as a therapeutic. In this study, we characterized the microbiome of ranched southern Bluefin Tuna, Thunnus maccoyii, across four anatomic sites (gill, skin, digesta, and anterior kidney) and evaluated environmental and pathological factors that influence microbiome composition, including the impact of PZQ treatment on microbiome stability. Southern bluefin tuna gill, skin, and digesta microbiome communities are unique and potentially influenced by husbandry practices, location of pontoon growout pens, and treatment with the antiparasitic PZQ. There was no significant relationship between the fish mucosal microbiome and incidence or abundance of adult blood fluke in the heart or fluke egg density in the gill. An enhanced understanding of microbiome diversity and function in high-value farmed fish species such as bluefin tuna is needed to optimize fish health and improve aquaculture yield. Comparison of the bluefin tuna microbiome to other fish species, including Seriola lalandi (yellowtail kingfish), a common farmed species from Australia, and Scomber japonicus (Pacific mackerel), a wild caught Scombrid relative of tuna, showed the two Scombrids had more similar microbial communities compared to other families. The finding that mucosal microbial communities are more similar in phylogenetically related fish species exposes an opportunity to develop mackerel as a model for tuna microbiome and parasite research.

genomics↗

bioRxiv2020

ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.

microbiology↗

bioRxiv2019

Temporal, environmental, and biological drivers of the mucosal microbiome in a wild marine fish, Scomber japonicus

Changing ocean conditions driven by anthropogenic activity may have a negative impact on fisheries by increasing stress and disease with the mucosal microbiome as a potentially important intermediate role. To understand how environment and host biology drives mucosal microbiomes in a marine fish, we surveyed five body sites (gill, skin, digesta, GI, and pyloric caeca) from 229 Pacific chub mackerel, Scomber japonicus, collected across 38 time points spanning one year from the Scripps Institution of Oceanography Pier, making this the largest and longest wild marine fish microbiome survey. Mucosal sites had unique communities significantly different from the surrounding sea water and sediment communities with over 10 times more diversity than sea water alone. Although, external surfaces such as skin and gill were more similar to sea water, digesta was similar to sediment. Both alpha and beta diversity of the skin and gill was explained by environmental and biological factors, especially sea surface temperature, chlorophyll a, and fish age, consistent with an exposure gradient relationship. We verified that seasonal microbial changes were not confounded by migrations of chub mackerel sub-populations by nanopore sequencing a 14 769 bp region of the 16 568 bp mitochondria. A cosmopolitan pathogen, Photobacterium damselae, was prevalent across multiple body sites all year, but highest in the skin, GI, and digesta between June and September. Our study evaluates the extent which the environment and host biology drives mucosal microbial ecology, establishing a baseline for long term monitoring surveys for linking environment stressors to mucosal health of wild marine fish.

ecology↗