Biology subjects

Perry, M.

Publications and source records attributed to Perry, M..

17 recordsLinked to original sources

bioRxiv2026

PEONY: a global reference database of DNA viral (vOTU) sequences from viral size-fractionated metagenomes (viromes)

We present an update to the PIGEON (Phages and Integrated Genomes Encapsidated or Not) reference database of DNA viral sequences (vOTUs, mostly dsDNA bacteriophages) from global ecosystems. To reflect the inclusion of only virus size-fractionated metagenome- (virome-)derived vOTUs, we reintroduce the database as PEONY (Phages Encapsidated ONlY) and present new data summarizing the utility of this database.

microbiology↗

bioRxiv2026

Food reward in Bottlenose Dolphins (Tursiops truncatus) and Belugas Whales (Delphinapterus leucas) reduces heart rate and increase heart rate variability.

1.BackgroundHeart rate (HR) and HR variability (HRV) reflect the autonomic modulation of cardiac activity and are key indicators of physiological state and stress in vertebrates. However, measuring these parameters in cetaceans has been historically challenging due to the difficulty of recording electrocardiograms (ECGs) underwater. MethodsWe developed an all-in-one ECG suction-cup to record HR during apnea, respiration and food rewards in bottlenose dolphins (Tursiops truncatus, N = 8) and belugas (Delphinapterus leucas, N = 2). Moreover, we obtain comparative measurements of ECG waveform and HR oscillation in one killer whale (Orcinus orca). ResultsSpecies-specific ECG patterns were observed, including biphasic T waves in all three species and bifid P waves unique to belugas. All three species exhibited oscillations in resting HR and pronounced bradycardia during short apnea ([~]1 min), reflecting respiratory-linked autonomic modulation. Moreover, HR oscillations persisted throughout apnea, possibly reflecting a mechanism to cyclically improve body oxygenation during diving. Short-term food deprivation had no significant effects on bottlenose dolphins and belugas HR, while subsequent feeding ad libitum reduced HR (by [~]20% in dolphins, [~]40% in belugas) and increased HRV, suggesting the activation of vagal modulation. ConclusionsThis study establishes baseline HR and HRV parameters during breathing, apnea and food reward in three cetacean species, highlighting autonomic modulation across different behaviors and conditions and validate a non-invasive tool for studying marine mammal physiology.

physiology↗

bioRxiv2026

Evolution and integration of a novel cell type in the housefly Love Spot

The addition of new neuron types is thought to underlie the evolution of complex nervous systems, yet the mechanisms by which they arise remain unclear. Here we investigate the evolution of a novel target detection photoreceptor in the housefly Musca domestica. In males, a dorso-frontal eye region known as the "Love Spot" enables rapid detection and tracking of females during mating flights. In this region, R7 photoreceptors - normally dedicated to color vision - are repurposed for target detection through altered Rhodopsin expression, physiology, and circuit connectivity. We show that these Love Spot R7 cells (LsR7) are initially specified as canonical R7 photoreceptors but later adopt a chimeric identity combining transcription factors normally associated with either color or motion vision. The sex-determination transcription factor Doublesex (Dsx) is strongly upregulated after R7 specification and, together with the transcription factor Spineless, drives the LsR7 gene regulatory program. Because Dsx upregulation occurs after initial axon targeting to the medulla, LsR7 axons subsequently shorten to connect with lamina neurons and OFF-pathway motion vision circuits. These findings show how new combinations of cell-identity regulators can generate novel neural cell types while revealing developmental constraints imposed by evolutionary history.

Developmental Biology↗

bioRxiv2026

Myelin basic protein is an RNA chaperone in microglial nuclear retro-transport

CNS oligodendrocytes generate myelin, an RNA-containing proteolipid substance that enhances axonal transmission. In multiple sclerosis (MS), myelin debris is phagocytosed by microglia (MG), and prior studies have detected myelin-derived mRNA in MG nuclei, suggesting a retrograde transport pathway. We report myelin basic protein (MBP) is a nucleic acid-binding and trafficking protein. We found that retro-transport of myelin RNA into the MG nucleus was phagocytosis and importin-dependent. Transcriptomic and proteomic analyses of MG nuclei revealed enrichment of myelin mRNAs and proteins, with MBP singularly detected in soluble and chromatin-associated fractions. MBP bound mRNA with high affinity (Kd {approx} 0.30 nM) and was sufficient to facilitate MG RNA nuclear import in vitro and in vivo. Functionally, MBP mediated the delivery of small interfering RNAs for targeted knockdown of toll-like receptor 4. These findings indicate MBP as an RNA-binding protein capable of MG nuclear import, providing insight into neuroinflammatory pathology of MS.

neuroscience↗

bioRxiv2025

Foraging ecology drives viral community structure in New Zealand's aquatic birds

Wild migratory birds play a major role in the global spread of viruses, yet the diversity, host range and transmission patterns of viruses harboured by migratory species in Aotearoa/New Zealand remain largely unknown. This knowledge gap is critical given New Zealands position along major migratory flyways spanning Oceania, Antarctica and east Asia, where understanding viral diversity is key to assessing the risk of viral introductions such as highly pathogenic avian influenza virus and viral dispersal across these regions. To address this, we conducted the first large-scale metatranscriptomic survey of wild birds from New Zealand and its subantarctic islands, collecting 1,348 samples from 31 host species spanning four avian orders. We identified 118 avian viruses from 17 families, including 107 novel species, greatly expanding our knowledge of avian viral diversity. Viral communities differed significantly by host order and foraging behaviour, with scavenger birds harbouring more diverse viromes than non-scavengers. Although no HPAI subtypes were detected, we recovered a low-pathogenic avian influenza A/H1N9 virus from red knots (Calidris canutus) and a divergent tobanivirus from Auckland Island teal (Anas aucklandica), the first putative avian member of the Tobaniviridae. Notably, we detected 12 mammalian-associated viruses, primarily in scavenger birds, including Hedgehog hepatovirus, Rabbit haemorrhagic disease virus 2, and sea lion astroviruses, with mammalian host reads confirming their dietary origin. This study establishes the first virome baseline for New Zealands migratory birds, highlighting the ecological role of foraging in shaping viral communities and improving regional preparedness for HPAI and other emerging avian pathogens.

microbiology↗

bioRxiv2025

The UTRs of Leishmania donovani vary in length and are enriched in potential regulatory structures

Leishmania spp. regulate gene expression largely post-transcriptionally, yet untranslated regions (UTRs) remain poorly delineated. We generated high-quality genome and transcriptome datasets for Leishmania donovani strain 1S2D (Ld1S) by combining PacBio HiFi de novo assembly with Oxford Nanopore direct RNA sequencing of promastigotes and axenic amastigotes. The genome assembly consists of 65 scaffolds totaling [~]33.3 Mb. Structural comparisons to LdBPK282A1 revealed numerous rearrangements, including some reshufling genes among polycistronic transcription units and validated by polycistronic reads from RNA sequencing. Promastigote and amastigote RNA sequencing produced 469,010 and 46,729 monocistronic reads containing a spliced-leader and a polyA tail sequences, defining 8,479 transcripts and supporting 7,415 of the 7,969 annotated protein coding genes, as well as 604 putative long non-coding RNAs. We annotated UTRs for 4,921 genes and observed that putative RNA G-quadruplexes were markedly enriched in UTRs. We also noted that 31.9% and 11.5% were expressed into multiple isoforms in promastigotes and amastigotes, respectively. Collectively, these data provide a comprehensive annotation of L. donovani genes and their UTRs and reveal widespread and stage-specific UTR length polymorphisms, and, overall, points to an important role of 3 UTR in post-transcriptional regulation in L. donovani. Author SummaryLeishmania donovani parasites cause visceral leishmaniasis, a deadly disease affecting hundreds of thousands of people worldwide. Unlike most eukaryotes, these parasites do not regulate their genes mainly at the level of transcription. Instead, control happens after the genes are transcribed, and much of this regulation depends on regions of RNA that are not translated into protein, called untranslated regions (UTRs). However, UTRs in Leishmania have remained poorly characterized. Here we generated high-quality genome and transcriptome resources for a clinical strain of L. donovani. By combining state-of-the-art long-read sequencing technologies, we precisely mapped thousands of UTRs and discovered that many genes produce transcripts with variable UTR lengths that differ between parasite life stages. We also found that UTRs are enriched in RNA structures called G-quadruplexes, which are known to influence gene regulation. These findings provide the most comprehensive view to date of UTRs in Leishmania and highlight their central role in controlling how genes are expressed during the parasites life cycle. Our work lays a foundation for future studies aimed at understanding parasite biology and identifying new targets for intervention.

genomics↗

bioRxiv2022

Urine production rate is critical in a model for catheter-associated urinary tract infection

Urinary catheters are used extensively in hospitals and long-term care and they are highly prone to infection. Understanding the pathways by which bacteria colonise a urinary catheter could guide strategies to mitigate infection, but quantitative models for this colonisation process are lacking. Here we present a mathematical model for bacterial colonisation of a urinary catheter, that integrates population dynamics and fluid dynamics. The model describes bacteria migrating up the outside surface of the catheter, spreading into the bladder and being swept through the catheter lumen. Computer simulations of the model reveal that clinical outcomes for long-term versus short-term catheterisation are controlled by different factors: the rate of urine production by the kidneys as opposed to urethral length, catheter surface properties and bacterial motility. Our work may help explain variable susceptibility to catheter-associated urinary tract infection (CAUTI) among individuals, and the mixed success of antimicrobial surface coatings. Our model suggests that for long-term catheterised patients, increasing fluid intake or reducing residual urine volume in the bladder may help prevent infection, while antimicrobial surface coatings are predicted to be effective only for short-term catheterised patients. Therefore, different catheter management strategies could be rationally targeted to long-term vs short-term catheterised patients.

biophysics↗

bioRxiv2022

A new paradigm for personal protection against ticks: efficacy of spatial repellents to reduce host seeking activities in three major tick species of medical importance

Addressing the prevalence of tick-borne disease requires robust chemical options as an integral component of Integrative Vector Management (IVM) program. Spatial repellency is a novel concept in tick bite prevention. To date, there is no standard for the evaluation of spatial repellency against ticks, despite the speculated value of volatilized chemicals in control systems. This study reports a novel vertical climb assay that was specifically created for the quantitative evaluation of spatial repellency in ticks. Controlled release devices (CRDs) were used to control the dispersion of multiple Active Ingredients (AIs) transfluthrin, metofluthrin, nootkatone, and DEET against adult females of three medically important tick species: Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis. Results of our study indicate significant associations between AI exposure and changing in tick climbing behavior when compared controls in the absence of the AI, from several perspectives, including changes in tick movement velocity, displacement, detachment, and rate of successful vertical climbing. Metofluthrin and transfluthrin caused strong reductions in host seeking activities against D. variabilis and A. americanum, while both demonstrated slightly weaker effects against I. scapularis. Further work is planned to evaluate spatial repellency in ticks in more natural environments and assess their potential in future tick control programs.

zoology↗

bioRxiv2021

Glyphosate and its formulations Roundup Bioflow and RangerPro alter bacterial and fungal community composition in the rat caecum microbiome

The potential health consequences of glyphosate-induced gut microbiome alterations have become a matter of intense debate. As part of a multifaceted study investigating toxicity, carcinogenicity and multigenerational effects of glyphosate and its commercial herbicide formulations, we assessed changes in bacterial and fungal populations in the caecum microbiota of rats exposed prenatally until adulthood (13 weeks after weaning) to three doses of glyphosate (0.5, 5, 50 mg/kg body weight/day), or to the formulated herbicide products Roundup Bioflow and RangerPro at the same glyphosate-equivalent doses. Caecum bacterial microbiota were evaluated by 16S rRNA sequencing whilst the fungal population was determined by ITS2 amplicon sequencing. Results showed that both fungal and bacterial diversity were affected by the Roundup formulations in a dose-dependent manner, whilst glyphosate alone significantly altered only bacterial diversity. At taxa level, a reduction in Bacteroidota abundance, marked by alterations in the levels of Alloprevotella, Prevotella and Prevotellaceae UCG-003, was concomitant to increased levels of Firmicutes (e.g., Romboutsia, Dubosiella, Eubacterium brachy group or Christensenellaceae) and Actinobacteria (e.g., Enterorhabdus, Adlercreutzia, or Asaccharobacter). Treponema and Mycoplasma also had their levels reduced by the pesticide treatments. Analysis of fungal composition indicated that the abundance of the rat gut commensal Ascomycota Kazachstania was reduced while the abundance of Gibberella, Penicillium, Claviceps, Cornuvesica, Candida, Trichoderma and Sarocladium were increased by exposure to the Roundup formulations, but not to glyphosate. Altogether, our data suggest that glyphosate and its Roundup RangerPro and Bioflow caused profound changes in caecum microbiome composition by affecting the fitness of major commensals, which in turn reduced competition and allowed opportunistic fungi to grow in the gut, in particular in animals exposed to the herbicide formulations. This further indicates that changes in gut microbiome composition might influence the long-term toxicity, carcinogenicity and multigenerational effects of glyphosate-based herbicides.

pharmacology and toxicology↗

bioRxiv2021

Dynamic Flux Balance Analysis Game

Flux balance analysis (FBA) for microbial communities often assumes a global objective function that all species cooperatively maximize in addition to maximizing their own growth. Combining community FBA with dynamic FBA to understand the time course and steady states of communities typically entails discretizing time and solving a community FBA model at each time point, a time-intensive process. We propose a dynamic community FBA model where species compete for metabolites to grow off of without needing to cooperate to maximize a community-level objective. An efficient method for computing steady state community compositions is provided, as well as methods for determining the stability of a steady state community to perturbations in biomass and invasion by species outside the community. The model and methods are applied to a model of four E. coli mutants with elements of competition (for shared metabolites) and cooperation (via mutants being auxotrophic for metabolites exported by other mutants), as well as a nine-species gut microbiome model.

systems biology↗

bioRxiv2021

Transient Kinetic Proofreading

We propose a new stochastic model for understanding the transient kinetic proofreading mechanism in a T-cell. Our model indicates that a stochastic version of absolute ligand discrimination is a consequence of the finite number of receptors on the cell surface; thus, pointing to receptor number control as being critical to T-cell activation. We propose four different metrics to characterize the performance of kinetic proofreading mechanisms. We explore the numerical experiments that explore the trade-offs between speed, specificity, sensitivity, and robustness of T-cell activation as a function of the model parameters. We also consider the impact of receptor clustering on these trade-offs.

immunology↗

bioRxiv2021

Membrane-Tethered Mucin 1 is Stimulated by Interferon in Multiple Cell Types and Antagonizes Influenza A Virus Infection in Human Airway Epithelium

Influenza A virus (IAV) causes seasonal epidemics and periodic pandemics, resulting in significant morbidity and mortality in the human population. Tethered mucin 1 (MUC1) is highly expressed in airway epithelium, the primary site of IAV replication, and also by other cell types that influence IAV infection, including macrophages. MUC1 has the potential to influence infection dynamics through physical interactions and/or signaling activity, and recent work suggests MUC1 acts as a releasable decoy receptor and anti-inflammatory molecule during IAV infection. Still, the modulation of MUC1 and its impact during viral pathogenesis remains unclear. Thus, we sought to further investigate the interplay between MUC1 and IAV in an in vitro model of primary human airway epithelium (HAE). Our data indicate that a recombinant IAV hemagglutinin (H3) and H3N2 virus can bind endogenous HAE MUC1. We find that infection of HAE cultures with H1N1 or H3N2 IAV strains does not trigger enhanced MUC1 shedding, but instead stimulates an increase in cell-associated MUC1 protein. We observed a similar increase after stimulation with either type I or type III interferon (IFN); however, inhibition of IFN signaling during H1N1 infection only partially abrogated this increase, indicating multiple soluble factors contribute to MUC1 upregulation during the antiviral response. We expanded these findings and demonstrate that in addition to HAE, primary human monocyte-derived macrophages also upregulate MUC1 protein in response to both IFN treatment and conditioned media from IAV-infected HAE cultures. We then developed HAE genetically depleted for MUC1 to determine its impact on IAV pathogenesis, finding that MUC1 knock-out cultures exhibited enhanced viral growth compared to control cultures for several IAV strains. Together, our data support a model whereby MUC1 antagonizes productive uptake of IAV in HAE. Infection then stimulates MUC1 expression on multiple cell types through IFN-dependent and -independent mechanisms that may further impact infection dynamics. Author SummaryThe mucosal surface of the respiratory epithelium is an important site of first contact for viral respiratory pathogens. Large and heavily glycosylated molecules known as tethered mucins extend from the cell surface and may physically restrict access to underlying cells. Recently, one of these tethered mucins, MUC1, has also been shown to influence cell signaling and inflammation. Still, despite its abundance in the airway and multifunctional capability, the role of MUC1 during influenza virus infection in the human respiratory tract remains unclear. Here, we demonstrate that influenza virus directly interacts with MUC1 in a physiologically-relevant model of human airway epithelium and find that MUC1 protein expression is elevated throughout the epithelium and in primary human monocyte-derived macrophages in response to important antiviral signals produced during infection. Using genetically-modified human airway cultures lacking MUC1, we then provide evidence of more efficient influenza virus infection in the absence of this mucin. Our data suggest that MUC1 not only physically restricts influenza virus uptake, but also represents a dynamic component of the host response that acts to further stem viral spread.

microbiology↗

bioRxiv2020

USP11 deubiquitinates monoubiquitinated SPRTN to repair DNA-protein crosslinks

SUMMARYDNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with DNA metabolic processes such as replication, transcription and recombination. SPRTN is a replication-coupled DNA-dependent metalloprotease that cleaves proteins crosslinked to DNA to promote DPC repair. SPRTN function is tightly regulated by a monoubiquitin switch that controls SPRTN chromatin accessibility during DPC repair. The deubiquitinase regulating SPRTN function in DPC repair is unknown. Here, we identify USP11 as a SPRTN deubiquitinase. USP11 interacts with SPRTN and cleaves monoubiquitinated SPRTN in cells and in vitro. USP11 depletion impairs SPRTN deubiquitination in response to formaldehyde-induced DPCs. Loss of USP11 causes an accumulation of unrepaired DPCs and cellular hypersensitivity to treatment with DPC-inducing agents. Our findings elucidate the function of USP11 in the regulation of SPRTN monoubiquitination and SPRTN-mediated DPC repair.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗

bioRxiv2019

Chromosomal length reference assembly for Diaphorina citri using single-molecule sequencing and Hi-C proximity ligation with manually curated genes in developmental, structural and immune pathways

BackgroundDiaphorina citri is a vector of "Candidatus Liberibacter asiaticus" (CLas), the gram-negative bacterial pathogen associated with citrus greening disease. Control measures rely on pesticides with negative impacts on the environment, natural ecosystems and human and animal health. In contrast, gene-targeting methods have the potential to specifically target the vector species and/or reduce pathogen transmission. ResultsTo improve the genomic resources needed for targeted pest control, we assembled a D. citri genome based on PacBio long reads followed by proximity ligation-based scaffolding. The 474 Mb genome has 13 chromosomal-length scaffolds. 1,036 genes were manually curated as part of a community annotation project, composed primarily of undergraduate students. We also computationally identified a total of 1,015 putative transcription factors (TFs) and were able to infer motifs for 337 TFs (33 %). In addition, we produced a genome-independent transcriptome and genomes for D. citri endosymbionts. ConclusionsManual annotation provided more accurate gene models for use by researchers and also provided an excellent training opportunity for students from multiple institutions. All resources are available on CitrusGreening.org and NCBI. The chromosomal-length D. citri genome assembly serves as a blueprint for the development of collaborative genomics projects for other medically and agriculturally significant insect vectors.

genomics↗

bioRxiv2019

Reproducible Tract Profiles (RTP): from diffusion MRI acquisition to publication

Reproducible Tract Profiles (RTP) comprises a set of methods to manage and analyze diffusion weighted imaging (DWI) data for reproducible tractography. The tools take MRI data from the scanner and process them through a series of analysis implemented as Docker containers that are integrated into a modern neuroinformatics platform (Flywheel). The platform guarantees that the entire pipeline can be re-executed, using the same data and computational parameters. In this paper, we describe (1) a cloud based neuroinformatics platform, (2) a tool to programmatically access and control the platform from a client, and (3) the DWI analysis tools that are used to identify the positions of 22 tracts and their diffusion profiles. The combination of these three components defines a system that transforms raw data into reproducible tract profiles for publication.\n\nGraphical abstractReproducible Tract Profiles (RTP) comprises a set of methods to manage and analyze diffusion weighted imaging (DWI) data for reproducible tractography. The RTP methods comprise two main parts. O_LIServer side software tools for storing data and metadata and managing containerized computations.\nC_LIO_LIClient side software tools that enable the researcher to read data and metadata and manage server-side computations.\nC_LI\n\nThe server-side computational tools are embedded in containers that are linked to a JSON file with a complete specification of the computational parameters. The data and computational infrastructure on the server is fully reproducible.

neuroscience↗

bioRxiv2018

HLA-DQA1*05 is associated with the development of antibodies to anti-TNF therapy

BackgroundAnti-tumour necrosis factor (anti-TNF) therapies are the most widely used biologic therapies for treating immune-mediated diseases. Their efficacy is significantly reduced by the development of anti-drug antibodies which can lead to treatment failure and adverse reactions. The biological mechanisms underlying antibody development are unknown but the ability to identify subjects at higher risk would have significant clinical benefits.\n\nMethodsThe PANTS cohort consists of Crohns disease patients recruited prior to first administration of anti-TNF, with serial measurements of anti-drug antibody titres. We performed a genome-wide association study across 1240 individuals from this cohort to identify genetic variants associated with anti-drug antibody development.\n\nFindingsThe Human Leukocyte Antigen allele, HLA-DQA1*05, carried by approximately 40% of Europeans, significantly increased the rate of anti-drug antibody development (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60 to 2.25; P=5.88x10-13). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32 to 2.70) and infliximab (HR, 1.92; 95% CI, 1.57 to 2.33), and for patients treated with mono-(HR, 1.75; 95% CI, 1.37 to 2.22) or combination therapy with immunomodulators (HR, 2.0; 95% CI, 1.57 to 2.58).\n\nInterpretationHLA-DQA1*05 is significantly associated with an increased rate of anti-drug antibody formation in patients with Crohns disease treated with infliximab and adalimumab. Pre-treatment HLA-DQA1*05 genetic testing may help personalise the choice of anti-TNF therapy and allow the targeted use of immunomodulator therapy to minimise risk and maximise response.

genomics↗

bioRxiv2017

Framework For Quality Assessment Of Whole Genome, Cancer Sequences

Working with cancer whole genomes sequenced over a period of many years in different sequencing centres requires a validated framework to compare the quality of these sequences. The Pan-Cancer Analysis of Whole Genomes (PCAWG) of the International Cancer Genome Consortium (ICGC), a project a cohort of over 2800 donors provided us with the challenge of assessing the quality of the genome sequences. A non-redundant set of five quality control (QC) measurements were assembled and used to establish a star rating system. These QC measures reflect known differences in sequencing protocol and provide a guide to downstream analyses of these whole genome sequences. The resulting QC measures also allowed for exclusion samples of poor quality, providing researchers within PCAWG, and when the data is released for other researchers, a good idea of the sequencing quality. For a researcher wishing to apply the QC measures for their data we provide a Docker Container of the software used to calculate them. We believe that this is an effective framework of quality measures for whole genome, cancer sequences, which will be a useful addition to analytical pipelines, as it has to the PCAWG project.

genomics↗