Biology subjects

Taylor, E.

Publications and source records attributed to Taylor, E..

At least 19 recordsLinked to original sources

bioRxiv2026

Integrative morphology and phylogenetics of Arcellidae (Amoebozoa:Arcellinida), with redescription of Arcella leidyana and Arcella artocrea and description of Galeripora purdoni sp. nov.

Arcellidae is a family of testate amoebae within Arcellinida (Amoebozoa), comprising three recognized genera: Arcella, Galeripora, and Antarcella. Although species in the family have been studied for nearly two centuries, many historically described taxa and major morphological groups remain unsampled at the molecular level. Here, we provide a comprehensive review of Arcellidae and generate new cytochrome c oxidase subunit I (COI) sequences for arcellid species from Canadian peatlands, focusing on tall-shelled Arcella historically classified in section Altae sensu Deflandre. COI phylogenetic analyses recover a strongly supported monophyletic clade corresponding to North American representatives of Altae, providing the first molecular corroboration of this morphologically defined group. Within this clade, we redescribe Arcella leidyana based on modern material from Eeyou Istchee (Quebec). We further describe Galeripora purdoni sp. nov. from a calcareous fen in eastern Ontario, representing a novel terrestrial lineage within the genus, and redescribe Galeripora artocrea, which we transfer to Arcella based on congruent molecular and morphological evidence. Phylogenomic analyses of Arcellidae isolates from the Protist 10,000 Genomes Project reveal an additional deep lineage basal to Arcella and Galeripora. Together, these results highlight hidden diversity and demonstrate the importance of integrative approaches for resolving arcellid systematics and refining its classification.

evolutionary biology↗

bioRxiv2026

Gene model for the ortholog of Lst8 in Drosophila yakuba

Gene model for the ortholog of Lst8 (Lst8) in the May 2011 (WUGSC dyak_caf1/DyakCAF1) Genome Assembly (GenBank Accession: GCA_000005975.1) of Drosophila yakuba. This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

genomics↗

bioRxiv2026

Molecular Glue-like Degraders of TEM β-Lactamases by Periplasmic Protease DegP

Antimicrobial resistance is one of the most serious challenges to global health, yet the development of new molecules with novel mechanisms of action to combat resistance is lacking. Here, we report the discovery of molecular glue-like compounds that recruit TEM-family {beta}-lactamases to the bacterial protease DegP for degradation. {beta}-lactamase inhibitor tazobactam was found to accelerate degradation of TEM {beta}-lactamases by DegP, which was further enhanced by linkerless incorporation of dipeptide motifs enriched among DegP substrates. The resulting molecular glue-like degraders showed improved synergy with {beta}-lactam piperacillin against resistant E. coli compared to tazobactam, as well as good pharmacokinetic properties for oral dosing. Collectively, this work establishes periplasmic targeted protein degradation as a promising new mechanism for combating {beta}-lactamase resistance.

molecular biology↗

bioRxiv2026

YdbL directly modulates YdbH-YnbE bridge formation to maintain Escherichia coli outer membrane homeostasis

Gram-negative bacteria pose a threat to global healthcare mainly because their outer membrane (OM) provides an intrinsic barrier to many antimicrobials. Key to this barrier function is the asymmetric structure of the OM, with phospholipids constituting the inner leaflet and lipopolysaccharides the outer leaflet. Although the mechanism of phospholipid transport between the inner membrane (IM) and OM remains poorly understood, recent studies implicate TamB, YhdP, and YdbH as functionally redundant proteins mediating this process in Escherichia coli. Accordingly, collective loss of these three paralogs is lethal and any one of them is sufficient for growth. YdbH is anchored to the IM and its periplasmic repeating {beta}-sheet groove domain interacts with the OM lipoprotein YnbE via {beta}-strand augmentation to form an intermembrane bridge. Additionally, YnbE multimerizes, and the periplasmic protein YdbL is proposed to modulate YnbE multimerization to facilitate its stacking on the C-terminus of YdbH. Here, we demonstrate that excess YdbL specifically inhibits the function of the YdbH-YnbE complex since overexpression of ydbL causes lethality in the {Delta}yhdP {Delta}tamB double mutant but the presence of both ydbH and ynbE in trans abrogates this lethality. We resolve high-resolution structural data for YdbL and ascertain its interaction site with the YnbE C-terminal -helix, with residues mediating this interface highly conserved and critical for YdbL function. Finally, we show that YdbL is protected from degradation by the protease DegP when complexed with YnbE. Overall, our data supports a model in which YdbL ensures proper YdbH-YnbE intermembrane bridge formation by directly interacting with YnbE.

microbiology↗

bioRxiv2025

Reducing Foetal Bovine Serum Culture Conditions does not affect GPCR Signalling

Animal use in research extends beyond the use of animal models to study physiology and disease. Many aspects of in vitro research use reagents derived from animals, most prolifically the use of foetal bovine serum (FBS) in growth media for cellular models. With the aim to reduce animal use, we investigated the effect of reduced FBS culture conditions on cell growth, as well as different stages of G protein-coupled receptor (GPCR) signalling, a wide area of research which might therefore impact many groups. We identified little differences on cell growth or GPCR signalling when reducing culture FBS percentage from 10% to 5%, using assays ranging from receptor activation to downstream transcription factors stimulation. In addition to diminishing animal use, the reduction of FBS use will also have economic and environmental benefits, which we hope will be of benefit to the wider research community.

pharmacology and toxicology↗

bioRxiv2025

Tissue-specific consequences of tag fusions on protein expression in transgenic mice

Genetic fusion of protein tags is widely used to study protein functions in vivo. It is well known that tag fusion can cause unwanted changes in protein stability, but whether this is an inherent property of the tagged protein, or can be influenced by the cell and tissue environment, is unclear. Using a series of genome edited mouse models, we show that tag-dependent changes in protein expression can vary across different primary cell and tissue contexts. In one case (Ncaph2), a C-terminal auxin-inducible degron fusion strongly increased protein stability in some tissues but decreased it in others. Destabilisation resulted from tissue-specific leakage of the auxin-inducible degron, which depended on TIR1 expression, and occurred selectively in the small intestine where basal concentrations of auxin / indole-3-acetic acid can reach levels that are sufficient to trigger protein degradation in cultured cells. Stabilisation occurred in post-mitotic cells via an endogenous degradation signal situated at the Ncaph2 C-terminus, which normally undergoes activation upon cell cycle exit, but is inactivated by C-terminal tag fusion. Our results highlight the underappreciated importance of cell and tissue environment in determining the consequences of tag fusions on protein expression, which may be particularly important in animal models that contain diverse cell types.

molecular biology↗

bioRxiv2025

PARP1 and PARP2 are dispensable for DNA repair by microhomology-mediated end-joining during mitosis.

Poly ADP-ribose polymerase (PARP) inhibitors are standard of care treatment for cancers with homologous-recombination deficiencies. Yet, as tumors develop resistance, complementary strategies are emerging, including targeting microhomology-mediated end joining (MMEJ). Given that PARP1 is widely described as a key promoter of MMEJ, one would expect PARP inhibition to suppress MMEJ--potentially making MMEJ inhibition redundant. MMEJ was originally described as a backup pathway, with seminal work linking PARP1 to MMEJ conducted in NHEJ-deficient cells, where MMEJ can be reactivated in G1. However, we now appreciate that MMEJ is a mitotic repair mechanism, but the function of PARP1 in this context remains unclear. Here, we systematically explore the effect that PARP/PARPi have on MMEJ activity in cells with intact NHEJ. Surprisingly, PARP inhibition leads to elevated Pol{theta}-dependent MMEJ levels at ISceI-mediated DSBs, which we find is due to PARP1s regulation of competing pathways at these breaks. Importantly, we show that PARP is dispensable for MMEJ at double-ended DSBs and is expendable for repair of DSBs during mitosis. Altogether, this data shifts the understanding of PARPs role in MMEJ and DNA repair pathway choice. Moreover, we believe this data further strengthens a rationale for PARPi/MMEJi combinatorial drug treatment in HR-deficient cancers.

molecular biology↗

bioRxiv2025

High-Throughput Human Gut Immune Co-Culture Model for Evaluating Inflammatory Bowel Disease Anti-Inflammatory Therapies

Current treatments for inflammatory bowel disease (IBD) are often ineffective long-term, as many patients ultimately become unresponsive to anti-inflammatory drugs. The need for improved therapeutics is urgent. Animal models utilized for drug development are limited by interspecies variability and poor translatability. However, most in vitro models lack the sophistication to model the key interplay of the immune system with the intestinal epithelium in line with the known role of the immune system in the etiology of the disease. To address this gap, we developed a primary intestinal epithelial cell co-culture system to incorporate elements of innate immune signaling. This system models immune-epithelial interactions using RepliGut(R) - Planar Transverse Colon cultured on a Transwell system with THP-1 derived macrophages in a receiver compartment of a 96-well plate. Epithelial barrier integrity and cell viability were maintained in co-culture with unstimulated macrophages. However, similar to the pathology associated with IBD, epithelial integrity was compromised in co-culture with LPS + IFN-{gamma} pre-stimulated macrophages as evidenced by declining TEER and cell viability and increased inflammatory cytokine release. Cotreatment with anti-inflammatory IBD therapeutics adalimumab or tofacitinib mitigated these effects, demonstrating the models ability to replicate key inflammatory responses and prevention. Reproducibility and scalability of the model system further position the model for high-throughput screening of anti-inflammatory drugs, improving drug discovery, and accelerating the translation of new IBD therapies into clinical practice. HighlightsO_LICo-culture model: RepliGut(R) - Planar Transverse Colon with THP-1 derived macrophages C_LIO_LIHigh throughput and human-relevant model C_LIO_LI"Healthy" co-culture resembling healthy intestine C_LIO_LI"Inflamed" co-culture mimicking IBD innate inflammatory signaling C_LIO_LIPotential to screen anti-inflammatory drugs relevant to IBD C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/654072v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@101a675org.highwire.dtl.DTLVardef@157605borg.highwire.dtl.DTLVardef@1770c97org.highwire.dtl.DTLVardef@dbc9c0_HPS_FORMAT_FIGEXP M_FIG Gut-immune co-culture model simulating healthy and inflamed intestine. The immune co-culture model consists of mature differentiated primary human transverse colon epithelial cells cultured on a 96-well Transwell(R) plate with macrophage differentiated THP-1 cells (THP-1m) cultured in the receiver plate. In this configuration, the THP-1m are located basally to the epithelial cells, allowing for apical treatment in the transwell and basal treatment in the receiver plate. In the unstimulated state, intestinal cells and immune cells maintain a stable co-culture. Upon stimulation with LPS and IFN-y, both cell types initiate an inflammatory response that results in release of cytokines, loss of intestinal barrier integrity, and cytotoxicity. C_FIG

immunology↗

bioRxiv2025

Wnt signaling drives stromal inflammation in inflammatory arthritis

The concept that fibroblasts are critical mediators of inflammation is an emerging paradigm. In rheumatoid arthritis (RA), they are the main producers of IL-6 as well as a host of other cytokines and chemokines. Their pathologic activation also directly causes cartilage and bone degradation. Yet, therapeutic agents specifically targeting fibroblasts are not available. Here, we find that Wnt receptors and modulators are predominantly expressed in stromal populations in the synovium. Importantly, non-canonical Wnt activation induces robust inflammatory gene expression including an abundance of cytokines and chemokines in synovial fibroblasts in vitro. Strikingly, the addition of Wnt ligands or inhibition of Wnt secretion exacerbates or reduces arthritis severity, respectively, in vivo in a murine model of inflammatory arthritis. These observations are relevant in human disease, as Wnt activation signatures are enhanced in fibroblasts derived from inflamed RA synovial tissue as well as fibroblasts across other inflammatory diseases. Together, these findings implicate Wnt signaling as a major driver of fibroblast-mediated inflammation and joint pathology. They further suggest that targeting the Wnt pathway is a therapeutically relevant approach to rheumatoid arthritis, particularly in patients who do not respond to conventional treatments and who often express fibroblast-predominant synovial phenotypes.

immunology↗

bioRxiv2024

Meioc-Piwil1 complexes regulate rRNA transcription for differentiation of spermatogonial stem cells

Ribosome biogenesis is vital for sustaining stem cell properties, yet its regulatory mechanisms are obscure. Herein, we show unique properties of zebrafish meioc mutants in which spermatogonial stem cells (SSCs) do not differentiate or upregulate rRNAs. Meioc colocalized with Piwil1 in perinuclear germ granules, but Meioc depletion resulted in Piwil1 accumulation in nucleoli. Nucleolar Piwil1 interacted with 45S pre-rRNA. piwil1+/-spermatogonia with reduced Piwil1 upregulated rRNAs, and piwil1+/-;meioc-/- spermatogonia recovered differentiation later than those in meioc-/-. Further, Piwil1 interacted with Setdb1 and HP1, and meioc-/- spermatogonia exhibited high levels of H3K9me3 and methylated CpG in the 45S-rDNA region. These results indicate that zebrafish SSCs maintain low levels of rRNA transcription with repressive marks similar to Drosophila piRNA targets of RNA polymerase II, and that Meioc has a unique function on preventing localization of Piwil1 in nucleoli to upregulate rRNA transcripts and to promote SSC differentiation.

developmental biology↗

bioRxiv2024

Asymptomatic infection and antibody prevalence to co-occurring avian influenza viruses vary substantially between sympatric seabird species following H5N1 outbreaks

Emerging infectious diseases are of major concern to animal and human health. Recent emergence of high pathogenicity avian influenza virus (HPAIV) (H5N1 clade 2.3.4.4b) led to substantial global mortality across a range of host species. Co-occurring species showed marked differences in mortality, generating an urgent need for better epidemiological understanding within affected populations. We therefore tested for antibodies, indicative of previous exposure and recovery, and for active viral infection in apparently healthy individuals (n=350) across five co-occurring seabird species on the Isle of May, Scotland, during 2023, following H5N1 HPAIV associated mortality in the preceding summer. Antibody prevalence to AIV subtypes varied substantially between species, ranging from 1.1% in European shags (Gulosus aristotelis) (to H5) to 78.7% in black-legged kittiwakes (Rissa tridactyla) (to H16 or both H13 and H16), and between 31-41% for three auk species (H5, H16 or both). At least 20.4% of auks had antibodies to an as yet unidentified subtype, suggesting further subtypes circulating in the population. We found low levels of active, but asymptomatic, AIV infection in individuals (1.6-4.5%), but excluded this as H5N1. Our results emphasise the importance of testing healthy individuals to understand the prevalence of co-circulating AIV subtypes in wild populations, and the potential for future reassortment events which could alter virus behaviour and impact.

ecology↗

bioRxiv2024

Insect size responses to climate changes vary across elevations according to seasonal timing

Widespread plastic and evolutionary responses to temperature have led to body size declines being proposed as a universal response to warming, but the high degree of variation in terrestrial ectotherms has challenged this view. We investigate whether temperature dependent development and growth rates in ectothermic organisms drive departures from universal size responses. Leveraging a long-term study of montane grasshoppers, we detect size shifts over recent decades that depend on elevation and species seasonal timing. Size shifts have been focused at low elevations with the earliest emerging species (those that overwinter as juveniles) getting bigger, and later season species getting smaller. The shifts correspond to warmer temperatures at low elevation increasing the sizes of the earliest season species but decreasing the sizes of the later season species. This is consistent with our hypothesis that the earliest season species may be able to take advantage of warmer conditions accelerating growth during early spring development, whereas warm temperatures may adversely impact later season species via mechanisms such as increased rates of energy use or thermal stress. Grasshoppers tend to capitalize on warm conditions by both getting bigger and reaching adulthood earlier. Our analysis further reinforces the need to move beyond expectations of universal responses to climate change to consider how environmental exposure and sensitivity varies across elevations and life histories.

ecology↗

bioRxiv2024

Sir2 and Fun30 regulate ribosomal DNA replication timing via Mcm helicase positioning and nucleosome occupancy

The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well-known, yet the specific mechanisms underlying this link remain uncertain. In Saccharomyces cerevisiae, the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA arrays (rDNA). We have previously reported that in the absence of SIR2, a derepressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy. By developing a method that can distinguish activation of closely spaced MCM complexes, here we show that the displaced MCMs at rDNA origins have increased firing propensity compared to the nondisplaced MCMs. Furthermore, we found that both, activation of the repositioned MCMs and low occupancy of the adjacent nucleosomes critically depend on the chromatin remodeling activity of FUN30. Our study elucidates the mechanism by which Sir2 delays replication timing, and it demonstrates, for the first time, that activation of a specific replication origin in vivo relies on the nucleosome context shaped by a single chromatin remodeler.

genetics↗

bioRxiv2024

Quantifying the IUCN Red List: Using historical assessments to calculate future extinction risk

The IUCN Red List of Threatened Species assigns species to discrete categories based on a common set of criteria to capture relative extinction risk. Some quantitative analyses require a continuous probability of extinction not provided by discrete categories. Furthermore, the criteria may not translate to extinction risk in a universal way across species, because some species attributes are not incorporated into the criteria. Here we calculate extinction risk using Markov Models parameterised with historical IUCN Red List assessment data, and we provide quantitative extinction risk for use in downstream analyses. We find that taxonomy, body size, and habitat specialism interact with extinction risk in ways not fully captured by the existing categories. For example, an Endangered habitat specialist appears equally at risk compared to a Critically Endangered habitat generalist. We hope our findings will support more accurate quantitative biodiversity analyses of species extinctions and declines using Red List data.

ecology↗

bioRxiv2023

Low-Cost 3D-Printed Tools Towards Robust Longitudinal Multi-Modal Pre-Clinical Imaging

1Window chamber models enable a range of preclinical in-vivo optical studies with high spatial resolution and contrast, most notably probing the tumour microenvironment (TME). However, there are multiple sources of experimental variability that can affect the quality of the resultant data, especially in the context of longitudinal data acquisition, where accurate registration between images acquired at different times is crucial to understanding changes to the spatially heterogeneous TME. Further, it is challenging to correlate the findings of these models to clinical imaging modalities such as magnetic resonance imaging (MRI), which typically have much lower resolution and derive contrast from different physical mechanisms; yet such correlations may assist in the translation of window-chamber-derived basic preclinical insights into the clinic. Here, we describe the development and construction of a low-cost 3D-printable window chambers and compatible toolset to improve the accuracy, precision, and repeatability of longitudinal pre-clinical imaging and inter-modality co-registration at different spatial resolution scales. Such improvements in our novel multi-modal experimental pipeline may assist researchers in the acquisition and translation of TME biomarkers and other pre-clinical measurements from the window chamber model into the clinic.

biophysics↗

bioRxiv2022

The APE2 nuclease is essential for DNA double strand break repairby microhomology-mediated end-joining.

Microhomology-mediated end-joining (MMEJ) is an intrinsically mutagenic pathway of DNA double strand break repair essential for proliferation of homologous recombination (HR) deficient tumors. While targeting MMEJ has emerged as a powerful strategy to eliminate HR-deficient (HRD) cancers, this is limited by an incomplete understanding of the mechanism and factors required for MMEJ repair. Here, we identify the APE2 nuclease as a novel MMEJ effector. We show that loss of APE2 blocks the fusion of deprotected telomeres by MMEJ and inhibits MMEJ in DNA repair reporter assays to levels comparable to Pol Theta suppression. Mechanistically, we demonstrate that APE2 possesses intrinsic flap-cleaving activity, that its MMEJ function in cells depends on its nuclease domain and further identify uncharacterized domains required for recruitment to damaged DNA. We conclude that HR-deficient cells are addicted to APE2 due to a previously unappreciated role in MMEJ, which could be exploited in the treatment of cancer.

molecular biology↗

bioRxiv2022

Survival intravascular photoacoustic imaging of lipid-rich plaque in cholesterol fed rabbits

Intravascular photoacoustic (IVPA) imaging is a promising modality for quantitative assessment of lipid-laden atherosclerotic plaques. Yet, survival IVPA imaging of the same plaque in the same animal is not demonstrated. Here, using a sheathed IVUS/PA catheter of 0.9 mm in diameter, we demonstrate MRI-guided survival IVPA imaging of same plaque in an aorta of a well-established rabbit model mimicking atherosclerosis in human patients. The IVUS/PA results were confirmed by histology. These advances open the opportunity to evaluate the effectiveness of a therapy that aims to reduce the size of atherosclerotic plaques and demonstrates the potential of translating the IVPA catheter into clinic for detection of vulnerable plaques that are at high risk for thrombosis.

biophysics↗

bioRxiv2021

Characterization of cognitive-motor function in women who have experienced intimate partner violence-related brain injury

Intimate partner violence (IPV) affects at least 1 in 3 women worldwide and up to 92% report symptoms consistent with brain injury (BI). Although a handful of studies have examined different aspects of brain structure and function in this population, none has characterized potential deficits in cognitive-motor function. This knowledge gap was addressed in the current study by having participants who had experienced IPV complete the bimanual Object Hit & Avoid (OHA) task on a Kinarm End-Point Lab. BI load, as assessed by the Brain Injury Severity Assessment (BISA) tool as well as measures of comorbidities (PTSD, anxiety, depression, substance use, history of abuse) were also collected. Results demonstrated BI load accounted for a significant amount of variability in the number of targets hit and average hand speed. PTSD, anxiety, and depression also contributed significantly to the variability in these measures as well as to the number and proportion of distractor hits, and the object processing rate. Taken together, these findings suggest IPV-related BI, as well as comorbid PTSD, anxiety, and depression, disrupt the processing required to quickly and accurately hit targets while avoiding distractors. This pattern of results reflects the complex interaction between the physical injuries induced by the episodes of IPV and the resulting impacts these experiences have on mental health.

neuroscience↗