Biology subjects

Thompson, T.

Publications and source records attributed to Thompson, T..

15 recordsLinked to original sources

bioRxiv2026

A trait-based framework for quantifying arthropod invasion potential: Predictive modeling with Tropilaelaps mites as a case study

Over the past decade, the global rise in invasive species has accelerated at an unprecedented rate, intensifying threats to ecosystems, human health, and economies worldwide. Newly invasive taxa, such as Tropilaelaps mites, are of particular concern for apiculture and agroecosystems. Despite growing concern about the spread of Tropilaelaps mites and other arthropods, limited resources are available to assess their invasive potential. We characterized 118 invasive arthropod species using available literature to identify key biological and ecological traits associated with invasive potential. We developed predictive generalized linear mixed models (GLMMs) to determine the traits most important for predicting invasive potential (number of invaded regions), and the top-performing models were subsequently applied to Tropilaelaps mercedesae. Several traits were identified as significant predictors of invasiveness, including the degree of human association, resilience at small population sizes, diet breadth, maximum annual number of generations, altitude range, and the interaction between human association and temperature range. Notably, T. mercedesae was predicted to be capable of invading 160 regions, ranking it within the top 10% most invasive species among those evaluated (12th out of 119), ranked just below the cosmopolitan Varroa destructor mite. These findings position T. mercedesae as a high-risk, yet under-recognized, invasive threat. Collectively, this demonstrates the power of predictive trait-based modeling to inform invasion risk prior to widespread establishment and underscores the urgency of reallocating resources toward surveillance, research, and proactive management strategies rather than relying on costly, often ineffective post-establishment eradication.

ecology↗

bioRxiv2026

Discovery of Membrane Channel Modulators via DNA-Encoded Library Screening Using Native-Like Membrane Protein Nanoparticles

Developing novel drugs against membrane proteins is a major challenge in drug discovery due to the difficulty of stabilizing these targets for high-throughput screenings. Pannexin 1 (PANX1) is a membrane channel protein involved in various physiological and pathological processes, making it a promising target for drug discovery. However, efforts to develop PANX1-targeting therapeutics have been hindered by the inherent challenges of stabilizing the protein channel and conducting effective pharmacological screening. Here, we report a proof-of-concept workflow that integrates the Salipro lipid nanoparticle platform with DNA-Encoded Library screenings in a detergent-free format. In this case study, the Salipro DirectMX method was used to generate functional PANX1 nanoparticles for drug discovery and characterisation. Using a high-stringency selection strategy and computational approaches, we identified a specific set of candidate compounds with selective PANX1 enrichment. Surface Plasmon Resonance analysis confirmed the identification of hit compounds. Cryo-Electron Microscopy of the Salipro-PANX1-Compound complex provided structural insights into a potential compound binding site. Electrophysiological recordings in PANX1-expressing Xenopus laevis oocytes demonstrated dose-dependent inhibition of PANX1-mediated ion conductance by the compounds. These findings establish a robust workflow for ligand discovery against challenging membrane protein targets and provide novel chemical starting points for the development of PANX1 modulators.

biochemistry↗

bioRxiv2025

Stable Inheritance of Transgene and Yellow Fluorescent Protein Gene Expression in Progeny of Transgenic Cacao (Theobroma cacao) Plants

Genetic engineering tools have the potential to rapidly and precisely improve the genome of slow-to-breed cacao. We previously developed an efficient protocol for transforming cacao using cotyledonary explants derived from secondary somatic embryos via Agrobacterium tumefaciens. In this study, we demonstrate that our transformation protocol is successful in elite cultivars, INIAPG-038 and Matina 1-6, producing fertile seeds with stable visual marker inheritance regardless of whether the transgenic plants were used as the pollen or ovule donor. Three vectors were used in the transformations, each containing genes for enhanced yellow fluorescent protein (eyfp) and neomycin phosphotransferase II (nptII). Three transgenic INIAPG-038 events and one transgenic Matina 1-6 event were used to evaluate seed fertility and the stability of transgene inheritance in cacao seeds and plants. The T1 progeny of these four transgenic events were analyzed for YFP expression and transgene presence. YFP expression segregated at a 1:1 ratio in all events when the transgenic plants were crossed with non-transgenic plants, while a 3:1 segregation was observed when transgenic events were crossed with each other. The transgenic plants exhibited a normal phenotype compared to non-transgenic control plants, producing seeds with a 97% germination rate.

plant biology↗

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

Training and match running distances and perceived exertion at sea-level and altitude in elite North American soccer: A natural longitudinal cross-over case series.

PurposeThere is limited real-world data on differential perceptions of exertion in professional soccer at altitude. In a natural cross-over design, we quantified responses to training and matches at sea level and altitude. MethodsTotal, and high-speed, running distance and differential session ratings of perceived exertion for breathlessness (s-RPE-B) and leg exertion (s-RPE-L) were collected from 19 professional soccer players (age: 27.3 {+/-} 3.4 years, stature: 181.2 {+/-} 5.9cm, mass: 78.7 {+/-} 8.1kg) at sea-level and altitude. Data were collected for matches raining sessions one and two days pre match. ResultsDifferences between altitude conditions were estimated through mixed-linear modeling, with 95% confidence intervals representing values highly compatible with our observed data. In matches, total distance may have been reduced (95% confidence intervals 43 to -833 m, surprisal [s] = 3.74) and s-RPE-B may have increased (-0.6 to 10.7, s = 3.66) at altitude. A clear perceptual shift was observed with s-RPE-B increasing relative to s-RPE-L (-13.4 to -7.17, s >13) at altitude. Training at altitude included higher total (318 to 661 m, s > 13), and high-speed (33.1 to 93 m, s > 13), running distances but s-RPE-L reduced (-14.2 to -1.01, s = 5.39) and s-RPE-B increased relative to s-RPE-L (-15.1 to -3.93, s = 10.3). ConclusionsOur key finding was breathlessness increased relative to leg exertion at altitude.

physiology↗

bioRxiv2025

NETSseq Reveals Inflammatory and Aging Mechanisms in Distinct Cell Types Driving Cerebellar Decline in Ataxia Telangiectasia

The cellular and molecular changes driving the neurological abnormalities associated with ataxia - telangiectasia (A-T) are not well understood. Here, we applied our proprietary Nuclear Enriched Transcript Sort sequencing (NETSseq) platform to investigate changes in cell type composition and gene expression in human cerebellar post-mortem tissue from A-T and control donors. Compared to single-nuclei technologies, NETSseq provided a more robust detection of genes with low abundance, a higher cell type specific expression pattern, and significantly lower levels of cross-contamination. We found dysregulation in neurotransmitter signaling in granule neurons, potentially underlying the impaired motor coordination in A-T. Astrocytes and microglia have evidence of accelerated aging, with astrocytes being characterized by neurotoxic signatures, while microglia showed activation of DNA damage response pathways. These findings highlight the importance of NETSseq as a resource for investigating mechanisms and biological processes associated with disease, providing high-sensitivity, cell-specific insights to advance targeted therapies for neurodegenerative diseases.

neuroscience↗

bioRxiv2024

Validation of a Microfluidic Device Prototype for Cancer Detection and Identification: Circulating Tumor Cells Classification Based on Cell Trajectory Analysis Leveraging Cell-Based Modeling and Machine Learning

Microfluidic devices (MDs) present a novel method for detecting circulating tumor cells (CTCs), enhancing the process through targeted techniques and visual inspection. However, current approaches often yield heterogeneous CTC populations, necessitating additional processing for comprehensive analysis and phenotype identification. These procedures are often expensive, time-consuming, and need to be performed by skilled technicians. In this study, we investigate the potential of a cost-effective and efficient hyperuniform micropost MD approach for CTC classification. Our approach combines mathematical modeling of fluid-structure interactions in a simulated microfluidic channel with machine learning techniques. Specifically, we developed a cell-based modeling framework to assess CTC dynamics in erythrocyte-laden plasma flow, generating a large dataset of CTC trajectories that account for two distinct CTC phenotypes. Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN) were then employed to analyze the dataset and classify these phenotypes. The results demonstrate the potential effectiveness of the hyperuniform micropost MD design and analysis approach in distinguishing between different CTC phenotypes based on cell trajectory, offering a promising avenue for early cancer detection. Author summaryEarly detection is currently the most effective method to combat cancer, as it maximizes treatment options and improves potential survival rates. However, the cost of early detection presents a significant barrier, limiting access for underrepresented groups and discouraging industrial partners from investing in the research and development of screening devices. This study provides an in-silico conceptual validation for the development of an innovative hyperuniform microchip designed to identify circulating tumor cells (CTCs) without the need for biomarker labeling. We created a cell-based modeling framework to examine CTC dynamics in erythrocyte-laden plasma flow, producing an extensive dataset of CTC trajectories that reflect two distinct CTC phenotypes. Two machine learning architectures were utilized to analyze this dataset and classify the phenotypes. The results demonstrate the potential effectiveness of the hyperuniform micropost MD design and analysis approach in distinguishing between different CTC phenotypes based on cell trajectory, offering a promising and cost-effective method for early cancer detection.

cancer biology↗

bioRxiv2022

Deciphering the non-coding code of pathogenicity and sexual differentiation in the human malaria parasite.

The complex life cycle of Plasmodium falciparum requires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. However, this cascade of transcripts is unlikely to be regulated by the limited number of identified parasite-specific transcription factors. Increasing evidence now suggests a major role for epigenetic mechanisms in gene expression in the parasite. In eukaryotes, many lncRNAs have been identified and shown to be pivotal regulators of genome structure and gene expression. To investigate the regulatory roles of lncRNAs in P. falciparum we explored the intergenic lncRNA distribution in nuclear and cytoplasmic subcellular locations. Using nascent RNA expression profiles, we identified a total of 1,768 lncRNAs, of which 58% were identified as novel lncRNAs in P. falciparum. The subcellular localization and stage-specific expression of several putative lncRNAs were validated using RNA fluorescence in situ hybridization (RNA-FISH). Additionally, the genome-wide occupancy of several candidate nuclear lncRNAs was explored using Chromatin Isolation by RNA Purification (ChIRP). ChIRP-seq of candidate lncRNAs revealed that lncRNA occupancy sites within the parasite genome are focal and sequence-specific with a particular enrichment for several parasite-specific gene families, including those involved in pathogenesis, erythrocyte remodeling, and regulation of sexual differentiation. We further validated the function of one specific lncRNA (lncRNA-ch14) using the CRISPR-Cas9 genome editing tool. Genomic and phenotypic analysis of the {bigtriangleup}lncRNA-ch14 line demonstrated the importance of this lncRNA in sexual differentiation and sexual reproduction. Our findings bring a new level of insight into the role of lncRNAs in pathogenicity, gene regulation and sexual differentiation. These findings also open new avenues for targeted approaches towards therapeutic strategies against the deadly malaria parasite.

microbiology↗

bioRxiv2022

An open source plant kinase chemogenomics set

129 protein kinases, selected to represent the diversity of the rice (Oryza sativa) kinome, were cloned and tested for expression in E. coli. 40 of these rice kinases were purified and screened using differential scanning fluorimetry (DSF) against 627 diverse kinase inhibitors, with a range of structures and activities targeting diverse human kinases. 37 active compounds were then tested for their ability to modify primary root development in Arabidopsis. Of these, 14 compounds caused a significant reduction of primary root length and two slightly increased root elongation compared with control plants. Two inhibitory compounds bind to the predicted orthologue of Arabidopsis PSKR1, one of two receptors for PSK, a small sulfated peptide that positively controls root development. Inhibition could not be rescued by the exogenous addition of the PSK peptide, suggesting that chemical treatment may inhibit both PSKR1 and its closely related receptor PSKR2. Of the compounds acting as root growth inhibitors in Arabidopsis, six conferred the same effect in rice. Compound RAF265 (CHIR-265), previously shown to bind the human kinase BRAF (B-Raf proto-oncogene, serine/threonine kinase), also binds to nine highly conserved rice kinases tested. The binding of human and rice kinases to the same compound suggests that human kinase inhibitor sets will be useful for dissecting the function of plant kinases.

plant biology↗

bioRxiv2022

The orphan ligand, Activin C, signals through activin receptor-like kinase 7

Activin ligands are formed from two disulfide-linked inhibin {beta} subunit chains. They exist as homodimeric proteins, as in the case of activin A (ActA; Inh{beta}A/Inh{beta}A) or activin C (ActC; Inh{beta}C/Inh{beta}C), or as heterodimers, as with activin AC (ActAC; Inh{beta}A:Inh{beta}C). While the biological functions of ActA and activin B (ActB) have been well-characterized, little is known about the biological function of ActC or ActAC. One thought is that the Inh{beta}C chain functions to interfere with ActA production by forming less active ActAC heterodimers. Here, we assessed and characterized the signaling capacity of ligands containing the Inh{beta}C chain. ActC and ActAC activated SMAD2/3-dependent signaling via the type I receptor, activin receptor-like kinase 7 (ALK7). Relative to ActA and ActB, ActC exhibited lower affinity for the cognate activin type II receptors and was resistant to neutralization by the extracellular antagonist, follistatin. In mature adipocytes, which exhibit high ALK7 expression, ActC elicited a SMAD2/3 response similar to ActB, which can also signal via ALK7. Collectively, these results establish that ActC and ActAC are active ligands that exhibit a distinct signaling receptor and antagonist profile compared to other activins.

biochemistry↗

bioRxiv2022

Blinding efficacy and adverse events following repeated transcranial alternating current, direct current, and random noise stimulation.

As transcranial electrical stimulation (tES) protocols advance, assumptions underlying the technique need to be retested to ensure they still hold. Whilst the safety of stimulation has been demonstrated mainly for a small number of sessions, and small sample size, adverse events (AEs) following multiple sessions remain largely untested. Similarly, whilst blinding procedures are typically assumed to be effective, the effect of multiple stimulation sessions on the efficacy of blinding procedures also remains under question. This is especially relevant in multisite projects where small unintentional variations in protocol could lead to inter-site difference. We report AE and blinding data from 1,019 participants who received up to 11 semi-consecutive sessions of active or sham transcranial alternating current stimulation (tACS), direct current stimulation (tDCS), and random noise stimulation (tRNS), at 4 sites in the UK and US. We found that AEs were often best predicted by factors other than tES, such as testing site or session number. Results from the blinding analysis suggested that blinding was less effective for tDCS and tACS than tRNS. The occurrence of AEs did not appear to be linked to tES despite the use of smaller electrodes or repeated delivery. However, blinding efficacy was impacted in tES conditions with higher cutaneous sensation, highlighting a need for alternative stimulation blinding protocols. This may be increasingly necessary in studies wishing to deliver stimulation with higher intensities.

neuroscience↗

bioRxiv2021

H3K4me1-marked Enhancer Activation in Resistant Prostate Cancers Implicates SOX4 and MENIN Inhibition as Therapeutic Strategies

Chromatin elements and regulators play important roles during progression of prostate cancer, however, their involvement in response to therapy is less well understood. Using comprehensive chromatin profiling of patient-derived tumors, we find that enhancer elements marked by H3K4me1 are highly enriched in aggressive therapy-resistant prostate cancers on important resistance-driving genes, such as those involved in FOXA1, NOTCH and TGF-{beta} signaling. Importantly, by targeting H3K4me1-elements through inhibition of the MLL complex, a H3K4 methyltransferase, we reduced the proliferative capacity and H3K4me1-associated loci in enzalutamide-resistant prostate cancer lines. We identify AR, FOXA1, HOXB13 and SOX4 as a subset of core TFs that are critical for establishing transcriptional networks via active enhancer reprogramming during acquisition of resistance to therapy. Knock-down of SOX4 reduced cell proliferation and disrupted the H3K4me1 enhancer landscape, further suggesting a role for this TF in therapy-resistance. Overall, our data implicate H3K4me1-marked enhancers as a key epigenetic feature of therapy-resistance, implicate SOX4 in enhancer reprogramming and suggest use of MLL/MENIN inhibitors as a potential therapeutic strategy in high-grade and locally advanced prostate cancers that do not respond to traditional therapies.

cancer biology↗

bioRxiv2020

The need to connect: Acute social isolation causes neural craving responses similar to hunger.

When people are forced to be isolated from one another, do they crave social interactions? To address this question, we used functional magnetic resonance imaging (fMRI) to measure neural responses evoked by food and social cues after participants (n=40) experienced ten hours of mandated fasting or total social isolation. After isolation, people felt lonely and craved social interaction. Midbrain regions showed selective activation to food cues after fasting and to social cues after isolation; these responses were correlated with self-reported craving. By contrast, striatal and cortical regions differentiated between craving food versus social interaction. Across deprivation sessions, we find that deprivation narrows and focuses the brains motivational responses to the deprived target. Our results support the intuitive idea that acute isolation causes social craving, similar to the way fasting causes hunger.

neuroscience↗

bioRxiv2018

CNTN5-/+ or EHMT2-/+ iPSC-Derived Neurons from Individuals with Autism Develop Hyperactive Neuronal Networks

Induced pluripotent stem cell (iPSC)-derived cortical neurons are increasingly used as a model to study developmental aspects of Autism Spectrum Disorder (ASD), which is clinically and genetically heterogeneous. To study the complex relationship of rare (penetrant) variant(s) and common (weaker) polygenic risk variant(s) to ASD, \"isogenic\" iPSC-derived neurons from probands and family-based controls, for modeling, is critical. We developed a standardized set of procedures, designed to control for heterogeneity in reprogramming and differentiation, and generated 53 different iPSC-derived glutamatergic neuronal lines from 25 participants from 12 unrelated families with ASD (14 ASD-affected individuals, 3 unaffected siblings, 8 unaffected parents). Heterozygous de novo (7 families; 16p11.2, NRXN1, DLGAP2, CAPRIN1, VIP, ANOS1, THRA) and rare-inherited (2 families; CNTN5, AGBL4) presumed-damaging variants were characterized in ASD risk genes/loci. In three additional families, functional candidates for ASD (SET), and combinations of putative etiologic variants (GLI3/KIF21A and EHMT2/UBE2I combinations in separate families), were modeled. We used a large-scale multi-electrode array (MEA) as our primary high-throughput phenotyping assay, followed by patch clamp recordings. Our most compelling new results revealed a consistent spontaneous network hyperactivity in neurons deficient for CNTN5 or EHMT2. Our biobank of iPSC-derived neurons and accompanying genomic data are available to accelerate ASD research.

neuroscience↗

bioRxiv2017

Molecular characterization of latent GDF8 reveals mechanisms of activation

Growth/differentiation factor 8 (GDF8) or myostatin negatively regulates muscle mass. GDF8 is held in a latent state through interactions with its N-terminal prodomain, much like TGF-{beta} Using a combination of small angle X-ray scattering and mutagenesis, we characterized the interactions of GDF8 with its prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully latent state and an activated or triggered state where the prodomain remains in complex with the mature domain. However, these states are not reversible, indicating the latent GDF8 is spring-loaded. Structural analysis shows that the prodomain:GDF8 complex adopts an open configuration, distinct from the latency state of TGF- and more similar to the open state of Activin A and BMP9 (non-latent complexes). We determined that GDF{beta}8 maintains similar features for latency, including the alpha-1 helix and fastener elements, and identified a series of mutations in the prodomain of GDF8 that alleviate latency, including I56E, which does not require activation by the protease Tolloid. In vivo, active GDF8 variants were potent negative regulators of muscle mass, compared to wild-type GDF8. Collectively, these results help characterize the latency and activation mechanisms of GDF8.

biochemistry↗