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Hudson, A.

Publications and source records attributed to Hudson, A..

16 recordsLinked to original sources
bioRxiv2026

The evaluation of the SumiOne™ spatial emanators against wild Anopheles funestus in experimental huts in Siaya County, western Kenya

Background Spatial Emanators (SEs) are a promising tool for complementing existing malaria vector control interventions. In 2025, the World Health Organization (WHO) issued a conditional recommendation for SEs, and two transfluthrin-based products were added to the WHO Prequalification List. As SEs are scaled up, additional products are needed to ensure reliable supply, competitive pricing, and continued innovation. Methods This study evaluated the efficacy of SumiOne SE, containing 10% metofluthrin, in experimental huts in Siaya County, western Kenya. SumiOne SE efficacy was evaluated in six experimental huts, three intervention and three control, using human landing catches (HLCs) and aspiration. Collections were conducted in two 12-night phases, alternating between HLC and aspiration every six nights. Outcomes included reductions in human landing rates, density, exophily and blood feeding inhibition of Anopheles mosquitoes. Results SumiOne SE significantly reduced indoor densities of An. funestus with 63% protective effect (IRR = 0.37, 95% CI: 0.20-0.69, p = 0.0087). Overall An. funestus density (indoor and outdoor combined) was reduced by 58% (IRR=0.42, 95% CI: 0.22-0.79; p=0.0222). The rate of exophily of An. funestus exiting was 34% (95% CI: 27-42) in the intervention huts compared to 2% (95% CI: 1-4) in the control huts (p< 0.0001). Blood feeding inhibition for An. funestus was 46% with 44% (95% CI: 36-51) of the collected mosquitoes being blood fed in the intervention huts compared to 81% (95% CI: 76-86) blood fed in the control huts, (p<0.0001). Conclusion These findings support SumiOne SEs potential as a complementary vector control tool, alongside existing core interventions such as Insecticide Treated Nets and Indoor Residual Spraying, particularly in contexts where additional protection is needed.

zoology↗
bioRxiv2026

Temporal genomics reveals rapid parallel adaptation in experimental populations of Trinidadian guppies (Poecilia reticulata)

Understanding the genomic basis of early adaptation is a central question in evolutionary biology. Although there is ongoing debate about whether early adaptation is more likely to be driven by polygenic responses or by loci of large effect, few studies of natural populations have been able to address this problem. Furthermore, early adaptation to a novel environment often coincides with founding events, making it difficult to disentangle neutral effects from adaptive genomic changes. Here we take advantage of the unique in situ guppy experimental system, in which we established replicate populations by translocating guppies from a high predation locality to four low predation localities. We present whole genome sequencing from the source population and the four experimental populations, sampled after [~]8-10 generations (first period), and again at [~]18-22 generations (second period). We find signatures of inbreeding only in the first period, despite documented population crashes in the second period. We show genome-wide dynamics of selection as well as selective change at single loci and uncover new targets of selection. Overall, we found signatures of selection at all levels; genome-wide, chromosome, and individual windows are more repeatable among replicates in the first period than in the second period.

evolutionary biology↗
bioRxiv2026

The single nucleotide polymorphism rs1053230 modulates kynurenine 3-monooxygenase stability and is associated with cognitive and mood phenotypes

BackgroundThe single nucleotide polymorphism (SNP) rs1053230 within the kynurenine 3-monooxygenase (KMO) gene encodes either an arginine (CGC) or cysteine (TGC) at amino acid residue 452. The rs1053230 genotype is associated with alterations in KMO expression and activity, and impaired cognition. Additionally, KMO intronic SNP rs2275163 is associated with schizophrenia endophenotypes. However, the direct functional consequences of these SNPs on KMO function have never been investigated. MethodsHere we performed the first in vitro cell-based examination of the rs1053230 genotype on KMO expression, activity, cellular localisation and KMO-protein interactions, as well as examination of the effects of rs1053230 on schizophrenia-relevant clinical measures. We also examined the effects of rs2275163 genotype on KMO pre-mRNA stability and alternative splicing. ResultsHEK293T cells expressing KMO-Arg452 or KMO-Cys452 with a red fluorescent protein (RFP) tag produced equivalent levels of KMO mRNA, protein and enzymatic activity, and localised to mitochondria to the same extent. However, cycloheximide-mediated inhibition of protein translation revealed a striking reduction in protein stability of KMO-Arg452-RFP. KMO-RFP-trap pull-down followed by tandem liquid-chromatography-mass spectrometry (LC-MS/MS) identified dramatic differences in protein partners between KMO variants. Indeed, gene ontology-term enrichment analysis revealed that terms associated with synaptic function were more highly enriched amongst KMO-Cys452 interacting proteins. rs1053230 genotype was found to associate with chronic, trait-like depressive mood symptoms in patients. rs2275163 genotype had no effect on KMO pre-mRNA. ConclusionsDifferences in protein stability and protein-protein interactions may underlie the mechanisms by which the KMO rs1053230 genotype influences neuronal function, leading to cognitive differences in psychiatric conditions.

molecular biology↗
bioRxiv2026

Targeting an RNA Editor to Impede H3K27M+ Pediatric Gliomas

Diffuse midline glioma (DMG) is a lethal pediatric brain tumor with no curative therapies. Immune checkpoint blockade (ICB) has shown limited efficacy in DMG, largely due to poor T cell infiltration, low immune checkpoint (IC) expression, and a low tumor mutational burden. Here, we identify adenosine deaminase acting on RNA (ADAR), an RNA-editing enzyme that suppresses endogenous dsRNA sensing, as a key mediator of immune evasion in H3K27M-mutant DMG. ADAR is significantly overexpressed in H3K27M tumors relative to wild-type high-grade gliomas, and its depletion selectively suppresses proliferation in patient-derived DMG cells. The H3K27M mutation was found to synergize with ADAR loss to increase retroelement expression, activate type I interferon signaling, and induce immune checkpoint expression. We further identify all-trans retinoic acid (ATRA) as a pharmacologic inducer of ADAR degradation. At clinically relevant doses, ATRA phenocopies ADAR depletion, enhancing antiviral and interferon responses while increasing tumor immunogenicity. In orthotopic immunocompetent DMG models, ATRA enhances CD8+ T cell infiltration and synergizes with ICB and irradiation to improve survival.

cancer biology↗
bioRxiv2025

Image-Based Meta- and Mega-Analysis (IBMMA): A Unified Framework for Large-Scale, Multi-Site, Neuroimaging Data Analysis

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA produced stronger effect sizes and revealed findings in brain regions that traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage. IBMMA has the potential to accelerate discoveries in neuroscience and enhance the clinical utility of neuroimaging findings.

neuroscience↗
bioRxiv2025

Direct observation of single intrinsically disordered proteins in solution

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) in structured proteins are integral to many biological processes including neurotransmitter regulation, microtubule regulation, and transcription. IDP/IDRs are heterogenous, existing in a conformational ensemble of various interconnected states without a definitive tertiary structure. The high dynamicity of IDPs/IDRs limits ensemble protein characterisation techniques from capturing their properties, and measurements at the single-molecule level are hampered by the necessity to label the protein or modify its microenvironment, affecting their biophysics. Consequently, our understanding of IDPs/IDRs is limited, translating to a lack of knowledge of their roles in related diseases including Alzheimers disease, Parkinsons disease, and various cancers. This work presents the first experimental observation of unmodified IDP/IDR conformational dynamics in vitro, at the single-molecule level in real time, achieved by trapping individual IDPs/IDRs in a nanoscale volume using nanoaperture optical tweezers. Our results reveal that IDPs/IDRs exhibit significantly larger conformational variations in solution compared to globular proteins of similar size, as expected. We demonstrate that phosphorylation of native tau-441 by glycogen synthase kinase 3-beta (GSK3{beta}-tau) induces compaction and reduced conformational dynamics. We further observed a disorder-to-order transition during binding of an IDR, the N-terminal region of Src-associated protein in mitosis of 68 kDa (Sam68), to G8.5 RNA. The capability of nanoaperture optical tweezers to monitor the dynamic behaviours of single, unmodified IDPs/IDRs provides a powerful approach to advance our understanding of their elusive behaviours and further decode their roles in associated diseases.

biophysics↗
bioRxiv2024

An AI-Driven Model of Consciousness, Its Disorders, and Their Treatment

Understanding disorders of consciousness (DOC) remains one of the most challenging problems in neuroscience, hindered by the lack of experimental models for probing mechanisms or testing interventions [1]. To address this, we introduce a generative adversarial AI framework [2] that pits deep neural networks--trained to detect consciousness across over 680,000 neuroelectro-physiology samples and validated on 565 patients, healthy volunteers, and animals--against interpretable, machine learning-driven neural field models [3]. This adversarial architecture produces biologically realistic simulations of both conscious and comatose brains that recapitulate empirical neurophysiological features across humans, monkeys, rats, and bats. Without explicit programming, the AI model retrodicts known DOC responses to brain stimulation and generates testable predictions about unconsciousness mechanisms. Two such predictions are validated here: selective disruption of the basal ganglia indirect pathway, supported by diffusion MRI in 51 DOC patients; and increased cortical inhibitory-to-inhibitory synaptic coupling, supported by RNA sequencing from resected brain tissue in six human coma patients and a rat stroke model. The model also identifies high-frequency subthalamic nucleus stimulation as a promising DOC intervention, supported here using electrophysiology data from human patients. This work introduces an AI framework for causal inference and therapeutic discovery in consciousness research and complex systems more broadly.

neuroscience↗
bioRxiv2023

Predicting neutralization susceptibility to combination HIV-1 monoclonal broadly neutralizing antibody regimens

Combination monoclonal broadly neutralizing antibodies (bnAbs) are currently being developed for preventing HIV-1 infection. Recent work has focused on predicting in vitro neutralization potency of both individual bnAbs and combination regimens against HIV-1 pseudoviruses using Env sequence features. To predict in vitro combination regimen neutralization potency against a given HIV-1 pseudovirus, previous approaches have applied mathematical models to combine individual-bnAb neutralization and have predicted this combined neutralization value; we call this the combine-then-predict (CP) approach. However, prediction performance for some individual bnAbs has exceeded that for the combination, leading to another possibility: combining the individual-bnAb predicted values and using these to predict combination regimen neutralization; we call this the predict-then-combine (PC) approach. We explore both approaches in both simulated data and data from the Los Alamos National Laboratorys Compile, Neutralize, and Tally NAb Panels repository. The CP approach is superior to the PC approach when the neutralization outcome of interest is binary (e.g., neutralization susceptibility, defined as inhibitory concentration < 1 {micro}g/mL. For continuous outcomes, the CP approach performs at least as well as the PC approach, and is superior to the PC approach when the individual-bnAb prediction algorithms have poor performance. This knowledge may be used when building prediction models for novel antibody combinations in the absence of in vitro neutralization data for the antibody combination; this, in turn, will aid in the evaluation and down-selection of these antibody combinations into prevention efficacy trials.

bioinformatics↗
bioRxiv2023

Criticality supports cross-frequency cortical-thalamic information transfer during conscious states

Consciousness is thought to be regulated by bidirectional information transfer between the cortex and thalamus, but the nature of this bidirectional communication - and its possible disruption in unconsciousness - remains poorly understood. Here, we present two main findings elucidating mechanisms of corticothalamic information transfer during conscious states. First, we identify a highly preserved spectral channel of cortical-thalamic communication which is present during conscious states but which is diminished during the loss of consciousness and enhanced during psychedelic states. Specifically, we show that in humans, mice, and rats, information sent from either the cortex or thalamus via{delta} /{theta}/ waves (~1.5-13 Hz) is consistently encoded by the other brain region by high{gamma} waves (~50-100 Hz); moroever, unconsciousness induced by propofol anesthesia or generalized spike-and-wave seizures diminishes this cross-frequency communication, whereas the psychedelic 5-methoxy-N,N/-dimethyltryptamine (5-MeO-DMT) enhances this interregional communication. Second, we leverage numerical simulations and neural electrophysiology recordings from the thalamus and cortex of human patients, rats, and mice to show that these changes in cross-frequency cortical-thalamic information transfer are mediated by excursions of low-frequency thalamocortical electrodynamics toward/away from edge-of-chaos criticality, or the phase transition from stability to chaos. Overall, our findings link thalamic-cortical communication to consciousness, and further offer a novel, mathematically well-defined framework to explain the disruption to thalamic-cortical information transfer during unconscious states.

neuroscience↗
bioRxiv2022

Differentiation of a CD4+/CD8αβ+ Double Positive T Cell Population From The CD8 Pool Is Sufficient To Mediate Graft-vs-Host Disease but not Graft-vs-Leukemia Effects

An important paradigm in allogeneic hematopoietic cell transplantations (allo-HCTs) is the prevention of graft-vs-host disease (GVHD) while preserving the graft-vs-leukemia (GVL) activity of donor T cells. From an observational clinical study of adult allo-HCT recipients, we identified a CD4+/CD8+ double positive T cell (DPT) population, not present in starting grafts, whose presence was predictive of [&ge;] grade 2 GVHD. Using an established xenogeneic transplant model, we reveal that the DPT population develop from antigen stimulated CD8 T cells which become transcriptionally, metabolically and phenotypically distinct from single-positive CD4 and CD8 T cells. Isolated DPTs were sufficient to mediate xeno-GVHD pathology when re-transplanted into naive mice but provided no survival benefit when mice were challenged with a human B-ALL cell line. Overall, this study reveals human DPTs as a T cell population directly involved with GVHD pathology. One Sentence SummaryHuman CD4+/CD8+ double positive T cells (DPTs) mediate xenogeneic GVHD but possess limited GVL activity.

immunology↗
bioRxiv2019

Defining the neural correlates of spontaneous theory of mind (ToM): An fMRI mega-analytic investigation

There is a major debate in the theory of mind (ToM) field, concerning whether spontaneous and explicit ToM are based on the same or two distinct cognitive systems. While there is extensive research on the neural correlates of explicit ToM, revealing consistent activation of the temporo-parietal junction (TPJ) and medial prefrontal cortex (mPFC), few studies investigated spontaneous ToM, with conflicting results, probably due to having small samples of participants. Here, we implemented a mega-analytic approach by pooling data from three fMRI studies, to achieve enough statistical power to better define the neurocognitive mechanisms underlying spontaneous ToM. Participants watched videos in which an agent acquires a true or false belief about the location of a ball. By analysing the blood-oxygen level dependent signal during the belief formation phase for false versus true beliefs, we found a cluster of activation in the right, and to a lesser extent, left posterior parietal cortex spanning the TPJ, but no mPFC activation. Region of interest (ROI) analysis on bilateral TPJ and mPFC confirmed these results and added evidence to the content-selectivity for false beliefs with positive content and asymmetry in laterality of the spontaneous ToM system. Interestingly, the whole brain analysis, supported by an overlap with brain maps, revealed maximum activation in areas involved in visuospatial working memory and attention switching functions, such as the supramarginal gyrus, the middle temporal gyrus, and the inferior frontal gyrus. Taken together, these findings suggest that spontaneous and explicit ToM rely on partially overlapping brain systems. However, spontaneous ToM tasks also show clear differences with explicit ToM tasks.

neuroscience↗
bioRxiv2019

Loss of a glutaredoxin gene underlies parallel evolution of trichome patter in Antirrhinum

Most angiosperms produce trichomes--epidermal hairs that have protective or more specialised roles. In almost all species trichomes are multicellular and, in the majority, secretory. Despite the importance of multicellular trichomes for plant protection and as a source of high-value products, little is known about the mechanisms that control their development. Here we use natural variation between Antirrhinum (snapdragon) species to examine how trichome distribution is regulated and has evolved. We show that a single gene, Hairy (H), which is needed to repress trichome fate, underlies variation in trichome distribution patterns between all Antirrhinum species except one. H encodes an epidermis-specific glutaredoxin and trichome distribution within individual plants reflects the location of H expression. Gene phylogenies and functional tests suggest that H gained its trichome-repressing role late in eudicot evolution and that Antirrhinum species with widespread trichomes evolved multiple times from a largely bald ancestor though independent losses of H activity. We also find evidence for an evolutionary reversal involving a suppressor mutation, and for a pleiotropic effect of H that might constrain the evolution of trichome patterns.

plant biology↗
bioRxiv2018

Early maltreatment experience increases resting-state functional connectivity in thetheory of mind (ToM) network

BackgroundEarly life stressful events, such as childhood maltreatment, significantly increase risk for the development of psychopathology and are associated with impairments in socio-cognitive skills including theory-of-mind (ToM). However, to date, no study has examined the resting-state activity of the ToM network in adults with maltreatment history.\n\nMethodsThirty-five women with a history of childhood maltreatment and 31 unaffected women completed a resting-state scan and a ToM localizer task. The peak coordinates from the localizer were used as the seed regions for the resting-state functional connectivity (RSFC) analyses (temporoparietal junction, dorsomedial prefrontal cortex, middle temporal gyrus and precuneus).\n\nResultsChild abuse was associated with increased RSFC between various ToM regions including the precuneus and the brainstem suggesting altered hierarchical processing in ToM regions. In addition, RSFC was also changed between the dorsomedial prefrontal cortex and the cerebellum.\n\nLimitationsA small and heterogeneous sample.\n\nConclusionsThe data indicate a lasting influence of early life stress on neural networks involved in social processing and may underlie the social difficulties reported by maltreated individuals.

neuroscience↗
bioRxiv2018

Spontaneous mentalizing after early interpersonal trauma: Evidence for hypoactivation of the temporoparietal junction

Experience of interpersonal trauma and violence alters self-other distinction and mentalizing abilities (also known as theory of mind, or ToM), yet little is known about their neural correlates. This fMRI study assessed temporoparietal junction (TPJ) activation, an area strongly implicated in interpersonal processing, during spontaneous mentalizing in 35 adult women with histories of childhood physical, sexual, and/or emotional abuse (childhood abuse; CA) and 31 women without such experiences (unaffected comparison; UC). Participants watched movies during which an agent formed true or false beliefs about the location of a ball, while participants always knew the true location of the ball. As hypothesized, right TPJ activation was greater for UC compared to CA for false versus true belief conditions. However, posttraumatic stress symptomatology (PTSS) appeared to play a role in driving the neural effect. In addition, CA showed increased functional connectivity relative to UC between the rTPJ and dorsomedial prefrontal cortex. Finally, the agents false belief about the presence of the ball speeded participants response (ToM index), but without group differences. These findings highlight that experiencing early interpersonal trauma can alter brain areas involved in the neural processing of ToM and perspective-taking during adulthood.

neuroscience↗
bioRxiv2018

Truncation and Motif Based Pan-Cancer Analysis Highlights Novel Tumor Suppressing Kinases.

A major challenge in cancer genomics is identifying driver mutations from the large number of neutral passenger mutations within a given tumor. Here, we utilize motifs critical for kinase activity to functionally filter genomic data to identify driver mutations that would otherwise be lost within mutational noise. In the first step of our screen, we define a putative tumor suppressing kinome by identifying kinases with truncation mutations occurring within or before the kinase domain. We aligned these kinase sequences and, utilizing data from the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas databases, identified amino acids that represent predicted hotspots for loss-of-function mutations. The functional consequences of new LOF mutations were validated and the top 15 hotspot LOF residues were used in a pan-cancer analysis to define the tumor-suppressing kinome. A ranked list revealed MAP2K7 as a candidate tumor suppressor in gastric cancer, despite the mutational frequency of MAP2K7 falling within the mutational noise for this cancer type. The majority of mutations in MAP2K7 abolished catalytic activity compared to the wild type kinase, consistent with a tumor suppressive role for MAP2K7 in gastric cancer. Furthermore, reactivation of the JNK pathway in gastric cancer cells harboring LOF mutations in MAP2K7 or JNK1 suppresses clonogenicity and growth in soft agar, demonstrating the functional importance of inactivating the JNK pathway in gastric cancer. In summary, our data highlights a broadly applicable strategy to identify functional cancer driver mutations leading us to define the JNK pathway as tumor suppressive in gastric cancer.\n\nSummaryA unique computational pan-cancer analysis pinpoints novel tumor suppressing kinases, and highlights the power of functional genomics by defining the JNK pathway as tumor suppressive in gastric cancer.

cancer biology↗