Biology subjects

Wilson, S.

Publications and source records attributed to Wilson, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Intrinsic protein disorder reveals divergent signaling architectures and lifestyle adaptation in Entamoeba species

Intrinsic protein disorder plays a central role in cellular regulation and host-pathogen interactions, yet its proteome-wide distribution and functional organization in amoebozoan parasites remain poorly understood. Here, we present the first comparative analysis of intrinsic disorder across the proteomes of Entamoeba histolytica, which causes amoebic dysentery, and two related species, E. dispar, and E. invadens. For comparison, we analyzed intrinsic protein disorder in two phylogenetically distant parasites, Plasmodium falciparum and Trypanosoma brucei. Overall, Entamoeba species exhibited significantly lower levels of intrinsic disorder than P. falciparum and T. brucei. Despite this, all organisms displayed a conserved functional trend in which increasing disorder was associated with a shift from metabolic and catalytic processes toward gene expression-related functions. However, notable organism-specific differences emerged. P. falciparum showed persistent enrichment of gene expression functions across all disorder levels, while T. brucei maintained metabolic, redox, and transport processes throughout the disorder spectrum. In contrast, Entamoeba species uniquely retained GTPase- and phosphorylation-associated signaling across all levels of disorder, with the strongest enrichment observed in the pathogenic species, E. histolytica and E. invadens. This pattern likely reflects a reliance on rapid environmental sensing, cytoskeletal remodeling, and vesicle trafficking, necessary for successful infection. Consistent with this, there was reduced enrichment of G-protein signaling in the non-pathogenic commensal, E. dispar, especially in highly disordered proteins. Secretome analysis further revealed that, unlike P. falciparum, E. histolytica possesses a more structurally ordered secretome, suggesting selection for stable catalytic proteins in the host intestinal environment. Finally, no consistent relationship was identified between intrinsic disorder and vaccine efficacy for several key antigenic targets. Together, these findings demonstrate that intrinsic disorder is differentially deployed across parasites, and utilization of disordered proteins has diverged in accordance with each organisms lifecycle and host interaction strategy. These findings highlight the role of intrinsic disorder in shaping parasitism.

microbiology↗

bioRxiv2026

Optic nerve innervation promotes Wnt/b-catenin pathway activity and progenitor cell proliferation in the zebrafish optic tectum

In the zebrafish visual system, accurate retinotopic mapping occurs throughout life as new neurons are generated and integrated into existing circuitry in both the retina and optic tectum (OT). To explore how OT development changes relative to innervation from the retina, we examined cell death and proliferation in genetic and surgical models that disrupt retinal innervation of the OT. Specifically, we compared lakritz (lak) mutants, which have no optic nerves due to a lesion in the atoh7 gene, with either wild-type or one-eyed fish generated through surgical eye removal. We observed elevated cell death, fewer proliferating progenitors, and fewer sox2+ OT neuroepithelial stem cells in lak mutant and denervated OT lobes. To examine whether light-mediated vision contributes to proliferation and survival in the optic tectum, we reared fish in constant darkness and then compared survival and proliferation of OT cells in innervated and non-innervated tecta. We found that OT cells were still more likely to survive and proliferate in the presence of optic nerve innervation even when fish were reared in the dark. To identify molecular pathways that could regulate OT growth, we examined the expression of known mitogens in the zebrafish optic tectum and found evidence that Wnt/{beta}-catenin pathway activity could promote innervation-dependent proliferation in lak mutant tecta. Expression of both wnt3a and the Wnt/{beta}-catenin target gene axin2, as detected by in situ hybridization and RT-qPCR, is decreased in non-innervated tectal lobes. Further supporting an innervation-dependent role for Wnt/{beta}-catenin pathway activation in the zebrafish OT, we found that lak mutants treated with a Wnt-pathway agonist, BIO, exhibited levels of OT cell proliferation that were indistinguishable from wild-type. Together these findings suggest that progenitor cells in the optic tectum produce Wnt3a in response to innervation by the optic nerve, providing new insight into how a vertebrate visual system coordinates growth across its sensory and recipient tissues.

Developmental Biology↗

bioRxiv2026

Interspecies synergism and antagonism induce differential and potentially exploitable susceptibility to various classes of antibiotics in a wound-like polymicrobial community

Chronic wounds are persistent and difficult to treat. Often this is because they are colonized by polymicrobial communities which contribute to changes in antimicrobial susceptibilities, making these infections harder to effectively clear. We explored the role a community can play in individual members survival when challenged by antibiotics, specifically looking at a community consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis, and Acinetobacter baumannii. Our data shows that communities can contribute to both increases and decreases in susceptibilities depending on the species and the antibiotic. The changes in susceptibilities can be due to interspecies cooperation or competition, with identifiable mechanisms. We also demonstrated that current antimicrobial susceptibility testing (AST) methods used in hospitals, which focus on determining the minimum inhibitory concentration (MIC) via determination of visible turbidity breakpoints, are not able to truly indicate the clearance of bacteria, as species can persist in higher antibiotic concentrations after visible turbidity is gone. To combat decreases in antibiotic susceptibilities contributed to by the community, we used our data from individual antibiotics to determine a potentially effective antibiotic combination, similar to combinatorial therapy used in hospitals to treat recalcitrant infections. Our data proved useful, as the combination of gentamicin and cephalexin was able to overcome polymicrobial synergism and clear the desired bacteria. This demonstrates that it is possible to determine effective antibiotic treatments for polymicrobial infections, whether they be combinatorial in nature or not. One simply must account for the role of the community in order to prescribe the most effective treatment.

microbiology↗

bioRxiv2026

Rapid and reproducible in vitro generation of human parvalbumin-expressing cortical interneurons

Parvalbumin-expressing cortical interneurons play a critical role in maintaining the balance between excitatory and inhibitory signalling and are essential for cognition, with dysfunction implicated in numerous brain disorders. Although human pluripotent stem cells have enabled the generation of diverse human neuronal types in vitro, including cortical interneurons, parvalbumin-expressing interneurons - unlike somatostatin-expressing interneurons - remain difficult to generate reliably and consistently. Here, we demonstrate the efficient and reproducible generation of parvalbumin-expressing cortical interneurons in vitro within 50 days of differentiation. Parvalbumin mRNA and protein were detected without forced gene expression, cell sorting, rodent co-culture or intracerebral transplantation, approaches commonly required by previous protocols. Single-cell transcriptomic analyses validated neuronal identity and authenticity, revealing enrichment for gene expression signatures of parvalbumin-expressing cortical interneurons in vivo. Together, these findings establish a robust method that facilitates interneuron research by enabling the reliable generation of authentic human parvalbumin-expressing cortical interneurons within a short time frame. eTOC blurbAzzouni et al. present a rapid and reproducible protocol for generating authentic human parvalbumin-expressing cortical interneurons from pluripotent stem cells in just 50 days, without forced gene expression or co-culture. Single-cell transcriptomics confirm robust acquisition of in vivo-like PVALB interneuron identity, enabling new opportunities for human interneuron research. HighlightO_LIOptimising SHH and WNT modulators enables consistent PVALB interneuron generation. C_LIO_LI10% of cells express PVALB mRNA within 50 days of 2D differentiation from hPSCs. C_LIO_LIPVALB expression occurs without gene forcing, sorting, co-culture or grafting. C_LIO_LIComparison of gene expression to in vivo interneurons confirms PVALB authenticity. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/710579v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1a53d13org.highwire.dtl.DTLVardef@14cd131org.highwire.dtl.DTLVardef@3a0f9corg.highwire.dtl.DTLVardef@1d7034d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

The protein interactome of the Neuron Specific Gene family (NSG1-3)

The Neuron-Specific Gene (NSG) family members (NSG1-3) play critical and diverse roles in neuronal protein trafficking, but their precise molecular functions remain poorly understood. Here, we employed proximity-labeling proteomics to map the interactomes of each NSG protein. Unlabeled mass spectrometry identified over 1,000 significantly enriched interactors compared with a cytoplasmic control, revealing substantial overlap between NSG1 and NSG2, and a more divergent profile for NSG3. Gene ontology and KEGG pathway analysis confirmed established associations with glutamatergic synapses and endosomal trafficking, while also uncovering unexpected links to presynaptic machinery, inhibitory synapses, and endoplasmic reticulum-associated protein translation, particularly for NSG3. Reciprocal biotinylation patterns and co-immunoprecipitation revealed novel heteromeric complex formation between NSG1 and NSG2, with limited interactions involving NSG3. All three NSGs biotinylated core AMPA receptor subunits and auxiliary proteins, while NSG1 and NSG2 also associated with NMDA receptors, GABA receptor subunits, as well as multiple presynaptic proteins. Moreover, NSG1 and NSG2 specifically biotinylated components of multiunit tethering complexes including neuron-specific retromer, and biotinylated a preponderance of ADAM10 substrates, reinforcing their role in proteolytic processing. Finally, despite the relatively divergent interactomes of NSG1 and NSG2 compared to NSG3, all family members robustly biotinylated amyloid precursor protein (APP), suggesting possible synergistic or competitive interactions that could shape APP proteolytic processing and/or trafficking. Together, these data provide a comprehensive systems-level view of NSG protein interactions, establishing a molecular framework for future investigations into NSG-mediated neural plasticity and disease mechanisms.

neuroscience↗

bioRxiv2025

TRPtracker: a community database for monitoring praziquantel sensitivity at TRPMPZQ variants

The anthelmintic praziquantel (PZQ) has been used for decades as the clinical therapy for schistosomiasis, and remains the only available drug. As a cheap and effective drug therapy for all human disease-causing Schistosoma species, usage of PZQ underpins mass drug administration strategies aimed at eliminating schistosomiasis as a public health problem by 2030. Concern over the potential emergence of resistance to PZQ is therefore warranted, as it would constitute a major threat to this approach. In terms of molecular adaptations conferring PZQ resistance, variation in the sequence and/or expression of the drug target is an obvious mechanism and should be a priority for surveillance efforts. The target of PZQ is a transient receptor potential ion channel, TRPMPZQ, which is established as a locus that regulates schistosome sensitivity to PZQ. Here, we describe the establishment of a community resource, TRPtracker, which coalesces data on TRPMPZQ natural variants together with measurements of individual variant sensitivity to PZQ. A compendium of laboratory-generated mutants in TRPMPZQ is also compiled in TRPtracker to map regions within TRPMPZQ critical for PZQ sensitivity. Aggregation of data from multiple research groups into TRPtracker permits rapid community-wide exchange of data, cataloguing which TRPMPZQ variants have been functionally profiled, where geographically these variants have been found, their frequency within populations and their potential impact on PZQ sensitivity.

microbiology↗

bioRxiv2025

Examining the heritability of functional brain networks in adolescence

Discovering mechanisms underlying mental illness requires disentangling genetic and environmental factors influencing mental health. Researchers have started investigating the brains role as a potential intermediate biomarker linking genes and environment to mental health; however, understanding how much genetics shapes adolescent brain function remains elusive. Using data from the ABCD study (5,247 unrelated, 330 dizygotic, 248 monozygotic twin subjects), we estimated the heritability of functional connectivity and topography using both SNP and twin data. SNP-based heritability was calculated using genetic correlation and the recently developed AdjHE-RE estimator. We found low SNP heritability for brain functional connectivity (median = 2e-10% Gordon, 5.8e-7% probabilistic) and topography (max = 2%). Twin estimates using ACE models replicated prior findings from the literature (median = 8.9e-6% Gordon, 6% probabilistic, 27% topography). This suggest that additive genetic effects are minimally associated with functional brain features in adolescents highlighting the importance of considering both genetic and environmental factors when studying the development of functional brain networks and their relevance to mental health.

genomics↗

bioRxiv2025

Schistosoma mansoni-induced host immunopathology is gut microbiota dependent

Despite progress in schistosomiasis control during recent decades in endemic areas, this parasitic blood-fluke infection continues to pose a substantial public health burden. In depth understanding of the mechanisms behind the complex immunopathology and drivers of morbidity in schistosomiasis is urgently needed. Chronic infection with the parasitic blood fluke Schistosoma mansoni manifests the most severe pathology in relation to egg-induced host immune responses and fibrosis development. Host immune homeostasis is influenced by the commensal gut microbiota, which may therefore also affect systemic immunopathology induced by S. mansoni. Both humans and experimental animal models show metabolomic changes related to gut microbial and liver metabolism during S. mansoni infection, further supporting a link between gut microbiota and regulation of S. mansoni pathology. To investigate whether a radically changed gut microbiota composition would result in changed S. mansoni egg-induced pathology, a mouse model combining antibiotic treatment and infection was established. In the model, the commensal gut microbial composition of female C57BL/6-NTac mice was altered by oral administration of a broad-spectrum ampicillin-vancomycin cocktail prior to infection with S. mansoni and throughout the experiment. An ecosystem view of the host immune milieu was collated by measuring a wide range of parameters: gut microbiome characterisation, immune profiling on the transcriptional level (ileum and liver) supported by flow cytometry of cells (spleen and mesenteric lymph nodes) and bead-based measurements of immune parameters in sera, short-chain fatty acid measurements in sera and caecal content, intestinal permeability assessment, liver enzyme levels in sera, and histology and stereology to characterise immunopathology (ileum and liver). The application of stereological principles to address the non-spherical nature of egg-induced liver granulomas and ileum inflammation supported by liver enzyme levels, collagen deposition, and immune parameters, enabled demonstration of significantly less granuloma formation in livers from antibiotics treated mice compared to controls. The observed difference in the degree of egg-induced inflammatory response in livers from infected mice mediated by antibiotics treatment, was not observed in ileum tissue and could not be explained by infection burden. Our mouse model results demonstrate a role for the gut microbiota and intestinal immune milieu in regulation of systemic S. mansoni infection-driven liver pathology and, hence, potential morbidity. In translational context, these findings warrant that drivers of gut microbial changes and intestinal immune milieu must be considered when pursuing novel holistic interventions for treatment or alleviation of persistent schistosomiasis.

immunology↗

bioRxiv2025

A Domain-Specific Language Model Approach for Identifying Immunogenic Epitopes from Publicly Available Data: EpitopeMiner

Personalized cancer vaccines represent a transformative approach in immunotherapy, leveraging tumor-specific antigens, such as neoantigens, to stimulate durable and targeted immune responses. However, identifying immunogenic neoantigen epitopes through conventional approaches - relying on in silico predictions followed by experimental validation - remains a significant challenge due to limitations of computational tools and scattering of experiment data. To address these challenges, we introduce EpitopeMiner, a domain-specific large language model (LLM) enhanced with a Retrieval-Augmented Generation (RAG) framework, specifically designed to identify immunogenic epitopes predicted by existing computational tools. EpitopeMiner utilizes a custom database of MHC-I-associated epitope-related literature to provide domain-specific knowledge, enhancing the precision and relevance of LLM-generated responses. EpitopeMiner offers three key features: First, the ability to identify epitopes with similar sequences and potentially similar immunogenic effects, which is especially valuable for neoantigens that are patient-specific and rarely found in public datasets. Second, it supports multiple epitope searches with structured outputs, enhancing scalability. Third, it provides original text chunks and paper identifiers, significantly simplifying validation and further exploration of the retrieved knowledge. Applying EpitopeMiner to well-characterized MHC class I epitopes demonstrates its ability to consistently retrieve relevant papers, efficiently providing targeted insights on T-cell response and immunogenicity, outperforming a commercial AI-powered literature tool. Notably, when applied to lymphoma patient-derived neoantigens, EpitopeMiner successfully retrieves immune response information for a few similar epitopes, despite operating with a relatively smaller database compared to the benchmark tool. All in all, EpitopeMiner bridges the gap between computational prediction and experimental validation, providing a scalable solution for extracting knowledge from public data, fostering cross-study synergies, and accelerating the development of personalized cancer vaccines.

cancer biology↗

bioRxiv2024

Saving the Dinaric lynx: multidisciplinary monitoring and stakeholder engagement support large carnivore restoration in human-dominated landscape

Translocations are central to large carnivore restoration efforts, but inadequate monitoring often inhibits effective conservation decision-making. Extinctions, reintroductions, poaching and high inbreeding levels of the Central European populations of Eurasian lynx (Lynx lynx) typify the carnivore conservation challenges in the Anthropocene. Recently, several conservation efforts were initiated to improve the genetic and demographic status, but were met with variable success. Here, we report on a successful, stakeholder-engaged translocation effort to reinforce the highly-inbred Dinaric lynx population and create a new stepping-stone subpopulation in the Southeastern Alps. We used multidisciplinary and internationally-coordinated monitoring using systematic camera- trapping, non-invasive genetic sampling, GPS-tracking of translocated and remnant individuals, recording of reproductive events and interspecific interactions, as well as the simultaneous tracking of the public and stakeholders support of carnivore conservation before, during and after the translocation process across the three countries. Among the 22 translocated wild-caught Carpathian lynx, 68% successfully integrated into the population and local ecosystems and at least 59% reproduced. Probability of dispersing from the release areas was 3-times lower when soft-release rather than hard-release method was used. Translocated individuals had lower natural mortality, higher reproductive success and similar ungulate kill rates compared to the remnant lynx. Cooperation with local hunters and protected area managers enabled us to conduct multi-year camera-trapping and non-invasive genetic monitoring across a 12,000-km2 transboundary area. Results indicate a reversal in population decline, as the lynx abundance increased for >40% during the 4-year translocation period. Effective inbreeding decreased from 0.32 to 0.08-0.19, suggesting a 2- to 4-fold increase in fitness. Furthermore, successful establishment of a new stepping-stone subpopulation represents an important step towards restoring the Central European lynx metapopulation. Robust partnerships with local communities and hunters coupled with transparent communication helped maintain high public and stakeholder support for lynx conservation throughout the translocation process. Lessons learned about the importance of stakeholder involvement and multidisciplinary monitoring conducted across several countries provide a successful example for further efforts to restore large carnivores in human-dominated ecosystems.

ecology↗

bioRxiv2024

tauX: A Gene Expression Ratio Strategy to Improve Machine Learning Applications in Precision Medicine

Machine learning algorithms identify patterns that would otherwise be difficult to observe in high-dimensional molecular and clinical data. For this reason, machine learning has the potential to have a profound impact on clinical decision making and drug target discovery. Nevertheless, there remain considerable technical challenges in adapting these tools for clinical use. These challenges include clinical feature engineering, model selection, and defining optimal strategies for model training. For cancer care, RNA sequencing of patient tumor biopsies has already proven to be a powerful molecular assay to characterize tumor-intrinsic and -extrinsic phenotypes influencing therapeutic response. To improve the predictive performance of RNA-sequencing data, we developed the tauX machine learning framework to refine gene expression features and improve the performance of machine learning algorithms. The tauX framework uses aggregated ratios of positively and negatively associated predictive genes to simplify the prediction task. We showed a significant improvement in predictive performance using a large database of synthetic gene expression profiles. We also show how the tauX framework can be used to elucidate the mechanisms of response and resistance to checkpoint blockade therapy using data from the Stand Up to Cancer (SU2C) Lung Response Cohort and The Cancer Genome Atlas (TCGA). The tauX strategy achieved superior predictive performance compared to models built upon established feature engineering strategies or widely used cancer gene expression signatures. The tauX framework is available as a freely deployable docker container (https://hub.docker.com/r/pfeiljx/taux).

bioinformatics↗

bioRxiv2024

The developing Human Connectome Project fetal functional MRI release: Methods and data structures

Recent advances in fetal fMRI present a new opportunity for neuroscience to study functional human brain connectivity at the time of its emergence. Progress in the field however has been hampered by the lack of openly available datasets that can be exploited by researchers across disciplines to develop methods that would address the unique challenges associated with imaging and analysing functional brain in utero, such as unconstrained head motion, dynamically evolving geometric distortions, or inherently low signal-to-noise ratio. Here we describe the developing Human Connectome Projects release of the largest open access fetal fMRI dataset to date, containing 275 scans from 255 fetuses and spanning the period of 20.86 to 38.29 post-menstrual weeks. We present a systematic approach to its pre-processing, implementing multi-band soft SENSE reconstruction, dynamic distortion corrections via phase unwrapping method, slice-to-volume reconstruction and a tailored temporal filtering model, with attention to the prominent sources of structured noise in the in utero fMRI. The dataset is accompanied with an advanced registration infrastructure, enabling group-level data fusion, and contains outputs from the main intermediate processing steps. This allows for various levels of data exploration by the imaging and neuroscientific community, starting from the development of robust pipelines for anatomical and temporal corrections to methods for elucidating the development of functional connectivity in utero. By providing a high-quality template for further method development and benchmarking, the release of the dataset will help to advance fetal fMRI to its deserved and timely place at the forefront of the efforts to build a life-long connectome of the human brain.

neuroscience↗

bioRxiv2024

Hydroxysteroid 17-beta dehydrogenase 13 (Hsd17b13) knockdown attenuates liver steatosis in high-fat diet obese mice

Hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) loss-of-function gene variants are associated with decreased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Our RNA-seq analysis of steatotic liver from obese mice -/+ Fenretinide treatment identified major beneficial effects of Fenretinide on hepatic gene expression including Hsd17b13. We sought to determine the relationship between Hsd17b13 expression and MASLD and to validate it as a therapeutic target by liver-specific knockdown. Hsd17b13 expression, which is unique to hepatocytes and associated with the lipid-droplet, was elevated in multiple models of MASLD and normalised with prevention of obesity and steatotic liver. Direct, liver- specific, shRNA-mediated knockdown of Hsd17b13 (shHsd17b13) in high-fat diet (HFD)-obese mice, markedly improved hepatic steatosis with no effect on body weight, adiposity or glycaemia. shHsd17b13 decreased elevated serum ALT, serum FGF21 levels and markers of liver fibrosis e.g. Timp2. shHsd17b13 knockdown in HFD-obese mice and Hsd17b13 overexpression in cells reciprocally regulated expression of lipid metabolism genes e.g. Cd36. Global lipidomic analysis of liver tissue revealed a major decrease in diacylglycerols (e.g. DAG 34:3) with shHsd17b13 and an increase in phosphatidylcholines containing polyunsaturated fatty acids (PUFA) e.g. PC 34:3 and PC 42:10. Expression of key genes involved in phospholipid and PUFA metabolism e.g. Cept1, were also reciprocally regulated suggesting a potential mechanism of Hsd17b13 biological function and role in MASLD. In conclusion, Hsd17b13 knockdown in HFD-obese adult mice was able to alleviate MASLD via regulation of fatty acid and phospholipid metabolism, thereby confirming HSD17B13 as a genuine therapeutic target for MASLD and development of liver fibrosis. KEY POINTSO_LIHSD17B13 loss-of-function gene variants are associated with decreased risk of metabolic dysfunction-associated (MA) steatotic liver disease and steatohepatitis (MASLD and MASH). C_LIO_LIRNA-seq analysis of steatotic liver identified beneficial effects of Fenretinide on hepatic gene expression including downregulation of Hsd17b13. C_LIO_LILiver-specific shRNA knockdown of Hsd17b13 in obese mice markedly improved hepatic steatosis and markers of liver health e.g. serum ALT, serum Fgf21 levels. C_LIO_LIHsd17b13 influenced expression of lipid/phospholipid metabolism genes e.g. Cd36 and Cept1 and phosphatidylcholines PC 34:3 and PC 42:10. C_LIO_LIOur study suggests a mechanism of HSD17B13s biological function and the strong rationale behind targeting HSD17B13 for MASLD/MASH. C_LI

physiology↗

bioRxiv2024

Knockout of AMPA receptor binding protein Neuron-Specific Gene 2 (NSG2) enhances associative learning and cognitive flexibility

The vast majority of gene mutations and/or gene knockouts result in either no observable changes, or significant deficits in molecular, cellular, or organismal function. However, in a small number of cases, mutant animal models display enhancements in specific behaviors such as learning and memory. To date, most gene deletions shown to enhance cognitive ability generally affect a limited number of pathways such as NMDA receptor- and translation-dependent plasticity, or GABA receptor- and potassium channel-mediated inhibition. While endolysosomal trafficking of AMPA receptors is a critical mediator of synaptic plasticity, mutations in genes that affect AMPAR trafficking either have no effect or are deleterious for synaptic plasticity, learning and memory. NSG2 is one of the three-member family of Neuron-specific genes (NSG1-3), which have been shown to regulate endolysosomal trafficking of a number of proteins critical for neuronal function, including AMPAR subunits (GluA1-2). Based on these findings and the largely universal expression throughout mammalian brain, we predicted that genetic knockout of NSG2 would result in significant impairments across multiple behavioral modalities including motor, affective, and learning/memory paradigms. However, in the current study we show that loss of NSG2 had highly selective effects on associative learning and memory, leaving motor and affective behaviors intact. For instance, NSG2 KO animals performed equivalent to wild-type C57Bl/6n mice on rotarod and Catwalk motor tasks, and did not display alterations in anxiety-like behavior on open field and elevated zero maze tasks. However, NSG2 KO animals demonstrated enhanced recall in the Morris water maze, accelerated reversal learning in a touch-screen task, and accelerated acquisition and recall on a Trace Fear Conditioning task. Together, these data point to a specific involvement of NSG2 on multiple types of associative learning, and expand the repertoire of pathways that can be targeted for cognitive enhancement.

neuroscience↗

bioRxiv2024

Rapid dynamics of electrophysiological connectome states are heritable

Time-varying changes in whole-brain connectivity patterns, or connectome state dynamics, are a prominent feature of brain activity with broad functional implications. While infra-slow (<0.1Hz) connectome dynamics have been extensively studied with fMRI, rapid dynamics highly relevant for cognition are poorly understood. Here, we asked whether rapid electrophysiological connectome dynamics constitute subject-specific brain traits and to what extent they are under genetic influence. Using source-localized EEG connectomes during resting-state (N=928, 473 females), we quantified heritability of multivariate (multi-state) features describing temporal or spatial characteristics of connectome dynamics. States switched rapidly every [~]60-500ms. Temporal features were heritable, particularly, Fractional Occupancy (in theta, alpha, beta, and gamma bands) and Transition Probability (in theta, alpha, and gamma bands), representing the duration spent in each state and the frequency of state switches, respectively. Genetic effects explained a substantial proportion of phenotypic variance of these features: Fractional Occupancy in beta (44.3%) and gamma (39.8%) bands and Transition Probability in theta (38.4%), alpha (63.3%), beta (22.6%), and gamma (40%) bands. However, we found no evidence for heritability of spatial features, specifically states Modularity and connectivity pattern. We conclude that genetic effects strongly shape individuals connectome dynamics at rapid timescales, specifically states overall occurrence and sequencing.

neuroscience↗

bioRxiv2024

Cognitive abilities are associated with rapid dynamics of electrophysiological connectome states

Time-varying changes in whole-brain connectivity patterns, or connectome state dynamics, hold significant implications for cognition. However, connectome dynamics at fast (> 1Hz) timescales highly relevant to cognition are poorly understood due to the dominance of inherently slow fMRI in connectome studies. Here, we investigated the behavioral significance of rapid electrophysiological connectome dynamics using source-localized EEG connectomes during resting-state (N=926, 473 females). We focused on dynamic connectome features pertinent to individual differences, specifically those with established heritability: Fractional Occupancy (i.e., the overall duration spent in each recurrent connectome state) in beta and gamma bands, and Transition Probability (i.e., the frequency of state switches) in theta, alpha, beta, and gamma bands. Canonical correlation analysis found a significant relationship between the heritable phenotypes of sub-second connectome dynamics and cognition. Specifically, principal components of Transition Probabilities in alpha (followed by theta and gamma bands) and a cognitive factor representing visuospatial processing (followed by verbal and auditory working memory) most notably contributed to the relationship. We conclude that the specific order in which rapid connectome states are sequenced shapes individuals cognitive abilities and traits. Such sub-second connectome dynamics may inform about behavioral function and dysfunction and serve as endophenotypes for cognitive abilities.

neuroscience↗

bioRxiv2023

Invasive traits of freshwater fish database (ITOFF)

AIMSpecies invasions are a major driver of global biodiversity loss, but only a minority of invasions are successful. Evidence suggests that invasive success is linked to life-history traits. Yet, data on invasive success and species traits remain fragmented across multiple sources. Here we present the Invasive Traits of Freshwater Fish (ITOFF) database, an interdisciplinary framework that integrates multiple datasets to elucidate the role of life-history traits in shaping invasive success. ITOFF allows seamless access to invasive species data and fosters collaborative actions through knowledge sharing. ITOFF is supported by an innovative web-application that makes complex relationships between invasive and native species accessible to a broad audience. The scientific contribution of ITOFF is illustrated by examining the role of life-history traits and phylogeny in invasion success. LOCATIONGlobal. METHODSGeneralized linear models were used to test the contribution of generation time, trophic level, longevity, and temperature range to invasive success. Through divisive cluster analysis we investigate the role of multiple traits in determining invasive success. Finally, we construct phylogenetic trees to investigate the role of evolutionary history in the invasion process. RESULTSITOFF unifies data for 1917 freshwater fish species representative of invasive species, those species they endanger, and species impacted by invasives but not considered endangered. Invasive species are generally characterized by greater temperature ranges, but are indistinguishable from impacted, endangered, and critically endangered species for the remaining life-history traits. Further, we show that invasive species are generally not distinct from impacted or endangered species when considering multiple traits or phylogeny. MAIN CONCLUSIONSITOFF provides an accessible platform for the improved forecasting of species invasions. ITOFF data shows that classical predictions of life-history traits determining invasive success do not hold amongst freshwater fish species. Forecasting of invasive species must therefore shift towards a wholistic approach encompassing the species and the environment.

ecology↗

bioRxiv2023

Dynamic changes in subplate and cortical plate microstructure precede the onset of cortical folding in vivo

Cortical gyrification takes place predominantly during the second to third trimester, alongside other fundamental developmental processes, such as the development of white matter connections, lamination of the cortex and formation of neural circuits. The mechanistic biology that drives the formation cortical folding patterns remains an open question in neuroscience. In our previous work, we modelled the in utero diffusion signal to quantify the maturation of microstructure in transient fetal compartments, identifying patterns of change in diffusion metrics that reflect critical neurobiological transitions occurring in the second to third trimester. In this work, we apply the same modelling approach to explore whether microstructural maturation of these compartments is correlated with the process of gyrification. We quantify the relationship between sulcal depth and tissue anisotropy within the cortical plate (CP) and underlying subplate (SP), key transient fetal compartments often implicated in mechanistic hypotheses about the onset of gyrification. Using in utero high angular resolution multi-shell diffusion-weighted imaging (HARDI) from the Developing Human Connectome Project (dHCP), our analysis reveals that the anisotropic, tissue component of the diffusion signal in the SP and CP decreases immediately prior to the formation of sulcal pits in the fetal brain. By back-projecting a map of folded brain regions onto the unfolded brain, we find evidence for cytoarchitectural differences between gyral and sulcal areas in the late second trimester, suggesting that regional variation in the microstructure of transient fetal compartments precedes, and thus may have a mechanistic function, in the onset of cortical folding in the developing human brain.

neuroscience↗