Biology subjects

Williams, L.

Publications and source records attributed to Williams, L..

At least 19 recordsLinked to original sources

bioRxiv2026

Testing Thirty Years of Hypotheses: Ancient Trout-Salmon Introgression and Limited Pre-Colonial Gene Flow Between Rainbow and Cutthroat Trout Shaped Pacific Salmonid Evolution

Introgression is the transfer of genetic material between species or populations through hybridization and backcrossing. While often deleterious or neutral in nature, introgression can also have beneficial consequences for the recipient lineage. Oncorhynchus is a genus of ray-finned fish (family Salmonidae) composed of nine species of Pacific trout and eight species of Pacific salmon, in which deep introgression has long been proposed to explain patterns of gene-tree-species-tree discordance, and in which hybridization is extensively observed between introduced and endemic species. In this study, we identified well-supported introgression between the ancestral lineage of Pacific trout and the ancestor of Chinook and coho salmon, a long-posited but previously untested hypothesis. While other salmon lineages (pink, chum, sockeye, and masu salmon) have been sympatric with trout for extended periods, providing an opportunity for hybridization to occur, we found no evidence of introgression between trout and these other salmon lineages. Our findings suggest mito-nuclear incompatibilities serve as a possible barrier to gene flow between the clade comprised of pink, chum, and sockeye salmon and all other lineages in Oncorhynchus. Within Pacific trout, we detected no historical introgression between cutthroat and rainbow trout lineages, suggesting that the extensive hybridization observed between them today reflects recent, primarily human-mediated contact rather than long-term gene flow. These findings show that ancestral introgression has shaped the evolutionary history of Oncorhynchus and should be accounted for in future comparative phylogenetic studies of the genus.

evolutionary biology↗

bioRxiv2026

Global topology of brain-wide co-fluctuations links task states, personality, and behavioral symptom dimensions

Functional connectivity in network neuroscience is traditionally characterized using time-averaged correlations between brain regions. While these summaries capture stable large-scale organization, they do not fully reflect the temporal structure of moment-to-moment interactions. Here, we investigate how the order of interaction used to represent brain dynamics shapes the organization recovered from neural data. We compare three interaction representations of fMRI dynamics: regional activation (node time series), pairwise co-fluctuations (edge time series), and higher-order triplet interactions (triangle time series); within a common topological framework using Mapper from topological data analysis (TDA). Across task and resting-state data, Mapper representations derived from pairwise co-fluctuations more distinctly segregate task conditions than activation-based or higher-order representations. This organization reflects structured coordination patterns beyond activation polarity and is driven by high-amplitude interaction events. Beyond task states, modularity quality computed across all Mapper representations is highest for edge time series and selectively associated with stable individual differences: higher modularity relates to higher conscientiousness and lower internalizing and externalizing symptom dimensions. Together, these findings suggest that behaviorally relevant information is reflected in the topology of moment-to-moment brain interactions. Topological analysis of interaction-level dynamics therefore provides a complementary and interpretable framework for linking large-scale neural coordination to cognition, personality, and mental health.

neuroscience↗

bioRxiv2026

Testing the efficacy of artificial flowers as a novel attractant for automated pollinator monitoring

Insect camera traps are a rapidly developing technology, enabling automated monitoring of insects. However, little has been reported on improving the attractants used for daytime flying insects on such cameras. This study compares the attractiveness of novel, 3D printed, artificial flowers with traditional methods of attracting insects (e.g. pan traps and solid coloured paper squares). We hypothesised that artificial flowers would attract a higher abundance and diversity of insects compared to traditional attractants by more accurately mimicking flowers. Additionally, we examined colour preference and average landing duration on the attractants. Artificial flowers, dry pan traps and paper squares, painted in yellow, white, or blue ultraviolet fluorescent paint, were filmed simultaneously to observe wild insect behavioural responses (landings and approaches). The results indicate overall preference for artificial flowers over the two traditional attractants when considering all insect groups together, and overall colour preferences for blue and yellow. When analysing insect groups separately, hoverflies preferred landing on artificial flowers over the other attractants. Bumblebees preferred approaching artificial flowers, and small insects preferred landing and approaching artificial flowers over the other attractants. Other flies preferred landing on pan traps and paper over artificial flowers. Hoverflies, small insects, wasps, and solitary bees responded more to yellow than the other colours, while bumblebees responded more to blue. Comparisons of landing durations revealed that hoverflies spent longer on the artificial flowers than paper. Other flies spent longer on the pan traps and paper. These results show that artificial flowers could offer an efficient attractant for insect camera traps as they attracted a higher abundance of key pollinating insects (hoverflies and bumblebees), and do not have worse attraction rates for the other insect groups (excluding other flies).

ecology↗

bioRxiv2025

The most abundant plant species of Eastern Australia and our knowledge of their traits

O_LIThe rule that most species are relatively rare and few are common has been of central importance to many branches of ecology. This rule also implies that just a few species make up the majority of plant biomass in ecosystems. Focussing plant trait research on the most common species in a region could be useful for many applications, including understanding macroscale patterns of species assemblages at the continental scale, identifying strategies of abundant species or estimating landscape-scale fluxes of carbon and water. C_LIO_LIHere, we rank species based on their total cover across an entire continental region-- Eastern and Central Australia--and report the extent of trait coverage in terms of vegetation cover. To calculate species abundance and trait coverage, we used [~]100,000 vegetation plots from the Harmonised Australian Vegetation plot database overlaid across Australias vegetation classification scheme (the National Vegetation Information System), and we extracted traits from AusTraits, the most comprehensive regional trait database. C_LIO_LIJust 113 plant species (<1% of species found in the region) or the combined species of 16 genera make up 50% of the entire vegetation; approximately 10% of species or the combined species from 10% of the genera (1132 species and 140 genera) make up 90% of vegetation cover. Plant trait coverage tended to be higher when expressed as a proportion of vegetation cover than as a proportion of species in the most common woody genera Acacia and Eucalyptus. Gaps in the trait coverage of very common species were obvious, particularly among the grasses of central Australia. Expressing trait coverage weighted by abundance revealed that only a few additional trait measurements of the most common species and genera would be needed to characterise the traits of most of the vegetation in this part of the continent. C_LIO_LISynthesis: Our results show that a small fraction of species dominates most of the continent. This means that strategic sampling of a few common yet unsampled species could dramatically boost trait coverage and help address the Raunkiaeran shortfall of traits. Targeting these species would substantially improve ecosystem flux estimates and understanding of successful plant strategies at continental scales, with major benefits for vegetation modelling. C_LI

ecology↗

bioRxiv2025

Thrombospondin Encapsulated Dense Particles accelerate wound healing and downregulate fibrotic phenotypes

Extracellular particles (EP) released by cells are heterogenous, with extracellular vesicles (EV) believed to be the major component. To investigate different EV subpopulations, we conducted a panel screen of 15 fluorescent EV markers in 4 adherent cell lines. Nanoflow cytometry identifies TSPAN14 as the best EV marker in 3 of 4 cell lines. Surprisingly, less than 50% of EPs are labelled by the top 2 EV markers in half the cell lines. The EV marker negative EPs are detergent resistant, non-lipophilic, dense and have Thrombospondin shells by dSTORM; and were thus named Thrombospondin Encapsulated Dense particles (ThrEDs). ThrEDs are ubiquitous, contain extracellular matrix regulators and are released following cell stress. ThrEDs accelerate scratch-wound closure and downregulate the fibrotic phenotype in Dupuytrens disease patient myofibroblasts. The TSP-1 C-terminus is exposed on the surface of ThrEDs, opening engineering applications.

cell biology↗

bioRxiv2025

Continuous Serial Electron Diffraction for High Quality Protein Structures

Determining macromolecular structures is crucial for understanding biological mechanisms and advancing drug discovery. Three-dimensional electron diffraction (3D ED), also known as microcrystal electron diffraction (MicroED) using continuous sample rotation has emerged as a powful method for solving structures from sub-micrometre-sized crystals. However, the resolution of MicroED data from protein crystals is often limited by radiation damage. Serial electron diffraction (SerialED) overcomes this limitation by merging single-shot diffraction patterns from thousands of crystals, but its widespread use has been hindered by the complexity and scarcity of equipment required for single shot data acquisition. Here, we introduce continuous SerialED (c-SerialED) - a simple, robust and widely accessible protocol. This approach collects diffraction data quickly and efficiently from all crystals within a given area, without prior crystal identification. We show that only using a standard cryo-EM instrument equipped with a simple widely available CMOS detector, c-SerialED greatly reduces radiation damage while improving the data quality. We demonstrate that c-SerialED enables determination of lysozyme structures at atomic resolution (0.83 [A]) and improves the data resolution of Dype Type Peroxidase Aa (DTPAa) crystals from 2.5 [A] (MicroED) to 1.3 [A]. Remarkably, the resulting structures are virtually free of radiation damage. The improved data quality and resolution allow visualization of radiation sensitive chemical features and protein-ligand interactions to state-of-the-art accuracy. By providing a convenient, fast, and damage-minimizing workflow on existing cryo-EM setups, c-SerialED significantly enhances the applicability of electron diffraction in structural biology. We anticipate our protocol will enable a wide range of studies requiring high-quality diffraction data from radiation-sensitive macromolecular crystals.

molecular biology↗

bioRxiv2025

Charting structural brain asymmetry across the human lifespan

Lateralization is a fundamental principle of structural brain organization. In vivo imaging of brain asymmetry is essential for deciphering lateralized brain functions and their disruption in neurodevelopmental and neurodegenerative disorders. Here, we present a normative framework for benchmarking brain asymmetry across the lifespan, developed from an aggregated sample of 128 primary neuroimaging studies, including 177,701 scans from 138,231 individuals, jointly spanning the age range from 20 post menstrual weeks to 102 years. This resource includes comprehensive, hemisphere-specific brain growth charts for multiple neuroimaging phenotypes: regional cortical grey matter volume, thickness, surface area, and subcortical volumes. Our findings reveal distinct spatial patterns of asymmetry, with early leftward asymmetry observed in association cortices and late rightward asymmetry in sensory regions. These trajectories support theories of the neuroplasticity of asymmetry and the role of both genetic and environmental factors in shaping brain lateralization. Additionally, we provide tools to generate asymmetry centile scores, which allow the quantification of individual deviations from typical asymmetry throughout the lifespan and can be applied to unseen data or clinical populations. We demonstrate the utility of these models by highlighting group-level differences in asymmetry in autism spectrum disorder, schizophrenia, and Alzheimers disease, and exploring genetic correlations with hemispheric specialization. To facilitate further research, we have made this normative framework freely available as an interactive open-access resource (upon publication), offering an essential tool to advance both basic and clinical neuroscience.

neuroscience↗

bioRxiv2024

Divergent effects of cytomegalovirus and rheumatoid arthritis on senescent CD4+ T cells

CD4+ T cell senescence has been linked to repeated antigen stimulation. However, how different types of chronic antigenic exposures impact T cell differentiation and function remains incompletely understood. Using rheumatoid arthritis (RA) and cytomegalovirus (CMV) as models for persistent stimulation in autoimmunity and chronic viral infection, we performed high-dimensional mass cytometry analyses to examine their effects on CD4+ T cell differentiation. We found that CMV seropositive adults have a significant population of highly differentiated CD27-CD28-CD4+ T cells that exhibited common features of senescence, including CD57 and cytotoxic granule expression. In contrast, CD27-CD28-CD4+ T cells were rare in RA patients and Epstein-Barr virus (EBV) or Herpes simplex virus (HSV) seropositive individuals. The few that were present exhibited a predominantly non-cytotoxic profile, with higher expression of TCF1, CD127, and Ki67. Among CMV seropositive individuals, RA was associated with reduced degranulation of cytotoxic granules and lower cytokine production by senescent CD4+ T cells. We did not find an association with age, sex, clinical characteristics, or medication usage by univariate linear regression analyses. However, in vitro tofacitinib treatment reduced T cell functional activity, suggesting contributions from both the disease and RA treatment. These data uncovered distinct influences from CMV and RA, and their combined impact on senescent CD4+ T cell differentiation and function.

immunology↗

bioRxiv2024

High KIR diversity in Uganda and Botswana children living with HIV

Killer-cell immunoglobulin-like receptors (KIRs) are essential components of the innate immune system found on the surfaces of natural killer (NK) cells. The KIRs encoding genes are located on chromosome 19q13.4 and are genetically diverse across populations. KIRs are associated with various disease states including HIV progression, and are linked to transplantation rejection and reproductive success. However, there is limited knowledge on the diversity of KIRs from Uganda and Botswana HIV-infected paediatric cohorts, with high endemic HIV rates. We used next-generation sequencing technologies on 312 (246 Uganda, 66 Botswana) samples to generate KIR allele data and employed customised bioinformatics techniques for allelic, allotype and disease association analysis. We show that these sample sets from Botswana and Uganda have different KIRs of different diversities. In Uganda, we observed 147 vs 111 alleles in the Botswana cohort, which had a more than 1 % frequency. We also found significant deviation towards homozygosity for the KIR3DL2 gene for both rapid (RPs) and long-term non-progressors (LTNPs)in the Ugandan cohort. The frequency of the bw4-80I ligand was also significantly higher among the LTNPs than RPs (8.9 % Vs 2.0%, P-value: 0.032). In the Ugandan cohort, KIR2DS4*001 (OR: 0.671, 95 % CI: 0.481-0.937, FDR adjusted Pc=0.142) and KIR2DS4*006 (OR: 2.519, 95 % CI: 1.085-5.851, FDR adjusted Pc=0.142) were not associated with HIV disease progression after adjustment for multiple testing. Our study results provide additional knowledge of the genetic diversity of KIRs in African populations and provide evidence that will inform future immunogenetics studies concerning human disease susceptibility, evolution and host immune responses.

genomics↗

bioRxiv2024

Solution-phase indexing by kinetic confinement enables rapid, simple, and instrument-free single cell transcriptional profiling

Existing tools for single cell genomics require complex physical frameworks for the indexing of cellular nucleic acids, including proprietary instrumentation, droplet emulsions, and laborious combinatorial indexing schemes. The complexity and cost of these tools significantly constrains the use of single cell technologies across basic and translational research. Here, we describe an instrument-free method that uses novel, bifunctional indexing reagents to deliver index sequences directly to single cells followed by a biophysical process known as Kinetic Confinement to perform high-fidelity indexing of target molecules across thousands of single cells simultaneously in single-tube, solution-phase reactions. Kinetic Confinement enables simple, fast, and flexible single cell experiments, and allows straightforward scaling to very large sample numbers. We anticipate that assays based on Kinetic Confinement will significantly expand the scope, use, and impact of single cell analysis across fundamental and applied research, as well as within therapeutic development and ultimately applied clinical diagnostics.

genomics↗

bioRxiv2024

PathoGD: an integrative genomics approach for CRISPR-based target design of rapid pathogen diagnostics

The design of highly specific primers and guide RNAs (gRNA) for CRISPR-based diagnostics is often a laborious process. Several tools exist for gRNA design, but most are tailored for genome editing applications. Here, we present PathoGD, an end-to-end bioinformatic pipeline comprising pangenome and k-mer modules for rapid and high-throughput design of primers and gRNAs for CRISPR-Cas12a-based pathogen detection. We validated and demonstrated high specificity of a subset of PathoGD-designed primers and gRNAs for the detection of Neisseria gonorrhoeae and Streptococcus pyogenes. PathoGD will serve as an important resource for designing CRISPR-based diagnostic assays for current and emerging pathogens.

bioinformatics↗

bioRxiv2024

Age dictates brain functional connectivity and axonal integrity following repetitive mild traumatic brain injuries

Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific signs and vulnerabilities. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following repetitive mild traumatic brain injuries (rmTBIs). In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and Neurite Orientation Dispersion and Density Imaging (NODDI). Utilizing the CHIMERA model, we conducted rmTBIs or sham (control) procedures on young (2.5-3 months old) and aged (22-month-old) male and female mice to model high risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposing effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean, radial, axial diffusivity, fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Inflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in aged animals. These findings provide a comprehensive understanding of the intricate interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBIs.

neuroscience↗

bioRxiv2023

Rational design of a SOCS1-edited tumor infiltrating lymphocyte therapy for solid tumors using CRISPR/Cas9 screens

Cell therapies such as Tumor Infiltrating Lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the anti-tumor activity of T cell therapies, large-scale in vitro and in vivo CRISPR/Cas9 screens were performed, with the suppressor of cytokine signaling 1 (SOCS1) gene identified as a top T cell-enhancing target. In murine CD8 T cell therapy models, SOCS1 served as a critical checkpoint in restraining the accumulation of T central memory cells in lymphoid organs as well as intermediate (Texint) and effector (Texeff) exhausted T cell subsets derived from progenitor exhausted T cell (Texprog) cells in tumors. A comprehensive CRISPR tiling screen of the SOCS1 coding region identified sgRNAs targeting the SH2 domain of SOCS1 as the most potent, with a sgRNA with minimal off-target cut sites used to manufacture KSQ-001, an engineered TIL therapy with SOCS1 inactivated by CRISPR/Cas9. KSQ-001 possessed increased responsiveness to cytokine signals and enhanced in vivo anti-tumor function in mouse models. These data demonstrate the use of CRISPR/Cas9 screens in the rational design of T cell therapies.

immunology↗

bioRxiv2023

Conserved allomorphs of MR1 drive specificity of MR1-restricted TCRs

Major histocompatibility complex class-1-related protein (MR1), unlike human leukocyte antigen (HLA) class-1, has until recently been reported to be monomorphic. Tumor cell-specific MR1 restricted T cell receptors (TCRs) have been described, offering potential therapeutic application for cancer treatment. We show that human T cells expressing a TCR derived from an MR1-restricted T cell clone, termed MC.7.G5 (7G5.TCRT), retain MR1-directed cytotoxicity. However, activity is not pan-cancer, as initially reported with the clone MC.7.G5. Recognition is restricted by an allelic variant of MR1 (MR1*04) which is present at approximately 1% of the population at the heterozygote level. The 7G5 TCR is not cancer specific, as 7G5.TCRT and 7G5.TCRT-like TCRs react to both cancer and healthy cells expressing MR1*04 alleles. These data demonstrate that healthy individuals can harbor T cells reactive to an MR1 variant displaying self-ligands expressed in cancer and benign tissues. Targeting MR1 in cancer will require identification of cancer-specific presented ligands, and careful confirmation of cancer specificity of TCRs. MR1*04 may behave as an alloantigen warranting further study.

cancer biology↗

bioRxiv2023

Frequent allopolyploidy with distant progenitors in the moss genera Physcomitrium and Entosthodon (Funariaceae) identified via subgenome phasing of targeted nuclear genes.

Allopolyploids represent a new frontier in species discovery among embryophytes. Within mosses, allopolyploid discovery is challenged by low morphological complexity. The rapid expansion of sub-genome sequencing approaches in addition to computational developments to identifying genome merger and whole-genome duplication using variation among nuclear loci representing homeologs has allowed for increased allopolyploid discovery among mosses. We confirm the intergeneric hybrid nature of Entosthodon hungaricus, and the allopolyploid origin of P. eurystomum and of one population of P. collenchymatum. We also reveal that hybridization gave rise to P. immersum, as well as to yet unrecognized lineages sharing the phenotype of P. pyriforme, and P. sphaericum. Our findings demonstrate the utility of a novel approach to phasing homeologs within loci and phasing loci across subgenomes, or subgenome assignment, called homologizer, when working with polyploid genomes, and its value in identifying progenitor species using target capture data.

evolutionary biology↗

bioRxiv2023

Optimizing CRE and PhiC31 mediated recombination in Aedes aegypti

Genetic manipulation of Aedes aegypti is key to developing a deeper understanding of this insects biology, vector-virus interactions and makes future genetic control strategies possible. Despite some advances, this process remains laborious and requires highly skilled researchers and specialist equipment. Here we present two improved methods for genetic manipulation in this species. Use of transgenic lines which express Cre recombinase allowed, by simple crossing schemes, germline or somatic recombination of transgenes, which could be utilized for numerous genetic manipulations. PhiC31 integrase based methods for site-specific integration of genetic elements was also improved, by developing a plasmid which expresses PhiC31 when injected into early embryos, eliminating the need to use costly and unstable mRNA as is the current standard.

bioengineering↗

bioRxiv2023

InVitro Biocompatibility Evaluation of Acellular Porcine Dura mater Grafts and Native Dura

Damage to the dura mater may occur during intracranial or spinal surgeries, which can result in cerebrospinal fluid leakage as well as other potentially fatal physiological changes. As a result, biological scaffolds derived from xenogeneic materials are typically used to repair and regenerate dura mater post intracranial or spinal surgeries. The extracellular matrix of xenogeneic dura scaffolds has been shown to exhibit better cell infiltration and regeneration than synthetic material. In this study, we investigated the biocompatibility of native and decellularized porcine dura. Cell proliferation, cell viability, and mechanical properties of dural grafts were evaluated post re-seeding on days 3,7, and 14. Live-dead staining and resazurin salts were used to quantify cell viability and cell proliferation, respectively. Micro indentation was conducted to quantify the mechanical integrity of the native and acellular dura graft. The results show that the acellular porcine dural graft provides a favorable environment for rat fibroblast cell infiltration. Cell viability, proliferation, and micro indentation results on the acellular grafts are comparable with the native control porcine dura tissue. In conclusion, the porcine scaffold material showed increasing viable cells at each time point. The mechanics and biocompatibility results provide promising insight into the potential use of porcine dura in future cranial dura mater graft applications.

bioengineering↗

bioRxiv2023

Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection through aging

Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here, we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mt-genome in different tissues throughout aging. We used ultra-sensitive Duplex Sequencing to profile [~]2.5 million mt-genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloging [~]1.2 million mitochondrial somatic and ultra low frequency inherited mutations, of which 81,097 are unique. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the Light Strand Origin of Replication, which consistently exhibits the highest mutation frequency. We show that rodents exhibit a distinct mitochondrial somatic mutational spectrum compared to primates with a surfeit of reactive oxygen species-associated G>T/C>A mutations, and that somatic mutations in protein coding genes exhibit signatures of negative selection. Lastly, we identify an extensive enrichment in somatic reversion mutations that "re-align" mito-nuclear ancestry within an organisms lifespan. Together, our findings demonstrate that mitochondrial genomes are a dynamically evolving subcellular population shaped by somatic mutation and selection throughout organismal lifetimes.

genomics↗