Biology subjects

Williams, N. M.

Publications and source records attributed to Williams, N. M..

11 recordsLinked to original sources

bioRxiv2026

Heatwaves do not impact bacteria within pollen provisions, despite accelerating blue orchard bee (Osmia lignaria) larval development

Many insect populations are experiencing thermal stress as a result of global change, making it imperative to investigate how their relationship with other organisms will be impacted by heat disturbances. Microbial symbionts, such as bacteria, have the potential to enhance or inhibit an insect's thermal tolerance. Solitary bee larvae host bacteria within their food stores ("pollen provisions"), which have been shown to benefit survival and development; however, it is unclear how heatwaves brought about by climate change will impact their relationships with these bacterial partners. In this study, we subjected blue orchard bee (Osmia lignaria) eggs and larvae to a 4-day heatwave (35 {degrees}C daytime:22 {degrees}C nighttime) or kept them at control temperatures (25 {degrees}C daytime:15 {degrees}C nighttime), then returned all bees to control temperatures for a 5-day recovery period. We assessed bacterial communities within pollen provisions and larval development stage pre-heatwave (Day 0), immediately post-heatwave (Day 4), and following the recovery period (Day 9). Bacterial community composition, diversity, and abundance were resilient to heat stress, but larval bees developed faster when subjected to a heatwave. This finding refutes the hypothesis that bacteria within pollen provisions modulate blue orchard bee responses to heat, suggesting instead that developmental effects could be more largely shaped by bee physiology or interactions with microorganisms other than bacteria.

ecology↗

bioRxiv2026

Local interaction networks reconstructed from global biodiversity data improve pollinator restoration decision making

Global pollinator declines threaten the health of ecosystems and food systems, underscoring the urgency of conservation actions such as habitat restoration. However, data gaps on plant use among pollinators continue to limit reliable design of restoration plant mixes. To address this, we present NECTAR (Network-Enhanced Conservation Tool for Analysis and Recommendation), a new modular framework that integrates multiple data modalities - including species distributions, phenological metrics, and phylogenetic data - to infer flower visitation and host plant interactions from spatial, temporal, and phylogenetic overlap, generating spatially explicit plant-insect interaction networks that guide planting recommendations for pollinator habitat restoration. We demonstrate the utility of NECTAR by generating a large plant-insect metaweb across California, comprising 2,473,729 spatially explicit interactions that included 3,792 pollinator species and 4,363 native plant species. NECTAR achieved high interaction recall across withheld interactions and independent datasets, substantially outperforming null models and matching or exceeding values reported in comparable studies. NECTAR's data-driven plant mix recommendations are predicted to support up to 2.4 times more pollinator species compared to existing resources and random selection of plants. This optimization facilitates the inclusion of multiple goals and constraints, and provides complementary decision-making information to existing resources. NECTAR offers a scalable, evidence-based framework for translating increasingly available global biodiversity data into locally actionable restoration guidance, with broad potential to improve pollinator habitat restoration worldwide.

ecology↗

bioRxiv2025

Discrete cytokine signaling networks instruct distinctsynovial pathotypes in inflammatory arthritis

Patients with rheumatoid arthritis (RA) display distinct patterns of synovitis. To define the inflammatory mechanisms driving this heterogeneity, we analyzed the inflamed synovium of wild-type (WT), Il6ra-/-, and Il27ra-/- mice with antigen-induced arthritis (AIA). Remarkably, each strain developed a joint pathology mirroring a major RA synovial pathotype: myeloid-rich (WT), fibroblast-rich/pauci-immune (Il6ra-/-), and lymphoid-rich (Il27ra-/-) synovitis. Histology confirmed minimal immune infiltration in Il6ra-/- joints, while WT and Il27ra-/- mice exhibited prominent immune involvement, including organized synovial lymphoid-like aggregates in Il27ra-/- mice. Transcriptomic and epigenomic profiling revealed both shared and distinct regulatory programs among genotypes. Il6ra-/- mice showed increased WNT, DKK, and AMPK signaling associated with fibroblast, chondrocyte, and osteoclast activation (e.g., Adamts19, Dkk1, Ecm1). Consistent with synovial ectopic lymphoid-like structures, Il27ra-/- mice showed enrichment of lymphocyte activation (e.g., Il17a, Il22, Bhlhe40). WT mice exhibited hallmarks of MAP kinase activation. These molecular signatures parallel those of fibroblast-, lymphoid-, and myeloid-rich synovitis in RA. Defining a STAT1-STAT3 regulatory interplay influencing transcriptional decisions in WT and Il27ra-/- mice, our findings offer insights into cytokine-driven disease heterogeneity. Together, these results establish a framework for mechanism-based classification of synovitis and introduce new mouse models to study the molecular drivers of synovial pathotypes and treatment response.

pathology↗

bioRxiv2025

Floral microbes provisioned by Osmia lignaria establish in larval food stores, but do not affect bee development or survival

Microbial dispersal and subsequent establishment among linked habitats can be used to examine drivers of community assembly and function. Flowers host microbial communities that can be acquired and vectored by bees to new flowers, establish within the adult bee gut, and enter food stores (e.g., pollen provisions) of developing larvae. Yet, whether microbes vectored by insects or applied for biocontrol can establish across these habitats and if they affect bee fitness remain unknown. Here, we applied microbes to flowers visited by blue orchard bees (Osmia lignaria) and compared microbial communities in flowers, adult bee guts, and pollen provisions before and after inoculation to determine microbial establishment, environmental filtering, and overlap across habitat types. We also inoculated provisions with microbes to test their effects on larval survival and development. Experimentally inoculated microbes were detected in all habitats, demonstrating that flowers are a source of microbial acquisition for adult and larval bees. Additionally, larval health was not impacted by microbe supplementation, indicating tolerance of bee larvae to floral microbes in Osmia.

microbiology↗

bioRxiv2024

Exploring the Epigenetic Influences on the Differentiation Capacity of Human iPSCs Derived from the Lateral Ganglionic Eminence: Implications for Striatal Medium Spiny Neuron Differentiation and Authenticity

Human pluripotent stem cells (hPSCs) are increasingly used to model human disease and as donor cells for regenerative medicine. However, the fidelity of hPSC-derived cell types remains a major concern, particularly when these cells are intended to replicate complex or region-specific subtypes, such as those required to explore and treat neurological diseases. Medium spiny neurons (MSNs), the principal projection neurons of the striatum, are one such target cell type relevant to disorders such as Huntingtons disease. While protocols for generating hPSC-derived MSNs (hPSC-MSNs) exist, the extent to which these cells faithfully recapitulate their genuine counterparts is unclear. Here, we generated isogenic human induced pluripotent stem cells (hiPSCs) from striatal (LGE) and non-neural (fibroblast) fetal tissues, and differentiated them into MSN-like cells alongside a naive human embryonic stem cell (hESC) line. Using DNA methylation profiling and single-cell RNA sequencing, we systematically compared the epigenetic and transcriptional features of these hPSC-MSNs to authentic fetal MSNs. Our findings reveal persistent epigenetic signatures inherited from the tissue of origin, which influence differentiation outcomes. While LGE-derived hiPSCs retained elements of a striatal-biased methylome and yielded MSN-like cells with enhanced similarity to authentic MSNs, all hPSC-MSNs remained epigenetically and transcriptionally distinct from genuine MSNs and we identified clusters of hPSC-derived cells with aberrant or incomplete phenotypes. These results demonstrate that even isogenic hiPSC lines exhibit variable differentiation potential due to residual epigenetic memory and protocol compatibility. We highlight the need for refined protocols and rigorous benchmarking of hPSC-derived models, particularly for regionally specified neuronal subtypes. Our study underscores the complex relationship between epigenetic status, cell lineage, protocol adaptation, and differentiation outcome. Paper SummaryHuman pluripotent stem cells (hPSCs) are widely used to study otherwise inaccessible human cell phenotypes. However, ensuring the molecular authenticity of hPSC-derived cell types remains critical, as differences between hPSC-derived cells and their native counterparts may impact the validity of these models. Here, medium spiny neurons (MSNs; relevant for studying basal ganglia function and disorders such as Huntingtons disease), serve as a valuable prototype for evaluating the fidelity of hPSC-derived cell types. This study generated human induced pluripotent stem cells (hiPSCs) from developing fetal striatal tissues and fibroblasts, differentiating them into MSN-like cells alongside a human embryonic stem cell (hESC) line. Using single-cell RNA sequencing and DNA methylation analysis, we compared these hPSC-derived MSNs to authentic fetal MSNs. Our findings reveal a significant epigenetic gap between hPSC-derived and authentic MSNs, suggesting that hPSC-MSNs do not acquire a complete and normal striatal epigenome. Additionally, while genetic expression of hPSC-MSNs was striatal-like, it was not equivalent, indicating abberant cells and a failure to reproduce an authentic phoenotype. This study provides insights into the challenges of achieving molecular authenticity in hPSC-derived cells and underscores the need for rigorous evaluation to enhance their utility in research and medicine.

cell biology↗

bioRxiv2022

Effector Th1 cells alter the transcriptional output of IL-6 in acute resolving inflammation

Cytokines that signal via STAT1 and STAT3 transcription factors instruct decisions affecting tissue homeostasis, anti-microbial host defense, and inflammation-induced tissue injury. To understand the coordination of these activities, we applied RNA-seq, ChIP-seq, and ATAC-seq to identify the transcriptional output of STAT1 and STAT3 in peritoneal tissues during acute resolving inflammation and inflammation primed to drive fibrosis. Bioinformatics focussed on the transcriptional signature of the immuno-modulatory cytokine IL-6 in both settings and examined how pro-fibrotic IFN{gamma}-secreting CD4+ T-cells altered the interpretation of STAT1 and STAT3 cytokine cues. In resolving inflammation, STAT1 and STAT3 cooperated to drive stromal gene expression affecting anti-microbial immunity and tissue homeostasis. The introduction of IFN{gamma}-secreting CD4+ T-cells altered this transcriptional program and channeled STAT1 and STAT3 to a previously latent GAS motif in Alu-like elements. STAT1 and STAT3 binding to this conserved sequence revealed evidence of reciprocal cross-regulation and gene signatures relevant to pathophysiology. Thus, we propose that effector T-cells re-tune the transcriptional output of IL-6 by shaping a regulatory interplay between STAT1 and STAT3 in inflammation.

immunology↗

bioRxiv2021

FAN1 nuclease activity affects CAG expansion and age at onset of Huntington's disease

The age at onset of motor symptoms in Huntingtons disease (HD) is driven by HTT CAG repeat length but modified by other genes. We used exome sequencing of 683 HD patients with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect. We identified damaging coding variants in candidate modifier genes from prior genome-wide association studies associated with altered HD onset or severity. Variants in FAN1 clustered in its DNA-binding and nuclease domains and were associated predominantly with earlier onset HD. Nuclease activities of these variants correlated with residual age at motor onset of HD. Mutating endogenous FAN1 to a nuclease-inactive form in an induced pluripotent stem cell model of HD led to rates of CAG expansion comparable to those observed with complete FAN1 knock out. Together, these data implicate FAN1 nuclease activity in slowing somatic repeat expansion and hence onset of HD.

neuroscience↗

bioRxiv2021

A meta-analysis of single visit pollination effectiveness

Many animals provide essential ecosystem services in the form of plant pollination. A rich literature documents considerable variation in the single visit pollination effectiveness of different plant visitors, but this literature has yet to be comprehensively synthesized. We conducted a hierarchical meta-analysis of 193 studies and extracted 1716 single visit effectiveness (SVE) comparisons for 252 plant species. We paired SVE data with visitation frequency data for 75 of these studies. Given the global dominance of honeybees in pollinator communities, we used these data to ask: 1) Do honeybees (Apis mellifera) and other floral visitors vary in their SVE?; 2) To what extent do plant and pollinator attributes predict the difference in SVE between honeybees and other visitors?; and 3) Is there a correlation between floral visitation frequency and SVE? We found that honeybees were significantly less effective than the most effective non-honeybee pollinator. Although not significantly different, honeybees also tended to be less effective than the mean community effectiveness. Honeybees were less effective as pollinators of crop plants and when compared to birds and other bees. Visitation frequency and pollination effectiveness were positively correlated, but this trend was largely driven by data from communities where honeybees were absent, suggesting that honeybees generally combine high visitation frequency and lower SVE. Our study demonstrates that non-honeybee floral visitors are highly effective pollinators of many crop and non-crop plants. While the high visitation frequency typically displayed by honeybees undoubtably makes them important pollinators, we show that honeybees are slightly less effective than the average pollinator and rarely the most effective pollinator of the plants they visit. As such, honeybees may be imperfect substitutes for the loss of wild pollinators and safeguarding global crop production will benefit from conservation of non-honeybee taxa. Open Research StatementAlthough we are fully committed to data transparency, we are also aware of different research teams working on related meta-analyses. As such, we prefer to wait until our paper is accepted to make data publicly available but are happy to share data upon request. Data will be permanently archived on Figshare following acceptance.

ecology↗

bioRxiv2020

Ecological dynamics of the almond floral microbiome in relation to crop management and pollination

O_LICrop tissues harbor microbiomes that can affect host health and yield. However, processes driving microbiome assembly, and resulting effects on ecosystem services, remain poorly understood. This is particularly true of flowering crops that rely on pollinators for yield. C_LIO_LIWe assessed effects of orchard management tactics and landscape context on the flower microbiome in almond, Prunus dulcis. Fourteen orchards (5 conventional, 4 organic, 5 habitat augmentation) were sampled at two bloom stages to characterize bacterial and fungal communities associated with floral tissues. The surveys were complemented by in vitro experiments to assess effects of arrival order and fungicides on nectar microbial communities, and effects of fungicides and microbes on honey bee foraging. Finally, a field trial was conducted to test effects of fungicides and microbes on pollination. C_LIO_LIAs bloom progressed, bacterial and fungal abundance and diversity increased, across all floral tissue types and management strategies. The magnitude by which microbial abundance and diversity were affected varied, with host proximity to apiaries and orchard management having notable effects on bacteria and fungi, respectively. C_LIO_LIExperiments showed immigration history and fungicides affected the composition of nectar microbial communities, but only fungicides affected pollinator foraging through reduced nectar removal. Neither treatment affected pollination services. C_LIO_LISynthesis and applications. Our results shed light on routes through which management practices can shape microbiota associated with flowers of a pollinator-dependent crop. With growing appreciation for the role of floral-associated microbes in affecting biotic interactions at the floral interface, understanding such drivers can potentially inform microbial-derived ecosystem services in agricultural landscapes, including pollination and biocontrol. C_LI

ecology↗

bioRxiv2020

The onset and prevalence of motor and psychiatric symptoms in Huntingtons disease

ObjectiveTo assess the prevalence, timing and functional impact of psychiatric, cognitive and motor abnormalities in Huntingtons disease (HD) gene carriers, we analysed retrospective clinical data from individuals with manifest HD. MethodsClinical features of HD patients were analysed for 6316 individuals in the European REGISTRY study from 161 sites across 17 countries. Data came from clinical history and the patient-completed Clinical Characteristics Questionnaire that assessed eight symptoms: motor, cognitive, apathy, depression, perseverative/obsessive behavior, irritability, violent/aggressive behavior, and psychosis. Multiple logistic regression was used to analyse relationships between symptoms and functional outcomes. ResultsThe initial manifestation of HD is increasingly likely to be motor, and less likely to be psychiatric, as age at presentation increases, and is independent of pathogenic CAG repeat length. The Clinical Characteristics Questionnaire captures data on non-motor symptom prevalence that correlate specifically with validated clinical measures. Psychiatric and cognitive symptoms are common in HD gene carriers, with earlier onsets associated with longer CAG repeats. 42.4% of HD patients reported at least one psychiatric or cognitive symptom before motor symptoms, with depression most common. Each non-motor symptom was associated with significantly reduced total functional capacity scores. ConclusionsPsychiatric and cognitive symptoms are common and functionally debilitating in HD gene carriers. They require recognition and targeting with clinical outcome measures and treatments. However, as it is impossible to distinguish confidently between non-motor symptoms arising from HD and primary psychiatric disorders, particularly in younger pre-manifest patients, non-motor symptoms should not be used to make a clinical diagnosis of HD.

neuroscience↗

bioRxiv2020

Bumblebee worker body size affects new worker production in different resource environments

O_LIBehavior and organization of social groups is thought to be vital to the functioning of societies, yet the contributions of various roles within social groups have been difficult to quantify. A common approach to quantifying these role-based contributions is evaluating the performance of individuals at conducting certain roles, these studies ignore how these performances might scale up to effects at the population-level. Manipulative experiments are another common approach to determine population-level effects, but they often ignore potential feedbacks associated with these various roles. C_LIO_LIHere, we evaluate the effects of worker size distribution in bumblebee colonies on worker production, using functional linear models. Functional linear models are a recent correlative technique that has been used to assess lag effects of environmental drivers on plant performance. We demonstrate potential applications of this technique to explore contributions of social animals to ecological phenomenon. C_LIO_LIWe found that the worker size distribution differentially affected new worker production across three resource environments. Specifically, more larger workers had mostly positive effects and more smaller workers had negative effects on worker production. Most of these effects were only detected under low or fluctuating resource environments suggesting that the advantage of colonies with larger-bodied workers becomes more apparent under stressful conditions. C_LIO_LIWe demonstrate the wider ecological application of functional linear models. We highlight the advantages and limitations when considering these models, and how they are a valuable complement to many of these performance-based and manipulative experiments. C_LI

ecology↗