Biology subjects

Lambert, P.

Publications and source records attributed to Lambert, P..

12 recordsLinked to original sources

bioRxiv2026

Rapid floral syndrome convergence in Penstemon through independent genetic variation

The repeated evolution of certain complex traits within a given lineage is compelling and presents an opportunity for understanding selective and genetic features that promote rapid multi-trait adaptation. The North American plant genus Penstemon is one such example, with numerous evolutionary shifts from ancestral bee syndrome to hummingbird syndrome flowers. Here, we traced the evolution of multi-trait floral phenotypes within a focal clade of Penstemon using a new whole genome phylogenomic estimate and found four independent origins of the hummingbird syndrome. We found strong evolutionary convergence in floral traits across these four origins and observed that the hummingbird syndrome assembled rapidly, without leaving a signal of stepwise modification of traits. Patterns of evolutionary correlations among floral traits in bee syndrome Penstemon species likely enable rapid shifts to hummingbird syndrome. Using phylogenomic tests for introgression, we found no evidence that adaptive introgression has fueled the four repeated origins of hummingbird syndrome flowers. Patterns of allele sharing were instead consistent with substantial levels of incomplete lineage sorting, suggesting repeated complex adaptation involves de novo mutation or adaptation from ancestral variation.

evolutionary biology↗

bioRxiv2025

River pollution threatens preferred macroinvertebrate prey of endemic fishes in Aotearoa, New Zealand

O_LIMacroinvertebrates are a critical source of food for riverine fishes. Anthropogenic stressors can transform riverine macroinvertebrate communities, yet the consequences of such transformations to the fishes that feed on them are poorly understood. Changes in any combination of food abundance, accessibility or quality may be referred to as changes in the foodscape of fishes. Stressor-driven increases of inaccessible prey that are difficult for fish to detect, capture or ingest, may render foodscapes less profitable to fishes. C_LIO_LIWe examined how nutrient enrichment, fine sediment, acid mine drainage (AMD), flooding and drying reshape fish foodscapes by altering the accessibility of macroinvertebrate prey for two New Zealand river fishes, Galaxias vulgaris and Gobiomorphus breviceps. We determined relative accessibility of macroinvertebrate taxa and traits to these fishes by comparing the abundance of prey taxa and traits in the environment with their corresponding abundances in fish diets. To make these comparisons, invertebrate and fish gut samples were collected from the same river reaches, at the same times, over three years. Environmental DNA (eDNA) metabarcoding of fish gut contents facilitated efficient diet characterisation of over 700 fish guts. Finally, to determine how multiple stressors might affect fish foodscapes, we related invertebrate trait-specific accessibilities to published data defining how the composition of those macroinvertebrate traits varies along stressor gradients. C_LIO_LIMacroinvertebrate traits that were most accessible to fishes were those promoting detection (e.g., active foraging behaviours exhibited by crawlers and scrapers) and ingestion (e.g., moderate size, morphologies lacking defensive structures), typical of mayfly and free-living caddisfly larvae. In contrast, prey with traits inhibiting detection (e.g., small size and burrowing behaviour) and ingestion by gape-limited fishes (e.g., large size), were less accessible to the fishes we studied. C_LIO_LITrait abundance-stressor relationships revealed that that increasing fine sediment, nutrients, AMD and drying, and decreased flooding frequency, favoured macroinvertebrates with traits that erode accessibility to fishes. These results show that multiple stressors may decrease the profitability of fish foodscapes by filtering out macroinvertebrate prey with traits promoting accessibility to fishes. C_LIO_LIFood web approaches to understanding multi-stressor impacts are rare, but are necessary to understand how the effects of multiple stressors on primary consumers then go on to affect predators of higher trophic position. A major barrier to fish foodscape research is the difficulty and cost of estimating trophic networks. We discuss how eDNA metabarcoding, coupled with trait-based approaches may help overcome these barriers, enabling generalisable assessments of foodscape changes caused by multiple stressors. C_LI

ecology↗

bioRxiv2025

E2 displacement of CIP2A from TOPBP1 activates the DNA damage response during papillomavirus life cycles

The papillomavirus life cycle is intricately linked to epithelial differentiation, and the virus manipulates the differentiation process to facilitate viral production. One such manipulation is activation of the DNA damage response (DDR) which promotes viral replication via homologous recombination. This report demonstrates that the papillomavirus transcription/replication/segregation factor E2 activates the DNA damage response (DDR). During differentiation, E2 displacement of CIP2A from TOPBP1 causes CIP2A to bind and inhibit PP2A resulting in DDR activation via ATM phosphorylation. The DDR promotes inhibitory interaction of DBC1 with the class III deacetylase SIRT1, which further boosts the DDR via increased acetylation and stability of viral and host proteins. E2 forms a complex with TOPBP1 and ATM, while preventing ATR activation by blocking TOPBP1-ATR interaction. This "ATM up ATR down" phenotype promotes viral replication via ATM promotion of homologous recombination, and cell proliferation via inhibition of ATR. We demonstrate this mechanism of DDR activation in multiple systems: keratinocytes expressing only E2, in foreskin keratinocytes immortalized by HPV16, in HPV16 positive keratinocytes derived from a cervical lesion, in pre-neoplastic lesions induced by mouse papillomavirus MmuPV1, in head and neck cancer cell lines that retain E2 expression, and in HPV16 positive oropharyngeal patient derived xenografts that retain E2 expression. ATM inhibition preferentially killed cells expressing E2, presenting a novel strategy for treating HPV early preneoplasia and a large subset of HPV+ oropharyngeal cancers retaining E2 expression and episomal genomes.

cancer biology↗

bioRxiv2025

Population-specific bycatch risks in two vulnerable anadromous clupeids: insights from otolith microchemistry

Otolith microchemistry analysis revealed that bycatch of European shads--allis shad Alosa alosa (L. 1758) and twaite shad Alosa fallax (Lacepede 1803)-- in western Iberian commercial fisheries removes individuals from a wide array of natal origins, with the most abundant source rivers suffering the heaviest losses. Spatial variation in bycatch risk was evident: specific marine areas exhibited high natal-origin diversity, reflecting complex dispersal. A. alosa showed extensive medium- and long-distance movements-- including rare longitudinal displacements along the Cantabrian slope--and greater natal origin diversity than A. fallax, whose dispersal was largely restricted to middle-distance, latitudinal migrations. In both species, bycatches were dominated by the most abundant continental populations--Mondego and Minho for A. alosa, and Ulla and Minho for A. fallax--suggesting that these rivers function as source populations exporting individuals to sink populations through marine dispersal. Despite their differing dispersal ranges, both species displayed dual resident-dispersive contingents coexisting within the same populations, reflecting an interplay of river proximity, philopatry and resource availability. The stronger philopatry and constrained range of A. fallax imply heightened vulnerability to localized bycatch pressure near natal rivers, whereas A. alosas broader dispersal and higher origin diversity expose multiple populations to risk at a regional scale. These species-specific dispersal capacities and metapopulation structures critically shape bycatch vulnerability. Incorporating natal-origin and dispersal data into transnational, ecosystem-based management--such as targeted temporal or spatial fishing restrictions at mixing hotspots--will be essential to safeguard metapopulation dynamics, mitigate bycatch mortality, and maintain ecological connectivity among European shad populations.

ecology↗

bioRxiv2025

Integrated single-cell and spatial analysis identifies context-dependent myeloid-T cell interactions in head and neck cancer immune checkpoint blockade response

BackgroundApproximately 15-20% of head and neck cancer squamous cell carcinoma (HNSCC) patients respond favorably to immune checkpoint blockade (ICB). Previous single-cell RNA-Seq (scRNA-Seq) studies identified immune features, including macrophage subset ratios and T-cell subtypes, in HNSCC ICB response. However, the spatial features of HNSCC-infiltrated immune cells in response to ICB treatment need to be better characterized. MethodsHere, we perform a systematic evaluation of cell interactions between immune cell types within the tumor microenvironment using spatial omics data using complementary techniques from both 10X Visium spot-based spatial transcriptomics and Nanostring CosMx single-cell spatial omics with RNA gene panel including 435 ligands and receptors. In this study, we used integrated bioinformatics analyses to identify cellular neighborhoods of co-localizing cell types in single-cell spatial transcriptomics and proteomics data. In addition, we used both publicly available scRNA-Seq and in-house spatial RNA-Seq data to identify spatially constrained Ligand-Receptor interactions in Responder patients. ResultsWith 522,399 single cells profiled with both RNA and protein from 26 patients, in addition to spot-resolved spatial RNA-Seq from 8 patients treated with ICB together with bioinformatics analysis of publicly available single-cell and bulk RNA-Seq, we have identified a spatial and cell-type specific context-dependency of myeloid and T cell interaction difference between Responders and Non-Responders. We defined further cellular neighborhood and the sources of chemokine CXCL9/10-CXCR3 interactions in Responders, emerging targets in ICB, as well as CXCL16-CXCR6, CCL4/5-CCR5, and other underappreciated and potential markers and targets for ICB response in HNSCC. In addition, we have contributed a rich data resource of cell-cell Ligand Receptor interactions for the immunotherapy and HNSCC research community. DiscussionOur work provides a comprehensive single-cell and spatial atlas of immune cell interactions that correlate with response to ICB in HNSCC. We showcase how integrating multiple technologies and bioinformatics approaches can provide new insights into potential immune-based biomarkers of ICB response. Our results suggested refining future studies using preclinical animal models in a more context-specific manner to elucidate potential underlying mechanisms that lead to improved ICB responses. What is already known on this topicMost cancer patients still do not experience clinical benefits from immune checkpoint blockade (ICB), necessitating the development of response biomarkers and new immunotherapeutic targets. What this study addsHere, we use integrated high-dimensional omics and bioinformatics approaches to identify immune cell-cell interaction markers associated with ICB response in patients with Head and neck squamous cell carcinoma. How this study might affect research, practice or policyWe identified spatial and cell-type specificity of Ligand-Receptor interactions between myeloid and T cells in ICB Responder patients that may help inform further mechanistic studies and biomarker development.

cancer biology↗

bioRxiv2025

Lessons learned from applying eDNA surveying to diadromous fish detection across the north-east Atlantic region

Regular monitoring of diadromous fishes is critical to inform their management and conservation. Yet, the in-situ data collection these species is challenging due to their complex life cycle and low abundance. Focusing on the sea lamprey (Petromyzon marinus, Petromyzontidae) and the European shads (Alosa alosa and A. fallax, Clupeidae), emblematic diadromous fishes in the Northeast Atlantic region, this study leverages the use of water environmental DNA (eDNA) samples to monitor their distribution range. For that aim, we developed quantitative PCR (qPCR) and digital PCR (dPCR) assays and applied them to detect sea lamprey and European shad DNA in a network of 44 river basins across Spain, France, Ireland, and the UK. We found that qPCR efficiently detected presence/absence of shads, while the higher sensitivity of dPCR was essential for detecting the lower abundant and partly sessile behaving sea lamprey in the amount of water collected. Moreover, sea lamprey showed significantly lower eDNA copies per litre of water compared to shads, probably due to their larvae spending several years burrowed within soft sediments, reducing eDNA shedding into the water column. The integration of historical datasets with this snapshot wide-ranging study enhances our understanding of the distribution of sea lamprey and European shad in Atlantic rivers. Importantly, the lessons learned within this international collaboration are critical towards a prevailing framework for conservation of migratory fishes, highlighting the need of well-designed sampling strategies coupled with species-specific assays applied to eDNA samples to bust long-term monitoring efforts of diadromous species.

ecology↗

bioRxiv2024

δ-containing GABAA receptors on parvalbumin interneurons modulate neuronal excitability and network dynamics in the mouse medial prefrontal cortex

In medial prefrontal cortex (mPFC), fast-spiking parvalbumin (PV) interneurons regulate excitability and microcircuit oscillatory activity important for cognition. Although PV interneurons inhibit pyramidal neurons, they themselves express {delta} subunits of GABAA receptors important for slow inhibition. However, the specific contribution of {delta}-containing GABAA receptors to the function of PV interneurons in mPFC is unclear. We explored cellular, synaptic, and local-circuit activity in PV interneurons and pyramidal neurons in mouse mPFC after selectively deleting {delta} subunits in PV interneurons (cKO mice). In current-clamp recordings, cKO PV interneurons exhibited a higher frequency of action potentials and higher input resistance than wild type (WT) PV interneurons. Picrotoxin increased firing and GABA decreased firing in WT PV interneurons but not in cKO PV interneurons. The {delta}-preferring agonist THIP reduced spontaneous inhibitory postsynaptic currents in WT pyramidal neurons but not in cKO pyramidal neurons. In WT slices, depolarizing the network with 400 nM kainate increased firing of pyramidal neurons but had little effect on PV interneuron firing. By contrast, in cKO slices kainate recruited PV interneurons at the expense of pyramidal neurons. At the population level, kainate induced broadband increases in local field potentials in WT but not cKO slices. These results on cells and the network can be understood through increased excitability of cKO PV interneurons. In summary, our study demonstrates that {delta}-containing GABAA receptors in mPFC PV interneurons play a crucial role in regulating their excitability and the phasic inhibition of pyramidal neurons, elucidating intricate mechanisms governing cortical circuitry. Significance statementBy selectively deleting {delta}-containing GABAA receptors in PV interneurons, we demonstrate the importance of these receptors on PV interneuron excitability, synaptic inhibition of pyramidal neurons, and circuit function.

neuroscience↗

bioRxiv2023

A framework for quantifiable local and global structure preservation in single-cell dimensionality reduction

The ability to explore high-dimensional single-cell transcriptomics data efficiently is crucial in many biological studies. Dimensionality reduction techniques have therefore emerged as a basic building block of analytical workflows. They generate low-dimensional embeddings that capture important structures in the data, and are often used in discovery, quality control, and downstream analysis. However, the trustworthiness of current methods and the rigour of popular evaluation criteria are limited. We tackle this in an empirical study of structure-preserving data embeddings, delivering two tools. First, we introduce ViScore: a robust scoring framework that improves both unsupervised and supervised quality metrics, with emphasis on scalability and fairness. Second, we introduce ViVAE : a deep learning model that achieves better multi-scale structure preservation and is equipped with new tools for interpretability. We demonstrate the potential of these contributions to advance the trustworthiness of single-cell dimensionality reduction in a quantitative comparison and focused case studies.

bioinformatics↗

bioRxiv2021

The measure of spatial position within groups that best predicts predation risk depends on group movement

Both empirical and theoretical studies show that an individuals spatial position within a group can impact the risk of being targeted by predators. Spatial positions can be quantified in numerous ways, but there are no direct comparisons of different spatial measures in predicting the risk of being targeted by real predators. Here we assess these spatial measures in groups of stationary and moving virtual prey being attacked by three-spined sticklebacks (Gasterosteus aculeatus). In stationary groups, the limited domain of danger best predicted the likelihood of attack. In moving groups, the number of near neighbours was the best predictor but only over a limited range of distances within which other prey were counted. Otherwise, measures of proximity to the groups edge outperformed measures of local crowding in moving groups. There was no evidence that predators preferentially attacked the front or back of the moving groups. Domains of danger without any limit, as originally used in the selfish herd model, were also a poor predictor of risk. These findings reveal that the collective properties of prey can influence how spatial position affects predation risk, via effects on predators targeting, hence selection may act differently on prey positioning behaviour depending on group movement.

animal behavior and cognition↗

bioRxiv2018

Flow-wise or path-wise: diffusion in a fragmented dendritic network and implications for eels

The European eel (Anguilla anguilla) is a catadromous species that reproduces at sea and inhabits continental waters during its growth phase. River fragmentation due to obstacles is considered one cause of the decline of this species. However, the colonization process of river catchments by eels is still poorly understood. In this article, we compare two scenarios for the diffusion of eels within river catchments: a path-wise scenario, in which movements are totally random, and a flow-wise scenario, in which movements are partially oriented. Based on these two scenarios, we attempted to predict the distribution of eels within dendritic river catchments, explicitly accounting for the presence of obstacles to movement. The model was fitted to a long-time series of electro-fishing data. The results suggest that the path-wise scenario is more predominant than the flow-wise scenario. Moreover, results show that the distribution of eels in river catchment depends on (i) the types of movements carried out by eels, (ii) the configuration of river networks and (iii) the positions of obstacles within catchments.

ecology↗

bioRxiv2018

The Specificity of IQGAP1 Toward the PI3K-Akt Pathway is Dependent on the IQ3 motif

Epidermal growth factor receptor (EGFR) and its downstream phosphatidylinositol 3-kinase (PI3K) pathway are commonly deregulated in many cancers including head and neck cancer (HNC). Recently, we have shown that the IQ motif-containing GTPase-activating protein 1 (IQGAP1) provides a molecular platform to scaffold all the components from the PI3K-Akt pathway and results in the sequential generation of phosphatidylinositol-3,4,5-triphosphate (PI3,4,5P3). This makes the IQGAP1-PI3K scaffold a promising therapeutic target. In addition to the PI3K-Akt pathway, IQGAP1 also scaffolds the Ras-ERK pathway. To identify an IQGAP1 mutant that specifically loses IQGAP1-PI3K signaling but not other functions, we have focused on the IQ3 motif since this region binds with both the PIPK1 and PI3K enzymes and a short peptide derived from this sequence blocks binding and PI3K signaling. An IQ3 deletion mutant ({Delta}IQ3) in IQGAP1 was functionally compared with wild-type (WT) IQGAP1. We found that the IQ3 domain specifically mediates the PI3K-Akt pathway but does not regulate the Ras-ERK pathway. The IQ3 deletion mutant lost interactions with PI3K-Akt components but retained its binding of ERK pathway components and cell surface receptors, EGFR and integrins. In addition, the IQ3 deletion mutant lost regulation of cell migration. Consistently, the IQ3 motif derived peptide blocked Akt activation and led to the blockage of invasion mediated by EGFR organized into an integrin complex by syndecan-4. Taken together, this work has defined the IQGAP1 IQ3 motif as a specific target sequence for the scaffolding of the PI3K-AKT pathway.

cell biology↗

bioRxiv2018

Role of IQGAP1 in Head and Neck Carcinogenesis

Head and neck squamous cell carcinoma (HNSCC) is a common cancer in humans. Phosphoinositide 3-kinase (PI3K)/AKT signaling, along with its downstream effector mTOR, is one of the most frequently altered pathways in HNSCC, and is downstream of growth factor signaling including that mediated by epidermal growth factor receptor (EGFR), which is also commonly upregulated in HNSCC. Recently, IQ motif-containing GTPase activation protein 1 (IQGAP1) has been reported to function as a scaffold for the enzymes involved in the PI3K/AKT signaling pathway. Iqgap1 gene expression is increased in human HNSCCs, raising the hypothesis that it acts as an oncogene in this cancer. Whether IQGAP1 is necessary for HNSCC development as well as what is its underlying mechanism are both unknown. Here we report on the role of IQGAP1 in HNSCC by performing a combination of in vitro studies using human cancer cell lines, and in vivo studies using a well-validated preclinical mouse model for HNSCC that is known to depend upon EGFR signaling. Cells knocked out for IQGAP1 lost AKT signaling. Disruption of IQGAP1-scaffolded PI3K/AKT signaling using a peptide that interferes with the ability of IQGAP1 to bind to PI3K reduced HNSCC cell survival. In vivo studies utilizing Iqgap1-null (Iqgap1-/-) mice demonstrated that IQGAP1 is necessary for efficient PI3K signaling upon EGF-stimulation. Treatment of Iqgap1-/- mice with the oral carcinogen, 4-nitroquinoline 1-oxide (4NQO), Iqgap1-/- led to significantly lower multiplicities of cancer foci as well as significantly lower numbers of high grade cancers than observed in similarly treated Iqgap1+/+ mice. IQGAP1 protein was increased in its expression in HNSCCs arising in the Iqgap1+/+ mice, consistent with that seen in human HNSCCs. We also observed a significant down-regulation of PI3K signaling in 4NQO-induced HNSCCs arising in the Iqgap1-/- mice, consistent with IQGAP1 contributing to carcinogenesis by promoting PI3K signaling. Our studies, therefore, support the hypothesis that IQGAP1 acts as an oncogene in head and neck carcinogenesis, and provide mechanistic insight into its role.

cancer biology↗