Biology subjects

Martin, M.

Publications and source records attributed to Martin, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Microtubule detyrosination enhances matrix remodeling and force transmission during endothelial sprouting

Angiogenic sprouting relies on the coordinated regulation of endothelial migration, force generation, and extracellular matrix (ECM) remodeling. While microtubules are known to regulate cell polarity and migration, how tubulin post-translational modifications reshape microtubule behavior and impact matrix-dependent migration programs remain unclear. Here, using sprouting angiogenesis as an integrative physiological context, we combine live-cell imaging, three-dimensional (3D) sprouting and microfluidic invasion assays, and 3D traction force microscopy to dissect the role of tubulin detyrosination and acetylation. We show that microtubule detyrosination, in contrast to acetylation, promotes directional persistence, sprout elongation and collective endothelial invasion. Detyrosinated microtubules remain dynamic and display more persistent growth, supporting sustained directional migration. Strikingly, microtubule detyrosination also enhances ECM remodeling, leading to increased matrix degradation and augmented traction force transmission. Functional inhibition experiments reveal that matrix degradation, rather than actomyosin contractility, is required for both elevated forces and enhanced sprouting. Together, these findings identify microtubule detyrosination as a key regulator linking cytoskeletal dynamics, cell migration and matrix remodeling during angiogenesis.

cell biology↗

bioRxiv2025

Early Aβ-induced changes in the enteric nervous system and gut: structure, function, and motility

Alzheimers disease is increasingly recognized as affecting not only the central nervous system but also the autonomic nervous system, comprising the enteric nervous system, and thus the gut. Given the structural and functional similarities between the enteric and central nervous system, including susceptibility to A{beta}, this study investigated the early and acute effects of monomeric A{beta} on primary enteric neurons in vitro and on intestinal motility ex vivo. Acute A{beta} application caused marked neuronal hyperexcitability, with increased spike frequencies and calcium influx, and led to enhanced intestinal contractility without altering frequency or timing. Prolonged 72-hour exposure did not induce cell death or apoptosis but significantly reduced neurite outgrowth and decreased synaptic markers and beta II tubulin. These findings suggest that acute A{beta} primarily drives the excitability of enteric neurons and intestinal motility, while prolonged exposure subsequently leads to structural and synaptic changes. Overall, the study points to early dysfunction of the enteric nervous system in Alzheimers disease and highlights the gut as a potential target for early interventions. Synopsis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/678722v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@18b5292org.highwire.dtl.DTLVardef@1da0ecforg.highwire.dtl.DTLVardef@1023b09org.highwire.dtl.DTLVardef@171e3fb_HPS_FORMAT_FIGEXP M_FIG C_FIG The pathology of Alzheimers disease is increasingly recognized in the enteric nervous system (ENS), suggesting an early contribution of the gut to the onset of the disease. This study investigated the acute and short-term effects of amyloid-{beta} (A{beta}) on intestinal motility and enteric neurons to elucidate early functional and structural changes beyond the brain. O_LIAcute A{beta} exposure enhanced intestinal contractility ex vivo. C_LIO_LIEnteric neurons showed hyperexcitability and increased Ca{superscript 2} influx. C_LIO_LIAfter 72 h, neuronal viability and apoptosis remained unaffected. C_LIO_LIProlonged exposure reduced neurite outgrowth and {beta}III-tubulin expression. C_LIO_LISynaptic density was significantly decreased. C_LI

neuroscience↗

bioRxiv2025

Generation of Valvular Interstitial Cells from Human Pluripotent Stem Cells

Heart valves are living structures whose sophisticated functions are mediated by a specialized population of mesenchymal cells known as valvular interstitial cells (VICs). Given their central role in valve homeostasis, VICs represent a promising cell population for studying heart valve diseases and developing novel therapies to treat them. Here, we describe a strategy for generating VICs from human pluripotent stem cells (hPSCs) by stage-specific manipulation of developmental signalling pathways. Our results demonstrate that hPSC-derived VICs show a high transcriptional similarity to primary human fetal VICs and can secrete key proteins of the valve extracellular matrix. We further investigate the heterogeneity of hPSC-derived VICs and identify two major subpopulations with distinct molecular and functional properties, mirroring the cellular diversity observed in vivo. Finally, we utilize an in vitro model of Noonan syndrome to demonstrate that hPSC-derived VICs can accurately recapitulate key aspects of valve disease. Collectively, these findings provide a reproducible method for the scaled generation of bona fide hPSC-derived VICs and establish their utility in disease modelling and tissue engineering applications. Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABS- We established a robust platform to generate bona fide valvular interstitial cells (VICs) from human pluripotent stem cells (hPSCs), recapitulating native VIC identity and function. - We delineated signaling pathways that promote the development of two distinct VIC subsets and identified a surface marker to distinguish between them. What are the clinical implications?- A renewable, human-specific source of VICs enables precise mechanistic studies of valve development and disease that are not possible with limited surgical specimens or animal models. - This platform creates opportunities for therapeutic applications, including drug discovery and tissue engineering approaches for valve repair.

cell biology↗

bioRxiv2025

Plant cells at the organ surface use mechanical cues to activate a specific growth control programme

During morphogenesis of multicellular organs, cells acquire distinct identities that meet specific functional requirements. Epidermal identity is widely considered essential for plant morphogenesis due to the role of the epidermis in both restricting and promoting growth. In the root, epidermal cells are partially covered by a protective root cap, and partially positioned at the organ surface. Here, we propose that epidermal cells at the organ surface have unique requirements for growth control due to high mechanical tension, while covered epidermal cells are mechanically shielded by the root cap. We present in silico and in vivo evidence that plants use surface mechanical cues to activate a cell-type specific growth control programme involving the small GTPase RAB-A5c, allowing them to maintain directional growth at the organ surface. Positional mechanical cues may thus be used to control expression of a sub-population of epidermal genes, linking gene regulation to surface-specific functional requirements.

plant biology↗

bioRxiv2025

Cracking the case: Differential adaptations to hard biting dominate cranial shape in rat-kangaroos (Potoroidae: Bettongia) with divergent diets.

Functional adaptation in the mammalian jaw is often best predicted by the hardest bites an animal makes. Therefore, even when closely related species have otherwise divergent diets, a shared biomechanically challenging resource should be reflected in similar adaptations to jaw biomechanics. We assessed this in two species of rat-kangaroos, whose otherwise divergent diets include the extremely tough-shelled seeds of Santalum spp. (sandalwood and/or quandong). We used geometric morphometrics to analyse cranial shape of 161 bettongs (Bettongia spp.), including all four extant species. We identified adaptations to higher bite forces in both species that crack open Santalum seeds. However, B. lesueur had shorter facial proportions, indicating higher mechanical advantage, while B. penicillata had a premolar morphology that likely focussed bites to a specific, reinforced position on the jaw. This represents an example of many-to-one mapping at the genus level. We also found differences in a subsample of captive northern bettongs compared to wild conspecifics, suggesting some role of phenotypic plasticity in shaping adult skulls. The large olfactory tracts of B. penicillata, that support search for underground fungi, might have constrained its cranium to retain longer proportions. Fungal abundance could potentially be an important consideration in identifying translocation sites for this species.

developmental biology↗

bioRxiv2025

Tumor-draining lymph node derived CD8⁺ T cells sustain durable systemic immunity after neoadjuvant IL-15 and PD-1 blockade.

The tumor-draining lymph node (tdLN) serves as a critical reservoir of tumor-reactive T cells, yet its contribution to preventing metastatic recurrence remains poorly understood. In this study, we investigate CD8 T cell clonal dynamics and memory responses induced by neoadjuvant anti-PD-1 therapy. We demonstrate that PD-1 blockade promotes the emergence of protective CD8 T cell memory, enriched with tumor-relevant clones that persist in the lymph nodes of long-term survivors. Furthermore, we show that combination of a neoadjuvant IL-15 superagonist with PD-1 blockade significantly increases clonal diversity, cytotoxicity, and clonal persistence in non-draining lymph nodes. These changes result in enhanced systemic antitumor immunity and durable memory that prevents tumor relapse. Our findings establish the tdLN as a critical immunologic hub that can be therapeutically targeted by IL-15 to augment PD-1 blockade efficacy and support a rationale for a phase II neoadjuvant combination immunotherapy trial in early-stage NSCLC. One sentence summaryNeoadjuvant IL-15 with PD-1 blockade expands lymph node clonal diversity and preserves stem-like CD8 T cell features, yielding superior antitumor efficacy, durable memory, and reduced metastatic recurrence.

immunology↗

bioRxiv2025

A molecular glue: LecRKI.9 creates stiff plasma membrane cell wall connections

Water stress challenges plasma membrane - wall attachment. When plants are exposed to strong hyperosmotic stress, water exits the cell leading to plasmolysis, where the plasma membrane detaches partially from the cell wall and reveals discrete and persistent attachment sites in the form of Hechtian strands. Although these structures have been observed in several species for more than a century, the molecular bases behind plasma membrane - wall attachment remains elusive. Through a screen of candidate proteins, we reveal that the overexpression of two lectin receptor-like proteins (LecRK-I.9 and LecTM) increases the density of plasma membrane - wall connections in N. Benthamiana. The extracellular lectin domain of LecRK-I.9 was able to remain in the wall during plasmolysis. Conversely, deletion of the lectin domain in the LecRK-I.9 overexpressor restored the density of Hechtian strands to WT levels. In Arabidopsis, upon hyperosmotic stress, LecRK-I.9 formed largely immobile clusters, whereas lectin-deleted versions of LecRK-I.9 clusters were mobile. Cluster density correlated with predicted tensile stress levels and mechanical reinforcement in the wall before plasmolysis, consistent with a scenario in which attachment of the lectin domain also reflects the wall properties. Last, while overexpressing LecRK-I.9 conferred resistance to low water potential conditions, deletion of the lectin domain in the LecRK-I.9 overexpressor restored a WT response to water stress. Altogether, this demonstrates that the lectin domain of LecRK-I.9 creates persistent plasma membrane - wall attachment sites, with physiological relevance for plant resistance to water stress. SIGNIFICANCE STATEMENTAs observed since the mid-19th century, when placed in hyperosmotic conditions, plant cells undergo plasmolysis and form thin membraneous threads called Hechtian strands. These structures reflect the presence of persistent plasma membrane - cell wall attachment sites. Yet, the molecular components behind these sites are unknown. Through a candidate screen approach, we identify and demonstrate that the lectin domain of a receptor-like kinase provides such molecular glue. We also show that the clustering of the receptor is patterned and correlate with mechanically reinforced cell walls. Conversely, we find that the promotion of attachment increases resistance to water stress. This work revisits an old plant cell biology classic, and opens new avenues of research for plant adaptation to their environment.

plant biology↗

bioRxiv2025

Prehistoric Global Migration of Vanishing Gut Microbes With Humans

The gut microbiome is crucial for health and greatly affected by lifestyle. Many microbes common in non-industrialized populations are disappearing or extinct in industrialized populations. Understanding which microbes have been long-term residents of the human gut, and may have co-evolved with humans, has implications for the importance of microbial biodiversity loss for health. However, the genetic complexities of microbial evolution and the plasticity of gut microbiome composition have made it challenging to define these long-term associations. Here, we performed deep metagenomic sequencing of the Tsimane horticulturalists of Bolivia and compared their gut microbiomes with the Hadza hunter-gatherers of Tanzania. These two populations, whose ancestors were separated for tens of thousands of years, share 1,231 microbial species, most of which are absent in industrialized populations. Population genetic analyses in 636 of these shared species revealed patterns of microbial divergence and gene flow consistent with prehistoric human co-migration, with estimated split times that approximately align with human migration out of Africa and into the Americas. Our findings indicate that a diverse gut microbiome co-migrated with humans around the globe, persisting over millennia. However, many of these species are now vanishing in industrialized populations, and the consequences for human health remain uncertain.

microbiology↗

bioRxiv2025

The Pseudomonas putida Type VI Secretion Systems Shape the Tomato Rhizosphere Microbiota

Bacterial competition mechanisms drive microbial community dynamics across diverse ecological niches. The Type VI Secretion System (T6SS) represents a sophisticated nanomachine used by Gram-negative bacteria for contact-dependent elimination of competitors through the delivery of toxic effectors. While the T6SS has been well-documented in mammalian gut microbiota development, its role in shaping plant rhizosphere communities remains poorly understood despite the ecological importance of rhizosphere microbiota. This study investigates how the three Pseudomonas putida KT2440 T6SS clusters influence the tomato rhizosphere microbiota in agricultural soil. Through comprehensive in vitro and in vivo analyses, we demonstrate that while the K2/K3-T6SSs remain inactive under standard laboratory conditions, they become specifically activated in the presence of plant pathogens, suggesting an adaptive response to competitive pressure. Our experiments with T6SS-deficient mutants reveal that the P. putida T6SSs are essential for effective rhizosphere colonisation, with mutant strains showing significantly reduced colonisation capabilities compared to wildtype strain in competitive soil environments. Most importantly, our data establish that the P. putida T6SSs directly shape the taxonomic diversity and community structure of the rhizosphere microbiota of tomato plants. These results place the T6SS as a critical factor driving the evolution of complex polymicrobial communities within the plant rhizosphere, paralleling its established role in the gut microbiota. This research advances our understanding of the ecological functions of the different T6SSs in P. putida and the molecular mechanisms underlying microbial community assembly in the rhizosphere. Thus, it offers valuable insights for agricultural applications involving beneficial microbes and plant health management strategies.

microbiology↗

bioRxiv2025

AEMB: a computationally efficient abundance estimation method for metagenomic binning

Metagenomic binning is a crucial step in metagenomic analysis, namely grouping together contigs that are predicted to originate from the same genome to enable the recovery of metagenome-assembled genomes (MAGs). It has been shown that using information from multiple samples yields better results than binning each sample independently. However, for N metagenomic samples, using full multi-against-multi binning requires N2 alignments, making it computationally challenging to apply in large-scale metagenomic studies. Here, we propose AEMB (Abundance Estimation for Metagenomic Binning), a novel mapping mode implemented in strobealign. AEMB is a computationally efficient abundance estimation method that uses a prefix-lookup vector as an indexing structure to reduce memory usage and randstrobes to estimate the abundance of contigs without performing base-level alignment. Compared to the hash table used in the previous version of strobealign, the indexing structure reduces peak memory usage by 25.2% with almost the same runtime. Furthermore, we implemented a fast abundance estimation method that skips base-level alignment. Altogether, AEMB reduces the runtime for abundance estimation by 88% to 96% compared to commonly used alignment methods such as Bowtie2 and BWA, while achieving similar binning results. AEMB is available as a mapping mode in strobealign https://github.com/ksahlin/strobealign and SemiBin2 (v2.1 and later) accepts its inputs for binning.

bioinformatics↗

bioRxiv2025

On the role of L-type Ca2+ and BK channels in a biophysical model of cartwheel interneurons

Cartwheel interneurons (CWCs) in the auditory system exhibit a range of activity patterns relevant to auditory function and pathologies. Although experiments have shown how these patterns can vary across individual neurons and can change under pharmacological manipulations, the field has lacked a computational framework in which to explore the contributions of particular currents to these observations and to generate new predictions about the effects of manipulations on CWCs. In this work, we address this deficiency by presenting a conductance-based CWC computational model. This model captures the diversity of CWC activity patterns observed experimentally and suggests parameter changes that may underlie differences across cells. Bifurcation analysis of this model provides an explanation of how distinct dynamic mechanisms contribute to these differences, while direct simulations suggest how cells with different baseline dynamics will respond to variations in certain experimentally-accessible potassium and calcium channel conductances. In addition to the full model that we introduce, we present a reduced model that preserves CWC dynamic regimes. We classify the reduced model variables in terms of distinct dynamic timescales and show that the key transitions in dynamic patterns can be explained based on equilibria of the averaged dynamics of the slowest model variables, in a regime where the faster model variables exhibit oscillations. Overall, this study predicts how changes in parameters will influence CWC behavior, suggests how bifurcations contribute to changes in CWC dynamics, and provides a theoretical foundation that supports our simulation findings. Author summaryCartwheel interneurons (CWCs) are the most common class of inhibitory interneurons in an auditory brainstem region involved in sound localization and are believed to be important for auditory processing and pathologies. Distinct patterns of CWC activity have been observed experimentally in a variety of conditions. In this work, we present two novel computational models that simulate the factors contributing to CWC dynamics. By harnessing this framework, we are able to reveal the contributions of key ion currents to modulating CWC activity. Indeed, we find that the factors present in CWC neurons can produce a complicated dynamic landscape, with a wide range of output patterns possible as the relative strengths of these factors are varied. Overall, our models represent useful tools for understanding experimental results and generating new predictions about CWC behavior. In particular, in the more reduced of the two models, we can perform mathematical analysis to make more detailed predictions about the effects of current modulation on whether CWC neurons will exhibit regular spiking or more complex forms of outputs.

neuroscience↗

bioRxiv2025

Neurotrophin-3 produced by motor neurons non-cell autonomously regulate the development of pre-motor interneurons in the developing spinal cord

The development of multicellular organisms requires proper interplays between cell-autonomous genetic programs controlled by combinations of transcription factors that regulate the differentiation of distinct cell populations and non-cell autonomous processes that coordinate the proliferation, the fate, the survival, the respective location, and the proper interactions of these populations. During the development of the nervous system, non-cell autonomous mechanisms determine neuronal fate, survival, distribution, axon guidance, and connectivity. Although similar processes are suggested to be at work in the formation of spinal motor circuits, the molecular mechanisms involved remain mostly elusive. Here, we provide evidence that the Onecut transcription factors regulate a non-cell autonomous mechanism that modulate pre-motor interneuron development. We show that conditional inactivation of the Onecut factors in spinal motor neurons affects the differentiation and the positioning of pre-motor interneuron populations. We identify that Neurotrophin-3 produced by motor neurons under the control of the Onecut factors non-cell autonomously regulate the production and the distribution of pre-motor interneuron populations. Thus, we elucidated one of the non-cell autonomous mechanisms that coordinate the formation of the spinal motor circuits.

neuroscience↗

bioRxiv2025

Wolbachia uses ankyrin repeats to target specific fly proteins

Arthropods, the most diverse phylum on Earth, are hosts to a plethora of bacterial parasites that secrete various effectors of unknown function during infection. The most prevalent of these is the intracellular bacterium Wolbachia pipientis. The microbe infects between 40-60% of insect species, causes important reproductive manipulations, and limits virus replication in arthropod vectors, becoming a promising biocontrol agent. Understanding the molecular basis of Wolbachia infection and Wolbachia-induced phenotypes is critical to the use of Wolbachia in vector control. These Wolbachia ankyrin repeat proteins (WARPs) represent a highly dynamic and diverse part of the Wolbachia pangenome and remain thus far, largely uncharacterized. Here, we perform molecular and genetic screens to identify interactions between Wolbachia wMel WARPs and their target host proteins in Drosophila melanogaster. Our results identify strong interactions of two Wolbachia proteins, WARP434 and WARP754, with two host targets (CG11327 and Ptp61F, respectively). Heterologous expression of these two WARPs is extremely toxic in Drosophila tissues and the toxicity is dependent on the ankyrin repeat domain of each WARP. Importantly, knockdown of the host targets alleviates toxicity, confirming WARP/target interactions. Finally, antibodies targeting both WARPs show expression by Wolbachia during infection of Drosophila cells. Understanding how Wolbachia manipulates its host biology and which host pathways it targets during infection will help us divine how the most prevalent intracellular bacterial parasite on Earth interacts with its insect hosts at the molecular level. Our screen is the first step towards that goal. ImportanceMolecular interactions drive co-evolutionary arms races between hosts and pathogens. These interactions shape the structure and function of both host and parasite proteins, enabling immunity or virulence during infection. Understanding the molecular details that unfold during these events illustrates not only how hosts and parasites co-evolve at the molecular level but also may help characterize the function of poorly understood proteins. The most prevalent intracellular infection on earth is Wolbachia pipientis, with between 40-60% of insects harboring the bacterial symbiont. Understanding how Wolbachia infects host cells and the molecular tools it uses to alter cell biology is critical to the use of the microbe in vector control. Here, we identify Wolbachia proteins used by the symbiont to interface with specific host proteins. Understanding the molecular mechanisms underlying this host-microbe interaction will shed light on how an important symbiont, used in the control of vector populations and disease transmission, uses WARPs to interact with host targets and how targeting this host protein contributes to infection.

microbiology↗

bioRxiv2025

Gut Microbe-Derived N-Acyl Serinol Lipids Shape Host Postprandial Metabolic Homeostasis

Although strong evidence links the gut microbiome to metabolic disease, the mechanisms linking microbiota to hormonal and metabolic responses to food are not well understood. After a meal, gut bacteria produce a wide array of small molecule, protein, and lipid metabolites originating from bacterial sources. Annotating physiological function to select gut microbe-derived metabolites is critical to understanding diet-microbe-host interactions, and to developing microbiome-inspired therapies to improve human health. Here, we have investigated the role of a poorly annotated class of gut microbiome-derived lipids called N-acyl amides in postprandial metabolic physiology. Here we show both bacterial overproduction and provision of exogenous N-acyl amides reorganize host hormone-driven metabolic transition after a meal. Moreover, N-acyl amides exert broad effects on the meal- and circadian-related reorganization of gene expression, metabolic hormones, and gut microbiome composition. Collectively, these results demonstrate that microbiota-derived N-acyl amides play a physiologic role in postprandial metabolic homeostasis in the host.

physiology↗

bioRxiv2025

The Staphylococcus aureus prophage-encoded SSBP attenuates virulence and enhances IL-6-mediated macrophage clearance

Pathogens often manipulate host immune responses to promote infection. Here, we describe a novel mechanism by which a secreted prophage-encoded single-stranded DNA-binding protein (SSBP) attenuates Staphylococcus aureus virulence while enhancing host immune defenses. SSBP, encoded by the ROSA-like prophage in a colonizing, reduced-virulence strain of S. aureus (NSA1385), significantly increases bacterial susceptibility to macrophage-mediated killing in vitro and reduces pathogenicity in a zebrafish infection model. Treatment with purified recombinant SSBP decreases bacterial survival within macrophages and demonstrates therapeutic potential. Notably, SSBP activates macrophages via interleukin-6 (IL-6), a pro-inflammatory cytokine that promotes bacterial clearance and macrophage activation. These findings uncover an unexpected prophage-derived mechanism in a colonizing S. aureus strain that attenuates virulence while stimulating host immunity, offering promising avenues for anti-infective therapies and immunomodulatory strategies.

microbiology↗

bioRxiv2025

A pan-gene catalogue of Asian cultivated rice

The rice genome underpins fundamental research and breeding, but the Nipponbare (japonica) reference does not fully encompass the genetic diversity of Asian rice. To address this gap, the Rice Population Reference Panel (RPRP) was developed, comprising high-quality assemblies of 16 rice cultivars to represent japonica, indica, aus, and aromatic varietal groups. The RPRP has been consistently annotated, supported by extensive experimental data and here we report the computational assignment, characterization and dissemination of stably identified pan-genes. We identified 25,178 core pan-genes shared across all cultivars, alongside cultivar-specific and family-enriched genes. Core genes exhibit higher gene expression and proteomic evidence, higher confidence protein domains and AlphaFold structures, while cultivar-specific genes were enriched for domains under selective breeding pressure, such as for disease resistance. This resource, integrated into public databases, enables researchers to explore genetic and functional diversity via a population-aware "reference guide" across rice genomes, advancing both basic and applied research.

genomics↗

bioRxiv2025

Acquisition of discrete immune suppressive barriers contributes to the initiation and progression of preinvasive to invasive human lung cancer.

Computerized chest tomography (CT)-guided screening in populations at risk for lung cancer has increased the detection of preinvasive subsolid nodules, which progress to solid invasive adenocarcinoma. Despite the clinical significance, there is a lack of effective therapies for intercepting the progression of preinvasive to invasive adenocarcinoma. To uncover determinants of early disease emergence and progression, we used integrated single-cell approaches, including scRNA-seq, multiplexed imaging mass cytometry and spatial transcriptomics, to construct the first high-resolution map of the composition, lineage/functional states, developmental trajectories and multicellular crosstalk networks from microdissected non-solid (preinvasive) and solid compartments (invasive) of individual part-solid nodules. We found that early disease initiation and subsequent progression are associated with the evolution of immune-suppressive cellular phenotypes characterized by decreased cytotoxic CD8 T and NK cells, increased T cell exhaustion and accumulation of immunosuppressive regulatory T cells (Tregs) and M2-like macrophages expressing TREM2. Within Tregs, we identified a unique population of 4-1BB+ Treg subset enriched for the IL2-STAT5 suppressive pathway with transcription profiles supporting discrete metabolic alterations. Spatial analysis showed increased density of suppressive immune cells around tumor cells, increased exhaustion phenotype of both CD4 and CD8 T cells expressing chemokine CXCL13, and spatial micro-complex of endothelial and lymphocyte interactions within tertiary lymphoid structures. The single-cell architecture identifies determinants of early disease emergence and progression, which may be developed not only as diagnostic/prognostic biomarkers but also as targets for disease interception. Additionally, our dataset constitutes a valuable resource for the preinvasive lung cancer research community.

cancer biology↗

bioRxiv2024

Testing hypotheses of skull function with comparative finite element analysis: three methods reveal contrasting results

Comparative finite element analysis often involves standardising aspects of the models to test equivalent loading scenarios across species. However, in the context of feeding biomechanics of the vertebrate skull, what is considered "equivalent" can depend on the hypothesis. We use 13 skulls from diverse group of marsupial bettongs and potoroos (Potoroidae) to demonstrate that that scaling muscle forces to standardise unique aspects of biting mechanics can produce contrasting results of comparative stress or strain that are differentially suited to test specific kinds of hypotheses. We propose three categories of hypotheses for skull biting mechanics which each involve a unique method of muscle scaling: those comparing (1) the skulls efficiency in distributing input muscle forces, via standardising input muscle force to size, (2) morphological biting adaptation through standardising mechanical advantage to simulate size-independent, equivalent bites, and (3) feeding ecology affected by size, such as niche partitioning, via standardising bite reaction force. SUMMARY STATEMENTCommon approaches for scaling muscle forces in skull finite element models might not always offer reliable results for all hypotheses. We provide a framework for selecting the appropriate method.

evolutionary biology↗