Biology subjects

Webb, S.

Publications and source records attributed to Webb, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Multi-scale modeling of human tissues from spatial transcriptomics with TERRA

Spatial transcriptomics maps gene expression at cellular resolution, revealing how cells organize into multicellular niches. Yet computational analyses remain dataset-specific, without a transferable representation of tissue organization that generalizes across datasets, tasks and tissues or predicts how tissues behave under perturbation. We present TERRA, a foundation model pretrained on 112 million human cells profiled by spatial transcriptomics. From a single pretrained backbone, TERRA yields embeddings at the scale of cells, the genes they express and the neighborhoods in which they reside, and supports spatial in silico perturbation, all applied zero-shot to unseen tissues. At the cell level, in newly generated spatial data for developing pancreas, TERRA identified an islet-associated capillary state which we posit represents a developmental precursor of the mature islet microvasculature. At the gene level, in untreated kidney sections, in silico knockout of immune-checkpoint targets predicted a gene program of immune-checkpoint-blockade-associated nephrotoxicity, which we validated in treatment-exposed tissue and recovered in blood. At the neighborhood level, TERRA mapped macrophages across tissues to identify recurring cross-organ niches, which we term archetypes, including a tumor-boundary niche associated with poor prognosis in kidney cancer. Together, TERRA captures the spatial and multicellular logic of human tissue and predicts, in silico, its response to perturbation, providing a multi-scale framework for tissue biology, therapeutic development and clinical application.

genomics↗

bioRxiv2026

A conserved mechanism for targeted cohesin loading organises specialised chromosomal domains

Cohesin organises chromosomes through loop extrusion, yet how cohesin loading is targeted to specific genomic regions to shape chromosome architecture remains poorly understood. Here, we identify a conserved mechanism that directs cohesin loading to specialised chromosomal domains in Schizosaccharomyces pombe. Mutation of a conserved interaction surface in the cohesin loader Scc4/Ssl3 abolishes cohesin enrichment at centromeres and ribosomal DNA while largely preserving cohesin levels along chromosome arms, demonstrating that domain-specific accumulation depends on targeted recruitment rather than global loading capacity. We further identify the nucleolar protein Dnt1 as a receptor for cohesin loading at rDNA and show that it is required for proper organisation of this domain. High-resolution MicroC-XL maps reveal that targeted cohesin loading positions loop-based interactions within pericentromeres and rDNA without disrupting larger-scale domain boundaries. Together, these findings show that domain-specific receptors acting through a conserved loader interface direct cohesin positioning and identify targeted loading as a conserved organising principle for specialised chromosomal domains.

cell biology↗

bioRxiv2026

Tumor Protein D54 (TPD54) regulates intracellular protein trafficking, cellular function and disease progression in melanoma

To facilitate survival, migration and evasion of immune surveillance, cancer cells tightly coordinate the synthesis and trafficking of a diverse repertoire of proteins to their cell surface and the surrounding tumor microenvironment. A key mechanism underlying this process is the intracellular membrane trafficking pathways, including vesicular transport systems. There remains a paucity of mechanistic insight into the regulatory components that mediate nascent protein trafficking and their dysregulation in cancer. Herein, we investigate Tumor Protein D54 (TPD54) as a central regulator of intracellular protein transport that is exploited by melanoma cells to promote disease progression. Integrative analyses of patient-derived tumor tissue specimens show that the expression of TPD52L2 (the gene encoding TPD54) is frequently overexpressed in melanoma and correlates with adverse clinical outcomes, including reduced responses to immune checkpoint blockade. Mechanistic investigations further revealed that TPD54 maintains Golgi integrity and orchestrates trafficking of early endosomes, anterograde vesicles and extracellular vesicles. Functionally, TPD54 augments the secretion of pro-cancerous cytokines, increases the cell surface expression of adhesion-signaling receptors (e.g. integrin-{beta}1 and desmoglein-2), promotes melanoma cell migration and elevates their capability to undergo vasculogenic mimicry. Targeting TPD52L2 in two mouse models of melanoma (B16-F10 and HCmel12) showed significant attenuation of tumor growth, disrupted tumor vasculature, enhanced anti-tumor immunity with infiltration of CD8+ T cells and reduced metastatic disease. Collectively, these findings establish TPD54 as a critical and previously underappreciated regulator of protein trafficking in cancer cells that directly contributes to disease progression and highlights its potential as a novel therapeutic target to combat melanoma.

cancer biology↗

bioRxiv2026

Generation, Characterization and Comparison of Ovine Induced Pluripotent and Embryonic-Disc Stem Cells

Pluripotent stem cells derived from livestock species represent valuable systems for studying early mammalian development and for establishing renewable, well-defined cell sources; however, direct comparative characterization of distinct pluripotent stem cell platforms in sheep remains limited. In this study, we established and evaluated two ovine pluripotent stem cell types: reprogrammed induced pluripotent stem cells (siPSCs) and embryonic disc-derived stem cells (sEDSCs). Both siPSCs and sEDSCs exhibited core features of pluripotency, including compact colony morphology, alkaline phosphatase activity, expression of key pluripotency-associated markers, and maintenance of a normal ovine karyotype. Flow cytometry and quantitative RT-PCR analyses revealed broadly overlapping yet distinguishable pluripotency marker expression profiles between the two cell types. Functional pluripotency was confirmed by embryoid body formation and in vitro differentiation into derivatives of all three germ layers. To further assess lineage-specific differentiation competence and compare functional outputs relevant to mesodermal differentiation, both pluripotent stem cell types were directed towards the adipogenic lineage. While siPSCs and sEDSCs were each capable of adipogenic differentiation, differences in differentiation efficiency and marker expression were observed. Together, these findings demonstrate that ovine siPSCs and sEDSCs share core pluripotency characteristics while retaining distinct molecular and functional properties, providing a robust comparative framework for studies of ovine pluripotency, lineage specification, and stem cell biology.

cell biology↗

bioRxiv2026

High density culture of bovine embryonic stem cell derived mesenchymal cells on edible scaffolds for structured cultivated meat

Developing structured cultivated meat requires integrated solutions that combine scalable cell sources with edible, foodgrade materials capable of supporting highdensity growth and differentiation. Here, we evaluate bovine mesenchymal stem cells derived from embryonic stem cells (ESCderived iMSCs) as a scalable adipogenic cell source and develop an integrated workflow combining these cells with edible plantbased scaffolds for structured biomass generation. Cell identity and functionality were assessed using transcriptomic, morphological, gene expression, flow cytometric, and adipogenic differentiation analyses, in both adherent and suspension culture systems. In parallel, lentil, pea, and soy-based scaffold formulations were screened for cell attachment, proliferation, and biomass accumulation. Soybased scaffolds supported uniform cell distribution and robust growth and outperformed lentil-based scaffolds. Under dynamic culture conditions, bovine iMSCs cultured on soy-based scaffolds achieved highdensity growth, showing biomass accumulation (cell wet weight/scaffold wet weight) reached an average cell wet weight to scaffold wet weight ratio of 15% within three days. Cultures demonstrated active glucose metabolism and retained adipogenic differentiation capacity, confirmed by lipid accumulation and positive oil red O staining. These findings demonstrate an integrated cell-scaffold platform for rapid threedimensional biomass generation. This approach supports the development of a cell culture strategy for structured cultivated meat by combining defined cell sources with foodgrade scaffold technologies to improve scalability, structure, and nutritional relevance. HighlightsO_LIBovine ESC-derived iMSCs enable scalable adipogenic cell production C_LIO_LIEdible soy-based scaffolds support 3D attachment and biomass accumulation C_LIO_LIDynamic culture achieved [~]15% cell wet weight fraction within 3 days C_LIO_LIiMSCs retained adipogenic differentiation capacity on edible scaffolds C_LIO_LIIntegrated cell-scaffold culture supports structured cultivated meat prototypes C_LI

cell biology↗

bioRxiv2026

Multiple pathways couple kinetochore orientation to the meiotic spindle cycle

Meiosis generates haploid gametes from a diploid progenitor. In meiosis I, homologous chromosomes segregate while sister chromatids co-orient toward the same spindle pole. The mechanisms underlying this specialized segregation pattern remain incompletely understood. Here we identify pathways required for meiosis I chromosome segregation through a forward genetic screen in Saccharomyces cerevisiae. We find that meiosis I is highly sensitive to perturbations in diverse components of the segregation machinery and define key functional interfaces within complexes important for this division. These include meiosis I-specific regulators that establish the specialized chromosome pattern, namely the monopolin complex that directs sister kinetochore co-orientation and the Spo13MOKIR-Cdc5Polo module that promotes meiosis I chromosome segregation. In addition, we identify mutations affecting the core segregation machinery, including the spindle pole body, spindle midzone, and outer kinetochore, which can disrupt coupling between the chromosome segregation program and the meiotic spindle cycle. Together, our findings reveal that multiple pathways coordinate chromosome segregation with the meiotic divisions and highlight the unique demands of meiosis I.

cell biology↗

bioRxiv2026

Derivation and characterization of an embryonic-derived muscle progenitor cell line from Atlantic salmon (Salmo salar)

Unlike mammals, teleost fish exhibit lifelong skeletal muscle growth, characterized by continued fiber hypertrophy and the formation of new muscle fibers maintained by a persistent progenitor cell population. However, the limited availability of stable muscle progenitor cell lines from commercially important species such as Atlantic salmon (Salmo salar) constrains mechanistic studies and emerging applications in cellular aquaculture. Here, we report the establishment and characterization of a novel embryonic-derived salmon muscle progenitor cell line, termed SsEC. These cells were derived from late embryonic stages and exhibited a spindle-shaped morphology, robust proliferative capacity, and sustained expansion beyond 30 passages under defined culture conditions. SsECs demonstrated a distinct extracellular matrix preference, with vitronectin supporting long-term maintenance and expansion. Molecular characterization confirmed stable expression of canonical myogenic markers, including myf5 and myod1, while transcriptomic profiling revealed enrichment of genes associated with muscle development and sarcomere organization relative to a non-myogenic salmon cell line. Directed differentiation to muscle, using a two-step protocol, induced efficient formation of multinucleated myotubes expressing myosin heavy chain and sarcomeric -actinin, with upregulation of key differentiation markers such as myog and Tnnt3a. Together, these findings establish SsECs as a robust in vitro model cell line for studying salmon muscle development and provide a novel platform for applications in aquaculture research and cellular seafood production.

cell biology↗

bioRxiv2026

An integrated single cell and spatial omics atlas of human prenatal development

Single cell genomics has enabled analysis of human prenatal development at unprecedented resolution. However, most studies have relied on dissociated tissues during restricted windows of development, limiting insights into how spatially distributed networks of cells, and multicellular niches emerge and adapt to distinct organ microenvironments in situ. Moreover, existing human developmental atlases have not yet been harmonised, and we thus lack a comprehensive catalogue of known cell types in the developing human body. Here, we introduce the Human Developmental Cell Atlas (HDCA), a unified structural, cellular and molecular resource for prenatal human development. The HDCA integrates published and unpublished single cell/nucleus RNAseq atlases across prenatal organs, and includes a newly generated, spatially resolved, multimodal cell atlas of intact human embryos. Spanning 4-22 post conceptional weeks, capturing embryonic and early to mid fetal stages, the HDCA contains [~]4.6 million cells/nuclei which resolve into [~]450 cell types, explorable with a bespoke web portal. For a global overview of the human embryos multicellular communities, we applied unsupervised deep learning to our intact human embryo spatial data, charting 114 tissue niches that are structural and signalling hubs for the cellular interactions of the embryo. Guided by these niches, we profiled cellular networks over space and time, not examinable using single-organ atlases. In so doing, we revealed tissue-specific fibroblast patterning from previously undescribed mesenchyme progenitors, early diversification of organ-specific blood capillaries and lymphatic vasculature, emergence of neural crest cell fates, the formation of placode-and neural crest-derived peripheral sensory neurons, and how tissue niches guide peripheral neuron maturation and axonal migration. The HDCA thus serves as a comprehensive step towards a comprehensive understanding of human prenatal development, and a template towards unravelling the biology of congenital disorders.

developmental biology↗

bioRxiv2026

Self-supervised learning for a gene program-centric view of cell states

Single-cell omics has extended the biological interrogation of cell state from examining the expression of individual genes to unbiased profiling of tens of thousands of genes at once. However, extracting biological insights from such high-dimensional data remains challenging. To enable downstream analyses, many computational approaches compress cell state into a single latent representation. This can obscure the structure of underlying gene programs (GP), defined as coordinated sets of biologically related genes, such as signalling pathway response modules or transcription factor targets. Here, we present Tripso, a self-supervised transformer deep learning model which learns multiple GP-specific embeddings from predefined GPs, while also enabling the discovery of novel, data-driven GPs. Tripso facilitates principled comparisons across development, disease, and experimental systems. Firstly, in a dataset of human hematopoietic cells spanning prenatal development through adulthood and aging and including newly generated data, Tripso resolved age-specific GP patterns, including elevated JAK-STAT activity in pediatric hematopoietic cells and postnatal shifts in IKZF1 GP activity during B cell differentiation. Secondly, leveraging Tripso GP embeddings and comparing in vivo to in vitro data, we hypothesized and experimentally validated that inhibition of the SEC61 translocon improved maintenance of hematopoietic stem cells in culture. Finally, Tripsos capacity for data-driven GP discovery revealed a previously uncharacterized tissue-resident memory T cell GP with increased activity in atopic dermatitis. Its spatial co-localization with sebaceous gland-associated immune niches was demonstrated in spatial transcriptomic and proteomic data. Thus, by moving beyond single embeddings of cellular states, Tripso enables interpretable and actionable discoveries, demonstrating how GP-centric modelling can generate hypotheses with substantial biomedical relevance. By anchoring cellular representations in meaningful GPs, Tripso establishes a principled and biologically grounded framework towards the development of interpretable virtual cell models.

bioinformatics↗

bioRxiv2026

A new chemical carcinogen and Western diet protocol to reliably induce advanced hepatocellular carcinoma in male and female mice

Background and AimsA combination of chemical carcinogens and Western diet have been used to induce hepatocellular carcinoma (HCC) in mice, but these models show low incidence of HCC in female mice, while mice that do develop HCC show a wide range of HCC stage development. Therefore, a more reliable mouse model that induces advanced stage HCC in both male and female mice is warranted, which will enable reliable preclinical testing of therapeutics for advanced HCC. The purpose of this study was to create a simple, yet tolerable and reliable chemical carcinogen and Western diet induced mouse model of advanced stage HCC for both male and female mice. Approach and ResultsWe report that providing mice with a Western diet at weaning and for their lifetime combined with the sequential administration of low dose diethylnitrosamine (DEN), thioacetamide (TAA), and sucrose water promotes stage 2-3 HCC by 30 weeks of age in 100% of male mice and 96% of female mice (4% had stage 1 HCC), with a low fatality rate. Spatial transcriptomics, proteomics, and western blotting revealed this model alters genes and proteins similar to human HCC. ConclusionsThis study introduces, for the first time, a reliable chemical carcinogen model that induces advanced HCC in both male and female mice. Importantly, the model was tolerable for mice and induced protein and gene signatures comparable to human HCC. This new protocol will be a valuable model for preclinical testing of new therapeutic approaches for advanced HCC.

cancer biology↗

bioRxiv2026

Predicting how perturbations reshape cellular trajectories with PerturbGen

A major challenge in biology is predicting how cells transition between states over time and how perturbations disrupt these transitions. Understanding such dynamics is critical for identifying interventions that reverse pathological programs or reprogram cells toward desired states. Although recent computational approaches can predict single-cell perturbation responses in silico, they cannot predict responses across dynamic cell trajectories, for example how early perturbations reconfigure later cell states. To address this gap, we introduce PerturbGen, a generative foundation model trained on over 100 million single-cell transcriptomes that predicts perturbation responses along cellular trajectories. PerturbGen predicts how genetic perturbation at source state shapes downstream states, alters gene programs and trajectories across time, for example in differentiation or disease progression. We apply PerturbGen to three newly generated multi-condition human single-cell datasets spanning immune responses, hematopoiesis and skin development. In an in vivo immune challenge, PerturbGen predicts that knocking out an IL1B signal in myeloid cells attenuates later cytokine-interferon programs, with downstream changes consistent with a reversal of IL-1{beta} stimulation signature. In hematopoiesis, anchoring perturbation-induced programs to human genetics enables simulation of monogenic blood disorders, recapitulates established disease-associated biology whilst systematically revealing lineage-specific programs, including in lineages where this was not previously possible. In skin organoids, PerturbGen predicted that Wnt activation enhances stromal differentiation recapitulating the trajectory observed in human prenatal skin, findings that were functionally validated by experimentally activating Wnt signaling. Together, PerturbGen extends modeling of gene perturbations from static to dynamic cellular systems. We envision PerturbGen enabling the creation of in silico, trajectory-aware perturbation atlases and virtual cells across diverse biological scenarios, supporting optimization of disease models and prioritization of candidate molecular interventions for therapeutic discovery.

bioinformatics↗

bioRxiv2026

Local Tumor Microenvironment Niches Correlate With Survival And Immunotherapy Response In Human Glioblastoma

Background: Glioblastoma (GBM) is an aggressive form of primary brain cancer. Recent efforts to characterize GBM using single-cell or spatial transcriptomics have revealed tremendous intra-tumoral heterogeneity among malignant cells and across different tumor areas. However, most studies have focused on malignant cells, and the spatial and cellular heterogeneity of the tumor microenvironment (TME) remains poorly understood. Consequently, it is unclear how TME compositions and organizations influence clinical outcomes for patients. Results: Spatial transcriptomics on 25 tumors, integrated with single-cell RNA sequencing and histological analyses, enabled the estimation of cellular composition within the TME across 46,000 spots (55-m wide). This analysis identified spatial associations between mesenchymal-like cancer cells and monocyte-derived macrophages and revealed six unique niches (N1-N6) characterized by distinct cellular composition and biological pathway activations. Deconvolution of large-scale bulk RNA-seq datasets using a spatial transcriptomics reference revealed that tumor niche composition significantly associated with patient survival and response to immunotherapy. Specifically, the N1 niche, characterized by the enrichment of mesenchymal-like cancer cells and monocyte-derived macrophages alongside hypoxic signature, was associated with lower overall survival. In contrast, the N5 niche, characterized by the enrichment of oligodendrocyte progenitor-like cancer cells and microglia-derived tumor-associated macrophages, was associated with longer patients survival. Analysis of data from patients treated with immunotherapy identified that niches N1 and N3, characterized by mixed mesenchymal-like and astrocyte-like cells, were associated with poor response to anti-PD-1 immune checkpoint inhibitors. Conclusions: Our results demonstrate that GBM exhibits significant spatial heterogeneity within the TMEs, comprising distinct niche classes, and that the specific niche compositions are associated with overall survival and immunotherapy responsiveness. Our results suggest incorporation of TME niche categories as biomarkers for risk stratification and therapeutic decisions for GBM patients.

cancer biology↗

bioRxiv2025

Altered aperiodic EEG spectral power during speech perception task is associated with verbal communication in youths with Autism Spectrum Disorder

Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairment, but its neural mechanisms are not well known. Excitation (E) / inhibition (I) imbalance is considered as a key neurobiological mechanism of ASD, and several electroencephalography (EEG)-based E/I balance metrics have been proposed in the previous studies. The goal of the present research was to focus on these metrics abstracted from the speech perception task to investigate their relation to language/communication in autistic youths. We used a high-density 128-channel EEG to register neural responses during speech perception task in the sex- and age-matched groups of youths with ASD (N = 162) and typically developing (TD) controls (N = 144), aged 7-18 years old. The results revealed alterations in the E/I measures in the ASD group, pointing to a higher level of excitation or neural noise in the cortex as well as broadband reduction of spectral power during speech perception. A greater neural noise reflected in the reduction of aperiodic exponent and offset was associated with lower verbal communication skills in youths with ASD. The findings suggested that the higher noisiness in the cortical systems may be a relevant marker to monitor in relation to language/communication in ASD.

neuroscience↗

bioRxiv2025

Sleep-like slow waves in wakefulness index post-stroke behavioural alterations

Increases in high-amplitude, low-frequency EEG oscillations during non-rapid eye movement (NREM) sleep serve as markers of neuronal silencing, which disrupts functional connectivity and is associated with a loss of awareness and responsiveness. Cortical slowing likewise occurs during wakefulness, upon sleep deprivation, and accompanies performance deterioration. Recent work has revealed similar oscillations (termed sleep-like slow waves) following stroke in brain regions close or connected to a brain lesion, offering a plausible but untested mechanism for stroke-related behavioural impairment. Here, we simultaneously recorded EEG and behavioural performance while 30 unilateral stroke patients (12 left hemisphere, 18 right hemisphere) and 27 age-matched healthy adults completed a computerised perceptual decision-making task. Sleep-like slow waves occurred more frequently in stroke patients relative to healthy controls. Furthermore, there was a significant correlation between slow wave occurrence and the accuracy and speed of perceptual reports in stroke patients, suggesting that variations in the occurrence of slow waves may contribute to cognitive heterogeneity post-stroke. Evidence that sleep-like slow waves predict deficits in perceptual decision-making following stroke indicates that stroke-induced lesions can destabilize cortical networks extending beyond the damaged regions, thereby contributing to broader cognitive impairments.

neuroscience↗

bioRxiv2025

Calyculin A Induces Premature Chromosome Condensation and Chromatin Compaction in G1-Phase HeLa Cells without Histone H1 Phosphorylation

We show here that treatment of HeLa cells with calyculin A, an inhibitor of Protein Phosphatases 1 and 2A, induces premature chromosome condensation (PCC) at any point in interphase of the cell cycle. Chromosomes in G1-phase PCC closely resemble metaphase chromatids in the light microscope, and measurements using FLIM-FRET show that they have the same level of chromatin compaction as metaphase chromosomes. However, histone H1 is not phosphorylated in G1- or early S-phase PCC. These results suggest that H1 phosphorylation is not required for mitotic chromosome condensation and chromatin compaction. They also confirm that Cdk1/cyclin B, which directly phosphorylates histone H1, is not active in G1 and thus is not essential for G1- PCC. We suggest that induction of G1-PCC involves protein kinases or other factors that are either held in an inactive state by protein phosphatases, or constitutively active but countered by phosphatases. The same factors may be involved in the onset of normal mitosis, becoming active when protein phosphatases are downregulated. Induction of PCC with calyculin A should provide a useful system for identifying and studying the biochemical pathways that are required for mitotic chromosome compaction, nuclear envelope breakdown, and other events of mitosis.

cell biology↗

bioRxiv2025

Cell atlas of the developing human meninges reveals a dura origin of meningioma

The vertebrate central nervous system is enveloped by the meninges, consisting of the pia, arachnoid, and dura layers. The arachnoid is hypothesised to give rise to the most common primary intracranial tumours, meningiomas. However, molecular evidence supporting this hypothesis is lacking. There are no effective medical therapies to treat meningiomas that are resistant to local interventions, encumbered by our limited understanding of their cellular origin. To address this limitation in our understanding of meningioma biology, we generated a comprehensive reference single cell and spatial transcriptomic atlas of human fetal meninges at post-conceptional weeks 5-13. We found that the meningeal layers develop concurrently, and identified an inner CDH1-positive dura cell layer expressing tight junction genes consistent with barrier function. We show that transcriptionally, meningioma cells resemble dura-lineage cells, and that common meningioma driver genes were expressed preferentially in the dura lineage. Our findings suggest that meningiomas originate from dura lineage cells. HIGHLIGHTSO_LIscRNA-seq and spatial transcriptomics reveals architecture of human fetal meninges development C_LIO_LIMeningeal layers are formed concurrently, by a gradual refinement of cell states C_LIO_LIA CDH1+ inner dura sublayer expresses tight junction genes like the arachnoid barrier C_LIO_LIMeningioma tumours likely originate from inner dura lineage cells, not arachnoid C_LI

developmental biology↗

bioRxiv2024

Eukaryotic composition across seasons and social groups in the gut microbiota of wild baboons

BackgroundAnimals coexist with complex microbiota, including bacteria, viruses, and eukaryotes (e.g., fungi, protists, and helminths). While the composition of bacterial and viral components of animal microbiota are increasingly well understood, eukaryotic composition remains neglected. Here we characterized eukaryotic diversity in the microbiomes in wild baboons and tested the degree to which eukaryotic community composition was predicted by host social group membership, sex, age, and season of sample collection. ResultsWe analyzed a total of 75 fecal samples collected between 2012 and 2014 from 73 wild baboons in the Amboseli ecosystem in Kenya. DNA from these samples was subjected to shotgun metagenomic sequencing, revealing members of the kingdoms Protista, Chromista, and Fungi in 90.7%, 46.7%, and 20.3% of samples, respectively. Social group membership explained 11.2% of the global diversity in gut eukaryotic species composition, but we did not detect statistically significant effect of season, host age, and host sex. Across samples, the most prevalent protists were Entamoeba coli (74.66% of samples), Enteromonas hominis (53.33% of samples), and Blastocystis subtype 3 (38.66% of samples), while the most prevalent fungi included Pichia manshurica (14.66% of samples), and Ogataea naganishii (6.66% of samples). ConclusionsProtista, Chromista, and Fungi are common members of the gut microbiome of wild baboons. More work on eukaryotic members of primate gut microbiota is essential for primate health monitoring and management strategies.

microbiology↗

bioRxiv2024

Sulfur-species in Zinc-specific Condylar Zones of a Rat Temporomandibular Joint

In this study, we performed synchrotron-based micro-X-ray fluorescence (-XRF) imaging of elements Zn and S, and X-ray absorption near edge spectroscopy (XANES) coupled with -XRF for identification of Zn and S species in the condylar zones of a rat temporomandibular joint (TMJ). Histologic localization of Zn and hypoxia-inducible factor-1 (HIF-1) were mapped using an optical microscope. These data were visually correlated with -XRF and XANES data to provide insights into plausible biological S-species in Z-enriched condylar zones of a rat TMJ. Furthermore, -XRF coupled with micro-X-ray diffraction (-XRD) was used to underline Z-incorporated biological apatite in the subchondral bone and bone of the rat TMJ. Results illustrated the potential dependence between biometal Zn and nonmetal S and their collective governance of cell and tissue functions in a zone-specific manner. Elemental Zn with organic and inorganic S-species at the cartilage-bone interface and transformation of plausible Zn-enriched mineralization kinetics of biological apatite from subchondral bone to condylar bone were ascertained using -XRF-XANES and -XRD. The coupled -XRF-XANES complementing with -XRD and immunohistology provided an informative view of S and Zn and their association with zone-specific biological pathways in situ. Understanding the spatial distributions of the main S-species with redox-inert Zn in regions of cartilage, bone, and the interface is essential for further unlocking questions surrounding formation and resorption-related biomineralization pathways as related to osteoarthritis or genetically inherited diseases. Using these complementary techniques with microspectroscopic spatial information provided insights into the associations between biometal Zn and nonmetal S and a window into detecting the plausible early-stage diagnostic biomarkers for humans with TMJ osteoarthritis.

bioengineering↗