Biology subjects

Nguyen, T. T.

Publications and source records attributed to Nguyen, T. T..

At least 19 recordsLinked to original sources

bioRxiv2026

Targeting SUFU-mediated GLI activity alleviates ciliopathic phenotypes

Ciliopathies are incurable, pleiotropic diseases that result from defective cilia. Several ciliopathic phenotypes arise from improper processing and activity of GLI transcription factors, yet attempts to rescue these phenotypes by overexpressing activator or repressor GLI isoforms have proven unsuccessful. Here, we demonstrate that modulating SUFU-GLI interactions restores GLI transcriptional activity and rescues ciliopathic phenotypes in vivo. As previous work identified increased accumulation of SUFU in ciliopathic conditions, we hypothesized that exploiting SUFU's epistatic relationship to the cilium could provide a novel therapeutic strategy for ciliopathies. Genetic introduction of either a single null allele (Sufu+/-) or point mutation allele (SufuD159R), which modulates SUFU-GLI binding, into a ciliopathic mouse model revealed that both interventions improved midfacial phenotypes; however, SufuD159R provided a more complete rescue by significantly improving mandibular phenotypes as well. Molecular examination of this genetic modification revealed restored GLI3 binding to DNA, GLI3 interaction with transcriptional cofactors, and GLI3-directed transcription of target genes, collectively driving the rescue of numerous ciliopathic phenotypes. These findings reveal cilium-independent functions for SUFU and establish that modulating SUFU-GLI interactions bypasses the need for ciliary GLI processing. Together, these data provide a promising therapeutic approach for ameliorating ciliopathic pathologies.

developmental biology↗

bioRxiv2026

Urban Vietnam at the microbiome transition: Co-existing enterotypes reflect the global industrialization patterns

Vietnam's rapid socioeconomic and dietary transition offers a rare window into how industrialization is reflected in the gut microbiome, yet Vietnamese populations remain underrepresented in global reference datasets. We investigated whether healthy Vietnamese adults in Hanoi harbor microbial community configurations associated with different stages of industrialization. Metagenomic data from stool samples of 183 clinically screened participants in Hanoi were analyzed alongside 629 publicly available metagenomic datasets from populations in low to middle income (LMI) and high income (HI) countries. Species-level taxonomic composition and gene-content-based metabolic pathways were characterized using community clustering and multivariable association analyses. Rather than forming a single population profile, the Vietnamese cohort separated into two enterotypes that mirrored the global industrialization gradient. Enterotype 1 more closely resembled populations from LMICs and showed greater microbial richness and diversity, whereas Enterotype 2 aligned with taxonomic and functional profiles observed in HICs. Both taxonomic and functional potential shows similar trajectories. Diet and lifestyle patterns describe some of the variance between enterotypes, supporting an association between contemporary exposures and microbiome structure without establishing causation. Antibiotic resistance profiles also varied between enterotypes, suggesting that the transition may encompass functions relevant to antimicrobial exposure. Together, these findings position urban Vietnam at a microbiome transition, where community states associated with different levels of industrialization coexist within a single population. This Vietnamese reference cohort expands representation in global metagenomic research and provides a baseline for tracking how rapid socioeconomic change may reshape microbial ecology, metabolic capacity, and antimicrobial resistance.

microbiology↗

bioRxiv2026

Inotropic effects of 3-hydroxybutyrate in a rodent heart: pressure-volume and isolated rat ventricular trabeculae analysis

An administration of 3 hydroxy-butyrate (3-OHB) in experimental animals or humans is associated with an increase of cardiac output (CO), but whether this hemodynamic benefit reflects direct myocardial inotropy or heart unloading due to peripheral vasodilation remains unclear. It is also unknown if myocardial effects are due to engagement of receptor-mediated inotropic response, or due to improvement of myocardial bioenergetics. To address these questions, we studied integrated cardiovascular response (pressure-volume analysis of the left ventricle) and isolated left ventricular (LV) trabeculae from normotensive male HanSD rats (age 20-30 weeks) after administration of 3-OHB (1 mmol/l) and drugs targeting adrenergic and cAMP-dependent signaling - metoprolol, adenylyl cyclase inhibitor 2,5-dideoxyadenosine and isoprenaline, during Tyrode solution perfusion and 1 Hz pacing. Pressure-volume analysis demonstrated increased left ventricular end-systolic elastance (+34%), improved ventriculo-arterial coupling (+65%) and increased LV efficiency (+28%), indicating direct inotropic effect of 3OHB. In isolated LV trabeculae, 3-OHB increased twitch force in both groups, but increase was greater in healthy hearts (+55.8%) than in the HF group (+35.6%) (p = 0.014). The inotropic effect of 3-OHB was not further augmented by coadministration of isoprenaline and was not attenuated by beta-1 adrenergic blockade or cAMP inhibition. Results suggest that 3-OHB directly improves LV inotropy and by a mechanism that is independent of receptor-mediated beta-adrenergic signaling, most consistent with a direct bioenergetic pathway. These findings support 3-OHB as a candidate inotropic agent with a mechanistic profile distinct from conventional cAMP-dependent inotropes.

physiology↗

bioRxiv2026

Spatial and developmental reprogramming enables root growth under high salinity in the extremophyte Schrenkiella parvula

High salinity severely restricts root growth in most plants, yet the extremophyte model Schrenkiella parvula maintains growth under otherwise inhibitory conditions through a previously unrecognized developmental reorganization of the primary root. Under high salinity, the elongation zone rapidly reorganizes into two distinct states: the bulged and gap zones. These zones form in response to ionic stress and emerge during a transient growth pause followed by resumed tip growth and localized lateral root emergence from the gap zone. Jasmonic acid (JA) is necessary to initiate this developmental transition, while cell-layer-resolved hormone profiling revealed spatiotemporally coordinated JA and auxin accompanying the maintenance of the distinct zones. The zone-specific expression profiling resolved transcriptomic networks spanning core development and broad or zone-specific stress responses, revealing spatial regulation of hormone signaling, cell-wall remodeling, and osmotic and oxidative stress pathways. Raman spectroscopy, metabolite profiling, and cellular imaging supported localized regulation of water availability, ionic balance, and suppression of ROS accumulation and cell death. These networks also identified orthologous genes co-opted for novel functions potentially used to sustain growth. Together, these findings reveal a spatially coordinated mechanism for maintaining root growth under salt stress and provide a framework for discovering genetic mechanisms that optimize growth under stress.

plant biology↗

bioRxiv2026

PRDM9 Alleles Guide Distinct Patterns of Recombination Localization in Atlantic Salmon

Meiotic recombination in many vertebrate lineages is directed to genomic regions by the DNA-binding protein PRDM9. To date, PRDM9 research has focused primarily on mammals, and its role in recombination localization has only recently been established in salmonids. PRDM9 binding specificity is determined by a tandemly repeated zinc-finger array that exhibits extensive allelic diversity within and between species. However, the extent to which PRDM9 variation shapes recombination landscapes in salmonids remains poorly understood. Here, we performed large-scale genotyping of PRDM9 in an aquaculture population of Atlantic salmon (Salmo salar) using long-read sequencing. By integrating PRDM9 genotypes with pedigree information and genome-wide recombination data, we generated PRDM9-specific linkage maps and sets of inferred crossover events. We show that the presence of specific PRDM9 alleles is associated with differences in recombination localization and identify patterns consistent with dominance interactions between alleles. Using population-averaged recombination rate estimates, we further link a previously described sequence motif enriched in European recombination hotspots to the presence of a common PRDM9 zinc-finger array allele (RPT6a). Together, our results demonstrate functional differences between PRDM9 alleles which contribute to divergence in recombination landscapes in Atlantic salmon, paralleling patterns observed in mammals. The broad geographic distribution of Atlantic salmon, combined with extensive pedigree data generated through aquaculture, highlights its potential as a powerful model for studying PRDM9 function and evolution beyond mammals.

genetics↗

bioRxiv2026

Microbial mechanistic requirements for eliciting a topical and intranasal immune response

The skin colonist Staphylococcus epidermidis elicits a potent antibody response that can be redirected against an antigen of interest, but this process relies on genetic engineering.1 Here, by adapting bioorthogonal chemistry methods to conjugate antigens to the cell surface, we make the process of generating a commensal vaccine rapid and efficient. A wide variety of bacteria displaying tetanus toxin fragment C (TTFC) elicit an antibody response when applied to mice topically, indicating that the inductive process is not limited to colonists. Colonization occurs at two different sites, the skin and nostril; by colonizing each with S. epidermidis-TTFC, we show that skin colonization yields a moderate IgG response, while nostril colonization elicits a highly potent systemic IgG response and an exuberant IgA response in the nostrils, lungs, and intestine. Two lines of evidence are consistent with the nasal-associated lymphoid tissue (NALT) as the inductive site for nostril colonization: imaging suggesting robust bacterial translocation, and the induction of commensal-specific B cells following colonization. On the skin, TTFC must be conjugated to live S. epidermidis to elicit an antibody response; in the nostrils, live S. epidermidis-TTFC and S. epidermidis mixed with TTFC are equally potent. Commensal vaccination yields a robust response in pet shop mice, and chemical conjugation facilitates antibody responses to a broad array of antigens, including a whole viral capsid and a rotavirus immunogen. Collectively, these findings provide compelling evidence of a translational path for commensal vaccines.

microbiology↗

bioRxiv2026

First-Trimester Non-Invasive Prediction of Preterm Birth Using Cell-Free DNA Fragmentomics

ObjectiveTo develop and validate a cell-free DNA (cfDNA) fragmentomic classifier for the early prediction of spontaneous preterm birth (PTB) using routine first-trimester non-invasive prenatal testing (NIPT) data. MethodsA nested case-control study was conducted within a prospective multicenter Vietnamese cohort comprising 286 pregnancies, including 82 spontaneous PTB cases and 204 term controls. Maternal plasma cfDNA collected during routine first-trimester NIPT (median gestational age, 12 weeks) was sequenced to a depth of approximately 20 million reads per sample. Five fragmentomic feature categories including copy number alterations, end-motif composition, nucleosome distance, fragment length, and joint fragment-lengthxend-motif were evaluated for PTB prediction. Machine learning classifiers were developed in a training cohort (n = 228, 65 PTB vs 163TB) and tested in a validation cohort (n = 58, 17 PTB vs 41 TB). ResultsAmong the five fragmentomic feature classes evaluated, 4-mer end-motif (EM) profiles exhibited the most pronounced differences between PTB and term control samples. Consistent with these findings, the EM-based classifier demonstrated the highest discriminative performance in the validation cohort, achieving an AUC of 0.970 (95% CI, 0.912-1.000). At a specificity >90%, the model achieved a sensitivity of 94% (95% CI, 78-100%). ConclusionThese findings demonstrate that cfDNA EM signatures derived from routine first-trimester NIPT can accurately identify pregnancies at risk of spontaneous preterm birth, without additional blood collection or sequencing, thereby extending the clinical utility of existing prenatal screening infrastructure. KEY POINTSO_ST_ABSWhat is already known about this topic?C_ST_ABSO_LICurrent first-trimester prediction strategies based on maternal characteristics, cervical length, and biochemical markers have limited predictive accuracy, particularly in nulliparous women. C_LIO_LIExisting cfDNA-based approaches have shown only modest performance or require additional assays, limiting clinical applicability. C_LI What does this study add?O_LIExisting NIPT sequencing data can be repurposed (without additional blood sampling or sequencing) for accurate prediction of spontaneous preterm birth (AUC=0.970). C_LIO_LIA classifier employing 4-mer end-motif (EM) profiles achieved an AUC of 0.970. At a specificity >90%, the model achieved a sensitivity of 94%. C_LI

genomics↗

bioRxiv2026

Self-Calibrated Hyperspectral Neural Radiance Fields for 3D Reconstruction of Bone and Bone Analogues

Hyperspectral imaging (HSI) has gained increasing attention for bone assessment because it captures rich wavelength dependent information associated with mineralised tissue. HSI provides detailed spectral information related to material composition, while 3D geometric information supports the analysis of surface morphology and structural detail. However, integrating spectral and geometric information remains challenging, particularly when conventional reconstruction pipelines depend on external pose estimation. To address this challenge, we propose BoNeRF-HS, a self-calibrated hyperspectral neural radiance field for 3D reconstruction. BoNeRF-HS jointly optimises camera intrinsics, volume density, and hyperspectral radiance, removing the need for COLMAP based poses. To improve spectral modelling, we incorporate a gated spectral adapter head that learns wavelength dependent radiance features for hyperspectral view synthesis. We evaluate BoNeRF-HS on a multi-view hyperspectral dataset containing mouse bone, trabecular bone analogue, and cortical bone analogue samples. Experimental results demonstrate that our framework achieves improved reconstruction quality, and better preservation of bone surface details compared with existing approaches.

bioengineering↗

bioRxiv2026

Activating adaptor-like sequences in pericentrin mediate its transport by dynein

Right before a cell divides, the centrosome rapidly increases its size and microtubule organizing activity through a process termed centrosome maturation. PCNT, a coiled-coil centrosomal protein, is synthesized and transported to the centrosome simultaneously by dynein. This dynein-mediated co-translational transport of PCNT facilitates centrosome maturation and mitotic spindle formation. How dynein engages and transports PCNT, however, remains unclear. Here we find that PCNT residues 1393-1525 are required for mediating dynein-dynactin interaction. PCNT (1393-1525) also shares similar sequence features with canonical dynein cargo adaptors. PCNT is predicted to interact with dynein heavy chains through similar contact sites used by canonical dynein cargo adaptors. Introducing point mutations at those contact sites abolishes dyneinmediated transport in a peroxisome motility assay. Our results suggest that PCNT contains adaptorlike sequences to bind and activate dynein directly during its transport to the centrosome. Our data also suggest that dynein may engage with some of its cargoes directly without an adaptor.

cell biology↗

bioRxiv2026

A BRRF1-CCR4-NOT axis underlies conserved transcriptome-wide loss of splicing fidelity during gammaherpesvirus reactivation

Gammaherpesvirus reactivation drives a collapse of host mRNA splicing fidelity that extends across the transcriptome, with exon skipping affecting up to [~]57% of expressed genes, exceeding the effects of depletion of any of 186 splicing factors. Combining five Epstein-Barr virus (EBV) and Kaposis sarcoma-associated herpesvirus (KSHV) reactivation systems across B cell and epithelial models with deep poly(A)+ RNA sequencing of purified lytic cells, we find that most induced isoforms are predicted to undergo nonsense-mediated decay or to lose conserved protein domains, broadly compromising cell cycle, innate immune and RNA-processing pathways. The phenotype arises independently of viral DNA replication, indicating early host remodeling. A screen of EBV early genes identifies BRRF1 as a key driver: through a CIY(Y/E) motif conserved in KSHV ORF49, BRRF1 engages the nuclear CCR4-NOT complex through its CNOT9 and CNOT1 subunits, hijacking this canonically cytoplasmic deadenylation hub for nuclear disruption of host splicing.

pathology↗

bioRxiv2026

Widespread use of invalid statistical tests in biomedical machine learning

Cross-validation is routinely used to compare performance in biomedical artificial intelligence. Standard tests ignore correlation across cross-validation folds, inflating false-positive rates. In a PRISMA-guided meta-analysis of 184 studies (impact factor [≥] 15) across 30 biomedical fields, 97% use invalid tests. Among studies with abstract-level claims supported by invalid tests, 59% rely on a spurious comparison: one that loses significance after correcting for this correlation. On average, regaining significance requires a 43% larger effect. Extending these findings to the broader literature, we estimate that spurious comparisons occur in nearly two in three studies and support abstract-level claims in nearly one in three studies. Simulations confirm false-positive rates paradoxically approach 100% when cross-validation is repeated to improve stability. We introduce SHARP, a redesign of cross-validation, which best balances false-positive control and power among 13 benchmarked tests. These results reveal widespread fragility in biomedical artificial intelligence and offer a practical route to valid comparisons.

bioinformatics↗

bioRxiv2025

Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer

Systemic therapies are the standard of care for most pancreatic ductal adenocarcinoma (PDAC) patients but provide limited benefit due to pervasive resistance. The fibrotic tumor microenvironment (TME) is thought to drive resistance by restricting perfusion and drug delivery. Here, we show that therapeutically relevant drug concentrations are achieved even in poorly perfused, therapy-resistant murine PDAC tumors, indicating that impaired delivery alone does not explain drug resistance. Instead, we find TME exposure imprints a therapy-resistant state upon PDAC cells. These observations raised the question of how the TME imposes this state. Poor perfusion alters nutrient availability in the TME. To model this, we developed Tumor Interstitial Fluid Medium (TIFM), which recapitulates TME nutrient conditions. TIFM cultured PDAC cells acquire a therapy-resistant phenotype that mirrors resistance observed in the TME. In this state, cytotoxic and targeted therapies retain on-target activity but fail to trigger cell death, resulting in therapeutic tolerance. Mechanistically, drug tolerance is driven by suppression of apoptotic priming and can be reversed by inhibition of the anti-apoptotic regulator BCL-XL. These results identify TME-driven reprogramming of cell death as a key mechanism of therapy resistance in PDAC and establish TIFM as a physiologically relevant model for studying microenvironment-induced drug resistance.

cancer biology↗

bioRxiv2025

A neural network with episodic memory learns causal relationships between narrative events

Humans reflect on memories to make sense of ongoing events. Past work has shown that people retrieve causally related memories during comprehension, but the mechanisms underlying this process remain unclear. Here, we used a recurrent neural network augmented with a key-value episodic memory buffer and trained it to predict upcoming scenes while watching a television episode. At each time step, the model transformed the current scene into a value representing memory content and a key representing memory address, both stored as episodic memory. The model retrieved selective past values by applying self-attention over stored keys and integrated these memories with the current scene representation to generate predictions. The model retrieved memories similar to those retrieved by human participants watching the same episode during fMRI. Importantly, this similarity disappeared when causal relationships between events were controlled for. The model also represented causally related events with similar patterns, similar to how the human brain represents these events. These findings suggest that using two distinct memory representations allows the model to retrieve memories and organize events based on causal relationships, beyond semantic or perceptual similarities. Together, this work proposes a key-value episodic memory system as a candidate computational mechanism for how humans retrieve causally related memories to comprehend naturalistic events.

neuroscience↗

bioRxiv2025

The mevalonate pathway couples lipid metabolism to amino acid synthesis via ubiquinone-dependent redox control

The mevalonate pathway produces sterols and isoprenoids that support cancer cell growth, yet its broader metabolic functions remain incompletely defined. Here, we show that this pathway sustains amino acid biosynthesis by promoting mitochondrial NAD regeneration through ubiquinone-dependent electron transport. Statin-mediated inhibition of the mevalonate pathway impairs oxidative phosphorylation, lowers the NAD/NADH ratio, and suppresses de novo serine and aspartate synthesis, thereby activating the GCN2-eIF2-ATF4 amino acid deprivation response. The resulting depletion of serine-derived glycine and one-carbon units, together with reduced aspartate availability, limits purine and pyrimidine nucleotide production. Expression of the bacterial NADH oxidase LbNOX or the alternative oxidase AOX restores NAD levels and rescues statin-induced growth inhibition. These findings suggest that impaired NAD regeneration is a key mechanism contributing to the anti-proliferative activity of statins, linking the mevalonate pathway to mitochondrial electron transport- dependent control of amino acid metabolism. SignificanceThis study identifies the mevalonate pathway as a regulator of amino acid biosynthesis through mitochondrial electron transport-dependent NAD regeneration and reveals redox disruption as a key mechanism contributing to the anti-proliferative effects of statins.

cancer biology↗

bioRxiv2025

Cytokine Regulation of Human Antibody Responses to Influenza Vaccines

Studies show that human vaccine responses widely vary. Here, we analyzed data measuring 66 cytokines from 4 different inactivated influenza vaccine (IIV) cohorts over 5 seasons (N=581) and identified a significant correlation between baseline/day 0 serum IL-18 and IFN-{beta} concentrations and the vaccine-specific antibody response on day 28, suggesting these factors may have an adjuvant-like effect. To investigate this further, we tested the impact of 19 cytokines on the development of anti-influenza antibody response when administered together with the IIV vaccine in human tonsil and spleen organoids. We found that Type I IFNs (IFN-{beta} and others), IL-21, IL-12, IL-10, but not IL-18 or IFN-{gamma}, enhanced the antibody response. The live attenuated influenza vaccine (LAIV) induced a stronger antibody response than the inactivated one in organoids. Adding a single cytokine, IFN-{beta}, to IIV stimulation recapitulated most of the live vaccine-specific cytokine activation program. It increased the antibody response of the inactivated vaccine to that of the LAIV. Two other antibody-boosting cytokines, IL-12 and IL-21, were induced by LAIV but not by Type I IFNs, indicating different cytokines can affect different pathways leading to a robust antibody response. We then generated cytokine mRNA lipid nanoparticles (LNPs) to test the effect of cytokines on IIV response in a mouse model of immunization. We found that IL-21-LNPs augmented the quantity and breadth of the antibody responses, while IFN-{beta} LNPs enhanced durability. These findings identified parallel cytokine pathways regulating human vaccine responses and provide a rationale for using cytokines as adjuvants to mimic the effectiveness of live-attenuated vaccines without the risk of viral replication.

immunology↗

bioRxiv2025

Aeon: an open-source platform to study the neural basis of ethological behaviours over naturalistic timescales

Ethological behaviours are a powerful tool for neuroscience since they leverage the robust neural computations shaped by the species evolution to study the neural basis of cognitive functions. However, such behaviours are often transitory and dependent on factors that vary over space, time and number of individuals, making them difficult to capture with standard laboratory tasks. Here we present Aeon, an open-source platform designed for continuous, long-term study of self-guided behaviours in multiple mice and simultaneous recording of brain activity within large, customizable habitats. By integrating specialized modules for navigation, nesting and sleeping, escaping, foraging, and social interaction, Aeon enables the expression of key ethological behaviours while achieving experimental control and multi-dimensional quantifications from sub-millisecond to month-long durations. Its software architecture ensures robust data acquisition via many synchronized data streams and delivers a new standardised, unified data format that yields seamless, integrated analysis pipelines. Using assays such as digging-to-threshold and social foraging, Aeon reveals how mice adapt strategies in a changing environment and in response to conspecifics. Aeon bridges ecological relevance with rigorous experimental control to advance our understanding of how neural circuit activity gives rise to a range of highly conserved and adaptive behaviours.

neuroscience↗

bioRxiv2025

Multiple event segmentation mechanisms in the human brain

The human brain segments continuous experience into discrete events, with theoretical accounts proposing two distinct mechanisms: creating boundaries at points of high prediction error (mismatch between expected and observed information) or high prediction uncertainty (reduced precision in predictions). Using fMRI and computational modeling, we investigated the neural correlates of error-driven and uncertainty-driven boundaries. We developed computational models that generate boundaries based on prediction error or prediction uncertainty, and examined how both types of boundaries, and human-identified boundaries, related to fMRI pattern shifts and evoked responses. Multivariate analysis revealed a specific temporal sequence of neural pattern changes around human boundaries: early pattern shifts in anterior temporal regions (-11.9s), followed by shifts in parietal areas (-4.5s), and subsequent whole-brain pattern stabilization (+11.8s). The core of this dynamic response was associated with both error-driven and uncertainty-driven boundaries. Critically, both error- and uncertainty-driven boundaries were associated with unique pattern shifts. Error-driven boundaries were associated with early pattern shifts in ventrolateral prefrontal areas, followed by pattern stabilization in prefrontal and temporal areas. Uncertainty-driven boundaries were linked to shifts in parietal regions within the dorsal attention network, with minimal subsequent stabilization. In addition, within the core regions responsive to both types of boundaries, the timing differed significantly. These findings provide evidence for two overlapping brain networks that maintain and update representations of the environment, controlled by two distinct prediction quality signals: prediction error and prediction uncertainty.

neuroscience↗

bioRxiv2025

Enhanced cell aggregation in the Chlamydomonas reinhardtii rbo1 mutant in response to multifactorial stress combination

Global change factors associated with climate change and increased pollution are subjecting plants, microbes, and different ecosystems to conditions of multifactorial stress combination (MFSC). While recent studies centered on the effects of MFSC on different plants and ecosystems, much less is known about how these conditions impact unicellular organisms. Here, we report on the physiological and proteomic responses of wild type and respiratory burst oxidase homolog 1 (rbo1) mutant cells of Chlamydomonas reinhardtii to a MFSC of 5 different abiotic stresses. While several similarities were found between plant and C. reinhardtii responses to MFSC, our work revealed that MFSC induces aggregation in the unicellular organism C. reinhardtii. We further show that MFSC induced aggregation is enhanced in the rbo1 mutant and can be triggered by H2O2. As aggregation typically leads to reduced growth, respiration and/or photosynthesis, enhanced aggregation of unicellular organisms in different ecosystems subjected to MFSC could explain part of the negative impacts of MFSC on the services they provide. Our findings shed new light on the response of unicellular organisms to MFSC and suggest that one of the main drivers leading to multicellularity during evolution was early conditions of MFSC under an oxygenated environment.

plant biology↗