Biology subjects

Liao, J.

Publications and source records attributed to Liao, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Auditory Stimulus Information Entropy Modulates Inter-Brain Synchronization: Evidence from Wireless EEG Hyperscanning

Inter-brain synchronization (IBS) - reflecting inter-individual correlated neural activity during interaction - marks shared experiences like music listening. The ability of complex auditory stimuli (e.g., music) to induce IBS links to their information dynamics, notably the uncertainty they evoke, which challenges the nervous systems predictive coding. Based on mutual prediction theory (interacting individuals simultaneously process their own behavior and predict their partners; accurate mutual predictions lead to convergent neural representations and thus IBS), this study hypothesized that higher stimulus uncertainty enhances IBS (heightened uncertainty reduces independent predictability, promoting convergent representations and stronger IBS). Using information entropy to quantify uncertainty, the study conducted hyperscanning, manipulated entropy across Resting State and 6 Hz auditory stimuli (ASSR, MMN, AHER, Dream Wedding), and measured IBS via phase-locking values (PLV). Results showed frequency specificity: 6 Hz PLV increased with entropy (DW {approx} AHER > MMN {approx} ASSR > Resting State); Alpha band had highest PLV in Resting State. Critically, PLVs differed significantly between any two conditions, and each experimental conditions PLV was also significantly different from that of the Resting State. Findings confirm a 6 Hz-specific positive association between auditory uncertainty and IBS, suggesting musical elements may facilitate social interaction by modulating entropy, with entropy-IBS relations showing frequency dependence.

neuroscience↗

bioRxiv2025

Maternal SETDB1 enables development beyond cleavage stages by extinguishing the MERVL-driven 2-cell totipotency transcriptional program in the mouse embryo

Loss of maternal SETDB1, a histone H3K9 methyltransferase, leads to developmental arrest prior to implantation, with very few mouse embryos advancing beyond the 8-cell stage, which is currently unexplained. We genetically investigate SETDB1s role in the epigenetic control of the transition from totipotency to pluripotency--a process demanding precise timing and forward directionality. Through single-embryo total RNA sequencing of 2-cell and 8-cell embryos, we find that Setdb1mat-/+ embryos fail to extinguish 1-cell and 2-cell transient genes--alongside persistent expression of MERVL retroelements and MERVL-driven chimeric transcripts that define the totipotent state in mouse 2-cell embryos. Comparative bioinformatics reveals that SETDB1 acts at MT2 LTRs and MERVL-driven chimeric transcripts, which normally acquire H3K9me3 during early development. The dysregulated targets substantially overlap with DUXBL-responsive genes, indicating a shared regulatory pathway for silencing the 2-cell transcriptional program. We establish maternal SETDB1 as a critical chromatin regulator required to extinguish retroelement-driven totipotency networks and ensure successful preimplantation development.

genetics↗

bioRxiv2025

EHMT2 Controls Neural Crest-Derived Craniofacial Development but is Dispensable in Limb Development

Post-translational modifications of histones, such as methylation of histone H3 at lysine 9 (H3K9), play critical roles in regulating chromatin structure and gene expression. EHMT2 (also called G9A), a histone methyltransferase, mediates H3K9 mono- and dimethylation and has been implicated in both transcriptional repression and context-specific gene activation. Although global knockout of the mouse Ehmt2 gene results in early embryonic lethality, tissue-specific knockouts have uncovered diverse roles in organ development. However, how EHMT2 contributes to skeletal development in a lineage-specific manner remains to be fully elucidated. Here, we investigated the role of EHMT2 in skeletal development by conditionally inactivating Ehmt2 in neural crest-derived and mesoderm-derived progenitors using Wnt1-Cre and Prx1-Cre mouse lines, respectively. Loss of Ehmt2 function in neural crest cells led to postnatal growth failure and craniofacial defects, including delayed intramembranous ossification and malformations of the jaw and cranial base. Transcriptomic analysis of neural crest cells revealed disrupted chromatin regulatory networks, reduced expression of proliferation-associated genes, and upregulation of inflammatory pathways. In contrast, inactivation of Ehmt2 in Prx1-expressing mesodermal progenitors had minimal impact on limb and cranial bone development, with no significant alterations in bone mass or osteoblast function. Together, these results reveal a lineage-specific requirement for EHMT2 in neural crest-derived skeletal tissues, suggesting that distinct progenitor populations exhibit differential dependency for bone development.

cell biology↗

bioRxiv2025

Diffusive and advective fluid flow shapes chemoautotrophic bacterial communities and sulfur mineralogy in hydrothermal sediments off Milos

Hydrothermal fluid flow not only shapes mineral deposition on the ocean floor but also creates ecological niches by altering temperature and energy availability. In these niches, microbial life thrives and has an additional, often unrecognized impact on mineral formation. In a newly discovered vent field in medium depths off Milos, Greece, we show how contrasting hydrothermal regimes host fundamentally different bacterial metabolisms. Diffusive flow fosters acidic, sulfate-rich conditions that promote kaolinization and pyrite formation. Fatty acid {delta}13C values down to -39{per thousand} indicate acetyl-CoA-based sulfate reduction as the main metabolism, likely contributing to pyrite formation. In contrast, vigorous venting delivers hot, acidic, carbon-rich, and sulfate-depleted fluids that sustain the activity of sulfide-oxidizing chemoautotrophs. Fatty acid {delta}13C values of up to -4{per thousand} and elemental sulfur accumulation provide evidence of their activity. Without such hydrothermal influence, little microbial activity and only quartz-rich sediments can be observed. Combined multivariate lipid analyses highlight Eh as the strongest environmental control, with increasing average chain length of fatty acids as an adaptation to (hydro-)thermal stress. These results illustrate how different types of fluid flow influence the activity of chemoautotrophic bacterial communities that are involved in the formation of characteristic sulfur minerals in hydrothermal environments.

biochemistry↗

bioRxiv2025

Determine Interaction Affinity Changes of the SUMO E1 Activating Enzymes During SUMO Activation using Quantitative FRET technology

The heterodimeric E1 complex, Aos1-Uba2, catalyzes the first adenylation activation of the SUMO1 peptide in the SUMOylation cascade. The reaction affinity and dynamics of the Aos1-Uba2 heterodimer during the first step activation have yet to be determined. The Kd for the Aos1-Uba2 interaction provides a unique perspective for the activation step of the ubiquitin-like protein conjugation cascade. Here, we report for the first time the determination of the Aos1 and Uba2 interaction dissociation constant (Kd) and kinetics using the qFRET assay. We also used the SPR method to verify the interaction Kd between Aos1 and Uba2. We also determined the kinetics changes of Aos1-Uba2 when SUMOs and ATP were added to the reaction in real time. The results showed that forming a thioester bond between SUMO1 and Uba2 increases the FRET signal, indicating that the E1 heterodimer is more stable and bound to each other in SUMO and ATP. These results suggest that the qFRET method can be used to determine protein interaction affinity changes and track real-time changes in protein conformation and dynamics changes during biochemical reactions.

bioengineering↗

bioRxiv2025

Determine Protein Interaction Affinity without Purification Reveals a Two-enzyme Co-recognition of SUMOylation Substrate using Quantitative FRET (qFRET) Technology

Protein-protein interaction is the most fundamental process in life, and the quantification and manipulation of protein interaction activation or inhibition are critical for a comprehensive understanding of physiological processes and the development of new medicines that modulate protein-protein interactions. Due to its essential roles in physiology and pathology, many methodologies and technologies have been developed to determine the interaction events and parameters of interaction affinity. However, due to the nature of these methodologies, interactive partner needs to be purified, and large quantities of proteins are needed. This significantly limits quantitatively understanding of protein interaction and its application in therapeutics development. Recently, a quantitative FRET(qFRET) method was developed to determine purified protein-protein interaction affinity for purified proteins in vitro. Here, for the first time, we report the development of a high-throughput approach to determining the protein interaction affinity between two un-purified proteins using a quantitative FRET assay(qFRET). Two proteins, SUMO E2 conjugating enzyme, Ubc9, and RanGap1c, were first employed for the methodology development. We then determined the interaction affinities of Ubc9 and PIAS1 with influenza A virus NS1 protein without purifying two interactive partners. We found that both enzymes have high affinities to interaction affinity to the NS1, and this provides a kinetics explanation for the SUMOylation two-enzyme co-recognition mechanism to achieve high substrate specificity in vivo. The protein interaction affinity determination without purification provides several advantages over the current methods, including high accuracy, no tedious protein purification process, and high-throughput assay. The novel approach, so-called High-throughput determination of protein interaction affinity, KD, without purification using quantitative FRET assay, and scientific discoveries, representing a significant advancement in technology and scientific discovery, holds great potential for large-scale protein-protein interaction affinity determinations in vitro and in vivo. TeaserA novel qFRET technology for protein interaction affinity determination without protein purification for two-enzyme recognition.

bioengineering↗

bioRxiv2025

Medial Frontal Theta Reduction Impairs Rule Switching via Prediction Error

Cognitive flexibility, the ability to switch behavior in response to changing rules in an uncertain environment, is crucial for adaptive decision making. Prior research has hypothesized a key role of prediction error and theta oscillations in medial frontal cortex in this process. However, the causal link between such processes remains to be established. To address this, we combined neural stimulation, EEG, behavioral measurement, and computational modelling. Specifically, we applied high-definition transcranial direct current stimulation (HD-tDCS) to modulate theta oscillations as measured via EEG followed by a probabilistic reversal learning task. We find that anodal stimulation reduces theta power and rule prediction error, and it increases the number of trials needed to reliably switch between rules. These findings support the role of rule prediction error signaling as a key mechanism linking neural oscillations to behavioral adaptation and highlight the importance of theta power and rule prediction error for cognitive flexibility. Significance statementCognitive flexibility--the ability to adjust behavior when rules change--is critical for adaptive behavior in uncertain environments. Although prediction error signaling and theta oscillations in medial frontal cortex have been proposed as key mechanisms, their causal relationship remains unclear. Here, we combine high-definition transcranial direct current stimulation (HD-tDCS), EEG, behavioral assessment, and computational modeling to establish a mechanistic link. We show that anodal stimulation reduces frontal theta power and rule-level prediction errors, leading to less efficient rule switching. These findings provide causal evidence that supports behavioral flexibility, advancing our understanding of the neural computations underlying adaptive decision making.

neuroscience↗

bioRxiv2025

Sequential Amino Acid Mutagenesis-Driven De Novo Evolution of Adenine Deaminases Enables Efficient In Vivo Base Editing in Primate

Base editing allows for the precise modification of genetic information, providing new avenues for treating diseases1. The adenine base editor ABE8e is currently the most efficient and widely used tool for adenine base editing. ABE8e was developed through multiple rounds of directed evolution of Escherichia coli tRNA adenine deaminase, including phage-assisted continuous evolution (PACE)2,3. While PACE is highly effective, it is a complex system that poses challenges for implementation4. Despite its high efficiency, ABE8e is associated with limitations such as relatively higher bystander editing effects and elevated off-target activity5, which need to be addressed to further enhance its precision and safety. Here, we developed a novel method for the de novo discovery of evolved ABE components, particularly adenine deaminases. This process involves identifying candidate proteins through AI-based structural prediction and clustering, followed by the enhancement of deaminase editing activity through screening libraries created by sequential amino acid saturation mutagenesis. This evolutionary strategy simplifies the approach by employing saturation mutagenesis libraries tailored to specific segments, thereby enabling exploration of an expanded sequence space and increasing the likelihood of discovering adenine deaminases with superior capabilities. The newly developed hpABE5.20 here demonstrates a more refined editing window, reduced DNA off-target effects that are both sgRNA-dependent and -independent, and minimized RNA off-target activity, while maintaining robust editing efficiency relative to ABE8e. Furthermore, hpABE5.20 has been successfully applied for precise and effective therapeutic adenine base editing in cellular disease models, humanized mice, and non-human primates.

bioengineering↗

bioRxiv2025

A Proposed Statistical Approach for Conducting Longitudinal Assessment of Circulating Tumor DNA

As circulating tumor DNA (ctDNA) may reflect cancer progression, understanding its temporal evolution can inform clinical decision-making in precision oncology. Temporal changes in ctDNA often exhibit complex patterns, varying significantly between and within patients. Factors such as patient characteristics and treatment regimens can further impact these changes. Traditional statistical methods may fall short in adequately characterizing patient-level ctDNA evolution over time, highlighting the need for advanced approaches. In this study we provide a framework to guide the identification of optimal models for the analysis of genetic biomarkers in liquid biopsy settings. Specifically, we focus on hierarchical mixed-effects models as they provide both cohort and patient-level insights. To illustrate the versatility of these models, we conduct an exploratory analysis of a real-word data consisting of patients with advanced colorectal cancer. In our analysis, we discovered that a hierarchical linear spline mixed-effects model was most optimal. Based on this finding, we used the model to generate cohort and patient-level response patterns, where patient-level results compare ctDNA trajectories using different combinations of patient demographics, medical history, treatments regimen, and outcomes. Finally, we discuss how results could potentially assist in constructing a patient monitoring system to help inform patient care.

genomics↗

bioRxiv2025

Disentangling the impact of abiotic and biotic environmental factors and dispersal dynamics on bacterial pangenome fluidity

Understanding how pangenomes originate and evolve is crucial for predicting evolutionary trajectories and uncovering ecological interactions of bacterial pathogens. Pangenome fluidity has been attributed to adaptive evolution, yet the underlying ecological drivers for bacterial pathogens persisting in natural reservoirs remain poorly understood. Listeria monocytogenes (Lm), a foodborne pathogen causing fatal listeriosis, serves as an ideal model for investigating the ecological mechanisms underlying pangenome fluidity in bacterial pathogens due to its high evolutionary divergence, broad ecological versatility, and significant public health concern. Through pangenome analysis of 177 Lm isolates representing three evolutionary lineages (I, II, and III) that we isolated from soils across the United States, we found that substantial genome variation was strongly associated with climatic factors (e.g. precipitation and temperature), soil properties (e.g. aluminum, pH, and molybdenum), and bacterial community composition, particularly Nitrospirae, Planctomycetes, Acidobacteria, and Cyanobacteria. These factors exerted selective pressure across many gene functions, with pronounced effects on genes involved in cell envelope synthesis, defense mechanisms, and replication, recombination, and repair. Among Lm lineages occupying varied habitats, distinct pangenome properties were observed. Lineage III exhibited a highly fluid pangenome, which was attributed to local adaptation to nutrient-limited conditions and strong dispersal limitation. In contrast, lineage I maintained a conserved pangenome, likely due to frequent homogenizing dispersal. Consistent with these dispersal patterns, we identified an elevated risk of soil-to-human transmission in lineage I, evidenced by epidemiological links between three soil-derived and 17 clinical isolates. Collectively, this study reveals the pivotal role of environmental selection imposed by both abiotic factors and bacterial communities in governing the adaptive pangenome evolution in bacterial pathogens. It also highlights significant differences in pangenome flexibility, ecological niches, and transmission dynamics across lineages of the same pathogen species, underscoring the need for tailored source tracking strategies. AUTHOR SUMMARYStudying the full set of genes found in different strains of a bacterium (i.e. pangenome) helps us understand how bacterial pathogens develop and adapt to changes in the environment. Here, we focused on Listeria monocytogenes (Lm), a pathogen capable of spreading through food and surviving in diverse environments, to understand how environmental factors and the way that bacteria move across locations can influence the pangenome content in this important bacterium. By analyzing the genomes of 177 Lm strains representing three evolutionary lineages (I, II, and III) collected from soils across the United States, we found that variation in climate, soil chemistry, and surrounding bacteria (e.g., Nitrospirae) was closely linked to genetic differences among strains. These environmental conditions seemed to affect genes that help build the cell envelop, protect the bacteria from harm, and fix damaged DNA. We also observed different levels of genome flexibility across Lm lineages which were found to be related to how they move across different locations. Lineage III showed evidence of barriers to spreading, which may enhance genetic differentiation across populations, leading to a more flexible pangenome. In contrast, lineage I appeared to spread more readily and was epidemiologically linked to human clinical cases, which may facilitate genetic exchange that reduce pangenome diversity. This study shows that both non-living environmental conditions--like precipitation and pH--and nearby groups of bacteria play a big role in shaping how bacterial pathogens change their genes to survive. It also highlights that different subtypes of the same pathogen can have different gene flexibility and spread in different ways, calling for specific biocontrol measures.

genomics↗

bioRxiv2025

Bacteriophage protein Dap2 inhibits bacterial type III secretion system and synergizes with Dap1 to evade anti-phage immunity

The evolutionary arms race between bacterial immunity and phages has driven the emergence of sophisticated anti-defense systems (ADSs). However, certain ADSs exhibit incomplete suppression of their cognate defense systems, suggesting functional cooperation between multiple ADSs targeting the same bacterial safeguard. In this study, we characterize Dap2, a protein encoded by a Pseudomonas aeruginosa phage PaoP5, which directly binds to the Lon protease to prevent the degradation of the phage-encoded HNH endonuclease. Deletion of dap2 in PaoP5 exhibits significantly impaired genome packaging due to insufficient levels of HNH. Strikingly, Dap2 synergizes with its genomically adjacent partner Dap1, a previously identified HNH-binding protein providing partial Lon resistance, to achieve complete protection of HNH. Beyond anti-defense activity, Dap2 disrupts host virulence by sequestering the type III secretion system (T3SS) transcriptional activator ExsA, suppressing bacterial pathogenicity while redirecting metabolic resources toward phage progeny production. This study unveils a dual functional ADS that simultaneously modulates bacterial virulence and anti-phage immunity, both aimed at ensuring phage survival and maximizing progeny production. Furthermore, it elucidates a novel mechanism whereby phages employ synergistic ADS pairs (Dap1/Dap2) to achieve complete neutralization of a bacterial defense system, when individual components provide only partial protection. These findings significantly enhance our understanding of the intricate evolutionary arms race between phages and their bacterial hosts.

microbiology↗

bioRxiv2025

FOSL2 Directly Regulates FSHR and CYP11A1 Transcription: An Essential Transcription Factor for Gonadotropin-Dependent Folliculogenesis

The meticulous orchestration of gonadotropin-dependent folliculogenesis constitutes the cornerstone of female reproductive cyclicity and fertility, with FSH/FSHR signaling recognized as the master regulator. Achieving the necessary amplification of this signaling is essential for successful GTH-dependent folliculogenesis, yet the mechanisms remain inadequately defined. Our study utilizes single-cell and spatial transcriptomics to identify FOSL2 as an FSH-inducible transcription factor, exhibiting precise spatiotemporal co-expression with FSHR. FOSL2 knockdown in vitro resulted in notable reductions in granulosa cell proliferation, induced apoptosis, and disrupted gonadotropin-dependent folliculogenesis. In vivo studies using conditional FOSL2 deletion in mouse granulosa cells corroborated these results, demonstrating a complete halt in GTH-dependent folliculogenesis and resultant infertility. Mechanistic exploration unveiled that FSH/FSHR initiates FOSL2 expression via the cAMP/PKA/CREB cascade, while FOSL2 in turn enhances FSHR transcription through direct promoter binding, thereby establishing a self-amplifying loop. This loop represents a molecular switch, modeled to the all-or-nothing dynamics of GTH-dependent folliculogenesis. The evolutionary conservation of this mechanism was confirmed through cross-species analyses in sheep, where FOSL2 deficiency similarly attenuated FSH/FSHR signaling and inhibited follicular growth. Our findings advance the understanding of folliculogenesis by revealing a novel FOSL2-centered amplification loop for FSH/FSHR signaling, highlighting the indispensable role of FOSL2 in reproductive biology.

cell biology↗

bioRxiv2025

Physical Activity and Depressive Mood Shared the Structural Connectivity between Motor and Reward Network: a population-based study from the UK Biobank

BackgroundExercise has been revealed to leave a positive effect on alleviating depressive symptoms by various existing studies. However, the neural basis behind this phenomenon remains unknown, as well as its underlying biological mechanism.AimsUsing a large neuroimaging cohort from UK Biobank, this study aimed to identify structural connectivity (SC) patterns simultaneously linked with physical activity and depression, as well as its biological interpretation.Method492 participants with major depression disorder (MDD) and 535 healthy controls (HC) were extracted from the UK Biobank dataset. Partial least squares regression was first utilized to explore a replicable SC pattern simultaneously associated with physical activity and depressive mood. The neuromaps toolbox was applied to interpret the biological ontologies of the identified SC pattern. Neuroimaging-transcriptome association and enrichment analyses were conducted to explore its underlying genetic basis, pathways and cell types. The reproducibility and generalizability were tested on another independent MDD dataset (N=3,496) and bipolar disorder (BD) dataset (N=81).ResultsA SC pattern linked with exercise was identified to be both significantly correlated with depressive mood and group discriminative between MDDs and HCs, which primarily located between the motor-related regions and reward-related regions. This pattern was associated with multiple neurotransmitter receptors, such as serotonin and GABA receptors, and enriched in pathways like synaptic signaling and astrocytes cell type. The SC pattern and genetic results were also replicated in another independent MDD dataset and present commonalities with BD.ConclusionsThis study not only initially identified a reproducible shared SC pattern between physical activity and depressive mood, but also elucidated the underlying biological mechanisms, which enhanced our understanding of how exercise helps alleviate depression and may inform the development of novel neuromodulation targets.

neuroscience↗

bioRxiv2025

Intraguild parasitism promotes the persistence of facultative hyperparasitoids by extending temporal host availability

Intraguild predation (IGP) is pervasive in natural food webs, although theoretical models predict restricted parameter space for the coexistence of IG-prey and IG-predators. One potential mechanism is that IGP persistence might be increased when IG-prey extend resource availability for IG-predators. Here we test this hypothesis using manipulative experiments in combination with mathematical modeling. Our experiment system includes Drosophila flies (Drosophila melanogaster, basal resources), primary larval parasitoids (Asobara leveri, IG-prey) and facultative pupal hyperparasitoid (Pachycrepoideus vindemiae, IG-predator). We measured the performance of facultative pupal parasitoids with and without the primary larval parasitoid. Our study revealed that larval parasitoids significantly increased the number of pupal parasitoids emerged from limited host resources, due to the extended resource availability to facultative hyperparasitoid. Specifically, immature primary parasitoids within Drosophila pupae can be explored by facultative hyperparasitoids for up to 14 days, while the healthy fly pupae are available to hyperparasitoids for only 5 days. Despite a significant reduction in offspring fitness of the facultative hyperparasitoids when reared on larval parasitoids versus healthy Drosophila pupae, adult female facultative hyperparasitoids showed no significant preference for healthy fly pupae over immature primary parasitoids. Our theoretical models demonstrated that an extended development period of the primary parasitoid can promote the persistence of the facultative hyperparasitoids and allow their coexistence with the primary parasitoid, although too prolonged development could drive the extinction of the primary parasitoid. As IG-prey often take longer time to develop after consuming the shared resources, extension of temporal resource availability could be a general mechanism contribute to the persistence of intraguild predators. Open research statementData are not yet available, but all of the original experimental data has been displayed in figures 2[~]4. The data will be made publicly available upon manuscript acceptance and archived in the Dryad Digital Repository.

ecology↗

bioRxiv2025

Top-down control of the descending pain modulatory system drives placebo analgesia

In placebo analgesia, prior experience and expectations lead to pain suppression by the administration of an inert substance, but causal evidence for its neural basis is lacking. To identify the underlying neural circuits, we reverse-translated a conditioned placebo protocol from humans to mice. Surprisingly, the placebo effect suppresses both nociception and unconditioned emotional-motivational pain-related behavior. Descending pain modulatory neurons in the periaqueductal gray (PAG) are critical for both morphine and placebo antinociception. The placebo effect depends on input to the PAG from the medial prefrontal and anterior cingulate cortices, but not anterior insular cortex. Conditioning enhances noxious stimulus-evoked endogenous opioid release in the PAG to produce analgesia. Our results suggest that cortical control of the descending pain modulatory system (DPMS) is gated by rapid endogenous opioid signaling in the PAG during placebo trials. This study bridges clinical and preclinical research, establishing a central role for the DPMS in placebo analgesia.

neuroscience↗

bioRxiv2025

Follicular mural granulosa cells stockpile glycogen to fuel corpus luteum pre-vascularization

The corpus luteum (CL) arises from the luteinization of follicular granulosa cells (GCs) and theca cells, marked by rapid progesterone elevation and angiogenesis. Intriguingly, angiogenesis lags behind progesterone elevation, creating an avascular phase during which luteal cells must fuel intensive steroidogenesis without perfusion. How the avascular CL meets this energetic demand remains a mystery. Here, we reveal a novel cellular adaptive mechanism-GC energy storage (GCES)-that resolves this enigma. We demonstrate that upon luteinization initiation, GCs enter a metabolically quiescent state yet enhance glucose uptake via SLC2A1, converting the glucose into glycogen through the hCG (LH)-MAPK-RUNX1-Insulin signaling axis. Catabolism of this glycogen reserve supplies the energy required for the avascular CL, ensuring normal luteogenesis. GCES is evolutionarily conserved across species. Genetic or pharmacological disruption of GCES or glycogenolysis induces luteal insufficiency, whereas timely glucose administration enhances GCES, improving luteal function and optimize reproductive outcome in both mouse and ovine models. In human study, orally intake of glucose post-hCG significantly augments GCES and enhances progesterone production in women. These results advance luteal physiology by uncovering a universal reproductive principle with direct clinical implications.

developmental biology↗

bioRxiv2025

Transient pH changes drive vacuole formation in enzyme-polymer condensates

Intracellular membraneless organelles formed by the phase separation of biomolecules are essential for cellular functioning. These biomolecular condensates often exhibit complex morphologies in response to biological stimuli. In vitro condensate models help elucidate the mechanism of formation and the associated function of these hierarchical assemblies. Here, we use an in vitro model to investigate the formation of hollow internal regions, or vacuoles, within the condensate interior in response to a pH change. Our experimental system is a pH-responsive complex coacervate formed by the anionic glucose oxidase enzyme phase separating with the weak polycation, DEAE-dextran. Fast rates of pH decrease and larger droplet sizes trigger vacuole development within the coacervates. We show that the emergence of vacuoles is a non-equilibrium process caused by the diffusion-limited exchange of condensate components during a fast pH change. We develop a theoretical model that captures how a phase-separating system responds dynamically to changes in system conditions, particularly pH. Our qualitative phase diagram aligns with our experimental results, showing that rapid pH changes shift the phase boundaries, triggering spinodal decomposition and inducing vacuole formation within the condensates. Our pH-sensitive in vitro coacervate model provides a platform to modulate the internal structure of ternary phase separating systems and gain insights into the mechanisms controlling condensate organization in vivo.

biophysics↗

bioRxiv2025

Carbon monoxide exposure stimulates growth and activity of primary producers in diverse soil ecosystems

Carbon monoxide (CO) is both a potent poison for many aerobic organisms and a desirable energy source for diverse microorganisms. Atmospheric emissions of this gas have increased since industrialization and their levels are highly elevated in many urban and natural environments; however, it is unresolved whether elevated levels of CO at environmentally relevant concentrations are primarily stimulatory or inhibitory to soil microbial communities. Here, we showed that CO exposure minimally affects microbial abundance, richness, and composition in diverse ecosystem soils, suggesting most microbes are tolerant of this gas. Genome-resolved metagenomic profiling showed that these soils harbored diverse bacteria capable of using CO an electron donor for aerobic respiration and carbon fixation. CO stimulated the growth of several of these putative CO-oxidizing bacteria in a dose-dependent manner, especially widespread proteobacterial and actinobacterial lineages. Additionally, we found a strong relationship between CO oxidation and carbon fixation and observed an enrichment of several carboxydotrophic MAGs capable of carbon fixation in most soil types. These findings highlight that environmentally relevant CO levels do not inhibit soil microbes, but instead foster the growth of distinct carboxydotrophic bacteria, suggesting a robust soil CO sink that could help mitigate anthropogenic CO emissions and contribute to carbon cycling in terrestrial ecosystems.

biochemistry↗