Biology subjects

Yao, S.

Publications and source records attributed to Yao, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Effects of Alternating Polarity Frequency on the Assembly of Electro-Methanogenic Microbial Communities

Electro-methanogenesis can enhance methane production and has attracted extensive interest, but the current strategies for building electro-methanogenic microbial communities suffer from several limitations. Alternating polarity has been shown as a new strategy to build electro-methanogenic communities, but the impact of alternation frequency on community assembly remains to be understood. In this study, the impact was evaluated using bioelectrochemical systems amended with granular activated carbon, and the working-electrode potential was alternated between +0.4 and -0.4 V vs. SHE at six frequencies ranging from 0.5 to 12 days. Among the tested conditions, 4-d alternation led to the best overall performance, producing approximately 250 L/L/kg cumulative biogas, 96% methane content, and a 45% methane yield, while preserving a stable and reproducible community structure. The community contained two Methanobacterium populations, two putatively electroactive Geobacter populations, and one putatively electroactive Pseudomonas population, together with diverse fermentative and syntrophic bacteria. Transcript-based analyses revealed clear frequency- and potential-dependent shifts in the activity of these functional groups. Redundancy analysis associated the Methanobacterium formicicum-related population with cathodic current and methane production, whereas the Geobacter sulfurreducens-related population was linked to anodic current and methane production. Bayesian and local-similarity networks further connected methanogen dynamics with specific electroactive, fermentative, and syntrophic partners. Collectively, these results establish alternating polarity frequency as a critical parameter for building robust communities capable of high-rate, high-quality methane production.

microbiology↗

bioRxiv2026

INS-fMRI: a novel method for mapping mesoscale connectome networks in vivo in nonhuman primates

Mapping brain connections is paramount in neuroscience. Lacking has been a method that can systematically map mesoscale (<1mm) connections in the brain in vivo at brainwide scale. Mesoscale mapping is particularly important for NHPs in which information is represented in submillimeter clusters (e.g. cortical columns, striosomes, thalamic rods). Here, we present a method called INS-fMRI, which comprises optical stimulation of single sites in the brain using pulsed Infrared Neural Stimulation (INS), coupled with mapping of functionally connected sites in the brain using ultrahigh field fMRI. It is the only method available for mapping mesoscale connections rapidly (multiple networks mapped within single MRI sessions), systematically (allowing comparison of networks within single individuals), in vivo (no animal sacrifice needed), at whole brain scale, and without viral transfection. This method has broad applicability to a wide range of neuroscience questions. It can be used at any brain site, on different animal models, and on different MRI platforms. The ability to probe circuits repeatedly within single individuals also opens doors for studying changes in mesoscale circuits over time (e.g. for development, aging, disease studies). In addition, as this method circumvents the need for viral transfection, there is exciting potential for human clinical application.

neuroscience↗

bioRxiv2026

An N-Terminally Acetylated Degron Specifically Recognized by the CTLHMKLN1-FAM72A E3 Ubiquitin Ligase for Regulatory Protein Degradation

N-terminal acetylation of cellular proteins has been implicated in their proteasomal degradation through the Ac/N-degron pathway. Despite representing a major branch of the N-degron system, only a limited number of degrons and their motifs have been identified and characterized in this pathway, and the mechanism underpinning the recognition of N-terminal acetylation has remained largely elusive. Here, by interrogating FAM72A-mediated degradation of UNG2, we pinpointed the N-terminally acetylated sequence of UNG2 as a bona fide Ac/N-degron specifically recognized by the CTLHMKLN1-FAM72A E3 ubiquitin ligase. Rather than relying solely on a single acetylated N-terminal residue, this degron features a consensus Nt-AcM1-[ILV]2-G3 motif that governs both E3 targeting and the intracellular stability of the neo-substrates uncovered through proteomic screenings. Cryo-EM structure of the UNG2-FAM72A-MKLN1 complex further elucidated the molecular details supporting the high specificity of degron recognition. Notably, this degron pathway is subject to multilayered regulation, highlighting the characteristic conditionality of degron system. Our findings thus define a distinct AcM-[ILV]-G/N-degron pathway and provide mechanistic insights into degron recognition dictated by both N-terminal acetylation and sequence motif context.

biochemistry↗

bioRxiv2026

3D-MAESTRO: A scalable, modular, portable pipeline for automated processing of large-scale volumetric brain microscopy data

Light microscopy is routinely used to explore the cellular and molecular structure of tissues, but the scale and complexity of data remains a bottleneck for discovery. We introduce 3D-MAESTRO (3D-Microscopy Automation and Execution with Scalable Tools, Rendering, and Orchestration): an automated image processing workflow for large-scale microscopy data, built for scalable execution across cloud and local computing environments. 3D-MAESTRO orchestrates denoising, stitching of image tiles, atlas registration, and segmentation. Its modular architecture permits the integration and benchmarking of new packages, ensuring that performance evolves as more efficient or accurate algorithms emerge. We introduce a new 3D image template for automated registration of mouse brains cleared with aqueous reagents and an efficient method for detection of fluorescent cells. We apply 3D-MAESTRO to lightsheet images of whole mouse brains in the context of diverse anatomical and functional experiments, illustrating high-throughput and reproducible mapping of microscopic structures across the brain.

neuroscience↗

bioRxiv2026

Oxytocin promotes advantageous inequity preference by modulating the fairness norm enforcement system

Aversion to inequity is innate in humans and constitutes a major contributor to social tension. Such aversion can be triggered either when one receives more (advantageous inequity-AI) or less (disadvantageous inequity-DI) than others. However, it remains unclear whether oxytocin can modulate how humans respond to inequity. The present pre-registered study combined behavioral measures, computational modelling, and fMRI in a novel monetary allocation evaluation paradigm to examine oxytocins modulation of behavioral and neural responses to inequity. Results showed that oxytocin increased perceived fairness and AI allocation choices via enhancing AI preference independent of gain vs. loss contexts, which was further confirmed by model-based results of oxytocin decreasing AI aversion. In parallel at the neural level, oxytocin increased fairness rating-related activity in regions within fairness-related norm enforcement systems involved in norm violation detection, salience processing, and cognitive control. Multivariate-based representational similarity analyses provided further evidence that oxytocin induced distinct representational patterns of inequity in these core regions. These results suggest that oxytocin promoted AI preference possibly by strengthening regulatory control to support the pursuit of economic self-interest, while simultaneously enhancing the salience of AI allocations. Our study provides new insights into behavioral and neural mechanisms through which oxytocin modulates fairness-related behavior.

neuroscience↗

bioRxiv2026

Reconstructing sequence-grammar trajectories enables interpretable and tunable cis- regulatory element design

Designing synthetic cis-regulatory elements (CREs) with cell-type-specific activity remains challenging, and optimization is usually treated as a black box, obscuring how regulatory grammar emerges and why design trajectories fail. Here, we present GO-CRE (Guided Optimization of Cis-Regulatory Elements), which combines efficient sequence generation, predictor-guided reinforcement learning, and trajectory-level interpretation. GO-CRE reconstructs iterative sequence changes in a shared sequence-grammar landscape and identifies coordinated update programs corresponding to search, commitment, and optimization. Productive trajectories in HepG2 and K562 progressively acquired cell-type-associated grammar, whereas SK-N-SH trajectories remained confined to local basins. In HepG2, trajectory analysis revealed a low-complexity polyG trap; introducing a polyG penalty redirected optimization toward HNF/FOXA-associated features. Final designs retained sequence diversity while converging on cell-type-associated motif patterns. Lentiviral MPRA validated cell-type-specific activity in K562 and HepG2 and showed higher average activity of HepG2 designs than endogenous CREs. Together, these findings establish sequence-grammar trajectory reconstruction as a basis for interpretable and tunable synthetic CRE design.

genomics↗

bioRxiv2026

An open-access CT-based 3D anatomical dataset of extant sharks across all major lineages

0Sharks exhibit extraordinary morphological diversity across a wide range of ecological niches, yet large-scale, high-resolution digital datasets of their internal anatomy remain limited. Here we present an open-access 3D shark anatomical repository derived from published X-ray computed tomography (CT) data, featuring manually segmented and systematically annotated models of the chondrocranium, visceral arches, axial skeleton, musculature, and viscera in standard STL format. The dataset comprises 117 individuals, representing 72 species across 25 families and all nine extant shark orders, with 115 full-body reconstructions and two head-only models. This open-access dataset offers a comprehensive resource for comparative anatomy, biomechanical simulations, evolutionary developmental biology and biomimetics research of extant sharks.

evolutionary biology↗

bioRxiv2026

Chromatin topology control by a muscle-specific ribosomal protein

Three-dimensional genome organization stabilizes cell-type-specific gene expression, yet the tissue-restricted factors that maintain chromatin insulation remain poorly understood. Here, we identify the muscle-specific ribosomal protein Rpl3l as an unexpected nuclear regulator of genome architecture in atrial cardiomyocytes. Rpl3l is enriched in the nucleus and nucleolus, where it binds its own genomic locus and stabilizes a CTCF-anchored chromatin boundary that represses the T-type calcium channel gene Cacna1h. Loss of Rpl3l weakens local chromatin insulation, increases long-range contacts across the Rpl3l-Cacna1h locus, derepresses Cacna1h, and increases susceptibility to atrial fibrillation (AF), which is suppressed by pharmacological inhibition of T-type calcium channels. Furthermore, AF-associated RPL3L variants exhibit impaired nucleolar localization, reduced rRNA binding, and defective repression of CACNA1H in human iPSC-derived atrial cardiomyocytes. Together, these findings reveal a ribosomal protein-chromatin axis linking genome insulation to ion-channel dosage control and cardiac rhythm stability, expanding the repertoire of cell-type-specific genome architecture regulators. HighlightsThe muscle-specific ribosomal protein Rpl3l exhibits unexpected nuclear and nucleolar enrichment. Rpl3l stabilizes a CTCF-anchored chromatin boundary to maintain atrial-specific local genome insulation. Loss of Rpl3l derepresses Cacna1h which encodes a T-type Ca2+ channel and increases atrial fibrillation susceptibility. Atrial fibrillation-associated RPL3L variants impair nucleolar targeting and CACNA1H repression

physiology↗

bioRxiv2026

Differentiation of Bacterial, Fungal, and Algal Communities on Coastal Concrete Versus Drainage Pipes and the Coexistence of Corrosion and Healing Potentials

Coastal concrete structures and drainage pipes are prone to microbially influenced deterioration. However, differences in microbial communities and their corrosion/healing potentials between these habitats remain unclear. Here, we compared bacterial(16S), fungal (ITS) and algal(18S) communities on coastal concrete(C) and drainage pipe(P) surfaces. Fungal and algal -diversity were significantly higher in P than in C, while bacterial diversity did not differ. {beta}-Diversity strongly separated bacterial and algal communities between habitats, but not fungi. A shared core "seed bank" of 575 bacterial, 520 fungal and 40 algal ASVs was identified. Students t-test revealed that P enriched oligotrophic degraders (Sphingomonas) and acid-producing fungi (Arxiella, Bisifusarium), whereas C selected for halotolerant EPS-producing bacteria (Tunicatimonas, Muricauda) and the extremotolerant alga Coelastrella. db-RDA linked these differences to salinity, NH4+-N, NO3--N, and COD. Functional prediction indicated a shift from metabolism pathways in C to signaling in P. Co-occurrence networks revealed cross-kingdom competition and within-kingdom cooperation, especially among algae. Importantly, both habitats harbored microorganisms with documented corrosion and healing potentials, but under natural conditions, net deterioration dominated, microbial healing is hardly to counteract the negative effects. This study provides a functional taxonomic framework for understanding and managing concrete microbiomes in coastal and sewer infrastructure. ImportanceConcrete is the most widely used construction material, and its deterioration in coastal and sewer environments poses significant economic and safety challenges. Microorganisms play a dual role in concrete durability -- they can both corrode and heal concrete, but the net outcome under natural conditions is poorly understood. Most studies have focused on bacteria alone, overlooking the contributions of fungi and algae, and few reports on the of coastal concrete which also exist the microbially influenced concrete corrosion (MICC) similar to sewer. Here, we simultaneously analyzed all three microbial kingdoms on coastal concrete and drainage pipes. We found that while concrete surfaces harbor a diverse "seed bank" of microorganisms potentially involved in both corrosion and healing, under natural conditions, net deterioration dominated, indicating microbial healing is hard to counteract the negative effects from the environment and microbial. Our work provides a functional framework to guide the development of microbiome-based strategies for enhancing concrete durability, such as activating rare healing taxa in drainage pipes or selecting for endogenous healers in marine environments.

microbiology↗

bioRxiv2026

Delivery of defective interfering RNA antivirals to the lungs using hyperbranched poly(beta-amino ester) nanoparticles

Hyperbranched poly(beta-amino ester) (hPBAE) nanoparticles represent a promising platform for nucleic acid delivery, particularly to the lungs. In this study, we evaluate the potential of hPBAE nanoparticles to deliver defective interfering RNA (diRNA) antivirals targeting betacoronaviruses under a range of formulations and storage conditions. hPBAE-diRNA nanoparticles demonstrated efficient cellular uptake of functional diRNA across diverse cell types, conferred protection against nuclease-mediated degradation, and exhibited low in vitro cytotoxicity. In vivo, these nanoparticles enabled effective delivery of functional diRNA to the lungs of golden hamsters without inducing adverse physiological effects. Collectively, these findings support hPBAE nanoparticles as a safe and effective platform for diRNA delivery for the treatment of respiratory viral infections. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=66 SRC="FIGDIR/small/721911v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@2fc386org.highwire.dtl.DTLVardef@1cda4f9org.highwire.dtl.DTLVardef@9f61borg.highwire.dtl.DTLVardef@1fc8461_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract.C_FLOATNO Defective interfering RNA was mixed with hyperbranched poly(beta-amino ester) nanoparticles and delivered to cells in vitro and to golden hamsters in vivo, to measure toxicity and the replication potential of the RNA. C_FIG

microbiology↗

bioRxiv2026

A 667-nucleotide sequence in the SARS-CoV-2 nsp15 coding region promotes genome encapsidation

Coronavirus genome encapsidation depends on cis-acting RNA elements that interact with viral structural proteins. While such packaging signals have been characterized in several coronaviruses, their definition in SARS-CoV-2 remains incomplete. Using synthetic defective SARS-CoV-2 genomes, we identify a 667-nucleotide region within the nsp15 coding sequence that preferentially binds SARS-CoV-2 nucleoprotein and enhances the accumulation of defective viral genomes both in vitro and in vivo. Sequential and targeted deletion analyses further delineate candidate RNA secondary structures within this region that contribute to this enrichment. These structures show similarity to elements within the putative packaging signal of SARS-CoV but are not conserved across other coronaviruses. Together, these findings support the presence of a structured RNA element within nsp15 that contributes to SARS-CoV-2 genome encapsidation and provide a framework for further structural and functional dissection of coronavirus packaging signals. IMPORTANCEThis study identifies a 667-nt region within the SARS-CoV-2 nsp15 coding sequence that binds nucleoprotein and promotes accumulation of defective viral genomes, revealing a previously unrecognized contributor to genome encapsidation. Mapping of candidate RNA structures within this region links SARS-CoV-2 packaging activity to conserved structural features observed in SARS-CoV, while highlighting key differences from other coronaviruses. These findings refine understanding of cis-acting packaging signals in SARS-CoV-2 and provide a foundation for further structural and functional analysis of coronavirus genome encapsidation. O_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC="FIGDIR/small/721935v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1b64611org.highwire.dtl.DTLVardef@1b21b7borg.highwire.dtl.DTLVardef@2a68b5org.highwire.dtl.DTLVardef@405fe1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHICAL ABSTRACTC_FLOATNO A part of the nsp15 coding sequence of SARS-CoV-2 promotes efficient transmission of defective viral genomes in vitro and in vivo. Using a sequential deletion library and targeted deletions within this region we identify RNA structures that may function as packaging signals. C_FIG

microbiology↗

bioRxiv2026

Toward CT-based Tractography: Presurgical White Matter Tract Mapping in Intracerebral Hemorrhage

Presurgical mapping of key white matter (WM) fiber tracts is crucial for intracerebral hemorrhage (ICH) surgery, but it currently relies on tractography from diffusion MRI (dMRI), which has limited applicability in urgent or resource-constrained settings due to long scan times and limited MRI availability. To bridge this gap, we developed a deep learning approach designed to reconstruct critical fiber tracts directly from routinely acquired CT scans, focusing on the corticospinal tract (CST) due to its high clinical relevance. By training a novel network on a curated dataset of 150 paired CT-dMRI scans (101 ICH patients and 49 healthy subjects), we enabled the direct mapping of the CST from CT images alone, bypassing the traditional requirement for dMRI. Our results demonstrate that the CT-derived tracts achieve high anatomical plausibility, with neurosurgeon expert assessments yielding a Likert score of 3.64. Furthermore, the clinical relevance of these reconstructions was validated by a significant correlation between CT-derived tract integrity and patient motor scores (r = 0.726, p = 3.731x 10-7). These findings suggest that in complex clinical scenarios, particularly where dMRI signal quality is compromised by lesion-induced distortion, this CT-based mapping may serve as a useful anatomical reference. Overall, by enabling CT-based WM mapping, our method potentially offers a practical route to gain the key advantages of tractography in resource-limited or time-critical settings

neuroscience↗

bioRxiv2026

Hippocampal Glucuronyl C5-epimerase promotes stress resilience by directly engaging PI3K through a non-enzymatic mechanism

Major depressive disorder (MDD) seriously affects human physical and mental health and causes global socioeconomic burdens. Stress-induced depressive etiology is linked to dendritic atrophy in the hippocampus, however, the underlying mechanism was poorly understood. Here, we identify that glucuronyl C5-epimerase (Glce), a heparan sulfae-modifying enzyme, as a critical regulator of hippocampal dendritic integrity and stress resilience. Genetic ablation of Glce in the hippocampal excitatory neurons is sufficient to induce dendritic atrophy and depressive-like behaviors, whereas its restoration rescues these deficits. Notably, Glce levels are reduced in the plasma of depressed individuals. We further find that Glce functions independently of its enzymatic activity, instead binding directly to and activating PI3K (p85/p110), thereby triggering an Akt/CREB/BDNF signaling cascade. Together, our findings uncover a non-canonical role for Glce and establish that Glce-PI3K-BDNF axis is essential for maintaining hippocampal structure and behavioral resilience, thereby highlighting a critical role of Glce in the pathophysiology of depression.

neuroscience↗

bioRxiv2026

The External Globus Pallidus is a Basal Ganglia Output Hub with Action-Specific Circuits

The external globus pallidus (GPe) is traditionally viewed as a homogeneous relay in the indirect basal ganglia pathway that broadly suppresses movement. Using whole-brain anterograde axon mapping, rabies tracing, single-neuron reconstruction, and single-nucleus RNA sequencing, we reveal that the GPe is a major basal ganglia output nucleus, composed of anatomically and molecularly distinct populations. Besides the neurons with canonical projections, and projections to striatum and cortex, the GPe contains specific neuronal populations that target the thalamus and brainstem directly, including the parafascicular thalamus (GPePf) and the pedunculopontine nucleus (GPePPN). These projection-defined subpopulations exhibit distinct behavioral functions. GPe-PPN neurons are selectively suppressed at locomotor onset, and bidirectional manipulation of this pathway is sufficient to promote or suppress locomotion. Notably, D2-MSN stimulation upstream of these neurons evokes locomotion, and co-activation of GPePPN pathway blocks this D2-MSN-evoked locomotion, demonstrating a disinhibitory circuit for action stemming from D2-MSNs. In contrast, GPePf neurons are not engaged during locomotion but are selectively recruited during skilled forelimb actions, and their activation disrupts forelimb movements without affecting locomotion. Together, these findings establish the GPe as a basal ganglia output hub composed of modules that mediate distinct behaviors. This organization revises canonical models of the indirect pathway by demonstrating that D2-MSNs can also facilitate, rather than only suppress, movement depending on the downstream GPe output channels they engage. In briefThe external globus pallidus (GPe), classically considered a relatively homogeneous relay within the indirect basal ganglia pathway, is revealed here as a major basal ganglia output hub. Distinct GPe subpopulations, defined by transcriptomic identity and projection target, form parallel channels to cortical, thalamic and brainstem structures with action-specific functions. These findings uncover a disinhibitory mechanism through which D2-MSNs can facilitate behavior, revising canonical models of basal ganglia function. HighlightsBrain-wide mapping reveals the GPe as a major basal ganglia output node GPe contains novel cell types defined by transcriptomic identity and projection specificity Projection-specific GPe circuits differentially control locomotion and skilled forelimb actions D2-MSNs can disinhibit downstream targets via specific GPe projections and promote action.

neuroscience↗

bioRxiv2026

Adapting Upright Light Sheet Fluorescence Microscopy for Imaging at Air-Liquid Interface

Light sheet fluorescence microscopy (LSFM) is increasingly appreciated as the gold standard for gentle, volumetric imaging with fast acquisition speeds and/or long imaging durations. However, the often-constrained sample space of these microscopes has precluded a specific class of biological specimens from being studied with these tools: those requiring an air-liquid interface (ALI). Here, we present a device for robust imaging at ALI on an upright light sheet microscope with dipping objectives. We demonstrate the system using three relevant use-cases: ex vivo embryonic mouse salivary glands, human epidermal equivalent cultures, and in vivo adult Drosophila melanogaster brains. While the device presented is engineered for one specific light sheet microscope design, it provides a blueprint for easy adaptation to other systems. In doing so, it can potentially spur the use of LSFM for model systems that have so far been unable to take advantage of this powerful technology.

bioengineering↗

bioRxiv2026

Pixel2Gene enables histology-guided reconstruction and prediction of spatial gene expression

Advances in spatial transcriptomics (ST) have fundamentally transformed our understanding of tissue biology by enabling gene expression profiling within intact spatial contexts and uncovering tissue organization and microenvironmental interactions. However, current high-resolution ST platforms remain constrained by high costs, limited tissue coverage, and technical artifacts, often yielding noisy, sparse, and incomplete data that compromise analytical accuracy, biological interpretation, and clinical utility. To address these challenges, we introduce Pixel2Gene, a deep learning framework that integrates co-registered histology images with ST data to enable histology-guided reconstruction and prediction of spatial gene expression. Pixel2Gene enhances existing expression measurements by denoising low-confidence data and reconstructing coherent expression patterns, while also predicting gene expression in unmeasured tissue regions and new samples lacking direct transcriptomic profiling. We systematically evaluated Pixel2Gene across multiple high-resolution ST platforms, including Visium HD, Xenium, and CosMx, spanning diverse tissue types and disease contexts using downsampling simulations and cross-platform comparisons in clinical samples. Across all settings, Pixel2Gene consistently improved data consistency, mitigated dropout effects, restored biologically meaningful spatial structure, and enabled accurate downstream analyses. By leveraging the scalability and ubiquity of routine histology, Pixel2Gene facilitates comprehensive, cost-effective ST profiling at whole-tissue scale, supporting large cohort studies, translational research, and next-generation biomarker discovery.

genomics↗

bioRxiv2026

Biosynthesis of 14-membered cyclopeptide alkaloids via non-heme-iron- and 2-oxoglutarate-dependent oxidative decarboxylation

Cyclopeptide alkaloids are an expanding class of plant peptide natural products defined by a macrocyclic ether-crosslink via a tyrosine-derived phenol. Classical cyclopeptide alkaloids are characterized by strained 13-to 15-membered cyclophanes and terminal modifications such as N-methylation and C-terminal styrylamine moieties. While synthetic access to many classical cyclopeptide alkaloids has been established, no biosynthetic route has been reported. Here, we elucidate the biosynthetic pathway of a 14-membered cyclopeptide alkaloid, lotusine A, from Chinese date tree (Ziziphus jujuba) which features peptide cyclization on a ribosomal precursor peptide by a split burpitide cyclase, non-heme-iron and 2-oxoglutarate-dependent oxidative decarboxylation affording the C-terminal hydroxystyrylamine, and SAM-dependent N-terminal -N,N-dimethylation. We apply discovered Z. jujuba enzymes in combination with a clubmoss cyclopeptide alkaloid cyclase for biosynthesis and diversification of analgesic adouetine X and anxiolytic sanjoinine A by combining in planta and in vitro reactions. Our work expands the biocatalytic repertoire of non-heme-iron- and 2-oxoglutarate-dependent enzymology to oxidative peptide decarboxylation and primes scaled metabolic engineering and chemoenzymatic synthesis of 14-membered cyclopeptide alkaloids with terminal posttranslational modifications.

biochemistry↗

bioRxiv2026

Shared and distinct default mode systems in mental time travel and affective experience over time

Overarching conceptualizations propose a critical role of the default mode network (DMN) in self-referential mental time travel, particularly in autobiographical memory retrieval and episodic future thinking, and internal (intrinsic) emotion generation and regulation. However, these conceptualizations have not been directly evaluated. Against this background, the present fMRI study aimed to identify both shared and distinct neural systems underlying autobiographical episodic processing across different temporal contexts - specifically, episodic memory retrieval (EMR) and episodic future thinking (EFT) - and to examine how these systems interact with affective experiences, including valence and arousal. Our findings demonstrated the central role of the DMN - encompassing the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and medial temporal lobe (MTL) - in both EMR and EFT. Importantly, we identified a functional dissociation along both valence and temporal dimensions: the ventromedial prefrontal cortex (vmPFC) was more strongly associated with positive experiences and simulations, whereas the dorsomedial prefrontal cortex (dmPFC) was consistently engaged during the processing of negative affect across past and future contexts. Moreover, representational similarity and parametric analyses indicated that the hippocampus supports differential processing of valence and arousal across temporal domains. Together, these findings provide empirical evidence for the involvement of cortical midline core DMN systems in autobiographical processing across time and suggest overlapping and distinct systems for the integration of emotional experiences across mental time travel.

neuroscience↗