SEARCH · bioRxiv Science

Search bioRxiv Science

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

500 records · Page 8Linked to original sources

bioRxiv2026

Structural mechanism of nuclear membrane sealing by LEM2-ESCRT-III

In open mitosis, re-establishing nucleocytoplasmic compartmentalization requires the LEM2-ESCRT machinery to coordinate spindle clearance with sealing of the remaining nuclear envelope pores. The structural basis of this topologically unique and fundamental membrane-remodeling process is poorly understood. Here, we combine biochemical reconstitution, cryo-electron tomography, subtomogram averaging and large-scale molecular dynamics simulations to define the structural mechanism of nuclear membrane sealing. We structurally resolve that LEM2s winged-helix domain (WH) co-polymerizes with the ESCRT-II/III protein CHMP7 to form a membrane-bound scaffold whose geometry is progressively remodeled by downstream ESCRT-III proteins as it transitions from the flat membrane surrounding the pore towards the negatively curved membrane neck. In parallel, LEM2 positions its intrinsically disordered low-complexity domain within the pore, where condensation around spindle microtubules mechanically couples the membrane-ESCRT-LEM2 scaffold to the spindle and narrows the remaining diffusion path, restoring compartmentalization before membrane closure is complete. Remarkably, the LEM2-WH domain alone forms tightly constricted membrane tubes, coating the negatively curved inner surface, revealing an intrinsic membrane-remodeling activity of the receptor itself. Together, our work establishes a structural framework for how receptor-ESCRT co-polymerization, low complexity domain-mediated sealing and receptor-driven membrane remodeling guide nuclear-envelope pores from spindle-containing openings to terminal constriction and fusion.

molecular biology↗

bioRxiv2026

Systemic hypoxia drives glycogen-fueled progression of lung adenocarcinoma

In advanced stages, lung adenocarcinoma obstructs airways and disrupts ventilation-perfusion relationships in the lung, causing systemic hypoxemia and enabling a feed-forward loop that accelerates malignancy. Systemic hypoxemia is also experienced due to common respiratory comorbidities such as chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), potentially accelerating malignancy. In a statewide electronic health record network, pre-existing COPD (598 matched pairs) or sleep apnea (235 matched pairs) independently predicted worse survival following incident lung cancer diagnosis. Since the mechanistic basis of the link between malignancy and hypoxia is not well understood, we created systemic hypoxia in KrasLSL-G12D/+;Trp53fl/fl (KP) mice by delivering low inspired oxygen concentrations (8% inspired oxygen; 8 h daily). Hypoxia nearly doubled tumor multiplicity and selectively remodeled cancer central carbon metabolism. Spatially resolved metabolomics revealed marked tumor-compartment glycogen accumulation, elevated tricarboxylic-acid cycle intermediates, and depleted glycolytic pools. Quantitative proteomics across cellular models and autochthonous tumors demonstrated that systemic hypoxia drives glycogen mobilization selectively through the lysosomal enzyme acid -glucosidase (GAA). Tumor-cell-autonomous deletion of GAA eliminated the hypoxia-driven growth advantage and disrupted downstream anabolic biosynthetic pathways. Thus, systemic hypoxia drives lung adenocarcinoma expansion by mobilizing lysosomal glycogen reserves through GAA to sustain proliferative growth.

cancer biology↗

bioRxiv2026

Hormetic heat shock activates HLH-30/TFEB independently of canonical nutrient-sensing pathways

In Caenorhabditis elegans, a brief, sublethal heat shock (HS) induces a hormetic response that increases resistance to subsequent stress and extends lifespan. These benefits require hlh-30, the ortholog of mammalian transcription factor EB (TFEB). Although HS induces robust HLH-30 nuclear translocation, how this response is regulated remains poorly understood. Nutrient- and energy-sensing pathways, including mTORC1 and AMPK, regulate HLH-30/TFEB subcellular localization under other physiological conditions, but whether they mediate its nuclear translocation during HS is unknown. Here, we show that, although HS inhibited mTORC1 and dephosphorylated its conserved HLH-30 S201 target site, HLH-30 S201 phosphorylation was dispensable for HS-induced HLH-30 nuclear localization and hormetic protection. Moreover, HS remained protective in hlh-30 mutants when mTORC1 activity was reduced, revealing an HLH-30-independent component of the hormetic response. HS also activated AMPK and aak-2 was required for hormetic protection but dispensable for HS-induced HLH-30 nuclear localization and autophagosome formation. Together, these findings demonstrate that although HS engages canonical mTORC1 and AMPK signaling, these pathways do not account for HS-induced HLH-30 nuclear localization and instead make distinct contributions to hormetic protection. Our findings reveal stress-specific regulation of HLH-30/TFEB and point to additional mechanisms that drive its activation during heat stress.

cell biology↗

bioRxiv2026

Complementary cytotoxicity of GD2-targeted photoimmunotherapy and 5-aminolevulinic acid photodynamic therapy in neuroblastoma and osteosarcoma

Phototherapy, a light-activated anticancer treatment, enables localized tumor-cell killing with distinct mechanisms of action. Photoimmunotherapy (PIT) produces immunogenic tumor cell death upon near-infrared light activation of a photoabsorber through antigen-specific targeting. Photodynamic therapy (PDT) produces reactive oxygen species through red-light activation of intracellular protoporphyrin IX generated from 5-aminolevulinic acid uptake and metabolism. PIT may have limited activity in antigen-low cells, whereas PDT has less precise tumor selectivity. We combined these modalities to define their interaction, broaden cytotoxicity, and determine whether dual treatment could reduce light-dose requirements. We conjugated dinutuximab, which targets the GD2 antigen, to IRDye 700DX and characterized plasma-membrane localization by confocal and widefield microscopy. PIT and PDT monotherapies were evaluated across agent and light doses in neuroblastoma (NB) and osteosarcoma (OS) cell lines. Combination matrices were tested using interaction, highest-single-agent, and Bliss analyses. Both monotherapies demonstrated significant light-dose-dependent effects in NB and OS. PIT produced no measurable cytotoxicity in antigen-blunted control cells, whereas PDT remained effective, confirming antigen-dependence of PIT and antigen-independence of PDT. The combination interaction was significant in SK-N-BE(2) but not LM7. At selected combinations, however, dual treatment produced greater killing than the more effective matched monotherapy in both SK-N-BE(2) and LM7 (Padj<0.022). Notably, lowest combination of PIT 10 J/cm2 plus PDT 10 J/cm2 achieved 90.3% killing in SK-N-BE(2), exceeding higher light-dose PIT or PDT monotherapy, suggesting a light-dose sparing effect. These findings establish potent and complementary PIT-PDT activity, supporting dual phototherapy to broaden cytotoxicity and reduce light-dose requirements in GD2-expressing tumor phototherapy.

cancer biology↗

bioRxiv2026

Cardiomyocyte prohibitin ablation reprograms cardiac metabolism revealing a pathogenic role for mTORC1 in dilated cardiomyopathy

Maintaining cardiac structure and function throughout the lifespan requires a delicate balance in carbon allocation between energetic and biosynthetic processes. At the nexus of this balance are prohibitins-1 and -2 (PHB1, 2) which form a ring-like complex in mitochondrial and plasma membranes responsible for coordinating cellular growth, metabolism and autophagy. Here we describe how ablation of the PHB complex in cardiomyocytes of adult mice (cPHB1KO) causes unrestrained mechanistic target of rapamycin complex 1 (mTORC1) activity and a Warburg-like reprogramming of glucose metabolism in heart toward enhanced de novo amino acid biosynthesis. These changes are accompanied by disruptions in mitochondrial Ca2+ handling and impaired autophagy, leading to severe dilated cardiomyopathy and mortality within 12 weeks. Using pharmacological and nutritional approaches, we further show that mTORC1 inhibition attenuates pathologic cardiac remodeling only in female cPHB1KO mice. Our findings illustrate novel mechanisms linking the PHB complex with altered carbon flux and pathogenesis of cardiomyopathy.

cell biology↗

bioRxiv2026

AnnFlux: object-conditioned neural stochastic differential equations for single-cell perturbation dynamics

Single-cell perturbation profiling measures responses to genetic and chemical interventions, yet most models learn a static map, ignoring how populations move over time and how perturbations combine. AnnFlux, an object-conditioned stochastic differential equation, learns a drift field in latent cell-state space. Conditioning on the perturbing object makes the field queryable one object at a time, yielding per-object drifts comparable across genes and drugs. By learning a drift field tailored to each perturbation context, it interpolates a held-out timepoint in an epithelial-mesenchymal transition time course and predicts unseen perturbations. Beyond point estimates, AnnFlux improves distributional fidelity and predicts responses to held-out perturbation combinations. An IFN-response signature predicted by AnnFlux was associated with TLS proximity in an independent pan-cancer spatial atlas. This framework maps perturbation-driven cell-state evolution as continuous trajectories and represents unseen perturbations using prior-knowledge embeddings.

bioinformatics↗

bioRxiv2026

Arabidopsis thaliana ACTIN DEPOLYMERIZING FACTORs are novel susceptibility factors for Colletotrichum higginsianum

Colletotrichum higginsianum (Ch) is a hemibiotrophic fungal pathogen that infects Brassicaceae plants, including Arabidopsis thaliana. The molecular mechanisms underlying the Ch-A. thaliana interaction are not fully understood. Particularly, the susceptibility factor against Ch infection remains to be determined. Here, we report that A. thaliana ACTIN DEPOLYMERIZING FACTORs (ADFs), ancient proteins that regulate the organization and dynamics of actin filaments (AFs), function as susceptibility factors during Ch infection. Among 11 ADFs encoded in A. thaliana genome, subclass I ADFs that include ADF1, -2, -3, and -4, express throughout the plant. We found that knockout mutant of ADF4 and transgenic plants in which the expression of all of subclass I members is suppressed (ADF1-4Ri) exhibited increased resistance to Ch. Cytological analyses revealed that both Ch penetration and secondary hyphae formation were suppressed in adf4 and ADF1-4Ri. This enhanced resistance was associated with suppression of Ch-induced AF fragmentation. In addition, we found that PENETRATION 2 (PEN2) plays a critical role in the Ch resistance in adf4 and ADF1-4Ri. Our findings suggest that subclass I ADFs promote AF fragmentation during Ch infection, thereby suppressing PEN2-associated mitochondria accumulation at Ch entry sites. Together, these results raise the possibility that Ch exploits host ADF-dependent actin regulation to facilitate successful infection.

plant biology↗

bioRxiv2026

Compression Sequencing enables ultra-sensitive and scalable scRNA-seq

Current sequencing methods are inefficient and bottlenecked by repeated sampling of highly abundant molecules, which dominate sequencing reads, limit assay throughput and sensitivity for rare targets. For example, single-cell RNA sequencing (scRNA-seq) can profile up to millions of cells, but remains severely constrained by sequencing cost, resulting in shallow gene coverage and high dropout rate. Here we report an information science-inspired method, Compression Sequencing, that tackles this fundamental inefficiency and enables highly improved (>100x) sequencing power. Our method works by performing an accurate and unbiased logarithmic transform on molecular abundances over a wide (5 logs) dynamic range, thus suppressing high-abundance targets and enriching rare ones, while maintaining quantitative accuracy. Applied to scRNA-seq libraries, our method allows ultra-sensitive detection of low-abundance transcripts (2-5x more UMIs), ultra-low sequencing cost (200x reduction), preserves accurate cell types and differential expression analysis over a 500-2,000 gene panel. In AML clinical samples, Compression Sequencing reproduces clinical diagnosis and additionally allows transcriptomic profiling at affordable cost (est. $10 per sample). Our approach thus enables ultra-sensitive and scalable single-cell analysis for large-scale functional genomics studies, drug discovery screens, AI cell model training, as well as affordable single-cell disease diagnostics.

bioengineering↗

bioRxiv2026

Microbial valerate is associated with CAR T dysbiosis and its supplementation enhances CAR T function in B-cell lymphoma

Anaerobe-depleting antibiotic exposure is associated with inferior progression-free survival after CD19 CAR T-cell therapy in large B-cell lymphoma, yet the cellular mechanisms linking gut dysbiosis to the CAR T-cell product and whether this imprint is reversible have remained undefined. In two independent CAR-T candidate cohorts, low stool valerate at the time of CAR-T eligibility identified a multi-metabolite-deficient dysbiotic gut microbiome state marked by depletion of fiber-fermenting commensals and loss of carbohydrate-fermentation, SCFA-biosynthesis, and amino-acid metabolism pathways. Reanalysis of single-cell RNA sequencing from 42 lymphoma patients stratified by piperacillin-tazobactam/imipenem/meropenem (PIM) exposure revealed that PIM-exposed CAR T-cell products were CD4-skewed, with significantly elevated AP-1/immediate-early gene (IEG) and cellular activation signatures that together predicted inferior progression-free survival. Ex vivo conditioning of CAR T-cells with valerate produced a chromatin and transcription factor program distinct from butyrate or propionate, characterized by KLF/SP/EGR family engagement, KLF4 promoter opening, and broad induction of AP-1/IEG and MHC class II transcripts, whereas butyrate drove broader chromatin remodeling with TBX21/EOMES/NF-{kappa}B gains and KLF2 promoter closure, and propionate induced an NFY-centered program with preferential commitment to low-mitochondrial-content states. Untargeted metabolomics confirmed valerate uptake and mitochondrial {beta}-oxidation in CAR T-cells, while dietary sodium valerate supplementation in meropenem-treated mice bearing A20 lymphoma significantly reduced tumor burden and extended survival compared with CAR T-cells alone. These findings identify stool valerate as a bedside-deployable biomarker of dysbiosis-imprinted CAR T-cell dysfunction and support ex vivo or dietary valerate supplementation as a clinically tractable strategy to improve CAR-T anti-tumor function in patients with disrupted gut microbiomes.

cancer biology↗

bioRxiv2026

Division of labor and low temperatures predict geographic variation in thermal tolerance of a North American paper wasp (Mischocyttarus mexicanus cubicola)

The biogeographic study of organismal thermal performance is fundamental to our understanding of how climate drives evolution. However, despite highly social insects being popular models for such studies, biogeographic comparisons of thermal functional traits seldom consider division of labor. Individuals within cooperative societies can operate in different microclimates, exposing different task groups to different selection pressures. Here we present a study of how thermal tolerance limits in a social paper wasp vary broadly across temperate and subtropical climates in eastern North America, testing whether division of labor between foundresses and non-reproductive workers generates adaptive variation in thermal performance within the colony. Cold tolerance rather than heat tolerance varied more predictably with environmental temperatures across latitudes, with temperate populations experiencing bouts of winter cold coma, unlike in subtropical populations. Within colonies, reproductive foundresses were also more cold-tolerant than workers, enabling them to remain mobile at cooler periods of early spring during crucial tasks of nest construction, before workers emerge. Together, these results broaden our understanding of how climate shapes thermal performance on both biogeographic and social scales.

ecology↗

bioRxiv2026

Temozolomide Induces Aberrant RNA Alkylation and Widespread Translational Repression

Temozolomide (TMZ) is a frontline alkylating chemotherapy, yet its direct impact on RNA modification and global translation dynamics remains poorly understood. Here, we demonstrate that TMZ induces pervasive RNA alkylation causing severe translational impairment. TMZ directly deposits aberrant methyl groups onto single-stranded mRNA in vitro, creating physical lesions that lower translational efficiency. In glioblastoma cells, acute TMZ exposure triggers a rapid, widespread accumulation of m7G on cellular RNAs, leading to the significant attenuation of global protein synthesis. Nanopore direct RNA sequencing identified distinct guanine-specific error signatures and sequence context preferences associated with TMZ-induced damage. Using a quantitative yeast spike-in ribosome profiling strategy, we mapped this translational repression at transcript-level, revealing a global downregulation of translational efficiency. This widespread repression disproportionately targets highly interconnected networks essential for cellular proliferation, specifically chromosome organization. We show that the severity of this translational repression is driven by a transcript's coding guanine density, stability and translation initiation speed. Together, our findings suggest that TMZ-induced alkylation targets stable, highly translated, guanine-rich transcripts. This establishes aberrant RNA methylation and subsequent translational arrest as a potential mechanism of temozolomide cytotoxicity.

biochemistry↗

bioRxiv2026

VLCFA-mediated inter-cell layer communication controls cellular pluripotency in Arabidopsis callus

Plants have remarkable capacity to reconstruct entire organ systems from tissue explants. In Arabidopsis two-step tissue culture system, pluripotency regulators are specifically expressed in the middle-cell layer of the stratified callus tissue. However, regulatory mechanisms underlying the radial patterning of callus remained unclear. Here, we found that very-long-chain fatty acids (VLCFAs) synthesized in the epidermis-like outermost layer are essential for pluripotency acquisition and successful shoot regeneration. Our genetic and transcriptomic analyses revealed that the regulatory roles of VLCFAs on pluripotency acquisition involve inter-cell layer signaling in callus tissue, while they are at least partly independent of ATML1/PDF2 functions and cuticular wax synthesis in the outermost layer. VLCFAs spatially restrict procambium cell identity by non-cell-autonomously suppressing cytokinin signaling, thereby allowing for establishment of the middle-cell layer. We propose that the inhibitory relationships between layer-specific regulators underlie the intricate balance of cellular fate determination in pluripotent callus.

plant biology↗

bioRxiv2026

OsPATROL1 overexpression accelerates stomatal opening to enhance photosynthetic induction and growth under fluctuating light in rice

Slow stomatal opening after increases in irradiance constrains carbon gain under fluctuating light, yet stomatal kinetics remain an underexplored target for crop improvement. Here, we investigated Oryza sativa PROTON ATPASE TRANSLOCATION CONTROL 1 (OsPATROL1), which encodes a Munc13-like protein implicated in stomatal regulation in Arabidopsis thaliana. OsPATROL1 overexpression had modest, condition-dependent effects on steady-state gas exchange and did not alter stomatal morphology or biochemical traits. In contrast, it consistently accelerated stomatal opening and photosynthetic induction, reducing the stomatal conductance time constant during induction by 41-43%. During 12 h of simulated natural fluctuating light, OsPATROL1-overexpressing plants maintained higher stomatal conductance and net CO2 assimilation rate, increasing cumulative assimilation by 8-12% while maintaining their intrinsic water-use efficiency (iWUE). Under artificial fluctuating light, overexpression alleviated growth reductions relative to steady light. Under glasshouse conditions, total biomass increased by 34-44%, accompanied by greater tiller number, root biomass, bleeding sap rate, and leaf nitrogen content. Taken together, these results indicate that OsPATROL1 overexpression accelerates stomatal opening, enhances photosynthetic induction and daytime carbon gain without compromising iWUE, and is associated with greater growth.

plant biology↗

bioRxiv2026

Distinct roles for partially redundant transcription factors in Caenorhabditis elegans mesoderm lineage development

Developmental transcription factors often have overlapping functions, making it difficult to define the distinct roles of individual factors during lineage specification. We investigated the partially redundant transcription factors TBX-35 and CEH-51 in the Caenorhabditis elegans embryonic MS mesodermal lineage using 4D lineage tracing, reporter imaging, genetics, and single-cell RNA sequencing. In tbx-35 mutants, MS descendants showed progressively slower cell cycles and a division pattern that increasingly resembled the cousin C lineage. Fate-regulator expression also shifted toward C-like features, including ectopic pal-1 and expanded HLH-1 expression, although mutant cells did not simply adopt normal C-lineage positions. Loss of tbx-35 also impaired a later MS-dependent Notch induction in the AB lineage while leaving an earlier induction intact. CEH-51 showed a different pattern of activity whereby its protein became enriched in anterior MS daughters, and ceh-51 mutants produced later, more restricted lineage defects that were strongest in descendants of cells with higher CEH-51 levels. Single-cell profiling identified overlapping but nonidentical sets of genes dependent on the two factors. TBX-35-dependent changes were strongest at earlier stages, whereas CEH-51-dependent genes became more prominent later and were enriched in anterior MS sublineages. Finally, temperature-shift experiments determined that the severity and onset of tbx-35 mutant phenotypes depend on the maternal temperature environment and cannot be explained by differences in residual CEH-51 expression. These findings reveal that TBX-35 and CEH-51 contribute differently across the MS lineage and that reliable mesoderm development is supported by overlapping zygotic and maternal regulatory inputs.

developmental biology↗

bioRxiv2026

A Generic Numbering Scheme for TMEM16 Scramblases

The TMEM16 family of calcium-activated phospholipid scramblases (CaPLSs) and chloride channels (CaCCs) performs diverse physiological functions that include regulation of blood coagulation and apoptotic signaling, through a shared ten-transmembrane-helix (TM) architecture organized around a hydrophilic lipid-translocating groove. Mechanistic studies of TMEM16 family members have been hampered by the absence of a unified positional reference framework that would permit direct comparison of structurally equivalent residues across paralogs with different sequence numbering systems. Here we introduce a generic numbering scheme for TMEM16 scramblases (GNS-TMEM16), modeled on the Ballesteros & Weinstein system established for class A G protein-coupled receptors. A reference alignment (TMEM16-RA) was constructed from twelve human and mouse TMEM16 scramblases (TMEM16C/D/E/F/G/J) using structure-based ClustalW alignment of the ten TM helices. From this alignment, a TM-specific reference residue (TsRR) was identified for each helix by hierarchical application of three criteria: (1) 100% conservation in the core TMEM16-RA; (2) conservation in an augmented reference alignment (TMEM16-ARA) incorporating a group of phylogenetically more distant homologs composed of nhTMEM16, afTMEM16, TMEM16K, TMEM16A, and TMEM16B; and (3) structural and functional considerations, including helix-perturbing character, groove localization, conserved motif membership, and central TM position. The resulting ten TsRRs are Y1.50, W2.50, R3.50, E4.50, F5.50, P6.50, E7.50, D8.50, W9.50, and E10.50, and are illustrated in mTMEM16F. Each residue is assigned the identifier N.m(k), where N is the TM number, m is the position relative to the TsRR (for which m = 50), and k is the absolute sequence number. Loop residues receive dual identifiers referenced to the TsRRs of both flanking helices. Application of the GNS-TMEM16 is illustrated with the comparisons of the groove-opening measurements using pairwise distances between residues identified by their N.m indices to be corresponding across mTMEM16F, afTMEM16, and nhTMEM16. The results bring to light the advantages of corresponding residues identification in different TMEM16 proteins and show that the mammalian scramblase undergoes substantially larger separation at the extracellular groove entrance than either fungal homolog. Comparison of mutagenesis data guided by N.m correspondence shows at the conserved (E3.55,R6.26) salt-bridge locus, Ala substitution reduces activity more than 100-fold in nhTMEM16 but less than 2-fold in afTMEM16, illustrating that the GNS identifies structural equivalence of position without implying functional equivalence of the residue, which is a distinct advantage of GNS in providing mechanistic interpretation across paralogs. Also described is a protocol for extending the GNS-TMEM16 to uncharacterized protein sequences, including AlphaFold-predicted models, using structural superposition to mTMEM16F. Thus, the presented GNS-TMEM16 provides a stable positional reference for the integration and comparative analysis of structural, computational, and functional data across the TMEM16 family, utilizing a construction strategy applicable to yet other polytopic membrane protein families sharing a common transmembrane fold.

biophysics↗

bioRxiv2026

Structural characteristics of important daily movement corridors for waterbirds in urban areas: A case study on Black-headed Gulls

Landscape management facilitating animal movement is essential for sustaining urban wildlife populations and ecosystem services. Although linear vegetation corridors effectively conserve terrestrial animal movements, it remains unclear which landscape elements serve as pathways for aquatic organisms. Urban waterbirds frequently utilize rivers, but the specific characteristics that render certain river segments crucial as movement corridors have yet to be elucidated. This study aims to identify the characteristics of river segments functioning as critical corridors based on waterbird movement strategies. We tracked the movement behaviors of the Black-headed Gull (Chroicocephalus ridibundus), a river-dependent species in daily movements, and identified key movement corridors in highly urbanized Tokyo, Japan. Using GPS tracking data from gulls, we evaluated how river sinuosity and surrounding feature heights influenced tendencies to follow rivers across various temporal scales and perceptual ranges. Furthermore, we predicted and mapped these tendencies across individual river segments in central Tokyo. Gulls tended to fly along river segments with tall features during instantaneous to mid-term decision-making. In contrast, they utilized straight channels for long-term decisions. Although results varied slightly depending on the spatial scale they can perceive, this overarching trend remained consistent. Furthermore, our model predicted that the lower reaches of the Sumida River serve as critical movement corridors. This predictive tendency was also highly robust across all time scales. While straightened river segments with high feature heights may provide unsuitable habitats for diverse taxa, we emphasize their ecological value and argue that they should be conserved as essential movement corridors for waterbirds.

ecology↗

bioRxiv2026

Evolutionary stabilisation of stressful metabolism via integrated biocomputing and essential-gene metabolic locking circuits

Synthetic genetic circuits enable microbial differentiation from growth to production, yet metabolic burden, imbalance and toxicity frequently drive strain degeneration. Yeast strains engineered to produce different terpene products exhibited divergent genetic responses to metabolic stresses, but commonly underwent progressive loss of induction of synthetic GAL regulatory circuits, either across the entire population or within subpopulations. Using di- and tri-input biocomputing circuits, the essential glutamine synthetase gene GLN1 was coupled to GAL induction, thereby enabling stabilisation and evolutionary adaptation of the synthetic genetic circuits and stressful heterologous terpene synthetic pathways. The integrated biocomputing and metabolic coupling circuit systems not only prevent strain degeneration but also enable interrogation of non-degenerative evolutionary shifts, providing a platform for metabolic engineering optimisation.

synthetic biology↗

bioRxiv2026

Glutamatergic system in the pelagic tunicates

Tunicates are a sister lineage to vertebrates, with compact, relatively simple nervous systems featuring a single central ganglion, reflecting a minimal complement of chordate functional architecture. Although glutamatergic neurons are the most abundant population in vertebrates, their ancestry remains unclear. Here, we used glutamate immunohistochemical labeling (Glutamate IR) to identify glutamatergic elements in the neural system of the pelagic tunicate Doliolum sp. (Thaliacea). Glutamate IR was observed in all major nerves of the central ganglion, including motor-like terminals on the circular bundles of swim muscles, which were themselves labeled. However, the neuronal somata in the central ganglion were not labeled, suggesting glutamate accumulation in axonal processes and terminals. In contrast, we did not identify GABA-containing neural elements. This study suggests that glutamatergic systems were elaborated in the common ancestor of tunicates and vertebrates, although the functional role of glutamate and its role in muscular control need further investigation in these pelagic tunicates.

zoology↗