Biology subjects

Song, Y.

Publications and source records attributed to Song, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Tailocin as an alternative weapon to type VI secretion system in bee gut symbionts

Antagonistic interactions often shape microbial communities, as co-residents compete for resources. One system of interbacterial antagonism involves tailocins: phage tail-like particles produced by some bacteria to kill close relatives. Their roles in natural communities are poorly studied. Here, we identified putative tailocin loci ubiquitously present in genomes of Snodgrassella species, core members of the bee gut microbiota. We purified tailocins from culture supernatants of different Snodgrassella strains and found that these inhibited growth of multiple Snodgrassella strains but not of strains of other species that cooccur in bee guts. Proteomic analyses corroborated the production of tailocins, and cryogenic electron microscopy imaging revealed their morphology and killing activity via membrane disruption. We generated single- and double-gene knockout mutants of a predator Snodgrassella strain that naturally possesses both tailocin and a type VI secretion system (T6SS) that was previously shown to function in intraspecies competition in bee guts. These mutants were used in tests for antagonism against a prey Snodgrassella strain in vivo. Co-inoculations within gnotobiotic honeybees including visualization within guts showed that both tailocin and T6SS are important for Snodgrassella in intraspecies competition. Each of these two antagonism mechanisms inhibits the establishment of susceptible strains within the ileum. Outcomes depend on the timing of colonization by competing strains, with both tailocin and T6SS giving a stronger advantage when the producing strain colonizes first. Thus, tailocin production can underlie priority effects that have been widely observed in the bee gut community and other host-associated bacterial communities.

microbiology↗

bioRxiv2026

High-resolution HLA and MICA/MICB typing of the 1000 Genomes panel: a resource for precision medicine

High-resolution characterization of human leukocyte antigen (HLA) and MICA/MICB variation is important for transplantation, immunogenetics, and the interpretation of disease associations within the major histocompatibility complex (MHC). However, publicly available population reference datasets remain limited in their resolution and coverage of these loci. We performed high-resolution typing of the 1000 Genomes Phase 3 panel across 13 HLA and MIC loci, generating HLA genotypes for 2,486 individuals, extended HLA-A, -B, and -C allele assignments, and MICA/MICB genotypes for 2,393 individuals representing 25 populations and five continental super-populations. Concordance with previously reported HLA genotypes was 96.2-97.4% at two-field resolution, and independent retyping confirmed the present assignments for samples exhibiting reciprocal genotype discrepancies with an earlier dataset. Analysis of extended class I variation within defined assay boundaries revealed that most of the 78 common three-field HLA lineages were dominated by a single extended sequence group. However, eleven lineages exhibited substantial heterogeneity, with the predominant group accounting for less than 80% of observed copies. The distinguishing sequence differences were noncoding, involving intronic and 3' untranslated regions, and their distributions varied among ancestral populations. These findings identify recurrent, population-relevant variants for which functional consequences remain to be established. Population analyses demonstrated extensive allelic diversity at classical class I loci and DRB1, whereas the greatest between-population differentiation occurred at selected class II and DRB-linked loci. Most common alleles were shared among populations but differed substantially in frequency. Multilocus haplotypes revealed characteristic population-associated combinations of HLA and MIC alleles and provided the basis for predicting MIC genotypes from existing HLA typing. Using two-field HLA-B and HLA-C genotypes, five-fold cross-validation achieved exact genotype prediction accuracies of 77.3% for MICA and 53.6% for MICB, compared with 4.6% and 21.6%, respectively, without HLA information. Together, these results provide an extended-resolution HLA and MIC reference resource, demonstrate the limited routine utility of universal fourth-field typing while identifying specific variants for functional investigation, and establish the potential for recovering MIC variation from existing HLA-typed cohorts. The resource also supports future investigations of MHC variation underlying disease associations and transplantation outcomes.

genetics↗

bioRxiv2026

Erythrocyte aging links hypocalcemia to impaired flow dynamics and oxygen transport through volume dysregulation

Red blood cells (RBCs) maintain their corpuscular volume through mechanotransducive ion-mediated processes in response to circulatory shear stress. However, with age, RBCs accumulate oxidative damage and undergo alterations in protein function, glucose metabolism and ion transport, raising fundamental questions about how volume homeostasis is preserved under mechanical load. Here, we investigated the differential responses of younger (YRBCs) and older RBCs (ORBCs) to fluid shear stress, with a focus on calcium-dependent regulation. We found that ORBCs exhibited a striking dependence on extracellular calcium to maintain volume stability. In calcium-depleted conditions, only ORBCs underwent pronounced post-shear swelling, with recovery only partially restored by ATP-dependent mechanisms. In contrast, calcium preserved volume homeostasis, identifying calcium-sensitive pathways as key compensatory regulators in metabolically compromised ORBCs. Notably, metabolically deficient YRBCs recapitulated the ORBC swelling phenotype, supporting a shift from ATP to calcium-dependent regulation with age. More importantly, shear-induced swelling impaired flow behaviour and oxygen delivery in ORBCs, linking defective volume control to microcirculatory dysfunction. Together, these findings potentially established calcium-dependent volume regulation as a critical adaptive mechanism in ageing RBCs and reveal a previously unrecognized hematological link to vascular dysfunction in hypocalcemia.

bioengineering↗

bioRxiv2026

Technology solutions for immune loci: integrated high-resolution KIR genotyping reveals allelic, structural, and KIR-HLA diversity across 24 human populations

High-resolution genotyping of killer cell immunoglobulin-like receptor (KIR) genes remains challenging because of extensive sequence homology, copy-number variation, and complex haplotype structures. Although KIR allelic variation influences receptor expression and function, routine typing has largely been limited to gene presence or absence. Here, we evaluated an integrated short-read sequencing system combining a four-reaction, two-stage multiplex PCR assay (ScisGo-KIR-v3), centralized cloud-based copy-aware allele analysis, and interactive genotype review. The system was applied to 2,298 individuals representing 24 populations from the 1000 Genomes Project, with matched high-resolution HLA class I genotypes. Independent validation against complete, phased PacBio KIR sequences from 48 samples demonstrated 98.6% automated copy-number concordance and 92.8% combined copy-number and allele concordance across 768 gene-sample comparisons. Following desktop review, all evaluated assignments were concordant with the reference sequences. In a separate comparison of four computational genotyping methods involving 311 shared samples, the automated Scisco pipeline showed the lowest overall mismatch with the four-method consensus (1.62%). Population analyses identified substantial allele diversity and distinct centromeric and telomeric haplotype-motif distributions. Although exact haplotype pairs were frequently ambiguous, structural assignments became increasingly resolvable at the motif level, and motif backgrounds exhibited characteristic allele compositions. Paired KIR and HLA analysis revealed inherited receptor-ligand configurations concealed by gene-content typing. Among 1,401 KIR3DL1/HLA-B Bw4 co-carriers, 57 lacked an allele annotated for ordinary surface expression, while 457 of 1,175 KIR2DS4 co-carriers of six specified HLA-C allotypes carried only truncated receptor forms. Allele-specific KIR2DL1 and KIR2DS5 classifications further distinguished receptor properties and published ligand-binding annotations that varied among populations. Although potential receptor-ligand repertoire composition differed across populations, analyses did not establish preferential KIR-HLA genetic association after accounting for population structure and multiple testing. Together, these findings demonstrate that integrated short-read KIR genotyping can provide scalable, high-resolution allele and copy-number information while explicitly retaining uncertainty in inferred haplotype structures. Compatibility with established HLA laboratory workflows provides a practical foundation for incorporating allele-resolved KIR analysis into immunogenetic research and future clinical investigations.

genetics↗

bioRxiv2026

Predictive dendrites as a foundation for biological learning

A fundamental challenge for neuroscience is to identify laws of synaptic plasticity that are consistent with experimental observations at the level of individual neurons, whilst also explaining the ability of neural networks to learn complex tasks. Here we investigate a candidate law in which neurons adjust synaptic strengths to minimize the mismatch between somatic and dendritic activity. We demonstrate that models based on this rule can effectively adjust synaptic weights across network layers to learn non-linear tasks. Moreover, minimizing mismatch between spiking activity and dendritic inputs leads to integrate-and-fire dynamics and spike-timing-dependent plasticity. The model reproduces the experimentally observed dependencies of plasticity upon initial synaptic weights and spike patterns, whilst also generating a series of testable predictions. Our results show that a single principle - minimization of somato-dendritic mismatch - links learning at the network level with fundamental properties of individual neurons, including membrane potential dynamics and canonical features of synaptic plasticity.

neuroscience↗

bioRxiv2026

Design of readers for pathological PTM proteoforms in Alzheimer's disease

Alzheimer's disease (AD) is characterized by heterogeneous Tau phosphorylation and aberrant amyloid-beta (Abeta) processing, yet molecular tools that distinguish closely related molecular states of tau and Abeta with predefined specificity remain difficult to develop. Here, we designed de novo protein readers targeting three disease-associated phospho-Tau regions and N-terminal pyroglutamate-modified Abeta (N3pG-Abeta). Screening 192 designs per target identified 51 modification-selective hits among 768 candidates (6.6%). Representative readers exhibited nanomolar to subnanomolar affinities for modified peptides, discriminated authentic modifications from unmodified or substitution-based controls, and preferentially recognized modified full-length targets. We further programmed local modification specificity by interface redesign, generating pT231 readers conditional on the phosphorylation state of neighboring S235 and S237. A 2.0-angstrom crystal structure of an N3pG-Abeta reader closely matched the computational design model (interface C-alpha RMSD = 0.52 angstrom), and redesign of pT231 readers tuned apparent binding affinities from greater than 1 uM to below 1 nM. In a human 3D neuronal culture with both pathological Abeta and tau, selective readers targeting N3pG-Abeta, Tau pT231, and Tau pT217 recognized disease-associated signals, exhibiting colocalization with related antibodies and much higher signal in the AD line than the control. Tau pT231 readers further quantitatively distinguish AD patients and control human brain lysates in dot-blot assays. Together, these results establish genetically encoded readers with programmable specificity for defined Tau and Abeta modification states, enabling molecular-state-resolved detection in human disease models and biological samples, and lay a foundation for controlled pathological molecular perturbation.

bioengineering↗

bioRxiv2026

Perceived social value is more strongly linked to gossip decisions with age in adolescence

Gossip is central to social exchange, yet how adolescents select what to share and with whom remains unclear. Across two independent samples aged 10-18 years (behavioural, n = 98; fMRI, n = 101 scanned), adolescents read information about absent third parties, chose whether and with whom to share it, and reported their appraisals. Sharing frequency showed no detectable age association. Valuation-to-decision coupling strengthened with age for interest in both samples, with a smaller age interaction for usefulness. Adolescents selected close friends more often with age when sharing. During scenario reading, before participants reported their choices, BOLD responses in a left inferior frontal cluster tracked subsequent interest ratings more strongly with age (n = 92), also within regions engaged by a separate mental-state judgment task. Together, these findings link age in adolescence to stronger valuation-to-decision coupling for interest and a greater proportion of sharing directed to close friends.

neuroscience↗

bioRxiv2026

Metabolite Relaxation Times at 3T From Birth to 7 Years

PurposeWith growing interest in pediatric MRS to understand the neurochemistry of brain development, it is essential to establish pediatric-specific metabolite T1 and T2 relaxation times for reliable quantification of metabolites. Furthermore, characterization of age-related changes in relaxation times may provide insight into developmental differences in tissue microstructure and cellular composition. Therefore, the goals of this study were two-fold: (1) to estimate metabolite T1 and T2 relaxation times in a pediatric cohort; and (2) to assess linear relationships between age and relaxation times. MethodsTI- and TE-series data were acquired from the bilateral thalamus in 20 and 25 participants aged between 0 and 7 years, respectively. Data were processed and modelled in Osprey 2.5.0. Metabolite T1 and T2 relaxation times of total N-acetylaspartate at 2.0 ppm (tNAA2.0), total creatine at 3.0 ppm (tCr3.0), total creatine at 3.9 ppm (tCr3.9), total choline (tCho), myo-inositol (mI) and the combined glutamate and glutamine (Glx) were estimated by fitting the modelled signal amplitudes to TI-series inversion recovery signal and TE-series exponential decay equations, respectively. Linear relationships with age were tested for metabolite T1 and T2 relaxation times using Spearman correlations. ResultstNAA2.0 and Glx showed significant changes in T1 with age. tNAA2.0, tCr3.0, tCho and mI showed significant decrease in T2 with age. ConclusionSeveral metabolites showed significant changes in relaxation times with age in the thalamus region. Therefore, use of age-specific relaxation correction for pediatric studies using the linear equations provided is encouraged for reliable quantification of metabolites.

neuroscience↗

bioRxiv2026

Protocol for Single-Cell Patch-Proteomics: identify specific proteins associated with electrophysiological properties from individual neurons

Single-cell patch-proteomics is a novel and powerful technique combining electrophysiological and quantitative proteomic characterization from individually sampled neurons. Following whole-cell patch clamp characterization of neuronal excitability, we collect intracellular contents and, using the latest advancements in Liquid Chromatography and Mass Spectrometry, identify and quantify peptides and their corresponding proteins. By cell-matched one-to-one associations between electrophysiological properties and protein abundance, this approach provides a means to elucidate molecular mechanisms of neuronal function on individual neuron basis.

neuroscience↗

bioRxiv2026

A Novel and Evolutionarily Conserved Metabolic Axis for Efficient Hepatic Lipid Catabolism Governed by Mfn2-Hsl-Mediated Mitochondria-Lipid Droplet Coupling

Inter-organelle contact between mitochondria and lipid droplets (LDs) is crucial for hepatic lipid homeostasis, but the tethering complex underlying this interaction remains unclear. To address this, we aimed to characterize the molecular machinery governing mitochondria-LD coupling and evaluate the evolutionary conservation of its metabolic functions. Using hepatocyte models from multiple species and in vivo experiments in yellow catfish with differential lipid and creatine diets, we explored the mechanism and evolutionary conservation of mitochondria-LD coupling. The key findings were: (1) A novel complex formed by mitofusin 2 on mitochondria and hormone-sensitive lipase on lipid droplets via specific residues orchestrates efficient hepatic lipid catabolism by mediating mitochondria-LD coupling; (2) Creatine enhances this coupling by transcriptionally upregulating mfn2 via hnf4, thereby promoting peridroplet mitochondria formation and alleviating hepatic lipid accumulation; (3) The Mfn2-phosphorylated HSL axis is evolutionarily conserved across fish and mammals, representing a potential therapeutic target for hepatic steatosis.

cell biology↗

bioRxiv2026

AI-Guided Multi-Objective Engineering of Glucoamylase Enables Acidification-Free Starch Saccharification

Glucoamylase is essential for industrial starch saccharification, but the limited thermostability and near-neutral pH tolerance of fungal glucoamylases necessitate cooling and acidification of liquefied starch. Here, we developed an artificial intelligence-guided strategy to simultaneously improve the thermostability, pH tolerance, and catalytic activity of glucoamylase from Penicillium oxalicum (PoGA). Two property-specific machine-learning models, CASPE-T and CASPE-A, identified substitutions associated with thermostability and pH tolerance, respectively. Experimental screening identified beneficial substitutions in 11 of 21 CASPE-T and 12 of 22 CASPE-A candidates. Folding-energy-guided recombination integrated the two traits while maintaining structural compatibility. The optimal variant, PoGA T513E/Q305N, exhibited 2.21-fold higher specific activity than the wild type, with half-life extended from 22.3 to 57.9 min at 60 degrees C and from 16.6 to 64.7 min at pH 8.0. Molecular dynamics simulations attributed these improvements to reinforcement of high-occupancy hydrogen-bonding networks, suppression of conformational fluctuations in the linker and carbohydrate-binding module, enhanced long-range dynamic coordination, and preservation of a compact catalytic architecture. At 60 degrees C and pH 6.5 without acidification, PoGA T513E/Q305N produced 219.9 g/L glucose and achieved 89.1% starch conversion, 31.4% higher than the wild type. This work provides an efficient framework for multi-objective enzyme engineering and sustainable starch biorefining.

synthetic biology↗

bioRxiv2026

Concurrent Supervised-Unsupervised Representative Subspace Clustering (CSU-RSC)

The biological heterogeneity of psychotic disorders (PDs) has motivated the identification of psychosis imaging neurosubtypes (PINs), which aims to stratify the PD population into subgroups with similar neurobiological underpinnings. Yet the influence of sex, although well documented in the literature, has not been well counted in the existing subtyping paradigm. Here, we introduce concurrent supervised-unsupervised representative subspace clustering (CSU-RSC), a general functional neurosubtyping framework that jointly estimates cluster-specific subspaces and a partition while softly incorporating a supervised label, aiming to identify sex-dominant subgroups based on differences in the spatial organization of brain networks. This soft supervising design differentiates CSU-RSC from unsupervised approaches that completely ignore a label as well as from supervised approaches that exclusively analyze each label group separately. On simulated data, CSU-RSC recovered the ground truth of subgroups more accurately than its unsupervised counterpart. Applied to resting-state fMRI from 1,239 individuals with psychosis, CSU-RSC identified two sex-dominant PINs that replicated across discovery and validation sets, and showed significant differences in clinical characteristics, including cognitive impairment and symptom severity, with the most cognitively impaired subtype being female-dominant. Projecting controls onto the patient-derived subspaces showed that the female-dominant pattern did not persist in controls, suggesting psychosis-specific sex heterogeneity. Overall, by incorporating sex as an explicit source of information, CSU-RSC highlights the value of sex for resolving biological heterogeneity and provides a basis for more reproducible and biologically informative patient stratification.

neuroscience↗

bioRxiv2026

A comparative single-cell transcriptomic atlas for diverse populations of vertebrate hair cells

Mechanosensitive hair cells vary widely in morphology and regenerative capacity across vertebrate organs and species. To investigate their underlying transcriptomic diversity, we integrated human, mouse, chicken, and zebrafish single-cell and single-nucleus RNA sequencing datasets and assembled a cross-species atlas of hair cells spanning organs, developmental stages, and species. Analysis of 29 hair cell populations, encompassing the major cochlear, vestibular, and lateral-line hair cell types, identified approximately 5,000 genes enriched in at least one hair cell population compared to supporting cells from the same organs. Unsupervised clustering of these hair cell-enriched (HCE) genes defined species-, organ-, and hair cell state-associated cohorts as well as broadly conserved hair cell-enriched programs. Using an AUC-based scoring framework, we further defined 884 pan hair cell-enriched (pan-HCE) genes with elevated expression in most developing and/or mature hair cell populations, including genes implicated in deafness, mechanotransduction, and synaptic transmission, along with genes not previously linked to hair cell function. Independent analysis of developing hair cells using the same metrics stratified pan-HCE genes based on when they are first enriched and identified an additional 97 genes that are transiently enriched. We used the pan- and developing HCE gene sets to assess transcriptional similarity between baseline hair cell states and hair cells produced during avian hair cell regeneration and in mouse cochlear organoids, as well as hair cell-like populations produced by fibroblast reprogramming. HCE gene sets with different developmental dynamics identified young vs. more mature hair cells when projected onto independent single-cell RNA sequencing datasets from developing zebrafish, mouse, and human. We provide a web-based resource of all HCE metrics and expression profiles, enabling future exploration of vertebrate hair cell gene expression across organs, species, and experimental contexts.

neuroscience↗

bioRxiv2026

Age-related differences in neurometabolite concentrations during early infancy: A cross-sectional analysis of the HBCD Release 1.0

Background: Developmental trajectories of low-concentration neurometabolites such as the neurotransmitter {gamma}-aminobutyric acid (GABA), and the antioxidants glutathione (GSH) and ascorbate (Asc) across early infancy remain unexplored. Advances in spectral editing enabled the measurement of these key molecules together with high-concentration metabolites like N-acetylaspartate (NAA) and glutamate (Glu) in the HEALthy Brain and Child Development (HBCD) study, the largest longitudinal study of early brain development in the United States. Purpose: To determine the age-associated trajectories of 14 key neurometabolites during early infancy from a cross-sectional 1H-MRS dataset. Materials and Methods: HBCD utilizes ISTHMUS, an integrated MRS sequence that includes both an unedited short-echo-time PRESS acquisition and an advanced 4-step Hadamard-encoded sequence, HERCULES to enable measurement of both high- and low-concentration metabolites. Metabolite quantification was carried out by the HBCD Data Coordinating Center (HDCC) using an automated Osprey pipeline, with data from 201 infants ages 0 - 10 weeks adjusted age included in the tabular imaging results in HBCD data release 1.0. After excluding preterm born infants and data with poor linewidth or model quality metric, we tested for linear associations with adjusted age for each metabolite. Results: Concentration estimates of total NAA (tNAA), total creatine (tCr) and glutamate (Glu) as well as the combined sum of glutamate and glutamine (Glx) significantly increased across ages 0 - 10 weeks, while myo-inositol (mI) decreased. GABA and GSH showed age-related trends, but did not reach significance. Levels of the lipid precursor phosphorylethanolamine (PE) and Asc are higher in the first months than established adult values. Conclusion: Multiple metabolites showed significant age-related changes during early infancy. While GABA and GSH did not, future work will establish whether the trends suggested here contribute to linear or non-linear patterns across the first years of life.

neuroscience↗

bioRxiv2026

A Conserved SIFamide Circuit Functions as the Insect Vagus Nerve

The insect functional homolog of the mammalian vagus nerve has remained elusive. Here, we identify the SIFamide (SIFa) peptidergic circuit as this homolog in Drosophila melanogaster. SIFa neurons project the longest axons from the brain to the hindgut ampulla, forming synapses with peripheral SIFa-receptor (SIFaR) neurons originating in the abdominal ganglion. This circuit is functionally plastic: sexual experience enhances synaptic strength at the hindgut, increasing excretion while reducing mating duration to to favor energy conservation and metabolic recovery. Mechanistically, this shift involves octopaminergic/tyraminergic gating and SIFa-mediated modulation of Adipokinetic Hormone (AKH) from the corpora cardiaca. We further uncover a feedback loop in which SIFaR/Allatostatin-A (AstA) neurons project back to the brain, signaling hindgut physiological status to SIFa neurons via AstA-R1. This hindgut projection is conserved across diverse insect orders. Thus, the SIFa-SIFaR circuit constitutes an evolutionarily conserved "insect vagus nerve" that integrates metabolic state and reproductive history to optimize survival strategies.

neuroscience↗

bioRxiv2026

Semaglutide-induced satiation, nausea, and food reward suppression are mediated by GLP-1 receptors in the area postrema

The GLP-1-based obesity drug semaglutide lowers bodyweight primarily by increasing satiation and satiety, whilst also reducing food reward and commonly causing nausea. The brainstem dorsal vagal complex (DVC) has been identified as a key site of action for these phenotypic components of semaglutides anorectic effect. However, which GLP-1 receptor (GLP-1R) populations within the DVC are recruited to mediate these phenotypic components, and whether they are dissociable, are translationally important but unresolved questions. We addressed these using metabolic and behavioural phenotyping, combined with activity-dependent genetic labelling ( Sema-TRAP) and chemogenetic manipulation of semaglutide-recruited brainstem circuits. Semaglutide potentiated satiation and satiety, caused behavioural proxies of nausea, and suppressed motivation for Western diet, in a largely sex-independent manner. It activated a substantial proportion of GLP-1R-expressing neurons in the brainstem area postrema (AP), but surprisingly most semaglutide-activated neurons in the nucleus tractus solitarius (NTS) did not express GLP-1R. Chemogenetic reactivation of Sema-TRAP neurons in the NTS alone was sufficient to recapitulate the acute effects of semaglutide on satiation, nausea, food reward, and bodyweight. Knockdown of GLP-1R expression in the AP before Sema-TRAPing abolished the recruitment of Sema-TRAPNTS neurons which elicited all these effects, while leaving the effects of semaglutide on satiety and bodyweight intact. These data demonstrate that semaglutide recruits dissociable anorectic circuits to suppress eating via distinct behavioural mechanisms, with non-GLP-1R NTS neurons downstream of GLP-1RAP representing potential therapeutic targets to tune GLP-1-based obesity drugs towards a better-tolerated effect profile.

neuroscience↗

bioRxiv2026

Dissection of centrosomal γ-TuRC activation pathways controlling microtubule density in interphase cells

Animal microtubule-organizing centers, including the centrosome and the Golgi apparatus, regulate microtubule nucleation and anchoring through the {gamma}-tubulin ring complex ({gamma}-TuRC) and CAMSAP-mediated minus-end stabilization. However, functional redundancy between these pathways has impeded dissection of their contributions to controlling microtubule organization and density. Here, we addressed this problem using combinatorial gene knockouts, protein depletions and Expansion Microscopy. By simultaneously eliminating CAMSAP2 and the {gamma}-TuRC-targeting proteins AKAP450, pericentrin, CDK5RAP2, myomegalin, ninein and AKNA, we generated viable RPE1 cells that lack both Golgi-derived microtubules and {gamma}-TuRC localization within the pericentriolar material and at subdistal appendages. Despite the disruption of these major microtubule-organizing pathways, overall microtubule density was only partially reduced. The remaining microtubules depended on CEP192 and NEDD1, which, together with ch-TOG, can activate {gamma}-TuRC at the centriole wall, in acentriolar cells, and in biochemical reconstitution assays. Our results demonstrate that in the absence of CAMSAP-mediated stabilization, interphase microtubule formation strongly relies on {gamma}-TuRC activation, which occurs through several redundant pathways.

cell biology↗

bioRxiv2026

Rapid Electrochemical Biosensing of Listeria monocytogenes Using Rationally Designed Host-Pathogen Interface Peptides

Rapid, selective detection of bacterial pathogens remains a central challenge. Here we report a label-free electrochemical biosensing approach that leverages protein-protein interaction (PPI)-derived peptides as recognition elements for rapid detection of Listeria monocytogenes (LM). The sensor design is inspired by the interaction between the LM virulence factor Internalin A (InlA) and the human host receptor E-cadherin (E-Cad1). Peptides derived from the InlA-binding domain of E-Cad1 were engineered as molecular recognition elements, with the E-Cad1(15-24) peptide displaying micromolar affinity and selective binding towards LM. Immobilization of these peptides on gold electrodes enabled bacterial detection by electrochemical impedance spectroscopy within 10 minutes, without labels or external signal amplification. A low peptide surface density was associated with enhanced binding-site accessibility and may facilitate multivalent interactions between the bacterial surface and the immobilized peptides. The platform produced a detectable response at experimentally tested concentrations as low as 1 CFU mL {superscript 1} and exhibited excellent selectivity under the conditions examined. This work introduces a chemically programmable, PPI-inspired biosensing paradigm that uses a reductionist approach and could potentially be extended to other pathogen targets.

bioengineering↗