Biology subjects

Jung, K.

Publications and source records attributed to Jung, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Natural product-derived azaphilones are selective scaffolds for covalent lysine liganding in live cells

Lysine-directed covalent liganding offers a promising strategy to expand the covalently ligandable proteome beyond cysteine. However, broadly applicable and selective lysine-reactive scaffolds remain limited. Here, we designed SCL-alkyne, a simplified azaphilone probe derived from the natural product sclerotiorin (SCL), for the global profiling of lysine reactivity in bacteria. SCL-alkyne displayed high intrinsic selectivity for lysine in vitro and in live Escherichia coli cells. In situ proteome profiling revealed that 84% of engaged sites belong to lysine residues and the protein N-terminus. Reactivity mapping provided an inventory of highly reactive sites showing that only a limited subset of reactive lysines is located in functional regions of proteins. Analysis of proteins enriched via the SCL-alkyne probe unraveled bacterial chemotaxis as a major target pathway which was confirmed by an impaired chemotactic response upon treatment of bacteria with SCL-alkyne. Competitive profiling of three structurally related azaphilone natural products identified 60 protein targets belonging to pathways related to iron-sulfur cluster assembly and antioxidant function. This study not only highlights the diverse modes-of-action of natural product azaphilones, but also establishes its core scaffold as effective lysine-reactive chemotype for identifying ligandable lysines.

biochemistry↗

bioRxiv2026

The glucocorticoid dexamethasone influences motility of the sulfate-reducing bacterium Desulfovibrio desulfuricans by targeting the filament cap protein FliD

Glucocorticoids such as dexamethasone (DXE) are first-line treatments for inflammatory bowel disease (IBD). Beyond their effects on the host immune system, accumulating evidence suggests that glucocorticoids can also influence the gut microbiota. Notably, IBD patients exhibit an increased intestinal colonization by sulfate-reducing Desulfovibrio spp. Here, we show that DXE modulates bacterial motility in the gut commensal Desulfovibrio desulfuricans through a metabolism-independent mechanism. To identify bacterial targets, we developed a DXE-derived chemical probe and performed affinity-based protein profiling, which revealed the flagellar cap protein FliD (Ddes_0530) as a principal binding partner. Structural modeling using AlphaFold3 and Boltz2 predicted DXE binding within a conserved groove of the FliD C-terminal domain. Furthermore, the tip of the flagellum of Desulfovibrio, but not that of Escherichia coli, could be fluorescently labeled with TAMRA-DXE, but not with the structurally related steroid probe TAMRA-norethiosterone, indicating that flagellar labeling is specific to DXE rather than the steroid scaffold itself. As a consequence of this interaction, transmission electron microscopy showed that DXE treatment prevented flagellation in a subpopulation and reduced flagellar length in D. desulfuricans strains ATCC 27774 and CCUG 72978, respectively. Quantitative motility tracking revealed a non-monotonic, dose-dependent modulation of swimming velocity, with peak stimulation at 10 {micro}M DXE, accompanied by straighter trajectories and enhanced net displacement. Together, these findings uncover a previously unrecognized mode of action for DXE which directly perturbs flagellar biogenesis and motility of an important gut microbiome member of IBD patients. SignificanceGlucocorticoids are widely prescribed for inflammatory conditions, yet their direct effects on gut bacteria remain largely unexplored. We demonstrate that dexamethasone, a synthetic glucocorticoid, binds to the flagellar cap protein FliD of the gut commensal Desulfovibrio desulfuricans, affecting flagellar assembly and altering motility behavior. Unlike previously characterized steroid-metabolizing bacteria such as Clostridium steroidoreducens, Desulfovibrio does not degrade dexamethasone, indicating that the observed effects result from direct drug-protein interaction. These findings establish a new paradigm for metabolism-independent drug-microbiome interactions and suggest that glucocorticoid effects on gut bacteria extend beyond enzymatic degradation pathways.

microbiology↗

bioRxiv2026

Reduction of Pollen Number and Anther Length in Bread Wheat Studied by a Nested Association Mapping Population

The number of pollen grains, which carry male gametes in seed plants, has attracted interest in genetics, evolution, and breeding. Rapid evolutionary reductions in pollen number and anther length were reported in selfing species as well as domesticated species, although this poses a challenge for hybrid breeding. Here, we studied the variation of pollen number and anther length of the hexaploid bread wheat (Triticum aestivum) by employing a quick pollen counting method. Pollen numbers in cultivars were lower than those in landraces among 54 lines of diverse geographic origins. Using the year of registration of traditional and modern cultivars, we found a reduction in pollen number over the past 150 years. We detected high heritability and variation among Asian landraces and cultivars. Thus, we conducted QTL mapping of pollen number as well as of anther length using nested association mapping lines in which Norin 61 was the common parent. Genomic loci encompassing Green Revolution genes (Rht-B1, Rht-D1, and Ppd-D1) showed significant effects on pollen number and anther length, but their contributions were relatively minor. Although anther length has often been used as a proxy for pollen number in bread wheat, our data showed that their correlations are not necessarily high. Interestingly, we identified a new QTL of pollen number that was not detected by measuring anther length, and, vice versa, a new QTL specific to anther length. These data suggest that pollen number has reduced rapidly in bread wheat but can be modified using the genetic diversity of landraces. Significance statementWe found that modern cultivars of bread wheat have reduced pollen number and shorter anther length, which are common in domesticated species but can be a challenge for hybrid breeding. Using underutilized Asian landraces and cultivars, we reported that new quantitative trait loci as well as loci used in the Green Revolution, are responsible for the traits, which can be employed to increase pollen numbers.

plant biology↗

bioRxiv2026

Topographic structure and function of locus coeruleus norepinephrine neurons

Norepinephrine (NE) is released throughout most of the central nervous system by neurons in the locus coeruleus (LC). We found a relationship between the morphologies, gene expression, and activity of LC-NE neurons in mice. Axonal projections of individual neurons were extensive but largely confined to subsets of brain regions. Axonal projections and graded gene expression correlated with locations of cell bodies in LC. In a behavioral task requiring ongoing learning from actions, neurons in dorsal LC projecting to the cerebral cortex were excited when mice made a different choice from the previous one and by reward prediction errors, a signal driving learning. Background activity of neurons in ventral LC was higher when mice ignored stimuli indicating potential reward availability. These observations reveal a topographically organized structure and function of a neurotransmitter system and show that it contains learning signals for flexible behavior.

neuroscience↗

bioRxiv2025

cuBNM: GPU-Accelerated Brain Network Modeling

Brain network modeling uses computer simulations to infer about latent neural properties at micro- and mesoscales by fitting brain dynamic models to empirical data of individual subjects or groups. However, computational costs of (individualized) model fitting is a major bottleneck, limiting the practical feasibility of this approach to larger cohorts and more complex models, and highlighting the need for scalable simulation implementations. Here, we introduce cuBNM, a Python package which leverages parallel processing of graphics processing units to massively accelerate simulations of brain network models. We show running simulations on graphics processing units is several hundred times faster compared to central processing units. We demonstrate the usage of cuBNM by running optimization of group-level and individualized low- and high-dimensional models. As examples of the utility of individualized models, we investigated test-retest reliability and heritability of simulated and empirical measures in the Human Connectome Project dataset. We found simulated features were fairly reliable and significantly heritable, suggesting their biological plausibility. Overall, cuBNM enables large-scale simulations of brain network models, opening new avenues for studying latent neural processes across diverse populations, dense networks, and high-dimensional models, which was previously impractical due to computational constraints.

neuroscience↗

bioRxiv2025

CRISPR-Induced NUT Suppression Promotes Differentiation and Enhances Trop2-Targeted Immunocytokine Response in NUT Carcinoma

NUT carcinoma (NC) is an aggressive malignancy driven by NUTM1 gene rearrangements with limited therapeutic options. Here, we show that direct suppression of NUTM1 using CRISPR/Cas9 induces squamous-like differentiation and upregulates TROP2 expression in NC cells. Building on this finding, we developed a TROP2-interferon beta (IFN-{beta}) mutein immunocytokine that selectively targets TROP2-expressing tumors. Combined NUTM1 suppression and TROP2-targeted immunotherapy synergistically enhanced cytotoxic and immune-mediated responses in vitro. Transcriptomic and spatial analyses of NC patient tumors revealed that differentiation status correlates with TROP2 expression, upregulated immune pathways, and favorable clinical outcomes. Our results suggest that overcoming differentiation blockade not only alters tumor phenotype but also creates a more immune-permissive microenvironment. These findings highlight the therapeutic potential of sequential tumor reprogramming followed by targeted immunotherapy in treating NC and propose a broader strategy for overcoming differentiation blockade in fusion-driven cancers.

cancer biology↗

bioRxiv2025

Epitranscriptomic control of stress adaptations in Escherichia coli

Bacterial stress responses have been studied at the phenotypic, transcriptional, and translational levels, demonstrating the presence of an "alarm" phase immediately after stress exposure. However, the contributions of RNA modifications during stress adaptation remain largely unexplored. Here, we map the epitranscriptomic changes of Escherichia coli after exposure to oxidative and acid stress using direct RNA sequencing of mRNA, rRNA, and tRNA, combined with mass spectrometry, deletion mutant phenotyping, and single-nucleotide PCR. We identified widespread, dynamic RNA modifications that include central metabolism transcripts and increased levels of rRNA methylations (m4Cm and m5C) under both stresses, with potential consequences for translation. In uncharged tRNAs, stress-specific modifications via the Mnm and Q pathways accumulated at the wobble position; these modifications proved crucial for survival. Together, these findings reveal a multifaceted layer of post-transcriptional regulation, establishing the first comprehensive view of the bacterial epitranscriptome during the alarm phase of stress adaptation.

microbiology↗

bioRxiv2025

AdiY Acts as a Cytoplasmic pH-Sensor via Histidine Protonation to Regulate Acid Stress Adaptation in Escherichia coli

The arginine-dependent acid resistance (Adi) system is a vital component that enables Escherichia coli and other enterobacteria to withstand the extreme acidity in the human gastrointestinal tract. It consists of the proton-consuming decarboxylation of arginine, catalyzed by AdiA, and the uptake of arginine, as well as the excretion of the more alkaline agmatine, catalyzed by the antiporter AdiC. The corresponding genes adiA and adiC are induced in E. coli under acidic conditions (pH < 5.5), a process that is tightly regulated by the AraC/XylS transcriptional activator AdiY. Here, we show that the pH-sensing mechanism of AdiY functions through the protonation of two histidines (His34 and His60) in the N-terminal domain. Replacing these histidine residues with alanine, glutamine or aspartate abolishes the pH-dependent activation of AdiY, both in vivo, as demonstrated by promoter-reporter assays, and in vitro, as indicated by the loss of DNA-binding activity detected by surface plasmon resonance spectroscopy. Biochemical analyses of purified wild-type AdiY using size-exclusion chromatography and intrinsic tryptophan fluorescence revealed a pronounced and reversible pH-dependent conformational change that does not occur in the pH-sensing-deficient AdiY variant. A model is proposed in which AdiY forms a monomer at physiological pH. At a lower intracellular pH, the protonation of histidine in AdiY causes a conformational change that leads to the binding of AdiY as a tetramer to the DNA. This work elucidates the molecular mechanism of a one-component signal transduction system that combines both sensory and responsive functions. ImportanceThroughout their life, Escherichia coli and other bacteria may encounter acidic environments, for example, when passing through the human stomach. Their chances of survival under these conditions depend on the number and efficiency of acid resistance systems. Although many acid resistance mechanisms have been extensively studied, the molecular mechanism by which bacteria sense low pH is not yet fully understood. This study demonstrates that the transcription factor AdiY acts as a direct pH sensor by using two histidines to detect intracellular acidification in E. coli. When these histidines become protonated, AdiY changes its conformation and activates genes that support cell survival under acid stress. These findings not only reveal a new way in which bacteria can perceive extremely low pH environments but also provide the basis for the development of AdiY as a pH reporter.

microbiology↗

bioRxiv2025

Vibrio spp. dominate the microbiome of the endosymbiotic algae in healthy coral tissues

Coral reefs are rapidly declining due to climate change, and natural recovery mechanisms can no longer keep pace. Coral probiotics have emerged as a promising restoration tool, yet their broad application is limited by our incomplete understanding of long-term microbial associations crucial to coral health. Microbes closely associated with the coral algal symbionts (Symbiodiniaceae) are particularly promising candidates, given their potential to enhance algal function and host resilience. Although recent studies have begun to characterize these Symbiodiniaceae-associated microbial communities, methodological differences in algal cell purification have led to inconsistent results. Here, we compared multiple sample processing steps to generate Symbiodiniaceae-enriched fractions from clonal fragments of Acropora nobilis, and examined the resulting microbial communities. We consistently detected members of Flavobacteraceae, Rhodobacteraceae, Rhizobiaceae, and the genus Marinobacter. Strikingly, Vibrio species dominated the Symbiodiniaceae fractions across protocols. We isolated and sequenced 11 Vibrio strains enriched in these fractions and identified genes related to both virulence and putative beneficial traits, including vitamin biosynthesis and antioxidant production. Despite confirming their high potential for virulence, the persistent association, spatial proximity to Symbiodiniaceae, and presence of genes suggesting beneficial functions point to possible mutualistic roles for these Vibrio strains within the coral holobiont. This work highlights the value of fraction-based sampling for resolving microbiome structure, and emphasizes the need to reassess the ecological roles of key microbial taxa. By advancing our understanding of Symbiodiniaceae-bacteria interactions, this work provides a foundation for exploring microbial contributions to coral health and resilience.

microbiology↗

bioRxiv2025

Plastic-hydrolytic enzyme classification using explainable deep learning

The rapid accumulation of plastic waste has emerged as a critical environmental threat, driving the need for scalable and effective biodegradation solutions. Hydrolytic plastic-degrading enzymes (PDEs) offer a promising solution, yet their functional classification remains limited by insufficient annotations and enzymatic diversity. In this study, we present an explainable deep learning framework, PEPIC, to classify nine types of PDEs directly from protein sequences. Using a curated dataset of experimentally validated enzymes and an expanded homologous dataset, we built an explainable deep learning model based on convolutional neural networks (PEPIC) for plastic-degrading enzyme prediction. We benchmarked PEPICs performance against state-of-the-art approaches. First, PEPIC demonstrated statistically significant improvements in predictive performance compared to state-of-the-art methods. Second, PEPIC calculates contribution scores for each amino acid in the protein sequence, indicating their influence on the predictions. The model interpretation revealed that regions highlighted by high contribution scores matched conserved catalytic triads and substrate-binding clefts across PET-, PCL-, and PLA-degrading enzymes. Furthermore, structural modeling confirmed the trustworthiness of PEPICs predictions. Finally, PEPIC predicted an uncurated enzyme as a PET-degrading enzyme, which was biologically validated to hydrolyze bis(2-hydroxyethyl) terephthalate (BHET). These findings demonstrate that PEPIC provides accurate and trustworthy predictions of PDEs, facilitating the discovery of novel enzymes and supporting the development of sustainable plastic biodegradation technologies.

bioinformatics↗

bioRxiv2025

Detection of stress-dependent m5C rRNA dynamics in Escherichia coli using m5C-Rol-LAMP

Numerous RNA modifications are known in prokaryotes, but their dynamics and function in regulation remain largely unexplored. In Escherichia coli, three methyltransferases catalyze the 5-methylcytosine (m5C) modification in ribosomal RNA. Here, we introduce m5C-rolling circle loop-mediated isothermal amplification (m5C-Rol-LAMP) as a novel qPCR-based method that offers high sensitivity and site- specific resolution to detect and quantify mC in total RNA. When applying m5C-Rol-LAMP to E. coli under heat stress (45 {degrees}C), we observe a site-specific increase of mC at position 1407 of 16S rRNA from 77% to 89%, while m5C levels at positions 967 (16S) and 1962 (23S) remain unchanged. In recovered cells (at 37{degrees}C), the m5C abundance partially returns to the no stress level. Under oxidative stress, the level of mC1407 also increases, but remains high in recovered cells. These results demonstrate for the first time a reversible, stress-dependent and site-specific change in the rRNA modification level of a bacterium. m5C-Rol-LAMP is a powerful and easy-to-use tool for studying m5C in all RNA species, allowing the quantitative and site-specific detection of this modification.

microbiology↗

bioRxiv2025

scTrimClust: A Fast Approach to Robust scRNA-seq Analysis Using Trimmed Cell Clusters

Detection of marker genes and other data analyses in single cell RNA-sequencing (scRNA-seq) experiments very much rely on the result of unsupervised clustering of cells. However, in 2-dimensional representation of clustering results, several cells appear as outliers or in the border area of a cluster suggesting that these cells may not adequately represent a particular cell type. We propose a novel and fast approach, scTrimClust, for identifying cells that may be interpreted of extreme specimens of their cell type. Identification is based on concave hulls build around each 2-dimensional cell cluster and the distance of each cell to the border area of its population. We study in two data examples, how cells with non-representative expression profile can influence the results of the analysis. We found that some sets of marker genes are little influenced by extreme cells while other sets are strongly modified, and must therefore be treated carefully. scTrimClust is also useful to compare the influence of other parameters of an scRNA-seq analysis, e.g. normalization or the clustering approach, on the results. We also provide a software implementation of scTrimClust.

bioinformatics↗

bioRxiv2025

Accounting for spatial interactions in the upscaling of ecosystem services

O_LIMaps of ecosystem service (ES) supply are frequently used to guide spatial planning, policy making, and ecosystem management. However, these are typically based upon coarse land-cover proxies. This approach lacks a strong mechanistic basis, and neglects spatial biodiversity dynamics and interactions among landscape properties that can modify ES provision. C_LIO_LIWe present an analytical framework for ES upscaling that incorporates spatial interactions between landscape properties to determine ES supply. The resulting models can be viewed as a spatially informed ES production function. The approach comprises seven steps that include several elements absent from most existing approaches, notably a procedure for identifying geodata variables that represent the true mechanistic drivers, the inclusion of spatial interactions in the upscaling model, and modification following expert feedback on the selected model. C_LIO_LIWe demonstrate the approach using two example ES from German grasslands: biodiversity conservation and water supply. We show that the inclusion of spatial interactions in the upscaling model improved model predictions from 15% to 33% depending on the ES evaluated. In addition, inclusion of spatial interactions led to reduced error associated with the upscaled estimates. C_LIO_LIBy overcoming several shortcomings of existing, upscaling approaches we generate resulting maps of ES supply that can more reliably inform spatial planning Further, the underlying models allow for simulation of changes in the drivers of ES supply and estimation of respective outcomes. These advantages have the potential to better link detailed local-scale ecological understanding and land management with large-scale ES supply mapping, and thus better inform decision making and spatial planning. C_LI

ecology↗

bioRxiv2025

Mobile species' responses to surrounding land use generate trade-offs among nature's contributions to people

Agricultural landscapes provide material, non-material and regulating contributions that affect human wellbeing. The responses of these natures contributions to people (NCP) to land-use patterns depend on supporting biota with different habitat requirements, generating trade-offs and synergies. Predictions of NCP trade-offs could inform land-use decisions, but these do not typically account for the effects of land-use patterns on the movement of NCP-providing species, nor for interactions among NCP providers. To explore spatial trade-offs and synergies in eight indicators of NCP, we used Bayesian models that allow for interactions among land uses and among NCP using data from 150 grassland sites across rural Germany. We found that spatial arrangements of forest and open habitat influenced many NCP: acoustic diversity, birdwatching potential, natural enemy abundance and pollination. In particular, the amount and proximity of land uses in the surrounding landscape, especially forest and open habitat, drove the supply of most NCP. However, NCP provided by smaller-bodied taxa (herbivory and pathogen infection) responded weakly to landscape factors. Multiple NCP provided by a given taxon responded differently to their surrounding landscape (e.g. bird-provided caterpillar predation and seed predation), leading to trade-offs among NCP over short distances ([≤]60 m). These were caused by different rates and directions of response to amount and location of land uses. Resulting spatial predictions revealed that grassland-dominated or mixed forest-grassland areas better maximize beneficial NCP and minimize detrimental NCP across landscapes than purely forest-dominated areas. This suggests promoting semi-natural vegetation in agricultural landscapes to provide greater-than-additive benefits to net NCP supply. Significance StatementLand use affects natures contributions to people (NCP), including those provided by mobile species, in complex ways. Variation in the responses of species to the amount and location of land uses results in NCP trade-offs across landscapes, but decision-makers lack the capacity to spatially predict these trade-offs. We predict how the supply of both beneficial and detrimental NCP and associated trade-offs vary across diverse rural landscapes and find that grassland-dominated or mixed forest-grassland areas deliver higher net NCP supply than forest-dominated areas in our study system. Our findings support policies for promoting semi-natural vegetation cover in agricultural landscapes, as these may provide non-additive benefits for NCP.

ecology↗

bioRxiv2024

A versatile dual reporter to identify ribosome pausing motifs alleviated by translation elongation factor P

Protein synthesis is influenced by the chemical and structural properties of the amino acids incorporated into the polypeptide chain. Motifs with consecutive prolines can slow down translation speed and cause ribosome stalling. Translation elongation factor P (EF-P) facilitates peptide bond formation in these motifs, thereby alleviating stalled ribosomes and restoring regular translational speed. Ribosome pausing at various polyproline motifs has been intensively studied using a range of sophisticated techniques, including ribosome profiling, proteomics, and in vivo screenings with reporters incorporated into the chromosome. However, the full spectrum of motifs which cause translational pausing in Escherichia coli has not yet been identified. Here we describe a plasmid-based dual reporter for rapid assessment of pausing motifs. This reporter contains two coupled genes encoding mScarlet-I and chloramphenicol acetyltransferase to screen motif libraries based on both bacterial fluorescence and survival. In combination with a diprolyl motif library, we use this reporter to reveal motifs of different pausing strengths in an E. coli strain lacking efp. Subsequently, we use the reporter for a high-throughput screen of four motif libraries, with and without prolines at different positions, sorted by fluorescence-associated cell sorting (FACS) and identify new motifs that influence translational efficiency of the fluorophore. Our study provides an in vivo platform for rapid screening of amino acid motifs that affect translational efficiencies.

molecular biology↗

bioRxiv2024

A distant TANGO1 family member promotes vitellogenin export from the ER in C. elegans

Vitellogenin belongs to the Large Lipid Transfer Protein superfamily and is thought to share a common ancestor with human Apolipoprotein B (ApoB) for systemic lipid transport1-5. Vitellogenin forms part of yolk granules (also known as yolk organelles), as maternal contribution of nutrients that support the embryonic development of oviparous animals6,7. In Caenorhabditis elegans, vitellogenin proteins (VIT-1 to VIT-6) are synthesized in the hermaphrodite intestine, secreted into the pseudocoelom and internalized by oocytes8-13. Although a general route for inter-tissue vitellogenin transport has been described, the full mechanism that underlies its intracellular trafficking within the intestine remains obscure9,12,13. In humans, transport and Golgi organization protein 1 (TANGO1) and TANGO1-like (TALI) proteins generate super-sized membrane carriers to accommodate bulky ApoB-containing lipoprotein particles for their export from ER exit sites14-17. Transport facilitated by TANGO1 family of proteins is considered as an alternative, COPII-independent ER exit pathway18-24. Thus far, TANGO1 orthologs have been discovered in most metazoans, except nematodes24,25. Here, we report the C. elegans protein R148.3 (now Transport and Golgi organization 1-like or TNGL-1) as a mediator of vitellogenin export from the ER. TNGL-1 depletion triggers VIT-2 accumulation in the intestinal ER lumen. TNGL-1 requires its C-terminal unstructured domain for its localization to ER exit sites. Like TANGO1, it utilizes a luminal globular domain for cargo engagement. Our findings support TNGL-1 as a distant TANGO1 family member.

cell biology↗

bioRxiv2024

Decoding the Escherichia coli epitranscriptome

Modifications of RNA, known as the epitranscriptome, affect gene expression, translation, and splicing in eukaryotes, with implications for developmental processes, cancer, and viral infections. In prokaryotes, regulation at the level of the epitranscriptome is still poorly understood. Here, we used Nanopore direct RNA sequencing of Escherichia coli to study RNA modifications and their changes under heat stress. With a single sequencing reaction, we detected most known modification types in rRNA, tRNA, and mRNA. RNA sequencing was complemented by a multifaceted approach that included mass spectrometry, deletion mutants, single-nucleotide PCR, and in vitro methylation. Known m5C and m6A sites in the rRNA were confirmed, but these types of modifications could not be localized in the mRNA. In response to heat stress, levels of m5C, m6A, and m6,6A increased in the 16S rRNA. Sequencing and mass spectrometry data demonstrated a decrease in tRNA modification abundance in the anticodon loop at 45 {degrees}C. In general, mRNA modifications at 37 {degrees}C were enriched in the coding regions of genes associated with general metabolism and RNA processing, which shifted to genes involved in cell wall synthesis and membrane transport under heat stress. This study provides new insights into the complexity of post-transcriptional regulation in bacteria. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/602490v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@11b9bc4org.highwire.dtl.DTLVardef@18f77feorg.highwire.dtl.DTLVardef@efdeaorg.highwire.dtl.DTLVardef@402859_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Adolescent maturation of cortical excitation-inhibition balance based on individualized biophysical network modeling

The balance of excitation and inhibition is a key functional property of cortical microcircuits which changes through the lifespan. Adolescence is considered a crucial period for the maturation of excitation-inhibition balance. This has been primarily observed in animal studies, yet human in vivo evidence on adolescent maturation of the excitation-inhibition balance at the individual level is limited. Here, we developed an individualized in vivo marker of regional excitation-inhibition balance in human adolescents, estimated using large-scale simulations of biophysical network models fitted to resting-state functional magnetic resonance imaging data from two independent cross-sectional (N = 752) and longitudinal (N = 149) cohorts. We found a widespread relative increase of inhibition in association cortices paralleled by a relative age-related increase of excitation, or lack of change, in sensorimotor areas across both datasets. This developmental pattern co-aligned with multiscale markers of sensorimotor-association differentiation. The spatial pattern of excitation-inhibition development in adolescence was robust to inter-individual variability of structural connectomes and modeling configurations. Notably, we found that alternative simulation-based markers of excitation-inhibition balance show a variable sensitivity to maturational change. Taken together, our study highlights an increase of inhibition during adolescence in association areas using cross sectional and longitudinal data, and provides a robust computational framework to estimate microcircuit maturation in vivo at the individual level.

neuroscience↗