Biology subjects

Qin, S.

Publications and source records attributed to Qin, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Charting sex divergence in the human brain across the lifespan

Biological sex fundamentally shapes human brain organization, but sex-specific normative neuroanatomical trajectories across the lifespan remain largely uncharted. Here, we constructed independent, sex-specific lifespan brain charts using structural neuroimaging data from 59,915 healthy individuals (29,760 males and 30,155 females) ranging in age from 266 postconception days to 100 years. By examining 296 structural phenotypes across global, cortical, and subcortical measures, these models revealed widespread sex differences in maturational timing, with males reaching peak milestones later than females. These trajectories demonstrate that sex differences evolve dynamically, with phenotype-specific windows of emergence and maximal separation. Compared with conventional sex-pooled references, sex-specific models achieved superior predictive accuracy and reduced misestimation of individual deviations in healthy populations. Across five neuropsychiatric conditions, sex-specific models improved the detection of extreme deviations and revealed both shared and sex-dependent patterns of disorder-related neuroanatomical abnormalities. These sex-specific charts establish tailored normative references for assessing brain development, ageing, and disease.

neuroscience↗

bioRxiv2026

Functional reorganization of large-scale brain systems underlies emotion regulation maturation

Emotion regulation via cognitive reappraisal is essential for socioemotional development and mental health, yet the organizational logic of its supporting brain systems across youth remains unclear. Using a large multisite cohort, we demonstrate that maturation of reappraisal capacity reflects reorganization of a distributed architecture rather than progressive strengthening of prefrontal control. Reappraisal robustly reduced negative affect, with non-linear gains concentrated between 6 and 10.5 years. Bayesian systems identification resolved this architecture into four functionally distinct systems-reappraisal-specific, common-appraisal, modifiable-emotion, and non-modifiable-emotion components-spanning prefrontal-control, salience, default-mode and dorsal-attention networks. Age-related variation in anterior temporal cortex, emerged as essential hub, statistically accounted for developmental gains in reappraisal success. Multivariate modelling together with intersubject analyses further identified a cross-site-generalizable whole-brain reappraisal signature and revealed an age-dependent shift in brain-behaviour coupling, with neurobehavioural convergence increasing with age. These findings establish distributed network reorganization as a core mechanism of emotion regulation development and provide mechanistic targets for stage-matched interventions.

neuroscience↗

bioRxiv2026

Programmable DNA-peptide nanostructures for multivalent regulation of intracellular signalling

The Wnt/{beta}-catenin pathway is constitutively active in most colorectal and other cancers. Tankyrase (TNKS) promotes Wnt signalling by PARylating AXIN, a rate-limiting scaffold subunit of the {beta}-catenin destruction complex, and its inhibition is a validated strategy for pathway downregulation. Existing small-molecule TNKS inhibitors that target the catalytic PARP domain suffer from off-target effects across the PARP family. Here, we present an alternative approach that targets the substrate binding domains of TNKS using a short TNKS-binding peptide (TBP) presented multivalently on DNA nanostructures. Such a strategy may be required to effectively disrupt the function of targets such as TNKS, which is known to form high-order assemblies in the cell. We engineered DNA nanostructures with two distinct geometries: a 2D triangle (~100 nm) displaying 27 copies of TBP, and a compact 3D tetrahedron (~10 nm) displaying 2 TBP copies. We show that both nanostructures assemble efficiently, can be functionalised with TBP in high yields, and retain binding to TNKS protein in vitro. DNA nanostructures are efficiently internalised to the cytoplasm by HeLa Kyoto and colorectal cancer cells, with TBP functionalisation enhancing rather than hindering uptake. In HeLa cells, both triangle-TBP and tetrahedron-TBP downregulated Wnt signalling to a similar extent despite an order-of-magnitude difference in TBP copy number, while the same concentration of free TBP had no effect. This finding likely reflects the two functions of the DNA nanostructures - intracellular delivery and multivalent display - whereby the smaller nanostructures more efficiently internalise the TBP ligand but have lower valency. These results establish DNA nanostructures as a modular, tuneable platform for multivalent inhibition of intracellular clustered targets such as TNKS.

biophysics↗

bioRxiv2026

Dynamic structural changes and inhibition of insect delta and epsilon glutathione S-transferases by ethacrynic acid and permethrin

Insect glutathione S-transferases (GSTs) play critical roles in xenobiotic detoxification and insecticide resistance, making them promising targets for selective pest-control strategies. Here, we performed a comparative analysis of GSTs representing multiple classes from beneficial insects, agricultural pests, and disease vectors. We found significant isozyme-specific variations in catalytic activity, stability, and conformational dynamics, notably, in relation to inhibition by the commercial chemical agents, ethacrynic acid (ECA) and permethrin (PER). Sequence similarity network analysis revealed distinct clustering of major GST classes and further highlighted the relatively recent evolutionary divergence of the insect-specific delta and epsilon classes. Structural modeling revealed highly conserved glutathione-binding sites (G-site), but substantial variation in the hydrophobic substrate-binding regions (H-site). Further, epsilon-class GSTs exhibited 4 helices oriented approximately 10{degrees} closer to the glutathione-binding site than delta enzymes, suggesting differences in active-site architecture. Steady-state kinetic analyses using 1-chloro-2,4-dinitrobenzene (CDNB) demonstrated that epsilon GSTs are generally more catalytically efficient. Inhibition studies revealed that ECA acts as a potent mixed-type inhibitor of delta-class GSTs, reducing catalytic efficiency by up to 56-fold, whereas PER produced weaker and more species-dependent effects. Notably, ECA binding strongly stabilized delta GSTs, as measured by differential scanning fluorimetry (DSF) and induced a selective rigidification of the 3/4 linker region and active-site motifs, as observed by hydrogen-deuterium exchange mass spectrometry (HDX-MS). Collectively, these findings demonstrate the importance of analyzing the conformational dynamics mediating insect GST inhibition and provide a framework for exploiting isozyme-specific structural features in the design of next-generation selective insecticides.

biochemistry↗

bioRxiv2026

Notch Signaling Reprograms Glial Lipid Metabolism to Promote Hypoxia Resistance

Hypoxia poses a major threat to the developing nervous system, where high metabolic demand is required to support brain growth, glial and neuronal maturation, and function. Although glial cells are essential for maintaining neural homeostasis under stress, how specific glial subtypes remodel metabolism to promote hypoxia tolerance remains poorly understood. Here, we identify a Notch-dependent lipid metabolic program in excitatory amino acid transporter 1 (Eaat1)-positive glia that supports hypoxia adaptation in the developing Drosophila larval brain. Using stimulated Raman scattering (SRS) microscopy combined with deuterium-labeled metabolic probes, we visualized substrate-specific metabolic activity in vivo at subcellular resolution. In control, non-adapted flies, we found that acute hypoxia markedly increased de novo lipogenesis in Eaat1-positive glia. In flies adapted to chronic hypoxia, Eaat1-positive glia exhibited a pre-programmed metabolic shift, characterized by reduced glucose-derived lipogenesis and enhanced acetate-derived lipid synthesis. Constitutive activation of Notch signaling in Eaat1-positive glia was sufficient to phenocopy this acetate-favored lipogenic state, suggesting that Notch promotes metabolic plasticity under oxygen-limited conditions. To define the transcriptional programs associated with this response, we performed single-nucleus RNA sequencing (snRNA-seq) of the developing Drosophila central nervous system and mapped Eaat-1expressing cell populations across hypoxia and Notch activation. Notch activation reshaped hypoxia-associated transcriptional responses and counteracted metabolic suppression caused by low oxygen. Together, our findings identify Eaat1-positiveglia as a metabolically adaptive glial population and reveal a conserved Notch-regulated mechanism that rewires lipid metabolism to support hypoxia tolerance in the developing brain. These results provide insight into glial metabolic strategies that may be relevant to hypoxia-associated neurological conditions, including neonatal hypoxic-ischemic brain injury and ischemic stroke.

Cell Biology↗

bioRxiv2026

A Tripartite Map of the Ventromedial Prefrontal Cortex

The ventromedial prefrontal cortex (VMPFC) has been repeatedly implicated in affect, valuation, and social cognition, yet how these diverse functions are organized within a single cortical territory has remained unresolved. Here, we integrate large-scale meta-analysis, individual-level task fMRI, artificial neural-network encoding models, and multimodal connectivity analyses to reveal the internal functional architecture of the human VMPFC. Across four complementary studies, we identify a robust tripartite organization along the anterior-posterior axis, comprising posterior affective, middle valuation, and anterior social functional motifs. Connectivity fingerprinting demonstrates that each motif is preferentially embedded within distinct large-scale brain networks, providing a mechanistic account of VMPFC functional specialization. This organization is reproducible at the level of individual subjects, generalizes to naturalistic stimuli, extends across development, and shows cross-species correspondence with non-human primates and multiple neurobiological markers. Together, these findings resolve a long-standing organizational question and establish a biologically grounded framework for interpreting VMPFC function.

neuroscience↗

bioRxiv2026

Long-lived yeast-derived lipids promote longevity via regional and systemic metabolic remodeling

Aging is marked by a progressive breakdown of intestinal integrity and metabolic homeostasis, which together drives systemic decline in physiology and reduces lifespan. Here, we found that dietary lipids extracted from a genetically engineered long-lived yeast strain robustly extend lifespan in Drosophila and further uncovered the mechanisms using deuterium oxide-probed stimulated Raman scattering microscopy to image metabolic dynamics and single nucleus RNA sequencing (scRNA-seq) to unveil the underlying pathways. These yeast lipids are enriched in shorter, more saturated fatty acids and phospholipids as revealed by Raman spectroscopy and lipidomics, contributing to increased membrane order and reduced lipid storage. Functionally, targeted dietary supplementation with these lipid components synergistically prolongs fly lifespan. We show that these lipids reverse age-related declines in gut lipid droplet abundance, enhance membrane lipid incorporation, and increase de novo lipid synthesis, thereby improving epithelial structural integrity and barrier function. snRNA-seq identifies transcriptional remodeling in metabolically active enterocytes, including upregulation of autophagy and protein turnover genes, alongside reduction of unsaturated fatty acid biosynthesis. In the brain, dietary lipids orchestrate a dual metabolic strategy--promoting energy conservation and enhanced signaling across most neuronal and glial populations, while selectively boosting mitochondrial function in memory-critical Kenyon cells. All these leads to the enhancement of gut-to-glia communication, particularly through EGFR and FGFR pathways. Finally, analysis of our data with the Fly Metabolic Analysis Pipeline (FLY-MAP) reveals that yeast lipids restructure gut metabolic modules to coordinate energy production, redox balance, and nutrient flexibility. Our study uncovers a cross-kingdom mechanism of metabolic longevity regulation, paving the way for leveraging yeast-derived nutritional components to support tissue homeostasis and promote healthy aging.

molecular biology↗

bioRxiv2026

Metabolic Drivers of Disease Activity and Complications in Crohns Disease: A Retrospective Cross-Sectional Study

BackgroundThis study aims to examine the independent relationships between individual components of metabolic syndrome (MetS) and two key clinical outcomes in patients with Crohns disease (CD): disease activity, as quantified by the Crohns Disease Activity Index (CDAI), and the occurrence of complications. MethodsThis retrospective cross-sectional study included 376 adults with newly diagnosed Crohns disease. Multiple linear regression was used to examine associations between metabolic parameters and CDAI scores, while multivariate logistic regression assessed links to complications. Analyses were also based on clinical CDAI cut-offs. Predictive nomograms were developed and internally validated via bootstrap resampling. ResultsMultiple linear regression indicated that higher CDAI scores were independently associated with lower BMI (B = -5.866, P < 0.001), lower HDL-C levels (B = -81.770, P < 0.001), higher triglycerides (B = 15.618, P = 0.001), and lower ESR (B = -0.375, P = 0.03). Multivariate logistic regression established low HDL-C (OR = 0.042, P < 0.001), low BMI (OR = 0.915, P = 0.034), and high triglycerides (OR = 1.792, P = 0.007) as significant independent risk factors for complications. The developed nomograms demonstrated strong predictive performance, with an adjusted R2 of 0.207 for the CDAI model and an AUC of 0.765 for the complication model. For both predictive tasks, the model incorporating separate TG and HDL-C measurements significantly outperformed the TG/HDL-C ratio model. ConclusionMetabolic disturbances demonstrate a significant association with increased disease severity and a higher risk of complication development in Crohns disease. Core tipO_LIDual-outcome study reveals HDL-C and TG differentially link to CD inflammation and complications, pointing to distinct mechanisms. C_LIO_LILow HDL-C is the strongest independent predictor for CD complications, underscoring its protective role beyond cholesterol transport. C_LIO_LIIndividual TG and HDL-C metrics outperform their ratio in prediction, challenging its use and suggesting independent pathways in CD. C_LIO_LILow BMI independently associates with both adverse outcomes, refining the "obesity paradox" and highlighting malnutritions key role. C_LIO_LIA practical, validated nomogram (AUC=0.765) integrates HDL-C, TG, and BMI to stratify complication risk, aiding clinical decision-making. C_LI

immunology↗

bioRxiv2026

A Genetic Tool for Specific Tracking of Mature Neutrophils

Tracking mature neutrophils remains challenging due to the lack of reliable cell surface markers. Although CD101 is a promising candidate for mature neutrophils, its stability under pathological conditions is unclear. Using a CD101-tdTomato reporter mouse model, we confirmed that the reporting system does not alter CD101 expression, and tdTomato fluorescence is predominantly expressed in mature neutrophils across peripheral tissues. Further analysis revealed that CD101+ and tdTomato+ neutrophils display identical characteristics of mature neutrophil, including poly-segmented nuclei, cell size, and key functions under homeostasis. By comparing tdTomato fluorescence with CD101 protein levels, we demonstrate that reduced CD101 expression under pathological states was not attributed to shedding or degradation. Our finding enhances CD101 as a robust and reliable marker of neutrophil maturity, providing a foundation for future applications in spatial transcriptomics and lineage tracing studies to dissect neutrophil heterogeneity and function. Highlights of the studyO_LIIn CD101-tdTomato homozygous mice, tdTomato is predominantly expressed in neutrophils and labels nearly 100% of mature neutrophils, aligning with the phenotype of CD101+ mature neutrophils; C_LIO_LIThe CD101-tdTomato reporting system does not interrupt CD101 expression or neutrophil functions; C_LIO_LICD101 remains a stable and reliable cell surface marker for labeling mature neutrophils, even under pathological conditions. C_LI

immunology↗

bioRxiv2026

Telomere-to-telomere assembly and haplotype analysis of tetraploid Dendrobium officinale illuminate Orchidaceae polyploid evolution and mycorrhizal symbiosis genes

Dendrobium officinale is a typical epiphytic orchid. We report the telomere-to-telomere (T2T) genome assembly for D. officinale, representing the first T2T reference genome within the Orchidaceae family. The assembly is anchored to 19 chromosomes and contains 38 complete telomeres and 15 characterized centromeres. We further generated haplotype-resolved assemblies of the autotetraploid genome, identifying 12,761 sets of tetra-allelic genes. Based on synonymous substitution analysis, we inferred that the autotetraploidization event occurred approximately 0.86 million years ago. A systematic analysis of the SWEET gene family across the genus Dendrobium revealed that the gene family size is shaped primarily by epiphytic types and environmental factors. In D. officinale from Langshan, eight SWEET genes were specifically expressed in roots, suggesting they may play specialized roles in the root mycorrhizal system, potentially contributing to the D. officinales ability to recruit and maintain fungal partners. Together, these resources provide valuable foundations for studies of orchid evolution, functional genomics, and molecular breeding.

bioinformatics↗

bioRxiv2026

MATR3 is essential for oocyte growth and maturation quality through a dual molecular mechanism

The molecular mechanisms governing mRNA accumulation during oocyte growth, essential for developmental competence, remain poorly understood. This study investigates the role of Matrin-3 (MATR3), a highly expressed RNA-binding protein in growing oocytes (GOs), using oocyte-specific knockout mouse models and human oocyte maturation arrest (OMA) samples. The results showed that MATR3 was more abundant in GOs than fully-grown oocytes (FGOs), highly expressed in the nucleus of non-surrounded nucleolus (NSN) oocytes, and exited the nucleus during the NSN-to-surrounded nucleolus (SN) transition. In OMA patients, MATR3 nuclear localization was missed, with smaller oocytes than FGOs. Further, Matr3 deletion in mouse GOs caused restricted oocyte growth, global transcription disorders, follicle development failure, blocked GO-granulosa cell communication (via reduced Gdf9 and Radixin expression), and infertility. Mechanistically, MATR3 regulated transcription by recruiting H3K9me2-demethylating lysine-specific demethylase 3B or binding target gene promoters, like Radixin. These findings reveal a critical role of MATR3 in orchestrating transcription and paracrine signaling during oogenesis and suggest its potential as a diagnostic and therapeutic target for OMA.

physiology↗

bioRxiv2025

Pan-cancer tumor classification by a holistic tumor microenvironment atlas

The tumor microenvironment (TME) heterogeneity presents a major bottleneck to effective cancer immunotherapies. We address this by establishing a pan-cancer tumor classification system based on the holistic TME cellular components. First, using single-cell transcriptomes from 1,271 patients across 26 cancer types, we compile a TME cellular atlas, leading to the identification of recurrent cell states and multicellular modules across cancer types. Among these, we highlight a type I interferon (IFN-I)-related multicellular module, including IFIT1+ tumor-associated macrophages, as a critical contributor to immune-activation TMEs. From a holistic perspective, pan-cancer TMEs exhibit trichotomous patterns predominantly driven by T, myeloid, and stromal compartments. Leveraging fine-grained TME cellular composition, we further stratify all tumors into 10 stable groups. These groups display varying responses to immune checkpoint blockade (ICB), and each rationally selected therapeutic strategy specifically perturbs the corresponding expression signature. Our pan-cancer tumor classification scheme reveals the underlying patterns of TME heterogeneity and provides a framework for stratifying patients, guiding treatment selection, and developing novel therapeutic options.

cancer biology↗

bioRxiv2025

Dynamic brain states during encoding and their post-encoding reinstatement predicts episodic memory in children

Episodic memory, the ability to rapidly learn and explicitly remember past events and experiences, plays a critical role in childrens academic learning and knowledge acquisition. The formation of lasting memories relies on the brains ability to dynamically organize its activity. How these neural configurations unfold moment-by-moment across encoding and offline phases remains poorly understood. To probe these dynamics, we applied a novel Bayesian Switching Dynamic Systems approach, a hidden Markov model with automatic state detection, to fMRI data from children performing scene encoding followed by an offline post-encoding rest. We identified four distinct brain states during encoding with unique activation modes between visual, medial temporal lobe, and frontoparietal and default mode network nodes. An "active-encoding" state with integrated visual-hippocampal and frontoparietal activity dominated encoding and predicted individual memory performance, while an inactive state negatively predicted performance. State transition dynamics revealed that flexible shifts into the active-encoding state enhanced memory formation, whereas transitions toward inactive states impaired it, demonstrating that memory success depends on dynamic neural flexibility. Critically, encoding states spontaneously reemerged during post-encoding rest. A "default-mode" state characterized by enhanced default mode network activity showed sustained maintenance during rest and robustly predicted memory outcomes, an effect specific to post-encoding, not pre-encoding rest. These findings establish that episodic memory emerges from coordinated brain state sequences bridging online encoding with offline consolidation, providing a computational framework for how moment-to-moment neural dynamics support memory formation in children. This work has broad implications for optimizing educational interventions and understanding developmental disorders affecting learning and memory.

neuroscience↗

bioRxiv2025

DEEPReditor-CMG: A deep-learning-based predictive RNA editor for crop mitochondria genomes

C-to-U RNA editing is a pervasive phenomenon in crop mitochondria, playing a pivotal role in the processing of functional proteins encoded by mitochondrial genes and serving as a crucial regulatory mechanism for nuclear control over mitochondrial gene expression. However, identifying editing sites across the mitochondrial genome with high precision remains a formidable challenge. To address this challenge and uncover the potential regulatory patterns of C-to-U RNA editing, this study compiled a comprehensive dataset of mitochondrial genome sequences from 13 crops, including Arabidopsis thaliana, Lactuca sativa var. Capitata, Oryza sativa Japonica, and Zea mays, among others, annotated with editing sites from NCBI. Utilizing TensorFlow 2.0, we constructed a rigorous hyperparameter optimization framework, which facilitated the development of the DEEPReditor-CMG model, demonstrating superior predictive capabilities. Based on the DEEPReditor-CMG model and three interspecies relationship indices, we discovered that species with closer phylogenetic relationships exhibit more similar C-to-U RNA editing mechanisms, providing valuable insights into the evolutionary conservation of RNA editing mechanisms. We further developed executable programs for predicting C-to-U RNA editing sites in crop mitochondrial genomes, leveraging the conserved nature of the crop RNA editing machinery to maximize prediction reliability and uncover new editing sites with great potential. This research not only deepens our understanding of C-to-U RNA editing and post-transcriptional regulatory mechanisms in crop mitochondria but also paves a novel avenue for investigating RNA editing mechanisms. Experimental data, computational code, and applications are publicly accessible at https://github.com/Qinsidong/DEEPReditor-CMG. HighlightsHigh-precision prediction model for C-to-U RNA editing in crops--DEEPReditor-CMG Three interspecies relationship indices describing C to U RNA editing Prediction tools based on the conservation of crop RNA editing mechanisms Open-sourced experimental data, computational code, and applications

bioinformatics↗

bioRxiv2025

Imaging Cellular Metabolic Rewiring with SuMMIT-SRS

Cells dynamically rewire their metabolic pathways in response to physiological and pathological cues. Such plasticity is particularly critical in neurons, stem cells, cancer cells, and immune cells, where biosynthetic demands can shift rapidly. However, current metabolic imaging techniques using isotope labeling typically track only one metabolite at a time, limiting their ability to capture the rapid dynamics of complex metabolic networks including coordinated precursor utilization, crosstalk, and turnover. Here, we present Subcellular Multiplexed Metabolic Isotope Tracing Stimulated Raman Scattering microscopy (SuMMIT-SRS), a platform that enables simultaneous visualization of multiple metabolic dynamics at subcellular resolution. By exploiting the distinct vibrational signatures of carbon-deuterium bonds derived from multiple deuterated amino acids, lipids, and monosaccharide tracers, SuMMIT-SRS maps co-regulated DNA, RNA, protein, and lipid synthesis at the same time and resolves various individual amino acid-mediated metabolic pathways within intact cells and tissues. We demonstrate SuMMITs broad utility across Drosophila fat body tissue and developing brain, tumor organoids, aged human neurons, and mouse liver, capturing cell type-specific metabolic rewiring under genetic and pathological perturbations. This approach extends SRS to multiplexed isotope tracing, offering a powerful tool to uncover dynamic and complex biosynthesis programs in development, health, and disease.

bioengineering↗

bioRxiv2025

3D multi-omic mapping of whole nondiseased human fallopian tubes at cellular resolution reveals a large incidence of ovarian cancer precursors

Uncovering the spatial and molecular landscape of precancerous lesions is essential for developing meaningful cancer prevention and early detection strategies. High-Grade Serous Carcinoma (HGSC), the most lethal gynecologic malignancy, often originates from Serous Tubal Intraepithelial Carcinomas (STICs) in the fallopian tubes, yet their minute size and our historical reliance on standard 2D histology contribute to their underreporting. Here, we present a spatially resolved, multi-omics framework that integrates whole-organ 3D imaging at cellular resolution with targeted proteomic, metabolomic, and transcriptomic profiling to detect and characterize microscopic tubal lesions. Using this platform, we identified a total of 99 STICs and their presumed precursors that harbor TP53 mutations in morphologically unremarkable tubal epithelium in all five specimens obtained from cancer-free organ donors with average-risk of developing ovarian cancer. Although these lesions comprised only 0.2% of the epithelial compartment, they displayed geographic diversity, immune exclusion, metabolic rewiring, and DNA copy number changes among lesions and normal fallopian tube epithelium discovered alterations in STIC-associated genes and the pathways they control. In sum, this platform provides a comprehensive 3D atlas of early neoplastic transformation, yielding mechanistic insights into tumor initiation and informing clinical screening strategies for detecting cancer precursors in whole organs at cellular resolution.

bioinformatics↗

bioRxiv2025

Brain Preparedness for Active Forgetting: Cortisol Awakening Response Proacts Prefrontal Control Over Hippocampal-Striatal Circuitry

Stress-related psychiatric pathologies (e.g., rumination in depression, intrusive memories in PTSD) involve impaired inhibitory control over emotional memories and disrupted cortisol circadian rhythms. However, how these mechanisms interact to support adaptive forgetting remains unclear. Here, by integrating multi-modal neuroendocrine profiling with fMRI-based memory suppression in 90 participants, we demonstrate that the cortisol awakening response (CAR)--a circadian surge priming the brain for daily demands--proactively and selectively enhances suppression of recently acquired but not overnight-consolidated emotional memories. This time-dependent facilitation manifests through dual neural mechanisms: Robust CAR broadly amplifies dorsolateral prefrontal cortex (dlPFC) engagement during suppression attempts and specifically strengthens top-down dlPFC control over hippocampal-striatal circuits exclusively for recent traces. Our findings bridge circadian biology, systems neuroscience, and clinical psychopathology to establish CAR as a neuroendocrine preparedness mechanism that proactively configures adaptive forgetting circuits across sleep-wake cycles, thereby informing circadian-based interventions for stress disorders.

neuroscience↗

bioRxiv2025

The interplay between glucose and aromatic compound regulation by two IclR-type transcription factors, LigR1 and LigR2, in Pseudomonas putida KT2440

The rhizosphere is a hotspot of microbial activity where plants release a diverse array of aromatic compounds, including shikimate pathway intermediates and monolignols. Pseudomonas putida KT2440, renowned for its metabolic versatility in this niche, uses largely uncharacterized regulatory and enzymatic strategies to utilize these compounds. We investigated two IclR-type transcriptional regulators, LigR1 and LigR2, that control expression of the uncharacterized lig1 and lig2 operons. We demonstrate that ligR1 deletion caused growth defects on glucose and 4-hydroxybenzoate accompanied by cell elongation and aggregation. Structural and functional analyses reveal that LigR1 and LigR2 activate the lig1 operon but repress the lig2 operon. LigR1 binding of 4-hydroxybenzoate induced repression by triggering tetramerization and increasing DNA-binding activity. In contrast, LigR2 responded to quinate, protocatechuate and 4-hydroxybenzoate to potently induce lig2 operon expression by relieving repression. While both operons cooperate in metabolizing these compounds, we propose the lig1 operon mediates influx through its major facilitator superfamily (MFS) transporter (PP_2604), whereas the lig2 operon catalyzes breakdown via a protocatechuate intermediate and the meta-cleavage pathway, supplying oxaloacetate to the TCA cycle. Importantly, we show that P. putida repurposes shikimate pathway intermediates for energy production. These findings challenge the canonical biosynthetic view of the shikimate pathway and redefine the metabolic flexibility of soil pseudomonads. We reveal a novel mechanism enabling P. putida to thrive in the chemically complex rhizosphere and open new avenues for exploring alternate roles of the shikimate pathway, emphasizing transcriptional regulators as tools to deconvolute complex metabolic landscapes. HighlightsO_LILigR1 and LigR2 transcriptionally regulate the lig1 and lig2 operons C_LIO_LILig1 operon is required for import of glucose and shikimate-derived compounds C_LIO_LILig2 operon metabolizes shikimate pathway compounds C_LIO_LIDysregulated LigR1/LigR2 expression impacts bacterial physiology C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=189 HEIGHT=200 SRC="FIGDIR/small/670189v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@9b461aorg.highwire.dtl.DTLVardef@175c73org.highwire.dtl.DTLVardef@1b6bd90org.highwire.dtl.DTLVardef@574e55_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗