Biology subjects

Chen, Y.-Y.

Publications and source records attributed to Chen, Y.-Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Engineered probiotics target granulomas to treat mycobacterial infection

Granulomas are a pathological niche for mycobacteria that remain difficult to access with conventional therapies. Here we show that probiotic Escherichia coli Nissle 1917 (EcN) infiltrates and colonizes granulomas and can be engineered as a delivery system that senses the local microenvironment and releases antimycobacterial payloads. Specifically, we leveraged the hypoxic microenvironment of necrotic granulomas to restrict bacterial growth, and developed a dual-mode lysis circuit combining intracellular and extracellular killing for sustained payload release with limited evolutionary escape. We further engineered EcN to express a mycobacteriophage-derived enzyme, generating a strain that suppressed drug-sensitive and drug-resistant mycobacteria in vitro and potentiated conventional antibiotic activity. Engineered probiotics also reduced mycobacterial burden in vivo, and in a murine model of rifampicin-resistant infection, combination treatment with pretomanid achieved greater bacterial reduction than either monotherapy. Together, these results establish a synthetic biology framework for targeting granulomatous infections with programmable living microbes.

synthetic biology↗

bioRxiv2026

Parent-Child Cortical Similarity Indexes Multiple Dimensions of Sensitivity in the Association Between Family Environment and Adolescent Internalizing Symptoms

Family environment is a robust predictor of adolescent internalizing symptoms, yet its strength varies across adolescents. We tested whether this variation is partly captured by how similar an adolescent's cortical structure is to their parent's and whether different forms of this similarity matter in different cortical systems. In 115 parent-child dyads from two cohorts, structural MRI quantified similarity across 400 cortical parcels in two forms: phenotypic similarity in regional morphometry and architectural similarity in interregional morphometric organization. Parent-child similarity was not directly associated with symptoms, whereas its interactions with family environment were jointly significant (chi-square(4) = 14.92, P = 0.005). Phenotypic similarity in the sensory-limbic system and architectural similarity in the association system each moderated the association between family environment and symptoms (both beta = 0.22). In both cases, the association was strongest among less similar dyads. The phenotypic interaction was distributed across sensory-limbic networks and was not reproduced by similarity to unrelated adults or by the child's cortical atypicality. The architectural interaction was concentrated in the dorsal attention and default mode networks and was distinguishable from unrelated-adult similarity but not from child atypicality. Together, these findings raise the possibility that markers of environmental sensitivity need not reside in the child alone. Parent-child cortical similarity may index a dyadic component of this sensitivity, one not adequately represented by a single similarity score but distributed across forms of similarity and cortical systems.

neuroscience↗

bioRxiv2026

A convergent behavioral-neural profile of parental dysregulation and the link between parent-child brain-state similarity and child negative affect

Parent-child neural similarity is often interpreted as a marker of attunement, but its developmental significance may not be uniformly positive across family environments. We tested whether the parent's own emotional and regulatory profile, measured both behaviorally and neurally, moderates the developmental significance of parent-child neural similarity. Applying a hidden Markov model (HMM-MAR; K = 6 states) to whole-brain fMRI timeseries from 32 parent-youth dyads who separately watched the same emotional film, we derived per-dyad measures of brain-state similarity. Parent-child dyads showed greater brain-state similarity than parent-shuffle null pairs (d = -0.55, p = .004), indicating dyad-specific alignment beyond responses shared across viewers of the same film. Parent self-reported internalizing showed only a weak direct relation to child negative affect (r = .31, p = .085). However, the association between neural similarity and child negative affect depended on parent internalizing (b = 5.62, p = .018; R^2): stronger parent-child similarity predicted higher child negative affect when parents reported higher, but not lower, internalizing. A parallel interaction emerged when parent internalizing was replaced by a neural index of the parent's own state dynamics (parent neural-state unpredictability, Htrans; b = 5.95, p = .004), indicating that the effect reflects the parent's broader regulatory profile rather than a single measurement modality. Both interactions were clearest in the primary model and only partially robust across model orders and parcellations. These findings suggest that dyadic neural similarity should be interpreted in context: resembling a parent with a dysregulated profile may confer risk rather than protection.

neuroscience↗

bioRxiv2026

MorphQ: label-free quantification and visualisation of complex morphology from standardised specimen images

O_LIQuantifying complex morphology from images remains difficult because predefined descriptors capture only selected traits. Yet, supervised machine learning models for images require labels and often produce task-specific features that are hard to interpret as biological traits. C_LIO_LIWe present MorphQ, a label-free, self-supervised method that learns a quantitative morphospace from standardised specimen images. Its encoder produces feature vectors for statistical analysis, and its decoder converts analysed positions in morphospace into human-interpretable images, including hypothetical forms not represented by sampled specimens or sampled taxa. C_LIO_LIUsing 1,868 Lepidoptera species, we tested whether MorphQs label-free features were more useful for downstream analysis than features from principal component analysis (PCA) or a supervised species-classification machine learning model. As a diagnostic probe of downstream biological utility, MorphQ features supported higher low-label family-classification accuracy than comparator features, and retained stronger family-level similarity for species absent from model training, indicating better generalisation to species not seen during model training. C_LIO_LITwo case studies link MorphQ morphospaces to species-level elevation and assemblage-level functional diversity while keeping statistical patterns visually inspectable. MorphQ provides a reproducible framework for constructing interpretable morphological trait spaces when predefined descriptors are incomplete and labelled data are limited. C_LI Data/code for peer review: An anonymised repository containing the source code, trained model weights, example data, configuration files and scripts required to reproduce the analyses is available at https://anonymous.4open.science/r/MorphQ-ECD4/.

ecology↗

bioRxiv2026

Family Conflict and Parent-Child Similarity in Affective Valuation

How children come to evaluate social-affective cues is shaped within the family, yet the neural expression of this process and its dependence on family relationships remain unclear. We tested whether parent-child similarity in the neural coding of affective judgment varies with family environment, and whether it relates to youth affective distress. Twenty-five parent-child dyads (youth, mean age 11.8; parents mean age 42 years) judged faces morphed along an angry-to-happy continuum as positive or negative during fMRI. For each participant, we defined an evaluative choice axis distinguishing faces judged positive from negative, independent of expression intensity. Using searchlight-based parent-child cross-decoding, we tested whether one dyad members evaluative coding predicted the other members judgments, indexing shared evaluative coding rather than shared sensitivity to expression intensity. Inference focused a priori on medial prefrontal cortex. There was no reliable average parent-child neural similarity across the sample. Instead, higher family conflict was associated with lower parent-child neural similarity in ventromedial prefrontal cortex (vmPFC). Demonstrating specificity to negative relational strain, this effect was not observed for complementary dimensions of family cohesion or identity. Moreover, the effect was specific to true dyads rather than random pairings and to vmPFC rather than a face-selective network or other medial prefrontal regions. Lower vmPFC similarity showed a preliminary association with higher youth affective distress. These findings indicate that affective valuation, rather than sensory encoding, may be a representational level at which perceived family conflict is reflected in parent-child neural similarity.

neuroscience↗

bioRxiv2026

Positive Interpretation of Emotional Ambiguity Across Development: LC-dlPFC Circuitry

Emotionally ambiguous facial expressions provide a tractable model for studying how uncertain affective information is resolved into categorical judgments. Here we tested whether developmental differences in this process are reflected in locus coeruleus (LC) circuitry and how these neural effects relate to behavioral and decision-process indices of interpretive bias. Participants from late childhood through middle-aged adulthood completed an angry-to-happy facial morph task during fMRI. Behavioral responses were analyzed using signal detection theory, and drift-diffusion modeling, and fMRI data were analyzed using LC-seeded generalized psychophysiological interaction and trial-level neural models. Positive bias increased systematically across development. Drift-diffusion analyses showed that this shift was captured specifically by drift intercept, a stimulus-independent evaluative component of evidence accumulation, rather than by perceptual sensitivity, starting point, or response caution. At the neural level, the association between LC-dlPFC coupling and positive bias was strongest in middle-aged adults. Trial-level analyses further indicated that dlPFC carried the clearer moment-to-moment evaluative signal, whereas LC contributed through slower temporal properties, indexed by the Hurst exponent, that shaped bias-related cortical coupling. Importantly, higher LC structural integrity (contrast-to-noise ratio) was associated with lower LC temporal persistence and, in turn, more negative LC-dlPFC coupling. Together, these findings suggest that age-related differences in positive interpretation are not simply differences in perceptual sensitivity or response tendency, but reflect age-graded variation in evaluative evidence accumulation supported by LC-dlPFC circuitry. This work extends recent evidence implicating LC-prefrontal connectivity in ambiguity processing and identifies evaluative drift bias as an age-graded circuit-level signature of emotional ambiguity resolution. Significance StatementHow the brain resolves emotionally ambiguous faces across development is poorly understood. Using psychometric, drift-diffusion, and fMRI analyses in youth, emerging adults, and middle-aged adults, we show that age-related increases in positive interpretation are explained by drift intercept, a stimulus-independent evaluative component of evidence accumulation, rather than by perceptual sensitivity or starting-point bias. LC-dlPFC coupling tracked this same bias dimension. Trial-level analyses suggested that dlPFC carried the clearer moment-to-moment evaluative signal, whereas LC contributed through slower temporal properties of bias-related coupling. These findings identify evaluative drift bias as a measurable circuit-linked mechanism of emotional ambiguity resolution.

neuroscience↗

bioRxiv2026

Verticillium dahliae ubiquitin-specific proteases coordinate key developmental processes and pathogenicity

Ubiquitin is a posttranslational modifier that is conserved among eukaryotes. Ubiquitination alters stability and folding of cellular proteins. Deubiquitinases (DUBs) reverse ubiquitination and often function as part of protein complexes. There are 32 predicted DUB-encoding genes present in the soil-borne phytopathogenic fungus Verticillium dahliae. Nuclear ubiquitin-specific protease 3 (Usp3) is a member of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, whereas Usp1 is predicted to associate with the COP9 signalosome (CSN), which controls specificities of cellular E3 ubiquitin ligase activities. A proteomics approach using biotin capture and identification (BioID) supports that Usp3 regulates gene expression beyond the transcription level. Western experiments showed a dysregulation in ubiquitinated cellular proteins in corresponding deletion strains. Usp3 and Usp1 are both required for fungal development. They regulate microsclerotia formation based on different environmental cues and provide redundant functions in controlling conidiation. Absence of both corresponding genes resulted in significant impairment of conidiospore formation, which is required for fungal propagation within the plant vascular system. This paralysed spreading ability reduced virulence on tomato plants (Solanum lycopersicum). In summary, V. dahliae responds to environmental cues by Usp3- and Usp1-mediated adjustment of gene expression and protein stability. This is important for key developmental processes of the V. dahliae disease cycle and its virulence towards the host plant. Author summaryUbiquitination and deubiquitination of proteins enable cells to rapidly react to environmental cues and adjust protein stabilities and subsequently transcriptomic profiles. Usp3 is a nuclear deubiquitinase subunit of the Spt-Ada-Gcn5 acetyltransferase (SAGA) transcriptional coactivator complex. Usp1 is predicted to be associated with the COP9 signalosome that regulates substrate specificities of the ubiquitin-proteasome system. BioID experiments suggest that other SAGA complex subunits, histone proteins, spliceosomal proteins, ribosomal proteins, a protein that tackles transcriptionally stalled RNAPII, and a protein that degrades mRNA with premature stop codons locate proximal to Usp3 within the cell. Deletion of USP3 led to the dysregulation of protein ubiquitination. A single deletion of USP1 did not significantly change ubiquitination profiles, however, a double deletion of USP1/3 significantly affected the ubiquitin-proteasome system. The altered ubiquitination profile correlated with a dysregulation of key developmental processes. Microsclerotia formation was decoupled from environmental cues in the {Delta}USP3 strain, whereas an additional deletion of USP1 reconnected it in a media-dependent manner. USP3 and USP1 contribute to a common governing process in conidiation, and the defect in spreading of the {Delta}USP1/3 strain is reflected by a significant reduction in plant pathogenicity.

microbiology↗

bioRxiv2026

Intermittent exposure to high ambient heat during the second half of gestation in mice causes mild alterations of reproductive endpoints in male embryos

Periods of elevated ambient temperature challenge the bodys ability to maintain internal homeostasis, and heat stress poses particular risks during pregnancy. Epidemiological studies associate gestational heat exposure with higher rates of congenital anomalies such as hypospadias, yet the direct link between gestational heat exposure and reproductive anomalies remains unknown. In this study, we examined the effects of intermittent heat exposure on reproductive development in male mouse offspring. Pregnant dams either remained at constant temperature of 22{degrees}C (control) or were exposed to 38{degrees}C for 2 hours daily (experimental) from embryonic day (E)10 to E18, modeling intermittent heat exposure during mid-to-late gestation. Embryos were collected at E18 for analysis. While heat exposure did not affect pregnancy outcomes, including placental development, litter size, sex ratio, or fetal growth, male embryos exhibited significantly reduced anogenital distance and increased hypospadias scores, which are both markers of disrupted androgen signaling. Despite these phenotypic changes, expression of genes involved in androgen synthesis in the fetal testis, as well as gene expression in external genitalia, remained unchanged. Instead, transcriptomic analysis revealed significant alterations in testicular pathways related to RNA splicing and mRNA processing. Together, these findings reveal that maternal heat stress disrupts reproductive development of male offspring, with altered gene regulatory processes being a potential driver.

developmental biology↗

bioRxiv2026

Specification of the interstitial cell lineage in the fetal mouse ovary requires balanced Notch signaling

The ovary contains two major somatic lineages, granulosa cells and interstitial cells, that arise from progenitors within the coelomic epithelium. However, how these two lineages diverge during ovarian development remains unclear. By analyzing joint single-nucleus transcriptomic and chromatin accessibility profiles of murine ovarian cells at the onset of ovary formation, we identified two somatic progenitor populations from the coelomic epithelium distinguished by expression of the nuclear receptors Nr5a1 and Nr2f2. Based on their transcriptomic trajectories, the Nr5a1+ epithelial cells preferentially transitioned toward the granulosa lineage whereas the Nr2f2+ epithelial cells differentiated into mesenchymal populations. This lineage relationship was supported by Nr2f2 lineage tracing experiments that fetal Nr2f2+ progenitors contribute to ovarian interstitial cells postnatally. To define the molecular features underlying this divergence, we performed differential gene expression and chromatin accessibility analyses and found that Nr2f2+ epithelial cells, but not Nr5a1+ cells, were enriched for Notch pathway components and Notch effector motifs. Consistently, lineage tracing of Notch-responsive cells marked Nr2f2+ interstitial cells in postnatal ovaries, whereas ectopic Notch activation in Nr5a1+ cells promoted expansion of the interstitial population accompanied by reduced granulosa cells. By integrating motif analysis with accessible chromatin-gene linkage, we also identified downstream targets regulated by Notch effectors in Nr2f2+ cells, which showed concordant changes upon ectopic Notch activation. These findings demonstrate that somatic cell fate is established early during ovarian development, with active Notch signaling specifying the interstitial lineage and a balanced Notch activity required for proper somatic lineage establishment. Significance StatementProper differentiation of somatic cell types in the fetal ovary lays the foundation for future ovarian function in adulthood. Understanding how each cell type is formed is essential for developing methods to intervene in ovarian diseases caused by cellular dysfunction. Given that common somatic progenitors give rise to both supporting and interstitial lineages, a main unanswered question is how these two lineages diverge apart from each other during ovarian development. By integrating joint single-nucleus transcriptomic and chromatin accessibility assays with lineage tracing, single cell RNA-sequencing, and mouse genetic models, we demonstrate the role of Notch signaling in specifying the interstitial lineage and separating it from the supporting cell fate.

developmental biology↗

bioRxiv2026

Blank Spectrum Correction as a Robust Solution to Artifacts in Quantitative X-ray Fluorescence Mapping

X-ray fluorescence microscopy (XFM) continues to develop as a powerful quantitative technique for high resolution, label-free, elemental mapping of biological, environmental, and material samples. Methods for rigorously fitting spectra, increasing throughput, accounting for background signals, and deconvoluting overlapping emission lines continue to evolve. We show here that quantitative fits of XFM data obtained after removing a baseline, calculated by connecting peak edges, can be unexpectedly dependent upon acquisition dwell-time and spectral aggregation leading to differences in apparent elemental content. Using mouse preimplantation embryos and ovarian follicles as model samples, we demonstrate how these variables influence quantitative comparisons between samples. We find that subtracting an empirically measured blank spectrum instead of a baseline provides quantitative XFM elemental mapping results that are independent of dwell time and spectral aggregation dependencies.

biophysics↗

bioRxiv2025

High-Frequency Activity Encodes the Temporal Dynamics of Hierarchical Prediction Errors in Humans: An Electrocorticography Study

Prediction error refers to the discrepancy between expected and actual sensory input. Its hierarchical organization has been demonstrated through decomposed brain responses in the local-global paradigm, where temporal regularities are established locally at individual stimulus transitions and globally across multi-tone sequence structures. In macaques and marmosets, local and global prediction-error signals have both been found in high-frequency oscillations (60-150 Hz) recorded with ECoG. In humans, however, these signals have primarily been observed in a lower frequency range (30-100 Hz) using EEG. Here, we recorded human ECoG to achieve higher signal fidelity, enabling examination of neural oscillations above 100 Hz (high-frequency activity, HFA), which are believed to be closely linked to local spiking activity. Eight participants listened to auditory sequences that either followed their local and global regularities (local and global standards) or violated them (local and global deviants). Robust HFA responses were observed for the local deviants, but these responses were reduced when the deviants were expected based on the global regularity, indicating both levels of prediction-error processes contribute to the observed activity. Importantly, these HFA responses could be decomposed into two subcomponents: an early component reflecting local prediction-error signals localized to lateral auditory regions, and a late component reflecting global prediction-error signals prominent in both lateral auditory and frontal cortices. Together, these findings demonstrate that neural oscillations above 100 Hz encode hierarchical prediction errors not only in non-human primates but also in humans.

neuroscience↗

bioRxiv2025

The adapt-to-nutrient NRPS-like secondary metabolite gene cluster facilitates Verticillium dahliae adaptation to different nutrient environments

Filamentous fungi produce a wide range of secondary metabolites to adapt to changing environments. RNA sequencing revealed that nine biosynthetic gene clusters (BGCs) of the phytopathogenic Verticillium dahliae react to different nutrient environments. The adapt-to-nutrient NRPS-like (ANN) cluster contributes to antibacterial activity and developmental processes important for the early biotrophic life cycle, but is dispensable for virulence on tomato (Solanum lycopersicum). Transcription of the core biosynthetic enzyme-encoding ANN3 is highly induced in nutrient-poor environment. ANN3 is transcriptionally controlled by global and in-cluster transcription factors. ANN3 is activated by early colonisation transcription factors Som1 and Vta2, but repressed by Mtf1, which governs late stages of disease progression. The in-cluster transcription factor Ann1, which represses ANN3, is less stable in nutrient-poor environment or when V. dahliae encounters antagonists. Ann1 promotes resting structure formation but suppresses conidiation and antibacterial activity. Possible products of the ANN cluster were revealed by comparing metabolites extracted from ANN3 regulator mutants and from the bacterial-fungal interaction zone. Our findings revealed that V. dahliae perceives different nutrient environments and changes its survival strategy by differential expression of the ANN secondary metabolite gene cluster. Author summaryVerticillium dahliae is an economically significant phytopathogen that is widely distributed. The fungus adjusts and adapts its survival strategy according to the surrounding environment. Transcriptome data revealed that the core biosynthetic gene ANN3 of the adapt-to-nutrient NRPS-like (ANN) cluster is most expressed in nutrient-poor environments. The expression of ANN3 is governed by in-cluster repressor Ann1 and global transcriptional regulators that regulate other metabolic processes. Transcription factors Som1 and Vta2 are involved in the early plant-root infection process, whereas Mtf1 regulates late stage of disease development. ANN3 is activated by Som1 and Vta2, but repressed by Mtf1. The repressor Ann1 is less stable in nutrient-poor environments or when bacterial competitors are present. Ann1 promotes dormancy and represses spreading by conidiation. Vegetative growth is reduced but antibacterial activity is promoted when ANN1 is deleted. Possible chemical products of the ANN cluster were identified by comparing the metabolites extracted from the regulator mutant strains and the bacterial-fungal interaction zone. In summary, our findings show how V. dahliae react to environmental signals to balance growth, survival, and competition through the ANN cluster.

genetics↗

bioRxiv2025

Automated Locus Coeruleus segmentation and age-related signal changes across Neuromelanin-sensitive MRI and T1/T2-weighted images

The locus coeruleus (LC) plays a key role in stress response, attention, and cognitive function, with its integrity closely linked to neuromelanin accumulation. Neuromelanin-sensitive MRI (NM-MRI) has enabled in vivo imaging of the LC, but automated segmentation remains challenging due to its small size, low contrast, and anatomical variability. This study aimed to evaluate the accuracy of automatic LC segmentation using multi-atlas nonlinear warping applied to high-resolution T1/T2-weighted images and to compare LC intensity characteristics across NM-MRI, T1w, and T2w images. Additionally, we examined developmental changes in LC signal from childhood through adulthood. We analyzed MRI data from 134 participants (ages 8[~]64) with NM-MRI, T1w, and T2w scans, alongside 652 participants (ages 6[~]22) from the Human Connectome Project in Development (HCP-D). LC intensity measures were compared across imaging modalities and analyzed for age-related trends. Automatic LC segmentation achieved high spatial overlap with manual tracings (up to 95% after one voxel 2D-dilation). Statistically estimated high (or low)-intensity values (mean {+/-} 2{sigma}) from automated LC masks provided a more stable and noise-resilient alternative to local peak intensity measures. Age-related LC signal changes are most clearly observed in NM-MRI and T2w imaging, with significant developmental shifts emerging during adolescence. These findings support the conventional T2w imaging as an indirect marker of neuromelanin accumulation and highlight the possibility of age-specific analyses in LC imaging studies.

neuroscience↗

bioRxiv2025

Glycogen metabolism in mouse embryonic Sertoli cells sustains the germ line through the lactate shuttle

Metabolites are key regulators of cell fate decisions, epigenetic remodeling, and lineage commitment. While genetic pathways governing testis differentiation are well studied, the role of metabolism remains poorly understood. In this study, we investigated a transient, male-specific accumulation of glycogen in supporting (Sertoli) cells of embryonic testis in mice. Although glycogen metabolism was dispensable for Sertoli cell differentiation, its disruption led to reduced lactate production and impaired PGCs ability to colonize the newly forming testis cords. Inhibiting lactate transport further revealed a critical metabolic coupling between Sertoli and germ cells during early testis development. Surprisingly, external lactate or glucose supplementation failed to rescue the germ cell phenotype. These findings suggest that glycogen accumulation supports a critical developmental window in which both Sertoli and germ cells are metabolically constrained and unable to rely on external carbon sources. This highlights a sensitive period during testicular development where nutrient scarcity could have long-term consequences for fertility.

developmental biology↗

bioRxiv2025

From Family Relationship to Regulation: Parent-Child Amygdala Activation Similarity is Linked to Prefrontal Recruitment and Youth Emotional Adaptation

Extensive research highlights the importance of parent-child similarity at psychological, behavioral, and physiological levels in fostering childrens adaptation. While emerging studies have begun to explore neural similarity, little is known about the factors that influence parent- child neural similarity during adolescence or how such similarity may support youth emotional adaptation when coping with heightened uncertainty. The current study investigated the relations among family relationship quality, parent-youth neural similarity, and youth emotional adaptation using task-based fMRI. With 50 participants (25 parent-youth dyads; parent: Mage = 43.88{+/-}7.42 years, 72% female; youths: Mage = 11.16{+/-}2.85 years, 44% female), we found that higher parent-youth neural similarity in the amygdala activation patterns during emotionally uncertain situations was associated with better youths emotional adaptation, as indicated by lower levels of anxiety and depression and higher resilience. This neural similarity mediated the beneficial effects of positive family relationships on youths emotional adaptation. Additionally, amygdala activation similarity was associated with amygdala to dorsolateral prefrontal cortex (dlPFC) connectivity during uncertainty in youth, revealed by generalized psychophysiological interaction (gPPI) analyses. This amygdala-dlPFC connectivity, in turn, was linked to better emotional adaptation in youth. Importantly, these findings were specific to uncertainty-related bottom-up processing, rather than effortful top-down regulation processing or responses to certain aversive stimuli. These findings offer new insight into how relational and neural factors jointly shape youth emotional adaptation, and suggest that parent-child neural similarity in the amygdala may serve as a mechanism for supporting implicit emotion regulation, helping youth cope with uncertain situations. Significance StatementDuring adolescence, youth begin to expand their social worlds beyond the family, yet family relationships continue to shape how they navigate emotionally complex environments. How do these relationships influence youth brain function and emotional well-being? Using task-based fMRI, we found that greater parent-child neural similarity in the amygdala during emotionally uncertain situations is associated with youths lower anxiety and depression and greater resilience. This amygdala neural similarity was also linked to prefrontal engagement in youth during early arousal stage, supporting adaptive implicit regulation under uncertainty. These findings suggest that neural alignment between parents and youths may serve as a key mechanism by which positive family relationships promote emotional adaptation, highlighting the enduring role of family context in adolescent brain development.

neuroscience↗

bioRxiv2025

Super-giga and tiny orchid genomes illuminate evolution of Orchidaceae

Orchidaceae (orchids) is commonly known as one of the largest families of seed plants, and grow in an extensive range of habitats worldwide. In the present study, we generated chromosome-level reference genomes for two orchids using a combination of PacBio, Illumina, and Hi-C sequencing, Cypripedium singchii has the largest genome and chromosomes among the sequenced species so far, with a genome size of 43.19 Gb (1C) with ten chromosomes, and Apostasia fujianica has the smallest known genome and chromosomes in Orchidaceae, with a genome size of 340.90 Mb (1C) with 35 chromosomes. We predicted a total of 32,412 and 21,724 protein-coding genes for C. singchii and A. fujianica, respectively. The overall BUSCO score was 85.01% for C. singchii and 91.80% in A. fujianica. Based on protein-coding sequences from 55 conserved single-copy families across 21 plant species, we constructed a high-confidence phylogenetic tree and estimated the divergence times. The high-quality genomes of super-giga and tiny orchids offer key insight for future evolutionary researches.

genomics↗

bioRxiv2025

Heterologous expression of carbonic anhydrase in Acinetobacter sp. Tol 5 for whole-cell biocatalysis

Carbonic anhydrase accelerates the hydration of carbon dioxide (CO2) and is an attractive biocatalyst for carbon capture and utilization. Acinetobacter sp. Tol 5 shows high adhesiveness via its cell-surface protein AtaA. We previously demonstrated its application to bacterial immobilization and gas-phase bioproduction. Here, we developed Tol 5 cells expressing carbonic anhydrase and evaluated CO2 conversion ability as whole-cell biocatalysts. A codon-optimized carbonic anhydrase from Sulfurihydrogenibium yellowstonense (SyCA) was produced in the cytoplasm, but the cells showed little activity as a whole-cell biocatalyst. To enhance activity, we fused six signal peptides (SPs) to SyCA for periplasmic expression. The Omp38-SP fusion of SyCA was properly processed to the mature size, yielding higher whole-cell activity. By contrast, the other constructs were either undetectable or remained unprocessed, resulting in lower activities. These results show that periplasmic expression of SyCA is important for efficient CO2 hydration in Tol 5 cells as whole-cell biocatalysts.

bioengineering↗

bioRxiv2025

Transcriptomic analysis of whole staged ovarian follicles reveals stage-specific folliculogenesis signatures in mice

Activation and maturation of ovarian follicles are essential for female reproduction, yet the underlying molecular and transcriptional mechanisms that govern these processes remain poorly understood. In this study, we used single follicle RNA-sequencing (RNA-seq) to identify transcriptional signatures of staged ovarian follicles, from primordial to secondary stages, to uncover the genes and pathways involved in early folliculogenesis. Our findings demonstrate that primordial follicles are transcriptionally distinct from growing follicles, with enrichment in DNA integrity and RNA processing pathways, which may play a role in preserving oocyte genomic stability and cell state during dormancy. Additionally, our analysis reveals minimal transcriptomic differences between primary and secondary follicles using traditional differential expression analysis. To better distinguish growing follicle stages, we introduce unsupervised approaches, including discrete-variable predictors of follicle stage and weighted gene co-expression analysis. We identified pathways involved in DNA integrity, meiotic arrest, and cellular metabolism that drive the transition from dormant to active follicle states, as well as pathways related to cellular growth, ECM organization, and biosynthesis in growing follicle stages. Our study offers novel insights into the molecular mechanisms governing early follicle activation and growth, providing a foundation for future research with applications in reproductive biology, contraception, and fertility preservation. Author SummaryThe development of ovarian follicles is essential for female fertility, but the molecular signals that control their growth remain unclear. In this study, we used advanced gene sequencing techniques to analyze the genetic activity of individual ovarian follicles at different stages of early development. We found that dormant follicles have unique gene expression patterns that help protect the genetic material of the egg and maintain their inactive state. In contrast, follicles that have begun to grow show increased activity in genes related to cell growth, communication, and structural changes. Interestingly, we observed that early growing follicles are more similar to each other than previously thought, prompting us to apply new analytical methods to better distinguish their developmental stages. Our findings highlight key biological pathways that regulate the transition from dormant to active follicles and uncover new genes that may play a role in this process. Understanding these mechanisms provides valuable insights into ovarian biology and could inform future research on fertility treatments, contraception, and reproductive health.

bioinformatics↗